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  1. Intensive postoperative glucose control reduces the surgical site infection rates in gynecologic oncology patients.

    Science.gov (United States)

    Al-Niaimi, Ahmed N; Ahmed, Mostafa; Burish, Nikki; Chackmakchy, Saygin A; Seo, Songwon; Rose, Stephen; Hartenbach, Ellen; Kushner, David M; Safdar, Nasia; Rice, Laurel; Connor, Joseph

    2015-01-01

    SSI rates after gynecologic oncology surgery vary from 5% to 35%, but are up to 45% in patients with diabetes mellitus (DM). Strict postoperative glucose control by insulin infusion has been shown to lower morbidity, but not specifically SSI rates. Our project studied continuous postoperative insulin infusion for 24h for gynecologic oncology patients with DM and hyperglycemia with a target blood glucose of controlled with intermittent subcutaneous insulin injections. Group 2 was composed of patients with DM and postoperative hyperglycemia whose blood glucose was controlled by insulin infusion. Group 3 was composed of patients with neither DM nor hyperglycemia. We controlled for all relevant factors associated with SSI. We studied a total of 372 patients. Patients in Group 2 had an SSI rate of 26/135 (19%), similar to patients in Group 3 whose rate was 19/89 (21%). Both were significantly lower than the SSI rate (43/148, 29%) of patients in Group 1. This reduction of 35% is significant (p = 0.02). Multivariate analysis showed an odd ratio = 0.5 (0.28-0.91) in reducing SSI rates after instituting this protocol. Initiating intensive glycemic control for 24h after gynecologic oncology surgery in patients with DM and postoperative hyperglycemia lowers the SSI rate by 35% (OR = 0.5) compared to patients receiving intermittent sliding scale insulin and to a rate equivalent to non-diabetics. Copyright © 2014. Published by Elsevier Inc.

  2. Genetic Algorithm Tuning of PID Controller in Smith Predictor for Glucose Concentration Control

    OpenAIRE

    Tsonyo Slavov; Olympia Roeva

    2011-01-01

    This paper focuses on design of a glucose concentration control system based on nonlinear model plant of E. coli MC4110 fed-batch cultivation process. Due to significant time delay in real time glucose concentration measurement, a correction is proposed in glucose concentration measurement and a Smith predictor (SP) control structure based on universal PID controller is designed. To reduce the influence of model error in SP structure the estimate of measured glucose concentration is used. For...

  3. Moderate glucose supply reduces hemolysis during systemic inflammation

    Directory of Open Access Journals (Sweden)

    Jägers J

    2018-03-01

    Full Text Available Johannes Jägers,1 Stephan Brauckmann,2 Michael Kirsch,1 Katharina Effenberger-Neidnicht1,3 1Institute of Physiological Chemistry, University Hospital Essen, Essen, Germany; 2Clinic for Anesthesiology and Intensive Care, University Hospital Essen, Essen, Germany; 3Institute of Physiological Chemistry, University Hospital Essen, Essen, Germany Background: Systemic inflammation alters energy metabolism. A sufficient glucose level, however, is most important for erythrocytes, since erythrocytes rely on glucose as sole source of energy. Damage to erythrocytes leads to hemolysis. Both disorders of glucose metabolism and hemolysis are associated with an increased risk of death. The objective of the study was to investigate the impact of intravenous glucose on hemolysis during systemic inflammation.Materials and methods: Systemic inflammation was accomplished in male Wistar rats by continuous lipopolysaccharide (LPS infusion (1 mg LPS/kg and h, 300 min. Sham control group rats received Ringer’s solution. Glucose was supplied moderately (70 mg glucose/kg and h or excessively (210 mg glucose/kg and h during systemic inflammation. Vital parameters (eg, systemic blood pressure as well as blood and plasma parameters (eg, concentrations of glucose, lactate and cell-free hemoglobin, and activity of lactate dehydrogenase were measured hourly. Clot formation was analyzed by thromboelastometry.Results: Continuous infusion of LPS led to a so-called post-aggression syndrome with disturbed electrolyte homeostasis (hypocalcemia, hyperkalemia, and hypernatremia, changes in hemodynamics (tachycardia and hypertension, and a catabolic metabolism (early hyperglycemia, late hypoglycemia, and lactate formation. It induced severe tissue injury (significant increases in plasma concentrations of transaminases and lactate dehydrogenase, alterations in blood coagulation (disturbed clot formation, and massive hemolysis. Both moderate and excessive glucose supply reduced LPS

  4. The Glucose-Insulin Control System

    DEFF Research Database (Denmark)

    Hallgreen, Christine Erikstrup; Korsgaard, Thomas Vagn; Hansen, RenéNormann N.

    2008-01-01

    This chapter reviews the glucose-insulin control system. First, classic control theory is described briefly and compared with biological control. The following analysis of the control system falls into two parts: a glucose-sensing part and a glucose-controlling part. The complex metabolic pathways...... are divided into smaller pieces and analyzed via several small biosimulation models that describe events in beta cells, liver, muscle and adipose tissue etc. In the glucose-sensing part, the beta cell are shown to have some characteristics of a classic PID controller, but with nonlinear properties...... control, the analysis shows that the system has many more facets than just keeping the glucose concentration within narrow limits. After glucose enters the cell and is phosphorylated to glucose-6-phosphate, the handling of glucose-6-phosphate is critical for glucose regulation. Also, this handling...

  5. Predictive models of glucose control: roles for glucose-sensing neurones

    Science.gov (United States)

    Kosse, C.; Gonzalez, A.; Burdakov, D.

    2018-01-01

    The brain can be viewed as a sophisticated control module for stabilizing blood glucose. A review of classical behavioural evidence indicates that central circuits add predictive (feedforward/anticipatory) control to the reactive (feedback/compensatory) control by peripheral organs. The brain/cephalic control is constructed and engaged, via associative learning, by sensory cues predicting energy intake or expenditure (e.g. sight, smell, taste, sound). This allows rapidly measurable sensory information (rather than slowly generated internal feedback signals, e.g. digested nutrients) to control food selection, glucose supply for fight-or-flight responses or preparedness for digestion/absorption. Predictive control is therefore useful for preventing large glucose fluctuations. We review emerging roles in predictive control of two classes of widely projecting hypothalamic neurones, orexin/hypocretin (ORX) and melanin-concentrating hormone (MCH) cells. Evidence is cited that ORX neurones (i) are activated by sensory cues (e.g. taste, sound), (ii) drive hepatic production, and muscle uptake, of glucose, via sympathetic nerves, (iii) stimulate wakefulness and exploration via global brain projections and (iv) are glucose-inhibited. MCH neurones are (i) glucose-excited, (ii) innervate learning and reward centres to promote synaptic plasticity, learning and memory and (iii) are critical for learning associations useful for predictive control (e.g. using taste to predict nutrient value of food). This evidence is unified into a model for predictive glucose control. During associative learning, inputs from some glucose-excited neurones may promote connections between the ‘fast’ senses and reward circuits, constructing neural shortcuts for efficient action selection. In turn, glucose-inhibited neurones may engage locomotion/exploration and coordinate the required fuel supply. Feedback inhibition of the latter neurones by glucose would ensure that glucose fluxes they

  6. Predictive models of glucose control: roles for glucose-sensing neurones.

    Science.gov (United States)

    Kosse, C; Gonzalez, A; Burdakov, D

    2015-01-01

    The brain can be viewed as a sophisticated control module for stabilizing blood glucose. A review of classical behavioural evidence indicates that central circuits add predictive (feedforward/anticipatory) control to the reactive (feedback/compensatory) control by peripheral organs. The brain/cephalic control is constructed and engaged, via associative learning, by sensory cues predicting energy intake or expenditure (e.g. sight, smell, taste, sound). This allows rapidly measurable sensory information (rather than slowly generated internal feedback signals, e.g. digested nutrients) to control food selection, glucose supply for fight-or-flight responses or preparedness for digestion/absorption. Predictive control is therefore useful for preventing large glucose fluctuations. We review emerging roles in predictive control of two classes of widely projecting hypothalamic neurones, orexin/hypocretin (ORX) and melanin-concentrating hormone (MCH) cells. Evidence is cited that ORX neurones (i) are activated by sensory cues (e.g. taste, sound), (ii) drive hepatic production, and muscle uptake, of glucose, via sympathetic nerves, (iii) stimulate wakefulness and exploration via global brain projections and (iv) are glucose-inhibited. MCH neurones are (i) glucose-excited, (ii) innervate learning and reward centres to promote synaptic plasticity, learning and memory and (iii) are critical for learning associations useful for predictive control (e.g. using taste to predict nutrient value of food). This evidence is unified into a model for predictive glucose control. During associative learning, inputs from some glucose-excited neurones may promote connections between the 'fast' senses and reward circuits, constructing neural shortcuts for efficient action selection. In turn, glucose-inhibited neurones may engage locomotion/exploration and coordinate the required fuel supply. Feedback inhibition of the latter neurones by glucose would ensure that glucose fluxes they stimulate

  7. Hepatic glucose output in humans measured with labeled glucose to reduce negative errors

    International Nuclear Information System (INIS)

    Levy, J.C.; Brown, G.; Matthews, D.R.; Turner, R.C.

    1989-01-01

    Steele and others have suggested that minimizing changes in glucose specific activity when estimating hepatic glucose output (HGO) during glucose infusions could reduce non-steady-state errors. This approach was assessed in nondiabetic and type II diabetic subjects during constant low dose [27 mumol.kg ideal body wt (IBW)-1.min-1] glucose infusion followed by a 12 mmol/l hyperglycemic clamp. Eight subjects had paired tests with and without labeled infusions. Labeled infusion was used to compare HGO in 11 nondiabetic and 15 diabetic subjects. Whereas unlabeled infusions produced negative values for endogenous glucose output, labeled infusions largely eliminated this error and reduced the dependence of the Steele model on the pool fraction in the paired tests. By use of labeled infusions, 11 nondiabetic subjects suppressed HGO from 10.2 +/- 0.6 (SE) fasting to 0.8 +/- 0.9 mumol.kg IBW-1.min-1 after 90 min of glucose infusion and to -1.9 +/- 0.5 mumol.kg IBW-1.min-1 after 90 min of a 12 mmol/l glucose clamp, but 15 diabetic subjects suppressed only partially from 13.0 +/- 0.9 fasting to 5.7 +/- 1.2 at the end of the glucose infusion and 5.6 +/- 1.0 mumol.kg IBW-1.min-1 in the clamp (P = 0.02, 0.002, and less than 0.001, respectively)

  8. UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness.

    Science.gov (United States)

    Toda, Chitoku; Kim, Jung Dae; Impellizzeri, Daniela; Cuzzocrea, Salvatore; Liu, Zhong-Wu; Diano, Sabrina

    2016-02-25

    The ventromedial nucleus of the hypothalamus (VMH) plays a critical role in regulating systemic glucose homeostasis. How neurons in this brain area adapt to the changing metabolic environment to regulate circulating glucose levels is ill defined. Here, we show that glucose load results in mitochondrial fission and reduced reactive oxygen species in VMH neurons mediated by dynamin-related peptide 1 (DRP1) under the control of uncoupling protein 2 (UCP2). Probed by genetic manipulations and chemical-genetic control of VMH neuronal circuitry, we unmasked that this mitochondrial adaptation determines the size of the pool of glucose-excited neurons in the VMH and that this process regulates systemic glucose homeostasis. Thus, our data unmasked a critical cellular biological process controlled by mitochondrial dynamics in VMH regulation of systemic glucose homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Genetic Algorithm Tuning of PID Controller in Smith Predictor for Glucose Concentration Control

    Directory of Open Access Journals (Sweden)

    Tsonyo Slavov

    2011-07-01

    Full Text Available This paper focuses on design of a glucose concentration control system based on nonlinear model plant of E. coli MC4110 fed-batch cultivation process. Due to significant time delay in real time glucose concentration measurement, a correction is proposed in glucose concentration measurement and a Smith predictor (SP control structure based on universal PID controller is designed. To reduce the influence of model error in SP structure the estimate of measured glucose concentration is used. For the aim an extended Kalman filter (EKF is designed. To achieve good closed-loop system performance genetic algorithm (GA based optimal controller tuning procedure is applied. A standard binary encoding GA is applied. The GA parameters and operators are specified for the considered here problem. As a result the optimal PID controller settings are obtained. The simulation experiments of the control systems based on SP with EKF and without EKF are performed. The results show that the control system based on SP with EKF has a better performance than the one without EKF. For a short time the controller sets the control variable and maintains it at the desired set point during the cultivation process. As a result, a high biomass concentration of 48.3 g·l-1 is obtained at the end of the process.

  10. Overnight Control of Blood Glucose in People with Type 1 Diabetes

    DEFF Research Database (Denmark)

    Boiroux, Dimitri; Duun-Henriksen, Anne Katrine; Schmidt, Signe

    2012-01-01

    In this paper, we develop and test a Model Predictive Controller (MPC) for overnight stabilization of blood glucose in people with type 1 diabetes. The controller uses glucose measurements from a continuous glucose monitor (CGM) and its decisions are implemented by a continuous subcutaneous insulin...... infusion (CSII) pump. Based on a priori patient information, we propose a systematic method for computation of the model parameters in the MPC. Safety layers improve the controller robustness and reduce the risk of hypoglycemia. The controller is evaluated in silico on a cohort of 100 randomly generated...... patients with a representative intersubject variability. This cohort is simulated overnight with realistic variations in the insulin sensitivities and needs. Finally, we provide results for the first tests of this controller in a real clinic....

  11. Chapter 10: Glucose control: insulin therapy*

    African Journals Online (AJOL)

    Insulin and its analogues lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits ... control on 2 or 3 oral glucose lowering drugs.

  12. The role of motivation, glucose and self-control in the antisaccade task.

    Directory of Open Access Journals (Sweden)

    Claire L Kelly

    Full Text Available Research shows that self-control is resource limited and there is a gradual weakening in consecutive self-control task performance akin to muscle fatigue. A body of evidence suggests that the resource is glucose and consuming glucose reduces this effect. This study examined the effect of glucose on performance in the antisaccade task - which requires self-control through generating a voluntary eye movement away from a target - following self-control exertion in the Stroop task. The effects of motivation and individual differences in self-control were also explored. In a double-blind design, 67 young healthy adults received a 25g glucose or inert placebo drink. Glucose did not enhance antisaccade performance following self-control exertion in the Stroop task. Motivation however, predicted performance on the antisaccade task; more specifically high motivation ameliorated performance decrements observed after initial self-control exertion. In addition, individuals with high levels of self-control performed better on certain aspects of the antisaccade task after administration of a glucose drink. The results of this study suggest that the antisaccade task might be a powerful paradigm, which could be used as a more objective measure of self-control. Moreover, the results indicate that level of motivation and individual differences in self-control should be taken into account when investigating deficiencies in self-control following prior exertion.

  13. Exogenous glucagon-like peptide-1 attenuates glucose absorption and reduces blood glucose concentration after small intestinal glucose delivery in critical illness.

    Science.gov (United States)

    Miller, Asaf; Deane, Adam M; Plummer, Mark P; Cousins, Caroline E; Chapple, Lee-Anne S; Horowitz, Michael; Chapman, Marianne J

    2017-03-01

    To evaluate the effect of exogenous glucagonlike peptide-1 (GLP-1) on small intestinal glucose absorption and blood glucose concentrations during critical illness. A prospective, blinded, placebo-controlled, cross-over, randomised trial in a mixed medical-surgical adult intensive care unit, with 12 mechanically ventilated critically ill patients, who were suitable for receiving small intestinal nutrient. On consecutive days, in a randomised order, participants received intravenous GLP-1 (1.2 pmol/ kg/min) or placebo (0.9% saline) as a continuous infusion over 270 minutes. After 6 hours of fasting, intravenous infusions of GLP-1 or placebo began at T = -30 min (in which T = time), with the infusion maintained at a constant rate until study completion at T = 240 min. At T = 0 min, a 100 mL bolus of mixed liquid nutrient meal (1 kcal/mL) containing 3 g of 3-O-methyl-D-gluco-pyranose (3-OMG), a marker of glucose absorption, was administered directly into the small intestine, via a post-pyloric catheter, over 6 minutes. Blood samples were taken at regular intervals for the measurement of plasma glucose and 3-OMG concentrations. Intravenous GLP-1 attenuated initial small intestinal glucose absorption (mean area under the curve [AUC] 0-30 for 3-OMG: GLP-1 group, 4.4 mmol/L/min [SEM, 0.9 mmol/L/min] v placebo group, 6.5 mmol/L/min [SEM, 1.0 mmol/L/min]; P = 0.01), overall small intestinal glucose absorption (mean AUC 0-240 for 3-OMG: GLP-1, 68.2 mmol/L/ min [SEM, 4.7 mmol/L/min] v placebo, 77.7 mmol/L/min [SEM, 4.4 mmol/lLmin]; P = 0.02), small intestinal glucose absorption and overall blood glucose concentration (mean AUC 0-240 for blood glucose: GLP-1, 2062 mmol/L/min [SEM, 111 mmol/L/min] v placebo 2328 mmol/L/min [SEM, 145 mmol/L/min]; P = 0.005). Short-term administration of exogenous GLP-1 reduces small intestinal glucose absorption for up to 4 hours during critical illness. This is likely to be an additional mechanism for the glucose-lowering effect of this agent.

  14. LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose.

    Science.gov (United States)

    Powell, David R; Smith, Melinda; Greer, Jennifer; Harris, Angela; Zhao, Sharon; DaCosta, Christopher; Mseeh, Faika; Shadoan, Melanie K; Sands, Arthur; Zambrowicz, Brian; Ding, Zhi-Ming

    2013-05-01

    LX4211 [(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol], a dual sodium/glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor, is thought to decrease both renal glucose reabsorption by inhibiting SGLT2 and intestinal glucose absorption by inhibiting SGLT1. In clinical trials in patients with type 2 diabetes mellitus (T2DM), LX4211 treatment improved glycemic control while increasing circulating levels of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). To better understand how LX4211 increases GLP-1 and PYY levels, we challenged SGLT1 knockout (-/-) mice, SGLT2-/- mice, and LX4211-treated mice with oral glucose. LX4211-treated mice and SGLT1-/- mice had increased levels of plasma GLP-1, plasma PYY, and intestinal glucose during the 6 hours after a glucose-containing meal, as reflected by area under the curve (AUC) values, whereas SGLT2-/- mice showed no response. LX4211-treated mice and SGLT1-/- mice also had increased GLP-1 AUC values, decreased glucose-dependent insulinotropic polypeptide (GIP) AUC values, and decreased blood glucose excursions during the 6 hours after a challenge with oral glucose alone. However, GLP-1 and GIP levels were not increased in LX4211-treated mice and were decreased in SGLT1-/- mice, 5 minutes after oral glucose, consistent with studies linking decreased intestinal SGLT1 activity with reduced GLP-1 and GIP levels 5 minutes after oral glucose. These data suggest that LX4211 reduces intestinal glucose absorption by inhibiting SGLT1, resulting in net increases in GLP-1 and PYY release and decreases in GIP release and blood glucose excursions. The ability to inhibit both intestinal SGLT1 and renal SGLT2 provides LX4211 with a novel dual mechanism of action for improving glycemic control in patients with T2DM.

  15. Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Reducing Blood-Brain Barrier Disruption after Controlled Cortical Impact in Mice: An 18F-Fluorodeoxyglucose PET/CT Study.

    Science.gov (United States)

    Qin, Xinghu; You, Hong; Cao, Fang; Wu, Yue; Peng, Jianhua; Pang, Jinwei; Xu, Hong; Chen, Yue; Chen, Ligang; Vitek, Michael P; Li, Fengqiao; Sun, Xiaochuan; Jiang, Yong

    2017-02-15

    Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several models of TBI. However, the effects of COG1410 on VEGF and glucose metabolism following TBI are unknown. The current study aimed to investigate the expression of VEGF and glucose metabolism effects in C57BL/6J male mice subjected to experimental TBI. The results showed that controlled cortical impact (CCI)-induced vestibulomotor deficits were accompanied by increases in brain edema and the expression of VEGF, with a decrease in cerebral glucose uptake. COG1410 treatment significantly improved vestibulomotor deficits and glucose uptake and produced decreases in VEGF in the pericontusion and ipsilateral hemisphere of injury, as well as in brain edema and neuronal degeneration compared with the control group. These data support that COG1410 may have potential as an effective drug therapy for TBI.

  16. Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?

    Science.gov (United States)

    Egi, Moritoki; Bellomo, Rinaldo; Reade, Michael C

    2009-01-01

    Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.

  17. Intraoperative tight glucose control using hyperinsulinemic normoglycemia increases delirium after cardiac surgery.

    Science.gov (United States)

    Saager, Leif; Duncan, Andra E; Yared, Jean-Pierre; Hesler, Brian D; You, Jing; Deogaonkar, Anupa; Sessler, Daniel I; Kurz, Andrea

    2015-06-01

    Postoperative delirium is common in patients recovering from cardiac surgery. Tight glucose control has been shown to reduce mortality and morbidity. Therefore, the authors sought to determine the effect of tight intraoperative glucose control using a hyperinsulinemic-normoglycemic clamp approach on postoperative delirium in patients undergoing cardiac surgery. The authors enrolled 198 adult patients having cardiac surgery in this randomized, double-blind, single-center trial. Patients were randomly assigned to either tight intraoperative glucose control with a hyperinsulinemic-normoglycemic clamp (target blood glucose, 80 to 110 mg/dl) or standard therapy (conventional insulin administration with blood glucose target, battery. The authors considered patients to have experienced postoperative delirium when Confusion Assessment Method testing was positive at any assessment. A positive Confusion Assessment Method was defined by the presence of features 1 (acute onset and fluctuating course) and 2 (inattention) and either 3 (disorganized thinking) or 4 (altered consciousness). Patients randomized to tight glucose control were more likely to be diagnosed as being delirious than those assigned to routine glucose control (26 of 93 vs. 15 of 105; relative risk, 1.89; 95% CI, 1.06 to 3.37; P = 0.03), after adjusting for preoperative usage of calcium channel blocker and American Society of Anesthesiologist physical status. Delirium severity, among patients with delirium, was comparable with each glucose management strategy. Intraoperative hyperinsulinemic-normoglycemia augments the risk of delirium after cardiac surgery, but not its severity.

  18. [Effects of blood glucose control on glucose variability and clinical outcomes in patients with severe acute pancreatitis in intensive care unit].

    Science.gov (United States)

    Wu, Jing; Sun, Qiuhong; Yang, Hua

    2015-05-19

    To explore the effects of blood glucose control on glucose variability and clinical outcomes in patients with severe acute pancreatitis in intensive care unit (ICU). A total of 72 ICU patients with severe acute pancreatitis were recruited and divided randomly into observation and control groups (n = 36 each). Both groups were treated conventionally. And the observation group achieved stable blood glucose at 6.1-8.3 mmol/L with intensive glucose control. The length of ICU and hospital stays, ICU mortality rate, transit operative rate, concurrent infection rate, admission blood glucose, glycosylated hemoglobin, mean insulin dose, mean blood glucose, blood glucose value standard deviation (GLUSD), glycemic liability index (GLUGLI) and mean amplitude of glycemic excursion (GLUMAGE) of two groups were compared. At the same time, the relationship between blood glucose variability, ICU mortality rate and its predictive value were analyzed by correlation analysis and receiver operating characteristic curve (ROC). The lengths of ICU and hospital stays of observation group were all significantly less than those of the control group [(11.7 ± 9.9) vs (15.9 ± 8.02) days, (21.8 ± 10.8) vs (28.2 ± 12.7) days, P blood glucose value and GLUSD of observation group were significantly lower than those of control group [(7.4 ± 1.1) vs (9.6 ± 1.2), (1.8 ± 1.0) vs (2.5 ± 1.3) mmol/L]. The differences were statistically significant (P curve analysis showed that, AUC of GLUGLI was 0.748 and 95% CI 0.551-0.965 (P glucose control in patients with severe acute pancreatitis helps reduce the blood sugar fluctuations, lower the risks of infectious complications and promote the patient rehabilitation. And GLUGLI is positively correlated with ICU mortality rate. It has good predictive values.

  19. Quick generation of Raman spectroscopy based in-process glucose control to influence biopharmaceutical protein product quality during mammalian cell culture.

    Science.gov (United States)

    Berry, Brandon N; Dobrowsky, Terrence M; Timson, Rebecca C; Kshirsagar, Rashmi; Ryll, Thomas; Wiltberger, Kelly

    2016-01-01

    Mitigating risks to biotherapeutic protein production processes and products has driven the development of targeted process analytical technology (PAT); however implementing PAT during development without significantly increasing program timelines can be difficult. The development of a monoclonal antibody expressed in a Chinese hamster ovary (CHO) cell line via fed-batch processing presented an opportunity to demonstrate capabilities of altering percent glycated protein product. Glycation is caused by pseudo-first order, non-enzymatic reaction of a reducing sugar with an amino group. Glucose is the highest concentration reducing sugar in the chemically defined media (CDM), thus a strategy controlling glucose in the production bioreactor was developed utilizing Raman spectroscopy for feedback control. Raman regions for glucose were determined by spiking studies in water and CDM. Calibration spectra were collected during 8 bench scale batches designed to capture a wide glucose concentration space. Finally, a PLS model capable of translating Raman spectra to glucose concentration was built using the calibration spectra and spiking study regions. Bolus feeding in mammalian cell culture results in wide glucose concentration ranges. Here we describe the development of process automation enabling glucose setpoint control. Glucose-free nutrient feed was fed daily, however glucose stock solution was fed as needed according to online Raman measurements. Two feedback control conditions were executed where glucose was controlled at constant low concentration or decreased stepwise throughout. Glycation was reduced from ∼9% to 4% using a low target concentration but was not reduced in the stepwise condition as compared to the historical bolus glucose feeding regimen. © 2015 American Institute of Chemical Engineers.

  20. An artificial pancreas for automated blood glucose control in patients with Type 1 diabetes

    DEFF Research Database (Denmark)

    Schmidt, Signe; Boiroux, Dimitri; Ranjan, Ajenthen

    2015-01-01

    Automated glucose control in patients with Type 1 diabetes is much-coveted by patients, relatives and healthcare professionals. It is the expectation that a system for automated control, also know as an artificial pancreas, will improve glucose control, reduce the risk of diabetes complications...... and markedly improve patient quality of life. An artificial pancreas consists of portable devices for glucose sensing and insulin delivery which are controlled by an algorithm residing on a computer. The technology is still under development and currently no artificial pancreas is commercially available....... This review gives an introduction to recent progress, challenges and future prospects within the field of artificial pancreas research....

  1. Glucose acutely reduces cytosolic and mitochondrial H2O2 in rat pancreatic beta-cells.

    Science.gov (United States)

    Deglasse, Jean-Philippe; Roma, Leticia Prates; Pastor-Flores, Daniel; Gilon, Patrick; Dick, Tobias P; Jonas, Jean-Christophe

    2018-05-14

    Whether H2O2 contributes to the glucose-dependent stimulation of insulin secretion by pancreatic β-cells is highly controversial. We used two H2O2-sensitive probes, roGFP2-Orp1 and HyPer with its pH-control SypHer, to test the acute effects of glucose, monomethylsuccinate, leucine with glutamine, and α-ketoisocaproate, on β-cell cytosolic and mitochondrial H2O2 concentrations. We then tested the effects of low H2O2 and menadione concentrations on insulin secretion. RoGFP2-Orp1 was more sensitive than HyPer to H2O2 (response at 2-5 vs. 10µM) and less pH-sensitive. Under control conditions, stimulation with glucose reduced mitochondrial roGFP2-Orp1 oxidation without affecting cytosolic roGFP2-Orp1 and HyPer fluorescence ratios, except for the pH-dependent effects on HyPer. However, stimulation with glucose decreased the oxidation of both cytosolic probes by 15µM exogenous H2O2. The glucose effects were not affected by overexpression of catalase, mitochondrial catalase or superoxide dismutase 1 and 2. They followed the increase in NAD(P)H autofluorescence, were maximal at 5mM glucose in the cytosol and 10mM glucose in the mitochondria, and were partly mimicked by the other nutrients. Exogenous H2O2 (1-15µM) did not affect insulin secretion. By contrast, menadione (1-5µM) did not increase basal insulin secretion but reduced the stimulation of insulin secretion by 20mM glucose. Subcellular changes in β-cell H2O2 levels are better monitored with roGFP2-Orp1 than HyPer/SypHer. Nutrients acutely lower mitochondrial H2O2 levels in β-cells and promote degradation of exogenously supplied H2O2 in both cytosolic and mitochondrial compartments. The glucose-dependent stimulation of insulin secretion occurs independently of a detectable increase in β-cell cytosolic or mitochondrial H2O2 levels.

  2. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock★

    Science.gov (United States)

    Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.; Biensø, Rasmus S.; Tagliazucchi, Guidantonio M.; Patel, Vishal R.; Forcato, Mattia; Paz, Marcia I.P.; Gudiksen, Anders; Solagna, Francesca; Albiero, Mattia; Moretti, Irene; Eckel-Mahan, Kristin L.; Baldi, Pierre; Sassone-Corsi, Paolo; Rizzuto, Rosario; Bicciato, Silvio; Pilegaard, Henriette; Blaauw, Bert; Schiaffino, Stefano

    2013-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle. PMID:24567902

  3. Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis.

    Science.gov (United States)

    Buckingham, Bruce A; Raghinaru, Dan; Cameron, Fraser; Bequette, B Wayne; Chase, H Peter; Maahs, David M; Slover, Robert; Wadwa, R Paul; Wilson, Darrell M; Ly, Trang; Aye, Tandy; Hramiak, Irene; Clarson, Cheril; Stein, Robert; Gallego, Patricia H; Lum, John; Sibayan, Judy; Kollman, Craig; Beck, Roy W

    2015-07-01

    Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor-based overnight predictive low-glucose suspend (PLGS) system. In two age-groups of children with type 1 diabetes (11-14 and 4-10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight. Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11-14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4-10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11-14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4-10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis. In 4-14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  4. Optimal glucose control in type 2 diabetes mellitus – a guide for the ...

    African Journals Online (AJOL)

    vascular complications. The family practitioner plays a significant role in the management of glycaemic control and thereby reducing the related morbidity and mortality. Monitoring of blood glucose control has become an integral part of disease ...

  5. Reducing Glucose Variability Due to Meals and Postprandial Exercise in T1DM Using Switched LPV Control: In Silico Studies.

    Science.gov (United States)

    Colmegna, Patricio H; Sánchez-Peña, Ricardo S; Gondhalekar, Ravi; Dassau, Eyal; Doyle, Francis J

    2016-05-01

    Time-varying dynamics is one of the main issues for achieving safe blood glucose control in type 1 diabetes mellitus (T1DM) patients. In addition, the typical disturbances considered for controller design are meals, which increase the glucose level, and physical activity (PA), which increases the subject's sensitivity to insulin. In previous works the authors have applied a linear parameter-varying (LPV) control technique to manage unannounced meals. A switched LPV controller that switches between 3 LPV controllers, each with a different level of aggressiveness, is designed to further cope with both unannounced meals and postprandial PA. Thus, the proposed control strategy has a "standard" mode, an "aggressive" mode, and a "conservative" mode. The "standard" mode is designed to be applied most of the time, while the "aggressive" mode is designed to deal only with hyperglycemia situations. On the other hand, the "conservative" mode is focused on postprandial PA control. An ad hoc simulator has been developed to test the proposed controller. This simulator is based on the distribution version of the UVA/Padova model and includes the effect of PA based on Schiavon.(1) The test results obtained when using this simulator indicate that the proposed control law substantially reduces the risk of hypoglycemia with the conservative strategy, while the risk of hyperglycemia is scarcely affected. It is demonstrated that the announcement, or anticipation, of exercise is indispensable for letting a mono-hormonal artificial pancreas deal with the consequences of postprandial PA. In view of this the proposed controller allows switching into a conservative mode when notified of PA by the user. © 2016 Diabetes Technology Society.

  6. Blood glucose control in the intensive care unit: benefits and risks.

    Science.gov (United States)

    Gunst, Jan; Van den Berghe, Greet

    2010-01-01

    Abnormal blood glucose levels are common during critical illness and are associated with outcomes that correspond to a J-shaped curve, the lowest risk associated with normoglycemia. Three proof-of-concept randomized-controlled-trials performed in the surgical, medical, and pediatric intensive care units of the Leuven University Hospital in Belgium demonstrated that maintaining strict age-adjusted normal fasting levels of glycemia (80-110 mg/dl in adults, 70-100 mg/dl in children, 50-80 mg/dl in infants) with intensive insulin therapy reduced morbidity and mortality as compared with tolerating stress hyperglycemia as a potentially beneficial response. Recently, concern has risen about the safety of this intervention, as a multicenter adult study reported an, as yet unexplained, increased mortality with targeting normoglycemia as compared with an intermediate blood glucose level of around 140 mg/dl. This apparent contradiction may be explained by several methodological differences among studies, comprising, among others, different glucose target ranges in the control groups, different feeding policies, and variable accuracy of tools used for glucose measurement and insulin infusion. Hence, efficacy and safety of intensive insulin therapy may be affected by patient-related and ICU setting-related variables. Therefore, no single optimal blood glucose target range for ICU patients can be advocated. It appears safe not to embark on targeting "age-normal" levels in intensive care units (ICUs) that are not equipped to accurately and frequently measure blood glucose, and have not acquired extensive experience with intravenous insulin administration using a customized guideline. A simple fallback position could be to control blood glucose levels as close to normal as possible without evoking unacceptable blood glucose fluctuations, hypoglycemia, and hypokalemia.

  7. The UPR reduces glucose metabolism via IRE1 signaling.

    Science.gov (United States)

    van der Harg, Judith M; van Heest, Jessica C; Bangel, Fabian N; Patiwael, Sanne; van Weering, Jan R T; Scheper, Wiep

    2017-04-01

    Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis. Since the UPR is strategically positioned to sense and integrate metabolic stress signals, it is likely that - apart from its adaptive response to restore proteostasis - it also directly affects metabolic pathways. Here we investigate the direct role of the UPR in glucose homeostasis. O-GlcNAc is a post-translational modification that is highly responsive to glucose fluctuations. We find that UPR activation results in decreased O-GlcNAc modification, in line with reduced glucose metabolism. Our data indicate that UPR activation has no direct impact on the upstream processes in glucose metabolism; glucose transporter expression, glucose uptake and hexokinase activity. In contrast, prolonged UPR activation decreases glycolysis and mitochondrial metabolism. Decreased mitochondrial respiration is not accompanied by apoptosis or a structural change in mitochondria indicating that the reduction in metabolic rate upon UPR activation is a physiological non-apoptotic response. Metabolic decrease is prevented if the IRE1 pathway of the UPR is inhibited. This indicates that activation of IRE1 signaling induces a reduction in glucose metabolism, as part of an adaptive response. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Korean Red Ginseng Improves Glucose Control in Subjects with Impaired Fasting Glucose, Impaired Glucose Tolerance, or Newly Diagnosed Type 2 Diabetes Mellitus

    OpenAIRE

    Bang, Hyangju; Kwak, Jung Hyun; Ahn, Hyeon Yeong; Shin, Dong Yeob; Lee, Jong Ho

    2014-01-01

    This study was designed to evaluate the effect of Korean red ginseng (KRG) supplementation on glucose control in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or newly diagnosed type 2 diabetes mellitus (T2DM). The study was a 12-week randomized, double-blinded, placebo-controlled (5 g of KRG [n=21] or placebo [n=20] in tablet form) trial. Glucose-related biomarkers, including serum and whole blood levels of glucose, insulin, and C-peptide, were measured by 2...

  9. Electrochemical sensing of glucose by reduced graphene oxide-zinc ferrospinels

    Energy Technology Data Exchange (ETDEWEB)

    Shahnavaz, Zohreh, E-mail: zohreh.shahnavaz@siswa.um.edu.my [Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur (Malaysia); Woi, Pei Meng, E-mail: pmwoi@um.edu.my [Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur (Malaysia); Center of Ionic Liquids, University of Malaya, 50603 Kuala Lumpur (Malaysia); Alias, Yatimah, E-mail: yatimah70@um.edu.my [Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur (Malaysia); Center of Ionic Liquids, University of Malaya, 50603 Kuala Lumpur (Malaysia)

    2016-08-30

    Highlights: • A facile in situ hydrothermal method for ZnFe{sub 2}O{sub 4} nanoparticles incorporation into graphene oxide sheets. • Excellent selectivity, reproducibility and stability properties compared to others Zn-based glucose sensor. • Amount of reduced graphene oxide directly affected the electro-catalytic activity of ZnFe{sub 2}O{sub 4}/rGO nanocomposite towards glucose detection. - Abstract: We have developed ZnFe{sub 2}O{sub 4} magnetic nanoparticles/reduced graphene oxide nanosheets modified glassy carbon (ZnFe{sub 2}O{sub 4}/rGO/GCE) electrode as a novel system for the electrochemical glucose sensing. Via a facile in situ hydrothermal route, the reduction of GO and the formation of ZnFe{sub 2}O{sub 4} nanoparticles occurred simultaneously. This enables the ZnFe{sub 2}O{sub 4} nanoparticles dispersed on the reduced graphene sheet. Characterization of nanocomposite by X-ray diffraction (XRD) and transmission electron microscopy (TEM) clearly demonstrate the successful attachment of ZnFe{sub 2}O{sub 4} nanoparticles to graphene sheets. Electrochemical studies revealed that the ZnFe{sub 2}O{sub 4}/rGO/GCE possess excellent electrocatalytic activities toward the oxidation of glucose and the performance of sensor is enhanced by integration of graphene nanosheets with ZnFe{sub 2}O{sub 4} nanoparticles.

  10. Closed-loop controlled noninvasive ultrasonic glucose sensing and insulin delivery

    Science.gov (United States)

    Park, Eun-Joo; Werner, Jacob; Jaiswal, Devina; Smith, Nadine Barrie

    2010-03-01

    To prevent complications in diabetes, the proper management of blood glucose levels is essential. Previously, ultrasonic transdermal methods using a light-weight cymbal transducer array has been studied for noninvasive methods of insulin delivery for Type-1 diabetes and glucose level monitoring. In this study, the ultrasound systems of insulin delivery and glucose sensing have been combined by a feedback controller. This study was designed to show the feasibility of the feedback controlled ultrasound system for the noninvasive glucose control. For perspective human application, in vivo experiments were performed on large animals that have a similar size to humans. Four in vivo experiments were performed using about 200 lbs pigs. The cymbal array of 3×3 pattern has been used for insulin delivery at 30 kHz with the spatial-peak temporal-peak intensity (Isptp) of 100 mW/cm2. For glucose sensing, a 2×2 array was operated at 20 kHz with Isptp = 100 mW/cm2. Based on the glucose level determined by biosensors after the ultrasound exposure, the ultrasound system for the insulin delivery was automatically operated. The glucose level of 115 mg/dl was set as a reference value for operating the insulin delivery system. For comparison, the glucose levels of blood samples collected from the ear vein were measured by a commercial glucose meter. Using the ultrasound system operated by the close-loop, feed-back controller, the glucose levels of four pigs were determined every 20 minutes and continuously controlled for 120 minutes. In comparison to the commercial glucose meter, the glucose levels determined by the biosensor were slightly higher. The results of in vivo experiments indicate the feasibility of the feedback controlled ultrasound system using the cymbal array for noninvasive glucose sensing and insulin delivery. Further studies on the extension of the glucose control will be continued for the effective method of glucose control.

  11. Ex vivo changes in blood glucose levels seldom change blood glucose control algorithm recommendations

    NARCIS (Netherlands)

    de Groene, L.; Harmsen, R. E.; Binnekade, J. M.; Spronk, P. E.; Schultz, M. J.

    2010-01-01

    Background. Hyperglycemia and glycemic variabilities are associated with adverse outcomes in critically ill patients. Blood glucose control with insulin mandates an adequate and precise assessment of blood glucose levels. Blood glucose levels, however, can change ex vivo after sampling. The aim of

  12. Meal Disturbance Effect on Control of Blood Glucose Level for Critically-ill Patients using In-silico Works

    Science.gov (United States)

    Yusof, N. F. M.; Som, A. M.; Ali, S. A.; Azman, N. H.

    2018-05-01

    This study was conducted to determine the effect of meal disturbance on blood glucose level of the critically ill patients and to simulate the control algorithm previously developed using in-silico works. The study is significant so as to reduce the mortality rate of critically ill patients who usually encounter hyperglycaemia or/and hypoglycaemia while in treatment. The meal intake is believed to affect the blood glucose regulation and causes the hyperglycaemia to occur. Critically ill patients receive their meal through parenteral and enteral nutrition. Furthermore, by using in-silico works, time consumed and resources needed for clinical evaluation of the patients can be reduced. Hovorka model was employed in which the simulation study was carried out using MATLAB on the virtual patient and it was being compared with actual patient in which the data were provided by Institut Jantung Negara (IJN). Based on the simulation, the disturbance on enteral glucose supplied had affected the blood glucose level of the patient; however, it remained unchanged for the parental glucose. To reduce the occurrence of hypoglycaemia and hyperglycaemia, the patient was injected with 30 g/hr and 10 g/hr of enteral glucose, respectively. In conclusion, the disturbance of meal received can be controlled through in-silico works.

  13. Impaired hippocampal glucose metabolism during and after flurothyl-induced seizures in mice: Reduced phosphorylation coincides with reduced activity of pyruvate dehydrogenase.

    Science.gov (United States)

    McDonald, Tanya S; Borges, Karin

    2017-07-01

    To determine changes in glucose metabolism and the enzymes involved in the hippocampus ictally and postictally in the acute mouse flurothyl seizure model. [U- 13 C]-Glucose was injected (i.p.) prior to, or following a 5 min flurothyl-induced seizure. Fifteen minutes later, mice were killed and the total metabolite levels and % 13 C enrichment were analyzed in the hippocampal formation using gas chromatography-mass spectrometry. Activities of key metabolic and antioxidant enzymes and the phosphorylation status of pyruvate dehydrogenase were measured, along with lipid peroxidation. During seizures, total lactate levels increased 1.7-fold; however, [M + 3] enrichment of both lactate and alanine were reduced by 30% and 43%, respectively, along with a 28% decrease in phosphofructokinase activity. Postictally the % 13 C enrichments of all measured tricarboxylic acid (TCA) cycle intermediates and the amino acids were reduced by 46-93%. At this time, pyruvate dehydrogenase (PDH) activity was 56% of that measured in controls, and there was a 1.9-fold increase in the phosphorylation of PDH at ser232. Phosphorylation of PDH is known to decrease its activity. Here, we show that the increase of lactate levels during flurothyl seizures is from a source other than [U- 13 C]-glucose, such as glycogen. Surprisingly, although we saw a reduction in phosphofructokinase activity during the seizure, metabolism of [U- 13 C]-glucose into the TCA cycle seemed unaffected. Similar to our recent findings in the chronic phase of the pilocarpine model, postictally the metabolism of glucose by glycolysis and the TCA cycle was impaired along with reduced PDH activity. Although this decrease in activity may be a protective mechanism to reduce oxidative stress, which is observed in the flurothyl model, ATP is critical to the recovery of ion and neurotransmitter balance and return to normal brain function. Thus we identified promising novel strategies to enhance energy metabolism and recovery from

  14. Arrhythmia causes lipid accumulation and reduced glucose uptake.

    Science.gov (United States)

    Lenski, Matthias; Schleider, Gregor; Kohlhaas, Michael; Adrian, Lucas; Adam, Oliver; Tian, Qinghai; Kaestner, Lars; Lipp, Peter; Lehrke, Michael; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

    2015-01-01

    Atrial fibrillation (AF) is characterized by irregular contractions of atrial cardiomyocytes and increased energy demand. The aim of this study was to characterize the influence of arrhythmia on glucose and fatty acid (FA) metabolism in cardiomyocytes, mice and human left atrial myocardium. Compared to regular pacing, irregular (pseudo-random variation at the same number of contractions/min) pacing of neonatal rat cardiomyocytes induced shorter action potential durations and effective refractory periods and increased diastolic [Ca(2+)]c. This was associated with the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and AMP-activated protein kinase (AMPK). Membrane expression of fatty acid translocase (FAT/CD36) and (14)C-palmitic acid uptake were augmented while membrane expression of glucose transporter subtype 4 (GLUT-4) as well as (3)H-glucose uptake were reduced. Inhibition of AMPK and CaMKII prevented these arrhythmia-induced metabolic changes. Similar alterations of FA metabolism were observed in a transgenic mouse model (RacET) for spontaneous AF. Consistent with these findings samples of left atrial myocardium of patients with AF compared to matched samples of patients with sinus rhythm showed up-regulation of CaMKII and AMPK and increased membrane expression of FAT/CD36, resulting in lipid accumulation. These changes of FA metabolism were accompanied by decreased membrane expression of GLUT-4, increased glycogen content and increased expression of the pro-apoptotic protein bax. Irregular pacing of cardiomyocytes increases diastolic [Ca(2+)]c and activation of CaMKII and AMPK resulting in lipid accumulation, reduced glucose uptake and increased glycogen synthesis. These metabolic changes are accompanied by an activation of pro-apoptotic signalling pathways.

  15. Blood glucose control and monitoring in the critically ill

    NARCIS (Netherlands)

    van Hooijdonk, R.T.M.

    2015-01-01

    This thesis deals with blood glucose control and blood glucose monitoring in intensive care unit (ICU) patients: two important aspects of care for and monitoring of critically ill patients. While the precise targets of blood glucose control in ICU patients remain a matter of debate, currently many,

  16. Phenylboronic acid functionalized reduced graphene oxide based fluorescence nano sensor for glucose sensing

    Energy Technology Data Exchange (ETDEWEB)

    Basiruddin, SK; Swain, Sarat K., E-mail: swainsk2@yahoo.co.in

    2016-01-01

    Reduced graphene has emerged as promising tools for detection based application of biomolecules as it has high surface area with strong fluorescence quenching property. We have used the concept of fluorescent quenching property of reduced graphene oxide to the fluorescent probes which are close vicinity of its surface. In present work, we have synthesized fluorescent based nano-sensor consist of phenylboronic acid functionalized reduced graphene oxide (rGO–PBA) and di-ol modified fluorescent probe for detection of biologically important glucose molecules. This fluorescent graphene based nano-probe has been characterized by high resolution transmission electron microscope (HRTEM), Atomic force microscope (AFM), UV–visible, Photo-luminescence (PL) and Fourier transformed infrared (FT-IR) spectroscopy. Finally, using this PBA functionalized reduced GO based nano-sensor, we were able to detect glucose molecule in the range of 2 mg/mL to 75 mg/mL in aqueous solution of pH 7.4. - Highlights: • Easy and simple synthesis of PBA functionalized reduced GO based nano probe. • PBA functionalized reduced GO graphene based nano-probes are characterized. • PBA functionalized reduced GO nano probe is used to detect glucose molecules. • It is very cost-effective and enzyme-free detection of glucose in solution.

  17. A Computer-Based Glucose Management System Reduces the Incidence of Forgotten Glucose Measurements: A Retrospective Observational Study.

    Science.gov (United States)

    Okura, Tsuyoshi; Teramoto, Kei; Koshitani, Rie; Fujioka, Yohei; Endo, Yusuke; Ueki, Masaru; Kato, Masahiko; Taniguchi, Shin-Ichi; Kondo, Hiroshi; Yamamoto, Kazuhiro

    2018-04-17

    Frequent glucose measurements are needed for good blood glucose control in hospitals; however, this requirement means that measurements can be forgotten. We developed a novel glucose management system using an iPod ® and electronic health records. A time schedule system for glucose measurement was developed using point-of-care testing, an iPod ® , and electronic health records. The system contains the glucose measurement schedule and an alarm sounds if a measurement is forgotten. The number of times measurements were forgotten was analyzed. Approximately 7000 glucose measurements were recorded per month. Before implementation of the system, the average number of times measurements were forgotten was 4.8 times per month. This significantly decreased to 2.6 times per month after the system started. We also analyzed the incidence of forgotten glucose measurements as a proportion of the total number of measurements for each period and found a significant difference between the two 9-month periods (43/64,049-24/65,870, P = 0.014, chi-squared test). This computer-based blood glucose monitoring system is useful for the management of glucose monitoring in hospitals. Johnson & Johnson Japan.

  18. Supplementation with a new trypsin inhibitor from peanut is associated with reduced fasting glucose, weight control, and increased plasma CCK secretion in an animal model.

    Science.gov (United States)

    Serquiz, Alexandre C; Machado, Richele J A; Serquiz, Raphael P; Lima, Vanessa C O; de Carvalho, Fabiana Maria C; Carneiro, Marcella A A; Maciel, Bruna L L; Uchôa, Adriana F; Santos, Elizeu A; Morais, Ana H A

    2016-12-01

    Ingestion of peanuts may have a beneficial effect on weight control, possibly due to the satietogenic action of trypsin inhibitors. The aim of this study was to isolate a new trypsin inhibitor in a typical Brazilian peanut sweet (paçoca) and evaluate its effect in biochemical parameters, weight gain and food intake in male Wistar rats. The trypsin inhibitor in peanut paçoca (AHTI) was isolated. Experimental diets were prepared with AIN-93G supplemented with AHTI. Animals had their weight and food intake monitored. Animals were anesthetized, euthanized, and their bloods collected by cardiac puncture for dosage of cholecystokinin (CCK) and other biochemical parameters. Supplementation with AHTI significantly decreased fasting glucose, body weight gain, and food intake. These effects may be attributed to increased satiety, once supplemented animals showed no evidence of impaired nutritional status and also because AHTI increased CCK production. Thus, our results indicate that AHTI, besides reducing fasting glucose, can reduce weight gain via food intake reduction.

  19. Reduced Expression of the Liver/Beta-Cell Glucose Transporter Isoform in Glucose-Insensitive Pancreatic Beta Cells of Diabetic Rats

    Science.gov (United States)

    Thorens, Bernard; Weir, Gordon C.; Leahy, John L.; Lodish, Harvey F.; Bonner-Weir, Susan

    1990-09-01

    Rats injected with a single dose of streptozocin at 2 days of age develop non-insulin-dependent diabetes 6 weeks later. The pancreatic beta islet cells of these diabetic rats display a loss of glucose-induced insulin secretion while maintaining sensitivity to other secretagogues such as arginine. We analyzed the level of expression of the liver/beta-cell glucose transporter isoform in diabetic islets by immunofluorescence staining of pancreas sections and by Western blotting of islet lysates. Islets from diabetic animals have a reduced expression of this beta-cell-specific glucose transporter isoform and the extent of reduction is correlated with the severity of hyperglycemia. In contrast, expression of this transporter isoform in liver is minimally modified by the diabetes. Thus a decreased expression of the liver/beta-cell glucose transporter isoform in beta cells is associated with the impaired glucose sensing characteristic of diabetic islets; our data suggest that this glucose transporter may be part of the beta-cell glucose sensor.

  20. The Effects of Initial Self-Control Exertion and Subsequent Glucose Consumption on Search Accuracy by Dogs

    Directory of Open Access Journals (Sweden)

    Miller, Holly C.

    2013-07-01

    Full Text Available Previous reports have suggested that canine self-control is sensitive to fatigue and that an initial act of behavioral inhibition (sit-stay 10 min relative to a control condition (cage 10 min can deplete self-control, increase risk-taking, and reduce subsequent persistence on a puzzle task. Glucose, but not a calorie-free placebo drink has been shown to replenish this depletion. The current study sought to complement and extend these findings by examining whether initial exertion of self-control would also affect canine working memory as measured by search accuracy on a subsequently administered invisible displacement rotation task. The results evidenced that initial self-control exertion (relative to the control condition resulted in poorer search accuracy. The consumption of glucose did not have a replenishing effect. If anything, glucose was associated with poorer search accuracy.

  1. Reducing of internal resistance lithium ion battery using glucose addition

    Science.gov (United States)

    Salim, Andri Pratama; Hafidlullah, Noor; Purwanto, Agus

    2016-02-01

    There are two indicators of battery performance, i.e : capacity and the internal resistance of battery. In this research, the affect of glucose addition to decrease the internal resistance of lithium battery was investigated. The ratio of glucose addition were varied at weight ratio 1%, 3%, and 5% and one mixtures without glucose addition. Lithium ferri phosphate (LiFePO4), polyvinylidene fluoride (PVDF), acetylene black (AB) and glucose were materials that used in this study. Both of mixtures were mixed in the vacuum mixer until became homogeneous. The slurry was coated on an aluminium foil sheet and the coated thickness was 200 µm. The performance of battery lithium was examined by Eight Channel Battery Analyzer and the Internal resistance was examined by Internal Resistance of Battery Meter. The result from all analyzer were showed that the internal resistance reduced as well as the battery capacity. The best internal resistance value is owned by mixtures with 3wt% ratio glucose addition. It has an internal resistance value about 64 miliohm.

  2. Reducing of internal resistance lithium ion battery using glucose addition

    International Nuclear Information System (INIS)

    Salim, Andri Pratama; Hafidlullah, Noor; Purwanto, Agus

    2016-01-01

    There are two indicators of battery performance, i.e : capacity and the internal resistance of battery. In this research, the affect of glucose addition to decrease the internal resistance of lithium battery was investigated. The ratio of glucose addition were varied at weight ratio 1%, 3%, and 5% and one mixtures without glucose addition. Lithium ferri phosphate (LiFePO 4 ), polyvinylidene fluoride (PVDF), acetylene black (AB) and glucose were materials that used in this study. Both of mixtures were mixed in the vacuum mixer until became homogeneous. The slurry was coated on an aluminium foil sheet and the coated thickness was 200 µm. The performance of battery lithium was examined by Eight Channel Battery Analyzer and the Internal resistance was examined by Internal Resistance of Battery Meter. The result from all analyzer were showed that the internal resistance reduced as well as the battery capacity. The best internal resistance value is owned by mixtures with 3wt% ratio glucose addition. It has an internal resistance value about 64 miliohm

  3. Reducing of internal resistance lithium ion battery using glucose addition

    Energy Technology Data Exchange (ETDEWEB)

    Salim, Andri Pratama; Hafidlullah, Noor; Purwanto, Agus, E-mail: aguspurw@gmail.com [Research Group of Battery & Advanced Material, Department of Chemical Engineering, Sebelas Maret University, Jl. Ir. Sutami 36 A Kentingan, Surakarta Indonesia 57126 (Indonesia)

    2016-02-08

    There are two indicators of battery performance, i.e : capacity and the internal resistance of battery. In this research, the affect of glucose addition to decrease the internal resistance of lithium battery was investigated. The ratio of glucose addition were varied at weight ratio 1%, 3%, and 5% and one mixtures without glucose addition. Lithium ferri phosphate (LiFePO{sub 4}), polyvinylidene fluoride (PVDF), acetylene black (AB) and glucose were materials that used in this study. Both of mixtures were mixed in the vacuum mixer until became homogeneous. The slurry was coated on an aluminium foil sheet and the coated thickness was 200 µm. The performance of battery lithium was examined by Eight Channel Battery Analyzer and the Internal resistance was examined by Internal Resistance of Battery Meter. The result from all analyzer were showed that the internal resistance reduced as well as the battery capacity. The best internal resistance value is owned by mixtures with 3wt% ratio glucose addition. It has an internal resistance value about 64 miliohm.

  4. Overnight glucose control in people with type 1 diabetes

    DEFF Research Database (Denmark)

    Boiroux, Dimitri; Duun-Henriksen, Anne Katrine; Schmidt, Signe

    2018-01-01

    This paper presents an individualized model predictive control (MPC) algorithm for overnight blood glucose stabilization in people with type 1 diabetes (T1D). The MPC formulation uses an asymmetric objective function that penalizes low glucose levels more heavily. We compute the model parameters...... algorithm uses frequent glucose measurements from a continuous glucose monitor (CGM) and its decisions are implemented by a continuous subcutaneous insulin infusion (CSII) pump. We provide guidelines for tuning the control algorithm and computing the Kalman gain in the linear state space model in innovation...

  5. Valine pyrrolidide preserves intact glucose-dependent insulinotropic peptide and improves abnormal glucose tolerance in minipigs with reduced beta-cell mass

    DEFF Research Database (Denmark)

    Larsen, Marianne Olholm; Rolin, Bidda; Ribel, Ulla

    2003-01-01

    levels of intact GLP-1 but increased levels of intact GIP (from 4543 +/- 1880 to 9208 +/- 3267 pM x min; P glucose tolerance (area under the curve [AUC] for glucose reduced from 1904 +/- 480 to 1582 +/- 353 mM x min; P =.05). VP did not increase insulin levels during the oral......The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important in blood glucose regulation. However, both incretin hormones are rapidly degraded by the enzyme dipeptidyl peptidase IV (DPPIV). The concept of DPPIV inhibition as a treatment...... glucose tolerance test (OGTT) but increased the insulinogenic index in normal animals (from 83 +/- 42 to 192 +/- 108; P

  6. Adjunctive therapy for glucose control in patients with type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Harris K

    2018-04-01

    Full Text Available Kira Harris,1,2 Cassie Boland,1,3 Lisa Meade,1,4 Dawn Battise1,5 1Pharmacy Practice Faculty, Wingate University School of Pharmacy, Wingate, NC, USA; 2Clinical Pharmacy Specialist – Novant Health Family Medicine Residency Program, Cornelius, NC, USA; 3Clinical Pharmacy Specialist – Novant Health Cotswold Family Medicine – Arboretum, Charlotte, NC, USA; 4Clinical Pharmacy Specialist – Piedmont HealthCare Endocrinology, Statesville, NC, USA; 5Clinical Pharmacy Specialist – Cabarrus Family Medicine – Harrisburg, Harrisburg, NC, USA Abstract: Type 1 diabetes mellitus (T1DM is characterized by relative or absolute insulin deficiency. Despite treatment with insulin therapy, glycemic goals are not always met, and insulin therapy is sometimes limited by adverse effects, including hypoglycemia and weight gain. Several adjunctive therapies have been evaluated in combination with insulin in patients with T1DM to improve glycemic control while minimizing adverse effects. Pramlintide, an amylin analog, can improve glycemic control, primarily through lowering postprandial blood glucose levels. Patients may experience weight loss and an increased risk of hypoglycemia and require additional mealtime injections. Metformin provides an inexpensive, oral treatment option and may reduce blood glucose, especially in overweight or obese patients with minimal risk of hypoglycemia. Metformin may be more effective in patients with impaired insulin sensitivity. Glucagon-like peptide-1 receptor agonists reduce primarily postprandial blood glucose and insulin dose and promote weight loss. They are expensive, cause transient nausea, may increase risk of hypoglycemia and require additional injections. Sodium–glucose transport-2 inhibitors improve glycemic control, promote weight loss and have low risk of hypoglycemia with appropriate insulin adjustment; however, these agents may increase the risk of diabetic ketoacidosis in patients with T1DM. Patient

  7. Notch controls the survival of memory CD4+ T cells by regulating glucose uptake.

    Science.gov (United States)

    Maekawa, Yoichi; Ishifune, Chieko; Tsukumo, Shin-ichi; Hozumi, Katsuto; Yagita, Hideo; Yasutomo, Koji

    2015-01-01

    CD4+ T cells differentiate into memory T cells that protect the host from subsequent infection. In contrast, autoreactive memory CD4+ T cells harm the body by persisting in the tissues. The underlying pathways controlling the maintenance of memory CD4+ T cells remain undefined. We show here that memory CD4+ T cell survival is impaired in the absence of the Notch signaling protein known as recombination signal binding protein for immunoglobulin κ J region (Rbpj). Treatment of mice with a Notch inhibitor reduced memory CD4+ T cell numbers and prevented the recurrent induction of experimental autoimmune encephalomyelitis. Rbpj-deficient CD4+ memory T cells exhibit reduced glucose uptake due to impaired AKT phosphorylation, resulting in low Glut1 expression. Treating mice with pyruvic acid, which bypasses glucose uptake and supplies the metabolite downstream of glucose uptake, inhibited the decrease of autoimmune memory CD4+ T cells in the absence of Notch signaling, suggesting memory CD4+ T cell survival relies on glucose metabolism. Together, these data define a central role for Notch signaling in maintaining memory CD4+ T cells through the regulation of glucose uptake.

  8. Novel glucose-sensing technology and hypoglycaemia in type 1 diabetes: a multicentre, non-masked, randomised controlled trial.

    Science.gov (United States)

    Bolinder, Jan; Antuna, Ramiro; Geelhoed-Duijvestijn, Petronella; Kröger, Jens; Weitgasser, Raimund

    2016-11-05

    Tight control of blood glucose in type 1 diabetes delays onset of macrovascular and microvascular diabetic complications; however, glucose levels need to be closely monitored to prevent hypoglycaemia. We aimed to assess whether a factory-calibrated, sensor-based, flash glucose-monitoring system compared with self-monitored glucose testing reduced exposure to hypoglycaemia in patients with type 1 diabetes. In this multicentre, prospective, non-masked, randomised controlled trial, we enrolled adult patients with well controlled type 1 diabetes (HbA 1c ≤58 mmol/mol [7·5%]) from 23 European diabetes centres. After 2 weeks of all participants wearing the blinded sensor, those with readings for at least 50% of the period were randomly assigned (1:1) to flash sensor-based glucose monitoring (intervention group) or to self-monitoring of blood glucose with capillary strips (control group). Randomisation was done centrally using the biased-coin minimisation method dependent on study centre and type of insulin administration. Participants, investigators, and study staff were not masked to group allocation. The primary outcome was change in time in hypoglycaemia (diabetes spent in hypoglycaemia. Future studies are needed to assess the effectiveness of this technology in patients with less well controlled diabetes and in younger age groups. Abbott Diabetes Care. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Reducing patient identification errors related to glucose point-of-care testing

    Directory of Open Access Journals (Sweden)

    Gaurav Alreja

    2011-01-01

    Full Text Available Background: Patient identification (ID errors in point-of-care testing (POCT can cause test results to be transferred to the wrong patient′s chart or prevent results from being transmitted and reported. Despite the implementation of patient barcoding and ongoing operator training at our institution, patient ID errors still occur with glucose POCT. The aim of this study was to develop a solution to reduce identification errors with POCT. Materials and Methods: Glucose POCT was performed by approximately 2,400 clinical operators throughout our health system. Patients are identified by scanning in wristband barcodes or by manual data entry using portable glucose meters. Meters are docked to upload data to a database server which then transmits data to any medical record matching the financial number of the test result. With a new model, meters connect to an interface manager where the patient ID (a nine-digit account number is checked against patient registration data from admission, discharge, and transfer (ADT feeds and only matched results are transferred to the patient′s electronic medical record. With the new process, the patient ID is checked prior to testing, and testing is prevented until ID errors are resolved. Results: When averaged over a period of a month, ID errors were reduced to 3 errors/month (0.015% in comparison with 61.5 errors/month (0.319% before implementing the new meters. Conclusion: Patient ID errors may occur with glucose POCT despite patient barcoding. The verification of patient identification should ideally take place at the bedside before testing occurs so that the errors can be addressed in real time. The introduction of an ADT feed directly to glucose meters reduced patient ID errors in POCT.

  10. The regulation of glucose transport in the heart of control and diabetic rats: With special emphasis on the glucose transporter

    International Nuclear Information System (INIS)

    Pleta, M. de Leoz.

    1989-01-01

    Glucose transport regulation with insulin and high perfusion pressure in the perfused rat hearts from control and diabetic rat hearts was investigated. [ 3 H]-cytochalasin B binding assay was used to study the distribution of glucose transporters within the subcellular membranes fractionated by linear sucrose density gradient centrifugation. In the present study, insulin increased glucose uptake in the perfused heart of control and diabetic animals. This coincided with an increase of glucose transporters on the plasma membrane. The increase in glucose transporters on the plasma membrane could not be accounted for by a decrease of glucose transporters from the microsomal membranes. High perfusion pressure did not change the number of glucose transporters on the plasma membrane compared to basal in the control and diabetic animals, though it increased glucose uptake above that observed for insulin in the control. Instead, high perfusion pressure altered the distribution of glucose transporters within the subcellular membranes in reverse to that with insulin, increasing an intermediate membrane pool believed to reside between the plasma membrane and microsomal membranes as well as the intracellular membrane pool

  11. Bile Acid Sequestration Reduces Plasma Glucose Levels in db/db Mice by Increasing Its Metabolic Clearance Rate

    NARCIS (Netherlands)

    Meissner, M.; Herrema, H.J.; Dijk, van Th.; Gerding, A.; Havinga, R.; Boer, T.; Müller, M.R.; Reijngoud, D.J.; Groen, A.K.; Kuipers, F.

    2011-01-01

    Aims/Hypothesis: Bile acid sequestrants (BAS) reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels.

  12. Replacement of glycaemic carbohydrates by inulin-type fructans from chicory (oligofructose, inulin) reduces the postprandial blood glucose and insulin response to foods: report of two double-blind, randomized, controlled trials.

    Science.gov (United States)

    Lightowler, Helen; Thondre, Sangeetha; Holz, Anja; Theis, Stephan

    2018-04-01

    Inulin-type fructans are recognized as prebiotic dietary fibres and classified as non-digestible carbohydrates that do not contribute to glycaemia. The aim of the present studies was to investigate the glycaemic response (GR) and insulinaemic response (IR) to foods in which sucrose was partially replaced by inulin or oligofructose from chicory. In a double-blind, randomized, controlled cross-over design, 40-42 healthy adults consumed a yogurt drink containing oligofructose or fruit jelly containing inulin and the respective full-sugar variants. Capillary blood glucose and insulin were measured in fasted participants and at 15, 30, 45, 60, 90, and 120 min after starting to drink/eat. For each test food, the incremental area under the curve (iAUC) for glucose and insulin was calculated and the GR and IR determined. Consumption of a yogurt drink with oligofructose which was 20% reduced in sugars significantly lowered the glycaemic response compared to the full-sugar reference (iAUC 120min 31.9 and 37.3 mmol/L/min, respectively; p inulin and containing 30% less sugars than the full-sugar variant likewise resulted in a significantly reduced blood glucose response (iAUC 120min 53.7 and 63.7 mmol/L/min, respectively; p inulin-type fructans (p inulin or oligofructose from chicory may be an effective strategy to reduce the postprandial blood glucose response to foods.

  13. Control of the intracellular redox state by glucose participates in the insulin secretion mechanism.

    Directory of Open Access Journals (Sweden)

    Eduardo Rebelato

    Full Text Available BACKGROUND: Production of reactive oxygen species (ROS due to chronic exposure to glucose has been associated with impaired beta cell function and diabetes. However, physiologically, beta cells are well equipped to deal with episodic glucose loads, to which they respond with a fine tuned glucose-stimulated insulin secretion (GSIS. In the present study, a systematic investigation in rat pancreatic islets about the changes in the redox environment induced by acute exposure to glucose was carried out. METHODOLOGY/PRINCIPAL FINDINGS: Short term incubations were performed in isolated rat pancreatic islets. Glucose dose- and time-dependently reduced the intracellular ROS content in pancreatic islets as assayed by fluorescence in a confocal microscope. This decrease was due to activation of pentose-phosphate pathway (PPP. Inhibition of PPP blunted the redox control as well as GSIS in a dose-dependent manner. The addition of low doses of ROS scavengers at high glucose concentration acutely improved beta cell function. The ROS scavenger N-acetyl-L-cysteine increased the intracellular calcium response to glucose that was associated with a small decrease in ROS content. Additionally, the presence of the hydrogen peroxide-specific scavenger catalase, in its membrane-permeable form, nearly doubled glucose metabolism. Interestingly, though an increase in GSIS was also observed, this did not match the effect on glucose metabolism. CONCLUSIONS: The control of ROS content via PPP activation by glucose importantly contributes to the mechanisms that couple the glucose stimulus to insulin secretion. Moreover, we identified intracellular hydrogen peroxide as an inhibitor of glucose metabolism intrinsic to rat pancreatic islets. These findings suggest that the intracellular adjustment of the redox environment by glucose plays an important role in the mechanism of GSIS.

  14. Discrete Blood Glucose Control in Diabetic Göttingen Minipigs

    Directory of Open Access Journals (Sweden)

    Berno J.E. Misgeld

    2016-07-01

    Full Text Available Despite continuous research effort, patients with type 1 diabetes mellitus (T1D experience difficulties in daily adjustments of their blood glucose concentrations. New technological developments in the form of implanted intravenous infusion pumps and continuous blood glucose sensors might alleviate obstacles for the automatic adjustment of blood glucose concentration. These obstacles consist, for example, of large time-delays and insulin storage effects for the subcutaneous/interstitial route. Towards the goal of an artificial pancreas, we present a novel feedback controller approach that combines classical loop-shaping techniques with gain-scheduling and modern H ∞ -robust control approaches. A disturbance rejection design is proposed in discrete frequency domain based on the detailed model of the diabetic Göttingen minipig. The model is trimmed and linearised over a large operating range of blood glucose concentrations and insulin sensitivity values. Controller parameters are determined for each of these operating points. A discrete H ∞ loop-shaping compensator is designed to increase robustness of the artificial pancreas against general coprime factor uncertainty. The gain scheduled controller uses subcutaneous insulin injection as a control input and determines the controller input error from intravenous blood glucose concentration measurements, where parameter scheduling is achieved by an estimator of the insulin sensitivity parameter. Thus, only one controller stabilises a family of animal models. The controller is validated in silico with a total number of five Göttingen Minipig models, which were previously obtained by experimental identification procedures. Its performance is compared with an experimentally tested switching PI-controller.

  15. Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

    Science.gov (United States)

    Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

    2013-10-16

    Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. © 2013 Elsevier B.V. All rights reserved.

  16. Are glucose levels, glucose variability and autonomic control influenced by inspiratory muscle exercise in patients with type 2 diabetes? Study protocol for a randomized controlled trial.

    Science.gov (United States)

    Schein, Aso; Correa, Aps; Casali, Karina Rabello; Schaan, Beatriz D

    2016-01-20

    Physical exercise reduces glucose levels and glucose variability in patients with type 2 diabetes. Acute inspiratory muscle exercise has been shown to reduce these parameters in a small group of patients with type 2 diabetes, but these results have yet to be confirmed in a well-designed study. The aim of this study is to investigate the effect of acute inspiratory muscle exercise on glucose levels, glucose variability, and cardiovascular autonomic function in patients with type 2 diabetes. This study will use a randomized clinical trial crossover design. A total of 14 subjects will be recruited and randomly allocated to two groups to perform acute inspiratory muscle loading at 2 % of maximal inspiratory pressure (PImax, placebo load) or 60 % of PImax (experimental load). Inspiratory muscle training could be a novel exercise modality to be used to decrease glucose levels and glucose variability. ClinicalTrials.gov NCT02292810 .

  17. Why control blood glucose levels?

    Science.gov (United States)

    Rossini, A A

    1976-03-01

    The controversy as to the relationship between the degree of control of diabetes and the progression of the complications of the disease has not been solved. However, in this review, various studies suggesting a relationship between the metabolic abnormality and the diabetic complications are examined. The disadvantages of the uncontrolled diabetes mellitus can be divided into two major categories-short-term and long-term. The short-term disadvantages of controlled diabetes mellitus include the following: (1) ketoacidosis and hyperosmolar coma; (2) intracellular dehydration; (3) electrolyte imbalance; (4) decreased phagocytosis; (5) immunologic and lymphocyte activity; (6) impairment of wound healing; and (7) abnormality of lipids. The long-term disadvantages of uncontrolled diabetes melitus include the following: (1) nephropathy; (2) neuropathy; (3) retinopathy; (4) cataract formation; (5) effect on perinatal mortality; (6) complications of vascular disease; and (7) the evaluation of various clinical studies suggesting the relationship of elevated blood glucose levels and complications of diabetes mellitus. It is suggested that until the question of control can absolutely be resolved, the recommendation is that the blood glucose levels should be controlled as close to the normal as possible.

  18. Davallialactone reduces inflammation and repairs dentinogenesis on glucose oxidase-induced stress in dental pulp cells.

    Science.gov (United States)

    Lee, Young-Hee; Kim, Go-Eun; Song, Yong-Beom; Paudel, Usha; Lee, Nan-Hee; Yun, Bong-Sik; Yu, Mi-Kyung; Yi, Ho-Keun

    2013-11-01

    The chronic nature of diabetes mellitus (DM) raises the risk of oral complication diseases. In general, DM causes oxidative stress to organs. This study aimed to evaluate the cellular change of dental pulp cells against glucose oxidative stress by glucose oxidase with a high glucose state. The purpose of this study was to test the antioxidant character of davallialactone and to reduce the pathogenesis of dental pulp cells against glucose oxidative stress. The glucose oxidase with a high glucose concentration was tested for hydroxy peroxide (H2O2) production, cellular toxicity, reactive oxygen species (ROS) formation, induction of inflammatory molecules and disturbance of dentin mineralization in human dental pulp cells. The anti-oxidant effect of Davallilactone was investigated to restore dental pulp cells' vitality and dentin mineralization via reduction of H2O2 production, cellular toxicity, ROS formation and inflammatory molecules. The treatment of glucose oxidase with a high glucose concentration increased H2O2 production, cellular toxicity, and inflammatory molecules and disturbed dentin mineralization by reducing pulp cell activity. However, davallialactone reduced H2O2 production, cellular toxicity, ROS formation, inflammatory molecules, and dentin mineralization disturbances even with a long-term glucose oxidative stress state. The results of this study imply that the development of oral complications is related to the irreversible damage of dental pulp cells by DM-induced oxidative stress. Davallialactone, a natural antioxidant, may be useful to treat complicated oral disease, representing an improvement for pulp vital therapy. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  19. Reducing risk of closed loop control of blood glucose in artificial pancreas using fractional calculus.

    Science.gov (United States)

    Ghorbani, Mahboobeh; Bogdan, Paul

    2014-01-01

    Healthcare costs in the US are among the highest in the world. Chronic diseases such as diabetes significantly contribute to these extensive costs. Despite technological advances to improve sensing and actuation devices, we still lack a coherent theory that facilitates the design and optimization of efficient and robust medical cyber-physical systems for managing chronic diseases. In this paper, we propose a mathematical model for capturing the complex dynamics of blood glucose time series (e.g., time dependent and fractal behavior) observed in real world measurements via fractional calculus concepts. Building upon our time dependent fractal model, we propose a novel model predictive controller for an artificial pancreas that regulates insulin injection. We verify the accuracy of our controller by comparing it to conventional non-fractal models using real world measurements and show how the nonlinear optimal controller based on fractal calculus concepts is superior to non-fractal controllers in terms of average risk index and prediction accuracy.

  20. Achieving the same for less: improving mood depletes blood glucose for people with poor (but not good) emotion control.

    Science.gov (United States)

    Niven, Karen; Totterdell, Peter; Miles, Eleanor; Webb, Thomas L; Sheeran, Paschal

    2013-01-01

    Previous studies have found that acts of self-control like emotion regulation deplete blood glucose levels. The present experiment investigated the hypothesis that the extent to which people's blood glucose levels decline during emotion regulation attempts is influenced by whether they believe themselves to be good or poor at emotion control. We found that although good and poor emotion regulators were equally able to achieve positive and negative moods, the blood glucose of poor emotion regulators was reduced after performing an affect-improving task, whereas the blood glucose of good emotion regulators remained unchanged. As evidence suggests that glucose is a limited energy resource upon which self-control relies, the implication is that good emotion regulators are able to achieve the same positive mood with less cost to their self-regulatory resource. Thus, depletion may not be an inevitable consequence of engaging in emotion regulation.

  1. Effect of fibre additions to flatbread flour mixes on glucose kinetics: a randomised controlled trial.

    Science.gov (United States)

    Boers, Hanny M; van Dijk, Theo H; Hiemstra, Harry; Hoogenraad, Anne-Roos; Mela, David J; Peters, Harry P F; Vonk, Roel J; Priebe, Marion G

    2017-11-01

    We previously found that guar gum (GG) and chickpea flour (CPF) added to flatbread wheat flour lowered postprandial blood glucose (PPG) and insulin responses dose dependently. However, rates of glucose influx cannot be determined from PPG, which integrates rates of influx, tissue disposal and hepatic glucose production. The objective was to quantify rates of glucose influx and related fluxes as contributors to changes in PPG with GG and CPF additions to wheat-based flatbreads. In a randomised cross-over design, twelve healthy males consumed each of three different 13C-enriched meals: control flatbreads (C), or C incorporating 15 % CPF with either 2 % (GG2) or 4 % (GG4) GG. A dual isotope technique was used to determine the time to reach 50 % absorption of exogenous glucose (T 50 %abs, primary objective), rate of appearance of exogenous glucose (RaE), rate of appearance of total glucose (RaT), endogenous glucose production (EGP) and rate of disappearance of total glucose (RdT). Additional exploratory outcomes included PPG, insulin, glucose-dependent insulinotropic peptide and glucagon-like peptide 1, which were additionally measured over 4 h. Compared with C, GG2 and GG4 had no significant effect on T 50 %abs. However, GG4 significantly reduced 4-h AUC values for RaE, RaT, RdT and EGP, by 11, 14, 14 and 64 %, respectively, whereas GG2 showed minor effects. Effect sizes over 2 and 4 h were similar except for significantly greater reduction in EGP for GG4 at 2 h. In conclusion, a soluble fibre mix added to flatbreads only slightly reduced rates of glucose influx, but more substantially affected rates of postprandial disposal and hepatic glucose production.

  2. The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load

    DEFF Research Database (Denmark)

    Hornbak, Malene; Banasik, Karina; Justesen, Johanne Marie

    2011-01-01

    -aged Danish individuals (nACADS=4,324; nACADM=4,337). The T2D-case-control study involved a total of ~8,300 Danish individuals (nACADS=8,313; nACADM=8,344). Results In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS associated with reduced measures of serum insulin at 30 min following...... an oral glucose load (per allele effect (beta)=-3.8% (-6.3%;-1.3%), P=0.003), reduced incremental area under the insulin curve (beta=-3.6% (-6.3%;-0.9%), P=0.009), reduced acute insulin response (beta=-2.2% (-4.2%;0.2%), P=0.03), and with increased insulin sensitivity ISIMatsuda (beta= 2.9% (0.5%;5.2%), P...

  3. Mediterranean diet reduces 24-hour ambulatory blood pressure, blood glucose, and lipids: one-year randomized, clinical trial.

    Science.gov (United States)

    Doménech, Mónica; Roman, Pilar; Lapetra, José; García de la Corte, Francisco J; Sala-Vila, Aleix; de la Torre, Rafael; Corella, Dolores; Salas-Salvadó, Jordi; Ruiz-Gutiérrez, Valentina; Lamuela-Raventós, Rosa-María; Toledo, Estefania; Estruch, Ramón; Coca, Antonio; Ros, Emilio

    2014-07-01

    The PREvención con DIeta MEDiterránea (PREDIMED) trial showed that Mediterranean diets (MedDiets) supplemented with either extravirgin olive oil or nuts reduced cardiovascular events, particularly stroke, compared with a control, lower fat diet. The mechanisms of cardiovascular protection remain unclear. We evaluated the 1-year effects of supplemented MedDiets on 24-hour ambulatory blood pressure (BP), blood glucose, and lipids. Randomized, parallel-design, controlled trial was conducted in 2 PREDIMED sites. Diets were ad libitum, and no advice on increasing physical activity or reducing sodium intake was given. Participants were 235 subjects (56.5% women; mean age, 66.5 years) at high cardiovascular risk (85.4% with hypertension). Adjusted changes from baseline in mean systolic BP were -2.3 (95% confidence interval [CI], -4.0 to -0.5) mm Hg and -2.6 (95% CI, -4.3 to -0.9) mm Hg in the MedDiets with olive oil and the MedDiets with nuts, respectively, and 1.7 (95% CI, -0.1 to 3.5) mm Hg in the control group (P<0.001). Respective changes in mean diastolic BP were -1.2 (95% CI, -2.2 to -0.2), -1.2 (95% CI, -2.2 to -0.2), and 0.7 (95% CI, -0.4 to 1.7) mm Hg (P=0.017). Daytime and nighttime BP followed similar patterns. Mean changes from baseline in fasting blood glucose were -6.1, -4.6, and 3.5 mg/dL (P=0.016) in the MedDiets with olive oil, MedDiets with nuts, and control diet, respectively; those of total cholesterol were -11.3, -13.6, and -4.4 mg/dL (P=0.043), respectively. In high-risk individuals, most with treated hypertension, MedDiets supplemented with extravirgin olive oil or nuts reduced 24-hour ambulatory BP, total cholesterol, and fasting glucose. http://www.clinicaltrials.gov. Unique identifier: ISRCTN35739639. © 2014 American Heart Association, Inc.

  4. Statistical transformation and the interpretation of inpatient glucose control data.

    Science.gov (United States)

    Saulnier, George E; Castro, Janna C; Cook, Curtiss B

    2014-03-01

    To introduce a statistical method of assessing hospital-based non-intensive care unit (non-ICU) inpatient glucose control. Point-of-care blood glucose (POC-BG) data from hospital non-ICUs were extracted for January 1 through December 31, 2011. Glucose data distribution was examined before and after Box-Cox transformations and compared to normality. Different subsets of data were used to establish upper and lower control limits, and exponentially weighted moving average (EWMA) control charts were constructed from June, July, and October data as examples to determine if out-of-control events were identified differently in nontransformed versus transformed data. A total of 36,381 POC-BG values were analyzed. In all 3 monthly test samples, glucose distributions in nontransformed data were skewed but approached a normal distribution once transformed. Interpretation of out-of-control events from EWMA control chart analyses also revealed differences. In the June test data, an out-of-control process was identified at sample 53 with nontransformed data, whereas the transformed data remained in control for the duration of the observed period. Analysis of July data demonstrated an out-of-control process sooner in the transformed (sample 55) than nontransformed (sample 111) data, whereas for October, transformed data remained in control longer than nontransformed data. Statistical transformations increase the normal behavior of inpatient non-ICU glycemic data sets. The decision to transform glucose data could influence the interpretation and conclusions about the status of inpatient glycemic control. Further study is required to determine whether transformed versus nontransformed data influence clinical decisions or evaluation of interventions.

  5. Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

    Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

  6. Effects of intensive glucose control on platelet reactivity in patients with acute coronary syndromes. Results of the CHIPS Study ("Control de Hiperglucemia y Actividad Plaquetaria en Pacientes con Sindrome Coronario Agudo").

    Science.gov (United States)

    Vivas, David; García-Rubira, Juan C; Bernardo, Esther; Angiolillo, Dominick J; Martín, Patricia; Calle-Pascual, Alfonso; Núñez-Gil, Iván; Macaya, Carlos; Fernández-Ortiz, Antonio

    2011-05-01

    Hyperglycaemia has been associated with increased platelet reactivity and impaired prognosis in patients with acute coronary syndrome (ACS). Whether platelet reactivity can be reduced by lowering glucose in this setting is unknown. The aim of this study was to assess the functional impact of intensive glucose control with insulin on platelet reactivity in patients admitted with ACS and hyperglycaemia. This is a prospective, randomised trial evaluating the effects of either intensive glucose control (target glucose 80-120 mg/dl) or conventional control (target glucose 180 mg/dl or less) with insulin on platelet reactivity in patients with ACS and hyperglycaemia. The primary endpoint was platelet aggregation following stimuli with 20 μM ADP at 24 h and at hospital discharge. Aggregation following collagen, epinephrine and thrombin receptor-activated peptide, as well as P2Y₁₂ reactivity index and surface expression of glycoprotein IIb/IIIa and P-selectin were also measured. Of the 115 patients who underwent random assignment, 59 were assigned to intensive and 56 to conventional glucose control. Baseline platelet functions and inhospital management were similar in both groups. Maximal aggregation after ADP stimulation at hospital discharge was lower in the intensive group (47.9 ± 13.2% vs 59.1 ± 17.3%; p=0.002), whereas no differences were found at 24 h. Similarly all other parameters of platelet reactivity measured at hospital discharge were significantly reduced in the intensive glucose control group. In this randomised trial, early intensive glucose control with insulin in patients with ACS presenting with hyperglycaemia was found to decrease platelet reactivity. Clinical Trial Registration Number http://www.controlledtrials.com/ISRCTN35708451/ISRCTN35708451.

  7. Institutional blood glucose monitoring system for hospitalized patients: an integral component of the inpatient glucose control program.

    Science.gov (United States)

    Boaz, Mona; Landau, Zohar; Matas, Zipora; Wainstein, Julio

    2009-09-01

    The ability to measure patient blood glucose levels at bedside in hospitalized patients and to transmit those values to a central database enables and facilitates glucose control and follow-up and is an integral component in the care of the hospitalized diabetic patient. The goal of this study was to evaluate the performance of an institutional glucometer employed in the framework of the Program for the Treatment of the Hospitalized Diabetic Patient (PTHDP) at E. Wolfson Medical Center, Holon, Israel. As part of the program to facilitate glucose control in hospitalized diabetic patients, an institutional glucometer was employed that permits uploading of data from stands located in each inpatient department and downloading of that data to a central hospital-wide database. Blood glucose values from hospitalized diabetic patients were collected from August 2007 to October 2008. The inpatient glucose control program was introduced gradually beginning January 2008. During the follow-up period, more than 150,000 blood glucose measures were taken. Mean glucose was 195.7 +/- 99.12 mg/dl during the follow-up period. Blood glucose values declined from 206 +/- 105 prior to PTHDP (August 2007-December 2007) to 186 +/- 92 after its inception (January 2008-October 2008). The decline was associated significantly with time (r = 0.11, p < 0.0001). The prevalence of blood glucose values lower than 60 mg/dl was 1.48% [95% confidence interval (CI) 0.36%] prior to vs 1.55% (95% CI 0.37%) following implementation of the PTHDP. Concomitantly, a significant increase in the proportion of blood glucose values between 80 and 200 mg/dl was observed, from 55.5% prior to program initiation vs 61.6% after program initiation (p < 0.0001). The present study was designed to observe changes in institution-wide glucose values following implementation of the PTHDP. Information was extracted from the glucometer system itself. Because the aforementioned study was not a clinical trial, we cannot rule out

  8. Adolescents with clinical type 1 diabetes display reduced red blood cell glucose transporter isoform 1 (GLUT1).

    Science.gov (United States)

    Garg, Meena; Thamotharan, Manikkavasagar; Becker, Dorothy J; Devaskar, Sherin U

    2014-11-01

    Type 1 diabetic (T1D) adolescent children on insulin therapy suffer episodes of both hyper- and hypoglycemic episodes. Glucose transporter isoform GLUT1 expressed in blood-brain barrier (BBB) and red blood cells (RBC) compensates for perturbed circulating glucose toward protecting the supply to brain and RBCs. We hypothesized that RBC-GLUT1 concentration, as a surrogate for BBB-GLUT1, is altered in T1D children. To test this hypothesis, we measured RBC-GLUT1 by enzyme-linked immunosorbent assay (ELISA) in T1D children (n = 72; mean age 15.3 ± 0.2 yr) and control children (CON; n = 11; mean age 15.6 ± 0.9 yr) after 12 h of euglycemia and during a hyperinsulinemic-hypoglycemic clamp with a nadir blood glucose of ~3.3 mmol/L for 90 min (clamp I) or ~3 mmol/L for 45 min (clamp II). Reduced baseline RBC-GLUT1 was observed in T1D (2.4 ± 0.17 ng/ng membrane protein); vs. CON (4.2 ± 0.61 ng/ng protein) (p < 0.0001). Additionally, baseline RBC-GLUT1 in T1D negatively correlated with hemoglobin A1c (HbA1c) (R = -0.23, p < 0.05) but not in CON (R = 0.06, p < 0.9). Acute decline in serum glucose to 3.3 mmol/L (90 min) or 3 mmol/L (45 min) did not change baseline RBC-GLUT1 in T1D or CON children. We conclude that reduced RBC-GLUT1 encountered in T1D, with no ability to compensate by increasing during acute hypoglycemia over the durations examined, may demonstrate a vulnerability of impaired RBC glucose transport (serving as a surrogate for BBB), especially in those with the worst control. We speculate that this may contribute to the perturbed cognition seen in T1D adolescents. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Proportional Insulin Infusion in Closed-Loop Control of Blood Glucose

    NARCIS (Netherlands)

    Grasman, Johan; Callender, Hannah L.; Mensink, Marco; Pietropaolo, Massimo

    2017-01-01

    A differential equation model is formulated that describes the dynamics of glucose concentration in blood circulation. The model accounts for the intake of food, expenditure of calories and the control of glucose levels by insulin and glucagon. These and other hormones affect the blood glucose level

  10. Hypothalamic vitamin D improves glucose homeostasis and reduces weight

    Science.gov (United States)

    Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weigh...

  11. Skeletal muscle neuronal nitric oxide synthase micro protein is reduced in people with impaired glucose homeostasis and is not normalized by exercise training.

    Science.gov (United States)

    Bradley, Scott J; Kingwell, Bronwyn A; Canny, Benedict J; McConell, Glenn K

    2007-10-01

    Skeletal muscle inducible nitric oxide synthase (NOS) protein is greatly elevated in people with type 2 diabetes mellitus, whereas endothelial NOS is at normal levels. Diabetic rat studies suggest that skeletal muscle neuronal NOS (nNOS) micro protein expression may be reduced in human insulin resistance. The aim of this study was to determine whether skeletal muscle nNOSmicro protein expression is reduced in people with impaired glucose homeostasis and whether exercise training increases nNOSmicro protein expression in these individuals because exercise training increases skeletal muscle nNOSmicro protein in rats. Seven people with type 2 diabetes mellitus or prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and 7 matched (sex, age, fitness, body mass index, blood pressure, lipid profile) healthy controls aged 36 to 60 years participated in this study. Vastus lateralis muscle biopsies for nNOSmicro protein determination were obtained, aerobic fitness was measured (peak pulmonary oxygen uptake [Vo(2) peak]), and glucose tolerance and insulin homeostasis were assessed before and after 1 and 4 weeks of cycling exercise training (60% Vo(2) peak, 50 minutes x 5 d wk(-1)). Skeletal muscle nNOSmicro protein was significantly lower (by 32%) in subjects with type 2 diabetes mellitus or prediabetes compared with that in controls before training (17.7 +/- 1.2 vs 26.2 +/- 3.4 arbitrary units, P glucose homeostasis have reduced skeletal muscle nNOSmicro protein content. However, because exercise training improves insulin sensitivity without influencing skeletal muscle nNOSmicro protein expression, it seems that changes in skeletal muscle nNOSmicro protein are not central to the control of insulin sensitivity in humans and therefore may be a consequence rather than a cause of diabetes.

  12. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.

    NARCIS (Netherlands)

    Patel, A.; MacMahon, S; Chalmers, J.; Neal, B.; Billot, L.; Woodward, M.; Marre, M.; Cooper, M.; Glasziou, P.; Grobbee, D.E.; Hamet, P.; Harrap, S.; Heller, S.; Liu, L.; Mancia, G.; Mogensen, C.E.; Pan, C.; Poulter, N.; Rodgers, A.; Williams, B.; Bompoint, S.; Galan, B.E. de; Joshi, R.; Travert, F.

    2008-01-01

    BACKGROUND: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. METHODS: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide

  13. Nurse- vs nomogram-directed glucose control in a cardiovascular intensive care unit.

    Science.gov (United States)

    Chant, Clarence; Mustard, Mary; Thorpe, Kevin E; Friedrich, Jan O

    2012-07-01

    Paper-based nomograms are reasonably effective for achieving glycemic control but have low adherence and are less adaptive than nurses' judgment. To compare efficacy (glucose control) and safety (hypoglycemia) achieved by use of a paper nomogram versus nurses' judgment. Prospective, randomized, open-label, crossover trial in an intensive care unit in postoperative patients with glucose concentrations greater than 8 mmol/L. Consenting nurses with at least 1 year of experience were randomized to use either their judgment or a validated paper-based nomogram for glucose control. After completion of 2 study shifts, the nurses used the alternative method for the next 2 study shifts. Glucose target level and safety and efficacy boundaries were the same for both methods. The primary end point was area under glucose time curve per hour. Thirty-four nurses contributed 95 shifts of data (44 nomogram-directed, 51 nurse-directed). Adherence to the nomogram was higher in the nomogram group than hypothetical adherence in the nurse-directed group for correct adjustments in insulin infusion (70% vs 37%; P unit where nurses generally accepted the need for tight glucose control, nurse-directed control was as effective and as safe as nomogram-based control.

  14. A bio-inspired glucose controller based on pancreatic β-cell physiology.

    Science.gov (United States)

    Herrero, Pau; Georgiou, Pantelis; Oliver, Nick; Johnston, Desmond G; Toumazou, Christofer

    2012-05-01

    Control algorithms for closed-loop insulin delivery in type 1 diabetes have been mainly based on control engineering or artificial intelligence techniques. These, however, are not based on the physiology of the pancreas but seek to implement engineering solutions to biology. Developments in mathematical models of the β-cell physiology of the pancreas have described the glucose-induced insulin release from pancreatic β cells at a molecular level. This has facilitated development of a new class of bio-inspired glucose control algorithms that replicate the functionality of the biological pancreas. However, technologies for sensing glucose levels and delivering insulin use the subcutaneous route, which is nonphysiological and introduces some challenges. In this article, a novel glucose controller is presented as part of a bio-inspired artificial pancreas. A mathematical model of β-cell physiology was used as the core of the proposed controller. In order to deal with delays and lack of accuracy introduced by the subcutaneous route, insulin feedback and a gain scheduling strategy were employed. A United States Food and Drug Administration-accepted type 1 diabetes mellitus virtual population was used to validate the presented controller. Premeal and postmeal mean ± standard deviation blood glucose levels for the adult and adolescent populations were well within the target range set for the controller [(70, 180) mg/dl], with a percent time in range of 92.8 ± 7.3% for the adults and 83.5 ± 14% for the adolescents. This article shows for the first time very good glucose control in a virtual population with type 1 diabetes mellitus using a controller based on a subcellular β-cell model. © 2012 Diabetes Technology Society.

  15. Valine Pyrrolidide Preserves Intact Glucose-Dependent Insulinotropic Peptide and Improves Abnormal Glucose Tolerance in Minipigs With Reduced β-Cell Mass

    OpenAIRE

    Larsen, Marianne Olholm; Rolin, Bidda; Ribel, Ulla; Wilken, Michael; Deacon, Carolyn F.; Svendsen, Ove; Gotfredsen, Carsten F.; Carr, Richard David

    2003-01-01

    The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important in blood glucose regulation.However, both incretin hormones are rapidly degraded by the enzyme dipeptidyl peptidase IV (DPPIV). The concept of DPPIV inhibition as a treatment for type 2 diabetes was evaluated in a new large animal model of insulin-deficient diabetes and reduced β-cell mass, the nicotinamide (NIA) (67 mg/kg) and streptozotocin (STZ) (125 mg/kg)–treated min...

  16. Bile acid sequestration reduces plasma glucose levels in db/db mice by increasing its metabolic clearance rate.

    Directory of Open Access Journals (Sweden)

    Maxi Meissner

    Full Text Available AIMS/HYPOTHESIS: Bile acid sequestrants (BAS reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. METHODS: Lean and diabetic db/db mice were treated with 2% (wt/wt in diet Colesevelam HCl (BAS for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-(13C]-glucose, [2-(13C]-glycerol, [1-(2H]-galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. RESULTS: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001, a ∼300% increased glucokinase flux (p = 0.001 and a ∼200% increased total hepatic glucose production rate (p = 0.0002. BAS treatment increased glucose metabolic clearance rate by ∼37% but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317 but not in liver (p = 0.189. Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030 and 3-fold in db/db mice (p = 0.002. CONCLUSIONS/INTERPRETATION: BAS induced plasma glucose lowering in db/db mice by increasing metabolic clearance rate of glucose in peripheral tissues, which coincided with decreased skeletal muscle long-chain acylcarnitine content.

  17. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    International Nuclear Information System (INIS)

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-01-01

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

  18. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

  19. Overnight glucose control in people with type 1 diabetes

    DEFF Research Database (Denmark)

    Boiroux, Dimitri; Duun-Henriksen, Anne Katrine; Schmidt, Signe

    2018-01-01

    This paper presents an individualized model predictive control (MPC) algorithm for overnight blood glucose stabilization in people with type 1 diabetes (T1D). The MPC formulation uses an asymmetric objective function that penalizes low glucose levels more heavily. We compute the model parameters...

  20. Hydroxycitric acid delays intestinal glucose absorption in rats

    NARCIS (Netherlands)

    Wielinga, PY; Wachters-Hagedoorn, RE; Bouter, B; van Dijk, TH; Stellaard, F; Nieuwenhuizen, AG; Verkade, HJ; Scheurink, AJW; Nieuwenhuizen, Arie G.; Verkade, Henkjan J.

    In this study, we investigated in rats if hydroxycitric acid (HCA) reduces the postprandial glucose response by affecting gastric emptying or intestinal glucose absorption. We compared the effect of regulator HCA (310 mg/kg) and vehicle (control) on the glucose response after an intragastric or

  1. Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production

    OpenAIRE

    Lam, Tony K.T.

    2007-01-01

    Brain glucose-sensing mechanisms are implicated in the regulation of feeding behavior and hypoglycemic-induced hormonal counter-regulation. This commentary discusses recent findings indicating that the brain senses glucose to regulate both hepatic glucose and lipid production.

  2. Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2017-04-01

    Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC 50 = 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU 50 = 3.5% ± 1.6%) or without insulin (GU 50 = 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.

  3. CNS-targets in control of energy and glucose homeostasis.

    Science.gov (United States)

    Kleinridders, André; Könner, A Christine; Brüning, Jens C

    2009-12-01

    The exceeding efforts in understanding the signals initiated by nutrients and hormones in the central nervous system (CNS) to regulate glucose and energy homeostasis have largely revolutionized our understanding of the neurocircuitry in control of peripheral metabolism. The ability of neurons to sense nutrients and hormones and to adopt a coordinated response to these signals is of crucial importance in controlling food intake, energy expenditure, glucose and lipid metabolism. Anatomical lesion experiments, pharmacological inhibition of signaling pathways, and, more recently, the analysis of conditional mouse mutants with modifications of hormone and nutrient signaling in defined neuronal populations have broadened our understanding of these complex neurocircuits. This review summarizes recent findings regarding the role of the CNS in sensing and transmitting nutritional and hormonal signals to control energy and glucose homeostasis and aims to define them as potential novel drug targets for the treatment of obesity and type 2 diabetes mellitus.

  4. Correlation between high blood IL-6 level, hyperglycemia, and glucose control in septic patients.

    Science.gov (United States)

    Nakamura, Masataka; Oda, Shigeto; Sadahiro, Tomohito; Watanabe, Eizo; Abe, Ryuzo; Nakada, Taka-Aki; Morita, Yasumasa; Hirasawa, Hiroyuki

    2012-12-12

    The aim of the present study was to investigate the relationship between the blood IL-6 level, the blood glucose level, and glucose control in septic patients. This retrospective observational study in a general ICU of a university hospital included a total of 153 patients with sepsis, severe sepsis, or septic shock who were admitted to the ICU between 2005 and 2010, stayed in the ICU for 7 days or longer, and did not receive steroid therapy prior to or after ICU admission. The severity of stress hyperglycemia, status of glucose control, and correlation between those two factors in these patients were investigated using the blood IL-6 level as an index of hypercytokinemia. A significant positive correlation between blood IL-6 level and blood glucose level on ICU admission was observed in the overall study population (n = 153; r = 0.24, P = 0.01), and was stronger in the nondiabetic subgroup (n = 112; r = 0.42, P glucose control (blood glucose level blood IL-6 level on ICU admission (P blood IL-6 level after ICU admission remained significantly higher and the 60-day survival rate was significantly lower in the failed glucose control group than in the successful glucose control group (P blood IL-6 level was correlated with hyperglycemia and with difficulties in glucose control in septic patients. These results suggest the possibility that hypercytokinemia might be involved in the development of hyperglycemia in sepsis, and thereby might affect the success of glucose control.

  5. Impact of Glucose Meter Error on Glycemic Variability and Time in Target Range During Glycemic Control After Cardiovascular Surgery.

    Science.gov (United States)

    Karon, Brad S; Meeusen, Jeffrey W; Bryant, Sandra C

    2015-08-25

    We retrospectively studied the impact of glucose meter error on the efficacy of glycemic control after cardiovascular surgery. Adult patients undergoing intravenous insulin glycemic control therapy after cardiovascular surgery, with 12-24 consecutive glucose meter measurements used to make insulin dosing decisions, had glucose values analyzed to determine glycemic variability by both standard deviation (SD) and continuous overall net glycemic action (CONGA), and percentage glucose values in target glucose range (110-150 mg/dL). Information was recorded for 70 patients during each of 2 periods, with different glucose meters used to measure glucose and dose insulin during each period but no other changes to the glycemic control protocol. Accuracy and precision of each meter were also compared using whole blood specimens from ICU patients. Glucose meter 1 (GM1) had median bias of 11 mg/dL compared to a laboratory reference method, while glucose meter 2 (GM2) had a median bias of 1 mg/dL. GM1 and GM2 differed little in precision (CV = 2.0% and 2.7%, respectively). Compared to the period when GM1 was used to make insulin dosing decisions, patients whose insulin dose was managed by GM2 demonstrated reduced glycemic variability as measured by both SD (13.7 vs 21.6 mg/dL, P meter error (bias) was associated with decreased glycemic variability and increased percentage of values in target glucose range for patients placed on intravenous insulin therapy following cardiovascular surgery. © 2015 Diabetes Technology Society.

  6. Bihormonal control of blood glucose in people with type 1 diabetes

    DEFF Research Database (Denmark)

    Batora, Vladimir; Tárnik, Marían; Murgaš, Ján

    2015-01-01

    -based activation of glucagon administration. The control algorithm consists of a Kalman filter, an insulin infusion model predictive controller (MPC), a proportional-derivative (PD) controller for glucagon infusion, and a meal time insulin bolus calculator. The PD controller is activated if the Kalman filter...... predicts hypoglycemia. Predictions utilize an ARMAX model describing glucose-insulin and glucose-glucagon dynamics. The model parameters are estimated from basic patient-specific data. A continuous glucose monitor provides feedback. We test the control algorithm using a simulation model with time......-varying parameters available for 3 patients. We consider a simulation scenario where meals are estimated correctly as well as overestimated by 30%. The simulation results demonstrate that during normal operation, the controller only needs insulin and does not need glucagon. During unexpected events, such as insulin...

  7. Flash Glucose-Sensing Technology as a Replacement for Blood Glucose Monitoring for the Management of Insulin-Treated Type 2 Diabetes: a Multicenter, Open-Label Randomized Controlled Trial.

    Science.gov (United States)

    Haak, Thomas; Hanaire, Hélène; Ajjan, Ramzi; Hermanns, Norbert; Riveline, Jean-Pierre; Rayman, Gerry

    2017-02-01

    Glycemic control in participants with insulin-treated diabetes remains challenging. We assessed safety and efficacy of new flash glucose-sensing technology to replace self-monitoring of blood glucose (SMBG). This open-label randomized controlled study (ClinicalTrials.gov, NCT02082184) enrolled adults with type 2 diabetes on intensive insulin therapy from 26 European diabetes centers. Following 2 weeks of blinded sensor wear, 2:1 (intervention/control) randomization (centrally, using biased-coin minimization dependant on study center and insulin administration) was to control (SMBG) or intervention (glucose-sensing technology). Participants and investigators were not masked to group allocation. Primary outcome was difference in HbA1c at 6 months in the full analysis set. Prespecified secondary outcomes included time in hypoglycemia, effect of age, and patient satisfaction. Participants (n = 224) were randomized (149 intervention, 75 controls). At 6 months, there was no difference in the change in HbA1c between intervention and controls: -3.1 ± 0.75 mmol/mol, [-0.29 ± 0.07% (mean ± SE)] and -3.4 ± 1.04 mmol/mol (-0.31 ± 0.09%) respectively; p = 0.8222. A difference was detected in participants aged glucose-sensing technology use in type 2 diabetes with intensive insulin therapy results in no difference in HbA1c change and reduced hypoglycemia, thus offering a safe, effective replacement for SMBG. ClinicalTrials.gov identifier: NCT02082184. Abbott Diabetes Care.

  8. Self-assembly of glucose oxidase on reduced graphene oxide-magnetic nanoparticles nanocomposite-based direct electrochemistry for reagentless glucose biosensor.

    Science.gov (United States)

    Pakapongpan, Saithip; Poo-Arporn, Rungtiva P

    2017-07-01

    A novel approach of the immobilization of a highly selective and stable glucose biosensor based on direct electrochemistry was fabricated by a self-assembly of glucose oxidase (GOD) on reduced graphene oxide (RGO) covalently conjugated to magnetic nanoparticles (Fe 3 O 4 NPs) modified on a magnetic screen-printed electrode (MSPE). The RGO-Fe 3 O 4 nanocomposite has remarkable enhancement in large surface areas, is favorable environment for enzyme immobilization, facilitates electron transfer between enzymes and electrode surfaces and possesses superparamagnetism property. The morphology and electrochemical properties of RGO-Fe 3 O 4 /GOD were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, cyclic voltammetry (CV) and amperometry. The modified electrode was a fast, direct electron transfer with an apparent electron transfer rate constant (k s ) of 13.78s -1 . The proposed biosensor showed fast amperometric response (3s) to glucose with a wide linear range from 0.05 to 1mM, a low detection limit of 0.1μM at a signal to noise ratio of 3 (S/N=3) and good sensitivity (5.9μA/mM). The resulting biosensor has high stability, good reproducibility, excellent selectivity and successfully applied detection potential at -0.45V. This mediatorless glucose sensing used the advantages of covalent bonding and self-assembly as a new approach for immobilizing enzymes without any binder. It would be worth noting that it opens a new avenue for fabricating excellent electrochemical biosensors. This is a new approach that reporting the immobilization of glucose oxidase on reduced graphene oxide (RGO) covalently conjugated to magnetic nanoparticles (Fe 3 O 4 NPs) by electrostatic interaction and modified screen printed electrode. We propose the reagentless with fabrication method without binder and adhesive agents for immobilized enzyme. Fe 3 O 4 NPs increasing surface area to enhance the immobilization and prevent

  9. Sodium-glucose co-transporter type 2 inhibitors reduce evening home blood pressure in type 2 diabetes with nephropathy.

    Science.gov (United States)

    Takenaka, Tsuneo; Kishimoto, Miyako; Ohta, Mari; Tomonaga, Osamu; Suzuki, Hiromichi

    2017-05-01

    The effects of sodium-glucose co-transporter type 2 inhibitors on home blood pressure were examined in type 2 diabetes with nephropathy. The patients with diabetic nephropathy were screened from medical records in our hospitals. Among them, 52 patients who measured home blood pressure and started to take sodium-glucose co-transporter type 2 inhibitors were selected. Clinical parameters including estimated glomerular filtration rate, albuminuria and home blood pressure for 6 months were analysed. Sodium-glucose co-transporter type 2 inhibitors (luseogliflozin 5 mg/day or canagliflozin 100 mg/day) reduced body weight, HbA1c, albuminuria, estimated glomerular filtration rate and office blood pressure. Although sodium-glucose co-transporter type 2 inhibitors did not alter morning blood pressure, it reduced evening systolic blood pressure. Regression analyses revealed that decreases in evening blood pressure predicted decrements in albuminuria. The present data suggest that sodium-glucose co-transporter type 2 inhibitors suppress sodium overload during daytime to reduce evening blood pressure and albuminuria.

  10. Facile synthesis of glucose-functionalized reduced graphene oxide (GFRGO)/poly(vinyl alcohol) nanocomposites for improving thermal and mechanical properties

    Energy Technology Data Exchange (ETDEWEB)

    Abdolmaleki, Amir, E-mail: abdolmaleki@cc.iut.ac.ir [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Nanotechnology and Advanced Materials Institute, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Center of Excellence in Sensors and Green Chemistry, Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Mallakpour, Shadpour, E-mail: mallak@cc.iut.ac.ir [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Nanotechnology and Advanced Materials Institute, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Center of Excellence in Sensors and Green Chemistry, Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Karshenas, Azam [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of)

    2017-03-15

    Highlights: • GFRGO composites were synthesized and used for fabrication of PVA/GFRGO NCs. • Attached glucose on RGO enhances RGO interaction with PVA hydroxyl groups. • PVA/GFRGO NCs exhibited enhanced thermal and mechanical properties. • FE-SEM and TEM micrographs prove good dispersion of GFRGO into PVA matrix. - Abstract: In this work, we provided a facile pathway to the modification of reduced graphene oxide (RGO) nanosheets by glucose as a biologically active molecule through covalent functionalization. Then, flexible and smooth poly(vinyl alcohol) (PVA)/glucose-functionalized reduced graphene oxide (PVA/GFRGO) nanocomposite (NC) films were fabricated using 0, 1, 3 and 5 wt% concentrations of RGO-glucose in water. As a reducing sugar, glucose can reduce graphene oxide. Thus, graphene oxide was converted to reduced graphene oxide (RGO) by hydrazine hydrate. Then, RGO was functionalized with glucose to achieve good dispersion in the polymer matrix. Due to the increased interfacial interaction between GFRGO and PVA matrix, the prepared PVA/GFRGO NCs showed a 52% increase in tensile strength and a 47% improvement in Young’s modulus by adding of only 5 wt% of GFRGO. Thermal analysis results showed that the thermal stability of the PVA/GFRGO NCs increased compared to the neat PVA film.

  11. Facile synthesis of glucose-functionalized reduced graphene oxide (GFRGO)/poly(vinyl alcohol) nanocomposites for improving thermal and mechanical properties

    International Nuclear Information System (INIS)

    Abdolmaleki, Amir; Mallakpour, Shadpour; Karshenas, Azam

    2017-01-01

    Highlights: • GFRGO composites were synthesized and used for fabrication of PVA/GFRGO NCs. • Attached glucose on RGO enhances RGO interaction with PVA hydroxyl groups. • PVA/GFRGO NCs exhibited enhanced thermal and mechanical properties. • FE-SEM and TEM micrographs prove good dispersion of GFRGO into PVA matrix. - Abstract: In this work, we provided a facile pathway to the modification of reduced graphene oxide (RGO) nanosheets by glucose as a biologically active molecule through covalent functionalization. Then, flexible and smooth poly(vinyl alcohol) (PVA)/glucose-functionalized reduced graphene oxide (PVA/GFRGO) nanocomposite (NC) films were fabricated using 0, 1, 3 and 5 wt% concentrations of RGO-glucose in water. As a reducing sugar, glucose can reduce graphene oxide. Thus, graphene oxide was converted to reduced graphene oxide (RGO) by hydrazine hydrate. Then, RGO was functionalized with glucose to achieve good dispersion in the polymer matrix. Due to the increased interfacial interaction between GFRGO and PVA matrix, the prepared PVA/GFRGO NCs showed a 52% increase in tensile strength and a 47% improvement in Young’s modulus by adding of only 5 wt% of GFRGO. Thermal analysis results showed that the thermal stability of the PVA/GFRGO NCs increased compared to the neat PVA film.

  12. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    Science.gov (United States)

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

  13. Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose Homeostasis

    DEFF Research Database (Denmark)

    Cortijo, Cedric; Gouzi, Mathieu; Tissir, Fadel

    2012-01-01

    glucose clearance. Loss of Celsr2 and 3 leads to a reduction of Jun phosphorylation in progenitors, which, in turn, reduces beta cell differentiation from endocrine progenitors. These results highlight the importance of the PCP pathway in cell differentiation in vertebrates. In addition, they reveal.......5 synchronously to apicobasal polarization of pancreas progenitors. Loss of function of the two PCP core components Celsr2 and Celsr3 shows that they control the differentiation of endocrine cells from polarized progenitors, with a prevalent effect on insulin-producing beta cells. This results in a decreased...

  14. [Predictors of mean blood glucose control and its variability in diabetic hospitalized patients].

    Science.gov (United States)

    Sáenz-Abad, Daniel; Gimeno-Orna, José Antonio; Sierra-Bergua, Beatriz; Pérez-Calvo, Juan Ignacio

    2015-01-01

    This study was intended to assess the effectiveness and predictors factors of inpatient blood glucose control in diabetic patients admitted to medical departments. A retrospective, analytical cohort study was conducted on patients discharged from internal medicine with a diagnosis related to diabetes. Variables collected included demographic characteristics, clinical data and laboratory parameters related to blood glucose control (HbA1c, basal plasma glucose, point-of-care capillary glucose). The cumulative probability of receiving scheduled insulin regimens was evaluated using Kaplan-Meier analysis. Multivariate regression models were used to select predictors of mean inpatient glucose (MHG) and glucose variability (standard deviation [GV]). The study sample consisted of 228 patients (mean age 78.4 (SD 10.1) years, 51% women). Of these, 96 patients (42.1%) were treated with sliding-scale regular insulin only. Median time to start of scheduled insulin therapy was 4 (95% CI, 2-6) days. Blood glucose control measures were: MIG 181.4 (SD 41.7) mg/dL, GV 56.3 (SD 22.6). The best model to predict MIG (R(2): .376; P<.0001) included HbA1c (b=4.96; P=.011), baseline plasma glucose (b=.056; P=.084), mean capillary blood glucose in the first 24hours (b=.154; P<.0001), home treatment (versus oral agents) with basal insulin only (b=13.1; P=.016) or more complex (pre-mixed insulin or basal-bolus) regimens (b=19.1; P=.004), corticoid therapy (b=14.9; P=.002), and fasting on admission (b=10.4; P=.098). Predictors of inpatient blood glucose control which should be considered in the design of DM management protocols include home treatment, HbA1c, basal plasma glucose, mean blood glucose in the first 24hours, fasting, and corticoid therapy. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  15. Roles of Protein Arginine Methyltransferases in the Control of Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Hye-Sook Han

    2014-12-01

    Full Text Available Glucose homeostasis is tightly controlled by the regulation of glucose production in the liver and glucose uptake into peripheral tissues, such as skeletal muscle and adipose tissue. Under prolonged fasting, hepatic gluconeogenesis is mainly responsible for glucose production in the liver, which is essential for tissues, organs, and cells, such as skeletal muscle, the brain, and red blood cells. Hepatic gluconeogenesis is controlled in part by the concerted actions of transcriptional regulators. Fasting signals are relayed by various intracellular enzymes, such as kinases, phosphatases, acetyltransferases, and deacetylases, which affect the transcriptional activity of transcription factors and transcriptional coactivators for gluconeogenic genes. Protein arginine methyltransferases (PRMTs were recently added to the list of enzymes that are critical for regulating transcription in hepatic gluconeogenesis. In this review, we briefly discuss general aspects of PRMTs in the control of transcription. More specifically, we summarize the roles of four PRMTs: PRMT1, PRMT 4, PRMT 5, and PRMT 6, in the control of hepatic gluconeogenesis through specific regulation of FoxO1- and CREB-dependent transcriptional events.

  16. Lowering Plasma Glucose Concentration by Inhibiting Renal Sodium-Glucose Co-Transport

    Science.gov (United States)

    Abdul-Ghani, Muhammad A; DeFronzo, Ralph A

    2017-01-01

    Maintaining normoglycaemia not only reduces the risk of diabetic microvascular complications but also corrects the metabolic abnormalities that contribute to the development and progression of hyperglycaemia (i.e. insulin resistance and beta-cell dysfunction). Progressive beta-cell failure, in addition to the multiple side effects associated with many current antihyperglycaemic agents (e.g., hypoglycaemia and weight gain) presents major obstacle to the achievement of the recommended goal of glycaemic control in patients with diabetes mellitus (DM). Thus, novel effective therapies are needed for optimal glucose control in subjects with DM. Recently, specific inhibitors of renal sodium glucose cotransporter 2 (SGLT2) have been developed to produce glucosuria and lower the plasma glucose concentration. Because of their unique mechanism of action (which is independent of the secretion and action of insulin), these agents are effective in lowering the plasma glucose concentration in all stages of DM and can be combined with all other antidiabetic agents. In this review, we summarize the available data concerning the mechanism of action, efficacy and safety of this novel class of antidiabetic agent. PMID:24690096

  17. Platelet indices and glucose control in type 1 and type 2 diabetes mellitus: A case-control study.

    Science.gov (United States)

    Zaccardi, F; Rocca, B; Rizzi, A; Ciminello, A; Teofili, L; Ghirlanda, G; De Stefano, V; Pitocco, D

    2017-10-01

    The relationship between platelet indices and glucose control may differ in type 1 (T1DM) and type 2 (T2DM) diabetes. We aimed to investigate differences in mean platelet volume (MPV), platelet count, and platelet mass between patients with T1DM, T2DM, and healthy controls and to explore associations between these platelet indices and glucose control. A total of 691 T1DM and 459 T2DM patients and 943 control subjects (blood donors) were included. HbA1c was measured in all subjects with diabetes and 36 T1DM patients further underwent 24 h-continuous glucose monitoring to estimate short-term glucose control (glucose mean and standard deviation). Adjusting for age and sex, platelet count was higher and MPV lower in both T1DM and T2DM patients vs control subjects, while platelet mass (MPV × platelet count) resulted higher only in T2DM. Upon further adjustment for HbA1c, differences in platelet count and mass were respectively 19.5 × 10 9 /L (95%CI: 9.8-29.3; p 1) and 101 fL/nL (12-191; p = 0.027) comparing T2DM vs T1DM patients. MPV and platelet count were significantly and differently related in T2DM patients vs both T1DM and control subjects; this difference was maintained also accounting for HbA1c, age, and sex. Platelet mass and the volume-count relationship were significantly related to HbA1c only in T1DM patients. No associations were found between platelet indices and short-term glucose control. By accounting for confounders and glucose control, our data evidenced higher platelet mass and different volume-count kinetics in subjects with T2DM vs T1DM. Long-term glucose control seemed to influence platelet mass and the volume-count relationship only in T1DM subjects. These findings suggest different mechanisms behind platelet formation in T1DM and T2DM patients with long-term glycaemic control being more relevant in T1DM than T2DM. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian

  18. Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Knop, F K; Vilsbøll, T; Madsbad, S

    2007-01-01

    AIMS/HYPOTHESIS: We investigated glucagon responses during OGTT and isoglycaemic i.v. glucose infusion, respectively, to further elucidate the mechanisms behind the glucose intolerance in patients with type 2 diabetes. MATERIALS AND METHODS: Ten patients (eight men) with type 2 diabetes (age: 64...... during the 2 days was obtained in both groups. In the control subjects no difference in glucagon suppression during the first 45 min of OGTT and isoglycaemic i.v. glucose infusion (-36 +/- 12 vs -64 +/- 23 mmol/l x 45 min; p = NS) was observed, whereas in the group of patients with type 2 diabetes...... significant glucagon suppression only occurred following isoglycaemic i.v. glucose infusion (-63 +/- 21 vs 10 +/- 16 mmol/l x 45 min; p = 0.002). The incretin effect was significantly reduced in patients with type 2 diabetes compared with control subjects, but no significant differences in the secretion...

  19. Impact of structured education on glucose control and ...

    African Journals Online (AJOL)

    Objective: To assess the impact of structured education on glucose control and hypoglycaemia in the management of Type-2 diabetes. Methods: A systematic review was done using Medline via Ovid and EMBASE databases of published English literature between 1980 and 2014. Included studies were randomized control ...

  20. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

    OpenAIRE

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2015-01-01

    Purpose Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused ...

  1. Nickel-functionalized reduced graphene oxide with polyaniline for non-enzymatic glucose sensing

    International Nuclear Information System (INIS)

    Zhang, Bing; He, Yu; Liu, Bingqian; Tang, Dianping

    2015-01-01

    We have developed a new class of organic–inorganic hybrid nanostructures based on the use of reduced graphene oxide (rGO), polyaniline, and a nickel metal nanostructure. It was applied to efficient non-enzymatic sensing of glucose based on its electrocatalytic oxidation. Scanning electron microscopy and energy-dispersive X-Ray were employed to characterize the material. It is shown that the doped polyaniline plays an important role in the formation of the hybrid nanostructures. Improved analytical performance is found when the hybrid nanostructures were placed on a glassy carbon electrode and used for non-enzymatic sensing of glucose at a typical working potential of +450 mV and a pH value of 13. Features include a fast response (∼2 s), high sensitivity (6,050 μA mM −1 cm −2 ), a linear range from 0.1 μM to 1.0 mM, and a low detection limit (0.08 μM). The response to glucose follows a Michaelis-Menten kinetic behavior, and the K M value was determined to be 0.241 μM. Reproducibility and specificity are acceptable. Fructose and maltose do not interfere significantly. Importantly, the methodology was validated and evaluated for the analysis of 15 spiked human serum specimens, receiving in a good accordance with the results obtained by the non-enzymatic glucose sensing and the commercialized personal glucose meter. (author)

  2. Performance Analysis of Fuzzy-PID Controller for Blood Glucose Regulation in Type-1 Diabetic Patients.

    Science.gov (United States)

    Yadav, Jyoti; Rani, Asha; Singh, Vijander

    2016-12-01

    This paper presents Fuzzy-PID (FPID) control scheme for a blood glucose control of type 1 diabetic subjects. A new metaheuristic Cuckoo Search Algorithm (CSA) is utilized to optimize the gains of FPID controller. CSA provides fast convergence and is capable of handling global optimization of continuous nonlinear systems. The proposed controller is an amalgamation of fuzzy logic and optimization which may provide an efficient solution for complex problems like blood glucose control. The task is to maintain normal glucose levels in the shortest possible time with minimum insulin dose. The glucose control is achieved by tuning the PID (Proportional Integral Derivative) and FPID controller with the help of Genetic Algorithm and CSA for comparative analysis. The designed controllers are tested on Bergman minimal model to control the blood glucose level in the facets of parameter uncertainties, meal disturbances and sensor noise. The results reveal that the performance of CSA-FPID controller is superior as compared to other designed controllers.

  3. Control of Blood Glucose for People with Type 1 Diabetes: an in Vivo Study

    DEFF Research Database (Denmark)

    Boiroux, Dimitri; Schmidt, Signe; Duun-Henriksen, Anne Katrine

    2012-01-01

    Since continuous glucose monitoring (CGM) technology and insulin pumps have improved recent years, a strong interest in a closed-loop articial pancreas for people with type 1 diabetes has arisen. Presently, a fully automated controller of blood glucose must face many challenges, such as daily...... variations of patient's physiology and lack of accuracy of glucose sensors. In this paper we design and discuss an algorithm for overnight closed-loop control of blood glucose in people with type 1 diabetes. The algorithm is based on Model Predictive Control (MPC). We use an oset-free autoregressive model...

  4. The effects of age, glucose ingestion and gluco-regulatory control on episodic memory.

    Science.gov (United States)

    Riby, Leigh Martin; Meikle, Andrew; Glover, Cheryl

    2004-09-01

    Previous research has been inconclusive regarding the impact of glucose ingestion and gluco-regulatory control on cognitive performance in healthy older adults. The aim of this research was to determine whether glucose specifically enhanced episodic memory in an older population. In addition, the link between individual differences in glucose regulation and the magnitude of the enhancement effect was examined. A within subjects, counterbalanced, crossover design was used with 20 participants (60-80 year olds), each serving as his/her control. Episodic memory was tested by presenting unrelated paired associates followed by immediate and delayed cued recall, and delayed recognition, under single and dual task conditions. In addition, a battery of cognitive tests was administered, including tests of semantic memory, working memory and speed of processing. Glucose ingestion was found to largely facilitate performance of episodic memory. Furthermore, subsidiary analyses found that gluco-regulatory efficiency predicted episodic memory performance in both control and glucose conditions. A boost in performance after glucose ingestion was particularly seen in the episodic memory domain. Notably, strong evidence was provided for the utility of gluco-regulatory control measures as indicators of cognitive decline in the elderly.

  5. Assessment of Model Predictive and Adaptive Glucose Control Strategies for People with Type 1 Diabetes

    DEFF Research Database (Denmark)

    Boiroux, Dimitri; Duun-Henriksen, Anne Katrine; Schmidt, Signe

    2014-01-01

    This paper addresses overnight blood glucose stabilization in people with type 1 diabetes using a Model Predictive Controller (MPC). We use a control strategy based on an adaptive ARMAX model in which we use a Recursive Extended Least Squares (RELS) method to estimate parameters of the stochastic...... and reduce the risk of hypoglycemia. We test our control strategies on a virtual clinic of 100 randomly generated patients with a representative inter-subject variability. This virtual clinic is based on the Hovorka model. We consider the case where only half of the meal bolus is administered at mealtime......, and the case where the insulin sensitivity varies during the night. The simulation results demonstrate that the adaptive control strategy can reduce the risks of hypoglycemia and hyperglycemia during the night....

  6. Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons.

    Science.gov (United States)

    do Carmo, Jussara M; da Silva, Alexandre A; Cai, Zhengwei; Lin, Shuying; Dubinion, John H; Hall, John E

    2011-05-01

    Although the central nervous system melanocortin system is an important regulator of energy balance, the role of proopiomelanocortin (POMC) neurons in mediating the chronic effects of leptin on appetite, blood pressure, and glucose regulation is unknown. Using Cre/loxP technology we tested whether leptin receptor deletion in POMC neurons (LepR(flox/flox)/POMC-Cre mice) attenuates the chronic effects of leptin to increase mean arterial pressure (MAP), enhance glucose use and oxygen consumption, and reduce appetite. LepR(flox/flox)/POMC-Cre, wild-type, LepR(flox/flox), and POMC-Cre mice were instrumented for MAP and heart rate measurement by telemetry and venous catheters for infusions. LepR(flox/flox)/POMC-Cre mice were heavier, hyperglycemic, hyperinsulinemic, and hyperleptinemic compared with wild-type, LepR(flox/flox), and POMC-Cre mice. Despite exhibiting features of metabolic syndrome, LepR(flox/flox)/POMC-Cre mice had normal MAP and heart rate compared with LepR(flox/flox) but lower MAP and heart rate compared with wild-type mice. After a 5-day control period, leptin was infused (2 μg/kg per minute, IV) for 7 days. In control mice, leptin increased MAP by ≈5 mm Hg despite decreasing food intake by ≈35%. In contrast, leptin infusion in LepR(flox/flox)/POMC-Cre mice reduced MAP by ≈3 mm Hg and food intake by ≈28%. Leptin significantly decreased insulin and glucose levels in control mice but not in LepR(flox/flox)/POMC-Cre mice. Leptin increased oxygen consumption in LepR(flox/flox)/POMC-Cre and wild-type mice. Activation of POMC neurons is necessary for the chronic effects of leptin to raise MAP and reduce insulin and glucose levels, whereas leptin receptors in other areas of the brain other than POMC neurons appear to play a key role in mediating the chronic effects of leptin on appetite and oxygen consumption.

  7. Combined functional CT/FDG-PET: demonstrates reduced hepatic phosphorylation of glucose in advanced colorectal cancer

    International Nuclear Information System (INIS)

    Miles, K.A.; Keith, C.J.; Griffiths, M.R.; Fuentes, M.; Bunce, I.

    2002-01-01

    Full text: This study describes a technique to quantify hepatic glucose phosphorylation using combined data from functional CT and FDG-PET and assesses the differences in phosphorylation between patients with either early or advanced colorectal cancer. Functional CT and FDG-PET were utilised to obtain measurements of perfusion and glucose uptake respectively within the livers of a series of 35 patients with colorectal cancer. Patients with PET evidence of extrahepatic tumour were considered to have advanced disease. The net influx constant (Ki) for FDG was determined from the liver SUV. CT measurements of hepatic perfusion were incorporated into FDG kinetic analysis to determine hepatic glucose phosphorylation fraction. SUV and Ki were significantly lower in the 12 patients with advanced disease (p=0.015 and p=0.013 respectively) whereas portal and total hepatic perfusion were increased (p=0.013 and p=0.008 respectively). Combining the PET and CT data yielded phosphorylation fractions of 1.14% and 0.74% for early and advanced disease respectively (p=0.002). Hepatic glucose phosphorylation can be determined by combining functional CT measurements of perfusion with PET measurements of FDG and is significantly reduced in patients with more advanced malignancy. Reduced hepatic glucose phosphorylation may be an important mechanism in the development of cancer cachexia. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  8. Combined functional CT/FDG-PET: demonstrates reduced hepatic phosphorylation of glucose in advanced colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Miles, K A [Southernex Imaging Group, QLD (Australia); Queensland University of Technology, QLD (Australia); Keith, C J [Southernex Imaging Group, QLD (Australia); Wesley Research Institute, QLD (Australia); Griffiths, M R [Queensland University of Technology, QLD (Australia); Fuentes, M [Southernex Imaging Group, QLD (Australia); Bunce, I [Wesley Research Institute, QLD (Australia)

    2002-07-01

    Full text: This study describes a technique to quantify hepatic glucose phosphorylation using combined data from functional CT and FDG-PET and assesses the differences in phosphorylation between patients with either early or advanced colorectal cancer. Functional CT and FDG-PET were utilised to obtain measurements of perfusion and glucose uptake respectively within the livers of a series of 35 patients with colorectal cancer. Patients with PET evidence of extrahepatic tumour were considered to have advanced disease. The net influx constant (Ki) for FDG was determined from the liver SUV. CT measurements of hepatic perfusion were incorporated into FDG kinetic analysis to determine hepatic glucose phosphorylation fraction. SUV and Ki were significantly lower in the 12 patients with advanced disease (p=0.015 and p=0.013 respectively) whereas portal and total hepatic perfusion were increased (p=0.013 and p=0.008 respectively). Combining the PET and CT data yielded phosphorylation fractions of 1.14% and 0.74% for early and advanced disease respectively (p=0.002). Hepatic glucose phosphorylation can be determined by combining functional CT measurements of perfusion with PET measurements of FDG and is significantly reduced in patients with more advanced malignancy. Reduced hepatic glucose phosphorylation may be an important mechanism in the development of cancer cachexia. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc.

  9. Inhaled insulin for controlling blood glucose in patients with diabetes

    Directory of Open Access Journals (Sweden)

    Bernard L Silverman

    2008-01-01

    Full Text Available Bernard L Silverman1, Christopher J Barnes2, Barbara N Campaigne3, Douglas B Muchmore31Alkermes, Inc, Cambridge, MA, USA; 2i3 Statprobe, Ann Arbor, MI; 3Eli Lilly and Company, Indianapolis, IN, USAAbstract: Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates. Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease. Despite the recognition of diabetes as a major health issue and the availability of a growing number of medications designed to counteract its detrimental effects, real and perceived barriers remain that prevent patients from achieving optimal blood glucose control. The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.Keywords: diabetes, inhaled insulin, cardiovascular disease, blood glucose

  10. Orexins control intestinal glucose transport by distinct neuronal, endocrine, and direct epithelial pathways.

    Science.gov (United States)

    Ducroc, Robert; Voisin, Thierry; El Firar, Aadil; Laburthe, Marc

    2007-10-01

    Orexins are neuropeptides involved in energy homeostasis. We investigated the effect of orexin A (OxA) and orexin B (OxB) on intestinal glucose transport in the rat. Injection of orexins led to a decrease in the blood glucose level in oral glucose tolerance tests (OGTTs). Effects of orexins on glucose entry were analyzed in Ussing chambers using the Na(+)-dependent increase in short-circuit current (Isc) to quantify jejunal glucose transport. The rapid and marked increase in Isc induced by luminal glucose was inhibited by 10 nmol/l OxA or OxB (53 and 59%, respectively). Response curves to OxA and OxB were not significantly different with half-maximal inhibitory concentrations at 0.9 and 0.4 nmol/l, respectively. On the one hand, OxA-induced inhibition of Isc was reduced by the neuronal blocker tetrodotoxin (TTX) and by a cholecystokinin (CCK) 2R antagonist, indicating involvement of neuronal and endocrine CCK-releasing cells. The OX(1)R antagonist SB334867 had no effect on OxA-induced inhibition, which is likely to occur via a neuronal and/or endocrine OX(2)R. On the other hand, SB334867 induced a significant right shift of the concentration-effect curve for OxB. This OxB-preferring OX(1)R pathway was not sensitive to TTX or to CCKR antagonists, suggesting that OxB may act directly on enterocytic OX(1)R. These distinct effects of OxA and OxB are consistent with the expression of OX(1)R and OX(2)R mRNA in the epithelial and nonepithelial tissues, respectively. Our data delineate a new function for orexins as inhibitors of intestinal glucose absorption and provide a new basis for orexin-induced short-term control of energy homeostasis.

  11. Blood glucose control for patients with acute coronary syndromes in Qatar.

    Science.gov (United States)

    Wilby, Kyle John; Elmekaty, Eman; Abdallah, Ibtihal; Habra, Masa; Al-Siyabi, Khalid

    2016-01-01

    Blood glucose is known to be elevated in patients presenting with acute coronary syndromes. However a gap in knowledge exists regarding effective management strategies once admitted to acute care units. It is also unknown what factors (if any) predict elevated glucose values during initial presentation. OBJECTIVES of the study were to characterize blood glucose control in patients admitted to the cardiac care unit (CCU) in Qatar and to determine predictive factors associated with high glucose levels (>10 mmol/l) on admission to the CCU. All data for this study were obtained from the CCU at Heart Hospital in Doha, Qatar. A retrospective chart review was completed for patients admitted to the CCU in Qatar from October 1st, 2012 to March 31st, 2013, of which 283 were included. Baseline characteristics (age, gender, nationality, medical history, smoking status, type of acute coronary syndrome), capillary and lab blood glucose measurements, and use of insulin were extracted. Time spent in glucose ranges of 10 mmol/1 was calculated manually. Univariate and multivariate logistic regression were performed to assess factors associated with high glucose on admission. The primary analysis was completed with capillary data and a sensitivity analysis was completed using laboratory data. Blood glucose values measured on admission and throughout length of stay in the CCU. Capillary blood glucose data showed majority of time was spent in the range of >10 mmol/l (41.95%), followed by 4-8 mmol/l (35.44%), then 8-10 mmol/l (21.45%), and finally 10 mmol/l on admission (p < 0.05) in a univariate analysis but only diabetes remained significant in a multivariate model (OR 23.3; 95% CI, 11.5-47.3). Diabetes predicts high glucose values on hospital admission for patients with ACS and patients are not being adequately controlled throughout CCU stay.

  12. The role of pre-operative and post-operative glucose control in surgical-site infections and mortality.

    Directory of Open Access Journals (Sweden)

    Christie Y Jeon

    Full Text Available The impact of glucose control on surgical-site infection (SSI and death remains unclear. We examined how pre- and post-operative glucose levels and their variability are associated with the risk of SSI or in-hospital death.This retrospective cohort study employed data on 13,800 hospitalized patients who underwent a surgical procedure at a large referral hospital in New York between 2006 and 2008. Over 20 different sources of electronic data were used to analyze how thirty-day risk of SSI and in-hospital death varies by glucose levels and variability. Maximum pre- and post-operative glucose levels were determined for 72 hours before and after the operation and glucose variability was defined as the coefficient of variation of the glucose measurements. We employed logistic regression to model the risk of SSI or death against glucose variables and the following potential confounders: age, sex, body mass index, duration of operation, diabetes status, procedure classification, physical status, emergency status, and blood transfusion.While association of pre- and post-operative hyperglycemia with SSI were apparent in the crude analysis, multivariate results showed that SSI risk did not vary significantly with glucose levels. On the other hand, in-hospital deaths were associated with pre-operative hypoglycemia (OR = 5.09, 95% CI (1.80, 14.4 and glucose variability (OR = 1.14, 95% CI (1.03, 1.27 for 10% increase in coefficient of variation.In-hospital deaths occurred more often among those with pre-operative hypoglycemia and higher glucose variability. These findings warrant further investigation to determine whether stabilization of glucose and prevention of hypoglycemia could reduce post-operative deaths.

  13. The role of pre-operative and post-operative glucose control in surgical-site infections and mortality.

    Science.gov (United States)

    Jeon, Christie Y; Furuya, E Yoko; Berman, Mitchell F; Larson, Elaine L

    2012-01-01

    The impact of glucose control on surgical-site infection (SSI) and death remains unclear. We examined how pre- and post-operative glucose levels and their variability are associated with the risk of SSI or in-hospital death. This retrospective cohort study employed data on 13,800 hospitalized patients who underwent a surgical procedure at a large referral hospital in New York between 2006 and 2008. Over 20 different sources of electronic data were used to analyze how thirty-day risk of SSI and in-hospital death varies by glucose levels and variability. Maximum pre- and post-operative glucose levels were determined for 72 hours before and after the operation and glucose variability was defined as the coefficient of variation of the glucose measurements. We employed logistic regression to model the risk of SSI or death against glucose variables and the following potential confounders: age, sex, body mass index, duration of operation, diabetes status, procedure classification, physical status, emergency status, and blood transfusion. While association of pre- and post-operative hyperglycemia with SSI were apparent in the crude analysis, multivariate results showed that SSI risk did not vary significantly with glucose levels. On the other hand, in-hospital deaths were associated with pre-operative hypoglycemia (OR = 5.09, 95% CI (1.80, 14.4)) and glucose variability (OR = 1.14, 95% CI (1.03, 1.27) for 10% increase in coefficient of variation). In-hospital deaths occurred more often among those with pre-operative hypoglycemia and higher glucose variability. These findings warrant further investigation to determine whether stabilization of glucose and prevention of hypoglycemia could reduce post-operative deaths.

  14. DiabetterTM Reduces Post Meal Hyperglycemia Via Enhancement Of Glucose Uptake Into Adipocytes And Muscles Cells

    International Nuclear Information System (INIS)

    Zainah Adam; Shafii Khamis

    2014-01-01

    Currently, there are lots of herbal products available in local markets that are used for treatment of diabetes mellitus. Most of these products are not standardized and lack of efficacy and safety data. DiaBetterTM is one of the local herbal products that have been used for treatment of diabetes. This study was carried out to determine the efficacy of DiaBetterTM in reducing hyperglycemia and to elucidate the mechanisms by which hyperglycemia is reduced. Antihyperglycemic evaluation was done in normal and streptozotocin-induced diabetic rats at different prandial states and the antihyperglycemic mechanisms elucidation was carried out in muscle and adipocytes cells using glucose tracer method (2-deoxy-[1-3H]-glucose). The results showed that DiaBetterTM significantly reduced post meal hyperglycemia in normal and diabetic rats, and improved glucose tolerance activity in diabetic rats particularly after 4 and 6 hours of administration. Antihyperglycemic mechanisms elucidation revealed that the DiaBetterTM significantly enhanced insulin-stimulated glucose uptake into adipocytes and muscle cells, with the highest magnitude of enhancement were 1.54-fold (p<0.01) and 1.46-fold (p<0.001), respectively. Molecular mechanisms that responsible for this enhancement were the increment of insulin sensitivity at cells membrane. Cytotoxic evaluation was also done and confirmed that DiaBetterTM was toxicologically safe against muscle and adipocytes cells. In conclusion, post-meal antihyperglycemic and glucose tolerance activity activity of DiaBetterTM was mediated through the enhancement of glucose uptake into adipocytes and muscle cells. Insulin sensitizing activity showed by DiaBetterTM suggests that this product has the potential to ameliorate insulin resistance condition. Therefore, it is suggested that DiaBetterTM can be used as dietary adjunct for the treatment of type 2 diabetes mellitus which related to insulin resistance. (author)

  15. Robust blood-glucose control using Mathematica.

    Science.gov (United States)

    Kovács, Levente; Paláncz, Béla; Benyó, Balázs; Török, László; Benyó, Zoltán

    2006-01-01

    A robust control design on frequency domain using Mathematica is presented for regularization of glucose level in type I diabetes persons under intensive care. The method originally proposed under Mathematica by Helton and Merino, --now with an improved disturbance rejection constraint inequality--is employed, using a three-state minimal patient model. The robustness of the resulted high-order linear controller is demonstrated by nonlinear closed loop simulation in state-space, in case of standard meal disturbances and is compared with H infinity design implemented with the mu-toolbox of Matlab. The controller designed with model parameters represented the most favorable plant dynamics from the point of view of control purposes, can operate properly even in case of parameter values of the worst-case scenario.

  16. Pre-gravid physical activity and reduced risk of glucose intolerance in pregnancy: the role of insulin sensitivity.

    Science.gov (United States)

    Retnakaran, Ravi; Qi, Ying; Sermer, Mathew; Connelly, Philip W; Zinman, Bernard; Hanley, Anthony J G

    2009-04-01

    Pre-gravid physical activity has been associated with a reduced risk of gestational diabetes mellitus (GDM), although neither the types of exercise nor the physiologic mechanisms underlying this protective effect have been well-studied. Thus, we sought to study the relationships between types of pre-gravid physical activity and metabolic parameters in pregnancy, including glucose tolerance, insulin sensitivity and beta-cell function. A total of 851 women underwent a glucose challenge test (GCT) and a 3-h oral glucose tolerance test (OGTT) in late pregnancy, yielding four glucose tolerance groups: (i) GDM; (ii) gestational impaired glucose tolerance (GIGT); (iii) abnormal GCT with normal glucose tolerance on OGTT (abnormal GCT NGT); and (iv) normal GCT with NGT on OGTT (normal GCT NGT). Pre-gravid physical activity was assessed using the Baecke questionnaire, which measures (i) total physical activity and (ii) its three component domains: work, nonsport leisure-time, and vigorous/sports activity. Glucose tolerance status improved across increasing quartiles of pre-gravid total physical activity (P = 0.0244). Whereas neither work nor nonsport leisure-time activity differed between glucose tolerance groups, pre-gravid vigorous/sports activity was significantly higher in women with normal GCT NGT compared to women with (i) abnormal GCT NGT (P = 0.0018) (ii) GIGT (P = 0.0025), and (iii) GDM (P = 0.0044). In particular, vigorous/sports activity correlated with insulin sensitivity (measured by IS(OGTT)) (r = 0.21, P sports activity emerged as a significant independent predictor of IS(OGTT) in pregnancy (t = 4.97, P sports activity is associated with a reduced risk of glucose intolerance in pregnancy, an effect likely mediated by enhanced insulin sensitivity.

  17. Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum

    Directory of Open Access Journals (Sweden)

    Jeffrey Thomas Cole

    2012-04-01

    Full Text Available Brain cells expend large amounts of energy sequestering calcium (Ca2+, while loss of Ca2+ compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P, a parent substrate to several metabolic major pathways, including glycolysis. In several tissues, G6P alters the ability of the endoplasmic reticulum to sequester Ca2+. This led to the hypothesis that G6P regulates Ca2+ accumulation by acting as an endogenous ligand for sarco-endoplasmic reticulum calcium ATPase (SERCA. Whole brain ER microsomes were pooled from adult male Sprague-Dawley rats. Using radio-isotopic assays, 45Ca2+ accumulation was quantified following incubation with increasing amounts of G6P, in the presence or absence of thapsigargin, a potent SERCA inhibitor. To qualitatively assess SERCA activity, the simultaneous release of inorganic phosphate (Pi coupled with Ca2+ accumulation was quantified. Addition of G6P significantly and decreased Ca2+ accumulation in a dose-dependent fashion (1-10 mM. The reduction in Ca2+ accumulation was not significantly different that seen with addition of thapsigargin. Addition of glucose-1-phosphate or fructose-6-phosphate, or other glucose metabolic pathway intermediates, had no effect on Ca2+ accumulation. Further, the release of Pi was markedly decreased, indicating G6P-mediated SERCA inhibition as the responsible mechanism for reduced Ca2+ uptake. Simultaneous addition of thapsigargin and G6P did decrease inorganic phosphate in comparison to either treatment alone, which suggests that the two treatments have different mechanisms of action. Therefore, G6P may be a novel, endogenous regulator of SERCA activity. Additionally, pathological conditions observed during disease states that disrupt glucose homeostasis, may be attributable to Ca2+ dystasis caused by altered G6P regulation of SERCA activity

  18. Strategies for glucose control in people with type 1 diabetes

    DEFF Research Database (Denmark)

    Boiroux, Dimitri; Finan, Daniel Aaron; Jørgensen, John Bagterp

    2011-01-01

    the patient. We minimize the risk of hypoglycemia by introducing a time-varying glucose setpoint based on the announced meal size and the physiological model of the patient. The simulation results are based on a virtual patient simulated by the Hovorka model. They include the cases where the insulin...... sensitivity changes, and mismatches in meal estimation. They demonstrate that the designed controller is able to achieve offset-free control when the insulin sensitivity change, and that having a time-varying reference signal enables more robust control of blood glucose in the cases where the meal size......In this paper we apply a robust feedforward-feedback control strategy to people with type 1 diabetes. The feedforward controller consists of a bolus calculator which compensates the disturbance coming from meals. The feedback controller is based on a linearized description of the model describing...

  19. Glucose metabolism in gamma-irradiated rice seeds

    International Nuclear Information System (INIS)

    Inoue, M.; Hasegawa, H.; Hori, S.

    1980-01-01

    Gamma-irradiation of 30 kR in rice seeds caused marked inhibition in seedling growth, and prevented the release of reduced sugar during the period of 25 to 76hr after soaking. The C 6 /C 1 ratio following irradiation continued to decrease up to the 76th hour of soaking; the control's ratio tended to increase with comparable soaking time. The percentage recovery of 14 C in carbon dioxide from glucose -1- 14 C was lower in irradiated than in control seeds. These results indicate that gamma-irradiation reduces the participation of the pentose phosphate pathway in glucose catabolism during an early period of germination. (author)

  20. Layer-by-layer assembly of functionalized reduced graphene oxide for direct electrochemistry and glucose detection

    Energy Technology Data Exchange (ETDEWEB)

    Mascagni, Daniela Branco Tavares [São Paulo State University - UNESP, Sorocaba, São Paulo (Brazil); Miyazaki, Celina Massumi [Federal University of São Carlos, UFSCar, Campus Sorocaba, SP (Brazil); Cruz, Nilson Cristino da [São Paulo State University - UNESP, Sorocaba, São Paulo (Brazil); Leite de Moraes, Marli [Federal University of São Paulo, Unifesp, Campus São José dos Campos, SP (Brazil); Riul, Antonio [University of Campinas - Unicamp, Campinas, São Paulo (Brazil); Ferreira, Marystela, E-mail: marystela@ufscar.br [Federal University of São Carlos, UFSCar, Campus Sorocaba, SP (Brazil)

    2016-11-01

    We report an electrochemical glucose biosensor made with layer-by-layer (LbL) films of functionalized reduced graphene oxide (rGO) and glucose oxidase (GOx). The LbL assembly using positively and negatively charged rGO multilayers represents a simple approach to develop enzymatic biosensors. The electron transport properties of graphene were combined with the specificity provided by the enzyme. rGO was obtained and functionalized using chemical methods, being positively charged with poly(diallyldimethylammonium chloride) to form GPDDA, and negatively charged with poly(styrene sulfonate) to form GPSS. Stable aqueous dispersions of GPDDA and GPSS are easily obtained, enabling the growth of LbL films on various solid supports. The use of graphene in the immobilization of GOx promoted Direct Electron Transfer, which was evaluated by Cyclic Voltammetry. Amperometric measurements indicated a detection limit of 13.4 μmol·L{sup ‐1} and sensitivity of 2.47 μA·cm{sup −2}·mmol{sup −1}·L for glucose with the (GPDDA/GPSS){sub 1}/(GPDDA/GOx){sub 2} architecture, whose thickness was 19.80 ± 0.28 nm, as determined by Surface Plasmon Resonance (SPR). The sensor may be useful for clinical analysis since glucose could be detected even in the presence of typical interfering agents and in real samples of a lactose-free milk and an electrolyte solution to prevent dehydration. - Highlights: • Direct electrochemistry of glucose oxidase at functionalized reduced graphene oxide. • Thickness (layer-by-layer) LbL film determined by Surface Plasmon Resonance (SPR). • Selective determination of glucose in the presence of several interferents. • Real sample test: commercial oral electrolyte solution and lactose-free milk.

  1. Layer-by-layer assembly of functionalized reduced graphene oxide for direct electrochemistry and glucose detection

    International Nuclear Information System (INIS)

    Mascagni, Daniela Branco Tavares; Miyazaki, Celina Massumi; Cruz, Nilson Cristino da; Leite de Moraes, Marli; Riul, Antonio; Ferreira, Marystela

    2016-01-01

    We report an electrochemical glucose biosensor made with layer-by-layer (LbL) films of functionalized reduced graphene oxide (rGO) and glucose oxidase (GOx). The LbL assembly using positively and negatively charged rGO multilayers represents a simple approach to develop enzymatic biosensors. The electron transport properties of graphene were combined with the specificity provided by the enzyme. rGO was obtained and functionalized using chemical methods, being positively charged with poly(diallyldimethylammonium chloride) to form GPDDA, and negatively charged with poly(styrene sulfonate) to form GPSS. Stable aqueous dispersions of GPDDA and GPSS are easily obtained, enabling the growth of LbL films on various solid supports. The use of graphene in the immobilization of GOx promoted Direct Electron Transfer, which was evaluated by Cyclic Voltammetry. Amperometric measurements indicated a detection limit of 13.4 μmol·L ‐1 and sensitivity of 2.47 μA·cm −2 ·mmol −1 ·L for glucose with the (GPDDA/GPSS) 1 /(GPDDA/GOx) 2 architecture, whose thickness was 19.80 ± 0.28 nm, as determined by Surface Plasmon Resonance (SPR). The sensor may be useful for clinical analysis since glucose could be detected even in the presence of typical interfering agents and in real samples of a lactose-free milk and an electrolyte solution to prevent dehydration. - Highlights: • Direct electrochemistry of glucose oxidase at functionalized reduced graphene oxide. • Thickness (layer-by-layer) LbL film determined by Surface Plasmon Resonance (SPR). • Selective determination of glucose in the presence of several interferents. • Real sample test: commercial oral electrolyte solution and lactose-free milk.

  2. Enhanced amperometric response of a glucose oxidase and horseradish peroxidase based bienzyme glucose biosensor modified with a film of polymerized toluidine blue containing reduced graphene oxide

    International Nuclear Information System (INIS)

    Wang, Fang; Gong, Wencheng; Wang, Lili; Chen, Zilin

    2015-01-01

    Reduced graphene oxide (RGO) was used to construct a bienzyme biosensor containing horseradish peroxidase (HRP) and glucose oxidase (GOx). A poly(toluidine blue) (pTB) film containing RGO acted as both enzyme immobilization matrix and electron transfer mediator. The bienzyme biosensor was characterized by electrochemical techniques and displays a highly sensitive amperometric response to glucose and hydrogen peroxide (H 2 O 2 ) at a potential as low as −0.1 V (vs. SCE). It is shown that use of RGO causes a strong enhancement on the amperometric responses. H 2 O 2 formed by the action of GOx in the presence of oxygen can be further reduced by HRP in the pTB film contacting the RGO modified electrode. In the absence of oxygen, glucose oxidation proceeds by another mechanism in which electron transfer occurs from GOx to the electrode and with pTB acting as the mediator. Amperometric responses to glucose and H2O2 follow Michaelis-Menten kinetics. The experimental conditions were optimized, and under these conditions glucose can be determined in the 80 μM to 3.0 mM range with a detection limit of 50 μM. H 2 O 2 , in turn, can be quantified in up to 30.0 μM concentration with a detection limit of 0.2 μM. The bienzyme biosensor is reproducible, repeatable and stable. Finally, it has been successfully applied to the determination of glucose in plasma samples. (author)

  3. A leptin-regulated circuit controls glucose mobilization during noxious stimuli.

    Science.gov (United States)

    Flak, Jonathan N; Arble, Deanna; Pan, Warren; Patterson, Christa; Lanigan, Thomas; Goforth, Paulette B; Sacksner, Jamie; Joosten, Maja; Morgan, Donald A; Allison, Margaret B; Hayes, John; Feldman, Eva; Seeley, Randy J; Olson, David P; Rahmouni, Kamal; Myers, Martin G

    2017-08-01

    Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor-expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores.

  4. Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

    Science.gov (United States)

    Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

    2014-09-01

    It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases. © 2014 John Wiley & Sons Ltd.

  5. Impact of postprandial glucose control on diabetes-related complications

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2016-01-01

    Conflicting findings in the literature and lack of long-term definitive outcome studies have led to difficulty in drawing conclusions about the role of postprandial hyperglycemia in diabetes and its complications. Recent scientific publications support the role of postprandial glucose (PPG......) as a key contributor to overall glucose control and a predictor of microvascular and macrovascular events. However, the need remains for definitive evidence to support the precise relationship between PPG excursions and the development and progression of cardiovascular complications of diabetes. Drawing...... complications is unclarified and is one of the remaining unanswered questions in diabetes. Nevertheless, current evidence supports PPG control as an important strategy to consider in the comprehensive management plan of individuals with diabetes....

  6. Evaluation of PD/PID controller for insulin control on blood glucose regulation in a Type-I diabetes

    Science.gov (United States)

    Mahmud, Farhanahani; Isse, Nadir Hussien; Daud, Nur Atikah Mohd; Morsin, Marlia

    2017-01-01

    This project introduces a simulation of Proportional-Derivative (PD) and Proportional-Integral-Derivative (PID) controller based on a virtual Type 1 Diabetes Mellitus (T1DM) patient: Hovorka diabetic model using MATLAB-Simulink software. The results of these simulations are based on three tuning responses for each controller which are fast, slow and oscillation responses. The main purpose of this simulation is to achieve an acceptable stability and fastness response towards the regulation of glucose concentration using PD and PID controller response with insulin infusion rate. Therefore, in order to analyze and compare the responses of both controller performances, one-day simulations of the insulin-glucose dynamic have been conducted using a typical day meal plan that contains five meals of different bolus size. It is found that the PID closed-loop control with a short rise time is required to retrieve a satisfactory glucose regulation.

  7. Hepatic Expression of Adenovirus 36 E4ORF1 Improves Glycemic Control and Promotes Glucose Metabolism Through AKT Activation.

    Science.gov (United States)

    McMurphy, Travis B; Huang, Wei; Xiao, Run; Liu, Xianglan; Dhurandhar, Nikhil V; Cao, Lei

    2017-02-01

    Considering that impaired proximal insulin signaling is linked with diabetes, approaches that enhance glucose disposal independent of insulin signaling are attractive. In vitro data indicate that the E4ORF1 peptide derived from human adenovirus 36 (Ad36) interacts with cells from adipose tissue, skeletal muscle, and liver to enhance glucose disposal, independent of proximal insulin signaling. Adipocyte-specific expression of Ad36E4ORF1 improves hyperglycemia in mice. To determine the hepatic interaction of Ad36E4ORF1 in enhancing glycemic control, we expressed E4ORF1 of Ad36 or Ad5 or fluorescent tag alone by using recombinant adeno-associated viral vector in the liver of three mouse models. In db/db or diet-induced obesity (DIO) mice, hepatic expression of Ad36E4ORF1 but not Ad5E4ORF1 robustly improved glycemic control. In normoglycemic wild-type mice, hepatic expression of Ad36E4ORF1 lowered nonfasting blood glucose at a high dose of expression. Of note, Ad36E4ORF1 significantly reduced insulin levels in db/db and DIO mice. The improvement in glycemic control was observed without stimulation of the proximal insulin signaling pathway. Collectively, these data indicate that Ad36E4ORF1 is not a typical sensitizer, mimetic, or secretagogue of insulin. Instead, it may have insulin-sparing action, which seems to reduce the need for insulin and, hence, to reduce insulin levels. © 2017 by the American Diabetes Association.

  8. Chronic benzylamine administration in the drinking water improves glucose tolerance, reduces body weight gain and circulating cholesterol in high-fat diet-fed mice.

    Science.gov (United States)

    Iffiú-Soltész, Zsuzsa; Wanecq, Estelle; Lomba, Almudena; Portillo, Maria P; Pellati, Federica; Szöko, Eva; Bour, Sandy; Woodley, John; Milagro, Fermin I; Alfredo Martinez, J; Valet, Philippe; Carpéné, Christian

    2010-04-01

    Benzylamine is found in Moringa oleifera, a plant used to treat diabetes in traditional medicine. In mammals, benzylamine is metabolized by semicarbazide-sensitive amine oxidase (SSAO) to benzaldehyde and hydrogen peroxide. This latter product has insulin-mimicking action, and is involved in the effects of benzylamine on human adipocytes: stimulation of glucose transport and inhibition of lipolysis. This study examined whether chronic, oral administration of benzylamine could improve glucose tolerance and the circulating lipid profile without increasing oxidative stress in overweight and pre-diabetic mice. The benzylamine diffusion across the intestine was verified using everted gut sacs. Then, glucose handling and metabolic markers were measured in mice rendered insulin-resistant when fed a high-fat diet (HFD) and receiving or not benzylamine in their drinking water (3600micromol/(kgday)) for 17 weeks. HFD-benzylamine mice showed lower body weight gain, fasting blood glucose, total plasma cholesterol and hyperglycaemic response to glucose load when compared to HFD control. In adipocytes, insulin-induced activation of glucose transport and inhibition of lipolysis remained unchanged. In aorta, benzylamine treatment partially restored the nitrite levels that were reduced by HFD. In liver, lipid peroxidation markers were reduced. Resistin and uric acid, surrogate plasma markers of metabolic syndrome, were decreased. In spite of the putative deleterious nature of the hydrogen peroxide generated during amine oxidation, and in agreement with its in vitro insulin-like actions found on adipocytes, the SSAO-substrate benzylamine could be considered as a potential oral agent to treat metabolic syndrome. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Clinical Use of Continuous Glucose Monitoring in Adults with Type 1 Diabetes.

    Science.gov (United States)

    Slattery, David; Choudhary, Pratik

    2017-05-01

    With the emphasis on intensive management of type 1 diabetes, data from studies support frequent monitoring of glucose levels to improve glycemic control and reduce glucose variability, which can be related to an increase in macro and microvascular complications. However, few perform capillary blood glucose that frequently. There are currently two available alternatives that this review will discuss, continuous glucose monitoring (CGM) and flash glucose monitoring. CGM has become an important diagnostic and therapeutic option in optimizing diabetes management. CGM systems are now more accurate, smaller, and easier to use compared to original models. Randomized controlled trials (RCTs) have demonstrated that CGM can improve Hemoglobin A1c (HbA1C) and reduce glucose variability in both continuous subcutaneous insulin infusion and multiple daily injection users. When used in an automated "insulin-suspend" system, reduced frequency of hypoglycemia and shorter time spent in hypoglycemic range have been demonstrated. Despite the potential benefits CGM has to offer in clinical practice, concerns exist on the accuracy of these devices and patient compliance with therapy, which may prevent the true clinical benefit of CGM being achieved, as observed in RCTs. Flash glucose monitoring systems FreeStyle ® Libre™ (Abbott Diabetes Care, Alameda, CA) are as accurate as many CGM systems available and have the added benefit of being factory calibrated. Studies have shown that flash glucose monitoring systems are very well tolerated by patients and effectively reduce glucose variability, increasing time in range.

  10. Leptin and the central nervous system control of glucose metabolism.

    Science.gov (United States)

    Morton, Gregory J; Schwartz, Michael W

    2011-04-01

    The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders.

  11. Synthesis of Silver-Chitosan Nanocomposites Colloidal by Glucose as Reducing Agent

    Directory of Open Access Journals (Sweden)

    Endang Susilowati

    2015-03-01

    Full Text Available Silver-chitosan nanocomposites colloidal was successfully performed by chemical reduction method at room temperature using glucose as reducing agent, sodium hydroxide (NaOH as accelerator reagent, silver nitrate (AgNO3 as metal precursor and chitosan as stabilizing agent. Compared to other synthetic methods, this work is green and simple. The effect of the amount of NaOH, molar ratio of AgNO3 to glucose and AgNO3 concentration towards Localized Surface Plasmon Resonance (LSPR absorption band of silver nanoparticles was investigated using UV-Vis spectrophotometer. The stability of the colloid was also studied for the first 16 weeks of storage at ambient temperature. The formation of silver nanoparticles was confirmed by the appearance of LSPR absorption peak at 402.4–414.5 nm. It is also shown that the absorption peak of LSPR were affected by NaOH amount, ratio molar AgNO3/glucose and concentration of AgNO3. The produced silver nanoparticles were spherical with dominant size range of 6 to 18 nm as shown by TEM images. All colloidals were stable without any aggregation for 16 weeks after preparation. The newly prepared silver-chitosan nanocomposites colloidal may have potential for antibacterial applications.

  12. Effect of low glycemic load diet with and without wheat bran on glucose control in gestational diabetes mellitus: A randomized trial

    Directory of Open Access Journals (Sweden)

    Ahmad Afaghi

    2013-01-01

    Full Text Available Background: A low-glycemic index diet is effective in blood glucose control of diabetic subjects, reduces insulin requirement in women with gestation diabetes mellitus (GDM and improves pregnancy outcomes when used from beginning of the second trimester. However there are limited reports to examine the effect of low glycemic load (LGL diet and fiber on blood glucose control and insulin requirement of women with GDM. Therefore, the aim of this study was to examine the effect of low glycemic load diet with and without fiber on reducing the number of women with GDM requiring insulin. Materials and Methods: All GDM women (n = 31 were randomly allocated to consume either a LGL diet with Fiber or LGL diet. Results: We found that 7 (38.9% of 18 women with GDM in Fiber group and 10 (76.9% in "Without Fiber" group required insulin treatment. Conclusion: The LGL diet with added fiber for women with GDM dramatically reduced the number needing for insulin treatment.

  13. Enzymatic sensing of glucose in artificial saliva using a flat electrode consisting of a nanocomposite prepared from reduced graphene oxide, chitosan, nafion and glucose oxidase

    International Nuclear Information System (INIS)

    Rabti, Amal; Argoubi, Wicem; Raouafi, Noureddine

    2016-01-01

    We report on the preparation of a nanoporous flat electrode by drop casting a nanocomposite consisting of reduced graphene oxide (rGO) and chitosan onto a polyester substrate. An underlying conductive surface is not required. The nanocomposite was characterized by scanning electron microscopy and electrochemical impedance spectroscopy. The 3D network of the composite was used as a scaffold for the immobilization of glucose oxidase (GOx). A well-defined signal related to direct GOx electrochemistry was registered and used to monitor levels of glucose. The resulting biosensor displays a linear response to glucose with a detection limit of 5 μM (at an S/N ratio of 3) and a sensitivity of 41.7 μA⋅mM"−"1∙cm"−"2. The sensor was applied to the determination of glucose in artificial saliva. (author)

  14. Puerarin reduces apoptosis in rat hippocampal neurons culturea in high glucose medium by modulating the p38 mitogen activated protein kinase and c-Jun N-terminal kinase signaling pathways.

    Science.gov (United States)

    Xu, Xiaohan; Wang, Jingbo; Zhang, Hong; Tian, Guoqing; Liu, Yuqin

    2016-02-01

    To investigate the neuroprotective etfect of puerarin on rat hippocampal neurons cultured in high glucose medium, and to examine the role of the p38 mitogen activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) signaling pathways in this effect. Primary cultures of hippocampal neurons were prepared from newborn Sprague Dawley rats. Neuron-specific enolase immunocytochemistry was used to identify neurons. The neurons were cultured with normal medium (control group) or with high-glucose medium (high-glucose group), and puerarin (puerarin group), a p38 MAPK inhibitor (SB239063; p38 MAPK inhibitor group) or a JNK inhibitor (SP600125; JNK inhibitor group) were added. After 72 h of treatment, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was performed to detect apoptosis, and western blotting was used to assess protein levels of p-p38, p38, p-JNK and JNK. In the high-glucose group, the neuronal apoptosis rate and the p-p38/p38 and p-JNK/JNK ratios were higher than in the control group. The p38 MAPK and JNK inhibitors prevented this increase in the apoptosis rate. The apoptosis rates in the puerarin group, the p38 MAPK inhibitor group and the JNK inhibitor group were significantly decreased compared with the high-glucose group. Moreover, protein levels of p-p38 and p-JNK were significantly reduced, and the p-p38/p38 and p-JNK/JNK ratios were decreased in the puerarin group compared with the high-glucose group. In addition, compared with the high-glucose group, p-p38 levels and the p-p38/p38 ratio were reduced in the p38 MAPK inhibitor group, and p-JNK levels and the p-JNK/JNK ratio were decreased in the JNK inhibitor group. Puerarin attenuates neuronal apoptosis induced by high glucose by reducing the phosphorylation of p38 and JNK.

  15. Glucose control in pregnant women with type 1 diabetes mellitus: Studies using a continuous glucose monitoring system

    NARCIS (Netherlands)

    Kerssen, Anneloes

    2005-01-01

    Pregnancy in women with type 1 diabetes mellitus is associated with neonatal morbidity. It is commonly agreed that the morbidity decreases when diabetic control is tightened. The most common methods for the determination of diabetic control are the self-monitoring of blood glucose levels (SMBG) and

  16. Comparative Simulation Study of Glucose Control Methods Designed for Use in the Intensive Care Unit Setting via a Novel Controller Scoring Metric.

    Science.gov (United States)

    DeJournett, Jeremy; DeJournett, Leon

    2017-11-01

    Effective glucose control in the intensive care unit (ICU) setting has the potential to decrease morbidity and mortality rates and thereby decrease health care expenditures. To evaluate what constitutes effective glucose control, typically several metrics are reported, including time in range, time in mild and severe hypoglycemia, coefficient of variation, and others. To date, there is no one metric that combines all of these individual metrics to give a number indicative of overall performance. We proposed a composite metric that combines 5 commonly reported metrics, and we used this composite metric to compare 6 glucose controllers. We evaluated the following controllers: Ideal Medical Technologies (IMT) artificial-intelligence-based controller, Yale protocol, Glucommander, Wintergerst et al PID controller, GRIP, and NICE-SUGAR. We evaluated each controller across 80 simulated patients, 4 clinically relevant exogenous dextrose infusions, and one nonclinical infusion as a test of the controller's ability to handle difficult situations. This gave a total of 2400 5-day simulations, and 585 604 individual glucose values for analysis. We used a random walk sensor error model that gave a 10% MARD. For each controller, we calculated severe hypoglycemia (140 mg/dL), and coefficient of variation (CV), as well as our novel controller metric. For the controllers tested, we achieved the following median values for our novel controller scoring metric: IMT: 88.1, YALE: 46.7, GLUC: 47.2, PID: 50, GRIP: 48.2, NICE: 46.4. The novel scoring metric employed in this study shows promise as a means for evaluating new and existing ICU-based glucose controllers, and it could be used in the future to compare results of glucose control studies in critical care. The IMT AI-based glucose controller demonstrated the most consistent performance results based on this new metric.

  17. Improved glucose control and reduced body weight in rodents with dual mechanism of action peptide hybrids.

    Directory of Open Access Journals (Sweden)

    James L Trevaskis

    Full Text Available Combination therapy is being increasingly used as a treatment paradigm for metabolic diseases such as diabetes and obesity. In the peptide therapeutics realm, recent work has highlighted the therapeutic potential of chimeric peptides that act on two distinct receptors, thereby harnessing parallel complementary mechanisms to induce additive or synergistic benefit compared to monotherapy. Here, we extend this hypothesis by linking a known anti-diabetic peptide with an anti-obesity peptide into a novel peptide hybrid, which we termed a phybrid. We report on the synthesis and biological activity of two such phybrids (AC164204 and AC164209, comprised of a glucagon-like peptide-1 receptor (GLP1-R agonist, and exenatide analog, AC3082, covalently linked to a second generation amylin analog, davalintide. Both molecules acted as full agonists at their cognate receptors in vitro, albeit with reduced potency at the calcitonin receptor indicating slightly perturbed amylin agonism. In obese diabetic Lep(ob/Lep (ob mice sustained infusion of AC164204 and AC164209 reduced glucose and glycated haemoglobin (HbA1c equivalently but induced greater weight loss relative to exenatide administration alone. Weight loss was similar to that induced by combined administration of exenatide and davalintide. In diet-induced obese rats, both phybrids dose-dependently reduced food intake and body weight to a greater extent than exenatide or davalintide alone, and equal to co-infusion of exenatide and davalintide. Phybrid-mediated and exenatide + davalintide-mediated weight loss was associated with reduced adiposity and preservation of lean mass. These data are the first to provide in vivo proof-of-concept for multi-pathway targeting in metabolic disease via a peptide hybrid, demonstrating that this approach is as effective as co-administration of individual peptides.

  18. Optimal glucose management in the perioperative period.

    Science.gov (United States)

    Evans, Charity H; Lee, Jane; Ruhlman, Melissa K

    2015-04-01

    Hyperglycemia is a common finding in surgical patients during the perioperative period. Factors contributing to poor glycemic control include counterregulatory hormones, hepatic insulin resistance, decreased insulin-stimulated glucose uptake, use of dextrose-containing intravenous fluids, and enteral and parenteral nutrition. Hyperglycemia in the perioperative period is associated with increased morbidity, decreased survival, and increased resource utilization. Optimal glucose management in the perioperative period contributes to reduced morbidity and mortality. To readily identify hyperglycemia, blood glucose monitoring should be instituted for all hospitalized patients. Published by Elsevier Inc.

  19. Static output feedback ℋ ∞ control for a fractional-order glucose-insulin system

    KAUST Repository

    N’Doye, Ibrahima

    2015-05-23

    This paper presents the ℋ∞ static output feedback control of nonlinear fractional-order systems. Based on the extended bounded real lemma, the ℋ∞ control is formulated and sufficient conditions are derived in terms of linear matrix inequalities (LMIs) formulation by using the fractional Lyapunov direct method where the fractional-order α belongs to 0 < α < 1. The control approach is finally applied to the regulation of the glucose level in diabetes type 1 treatment. Therefore, it is attempted to incorporate fractional-order into the mathematical minimal model of glucose-insulin system dynamics and it is still an interesting challenge to show, how the order of a fractional differential system affects the dynamics of the system in the presence of meal disturbance. Numerical simulations are carried out to illustrate our proposed results and show that the nonlinear fractional-order glucose-insulin systems are, at least, as stable as their integer-order counterpart in the presence of exogenous glucose infusion or meal disturbance. © 2015 Institute of Control, Robotics and Systems and The Korean Institute of Electrical Engineers and Springer-Verlag Berlin Heidelberg

  20. Four-Point Preprandial Self-Monitoring of Blood Glucose for the Assessment of Glycemic Control and Variability in Patients with Type 2 Diabetes Treated with Insulin and Vildagliptin

    Directory of Open Access Journals (Sweden)

    Andrea Tura

    2015-01-01

    Full Text Available The study explored the utility of four-point preprandial glucose self-monitoring to calculate several indices of glycemic control and variability in a study adding the DPP-4 inhibitor vildagliptin to ongoing insulin therapy. This analysis utilized data from a double-blind, randomized, placebo-controlled crossover study in 29 patients with type 2 diabetes treated with vildagliptin or placebo on top of stable insulin dose. During two 4-week treatment periods, self-monitoring of plasma glucose was undertaken at 4 occasions every day. Glucose values were used to assess several indices of glycemic control quality, such as glucose mean, GRADE, M-VALUE, hypoglycemia and hyperglycemia index, and indices of glycemic variability, such as standard deviation, CONGA, J-INDEX, and MAGE. We found that vildagliptin improved the glycemic condition compared to placebo: mean glycemic levels, and both GRADE and M-VALUE, were reduced by vildagliptin (P<0.01. Indices also showed that vildagliptin reduced glycemia without increasing the risk for hypoglycemia. Almost all indices of glycemic variability showed an improvement of the glycemic condition with vildagliptin (P<0.02, though more marked differences were shown by the more complex indices. In conclusion, the study shows that four-sample preprandial glucose self-monitoring is sufficient to yield information on the vildagliptin effects on glycemic control and variability.

  1. Impaired glucose-induced thermogenesis and arterial norepinephrine response persist after weight reduction in obese humans

    DEFF Research Database (Denmark)

    Astrup, A; Andersen, T; Christensen, N J

    1990-01-01

    A reduced thermic response and an impaired activation of the sympathetic nervous system (SNS) has been reported after oral glucose in human obesity. It is, however, not known whether the reduced SNS activity returns to normal along with weight reduction. The thermic effect of glucose was lower...... in eight obese patients than in matched control subjects (1.7% vs 9.2%, p less than 0.002). The increase in arterial norepinephrine after glucose was also blunted in the obese patients. After a 30-kg weight loss their glucose and lipid profiles were markedly improved but the thermic effect of glucose...... was still lower than that of the control subjects (4.2%, p less than 0.001). The glucose-induced arterial norepinephrine response remained diminished in the reduced obese patients whereas the changes in plasma epinephrine were similar in all three groups. The results suggest that a defective SNS may...

  2. Role of liver nerves and adrenal medulla in glucose turnover of running rats

    DEFF Research Database (Denmark)

    Sonne, B; Mikines, K J; Richter, Erik

    1985-01-01

    Sympathetic control of glucose turnover was studied in rats running 35 min at 21 m X min-1 on the level. The rats were surgically liver denervated, adrenodemedullated, or sham operated. Glucose turnover was measured by primed constant infusion of [3-3H]glucose. At rest, the three groups had...... identical turnover rates and concentrations of glucose in plasma. During running, glucose production always rose rapidly to steady levels. The increase was not influenced by liver denervation but was halved by adrenodemedullation. Similarly, hepatic glycogen depletion was identical in denervated and control...... rats but reduced after adrenodemedullation. Early in exercise, glucose uptake rose identically in all groups and, in adrenodemedullated rats, matched glucose production. Accordingly, plasma glucose concentration increased in liver-denervated and control rats but was constant in adrenodemedullated rats...

  3. Genetic impairment of AMPK{alpha}2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice

    DEFF Research Database (Denmark)

    Maarbjerg, Stine Just; Jørgensen, Sebastian Beck; Rose, Adam John

    2009-01-01

    and female mice over-expressing kinase-dead alpha2-AMPK (AMPK-KD) in skeletal and heart muscles. Wildtype and AMPK-KD mice were exercised at the same absolute intensity and the same relative intensity (30% and 70% of individual maximal running speed) to correct for reduced exercise capacity of the AMPK......-KD mouse. Muscle glucose clearance was measured using [3H]-2-deoxy-glucose as tracer. In wildtype mice glucose clearance was increased at 30% and 70% of maximal running speed by 40% and 350% in the quadriceps muscle, and by 120% and 380% in gastrocnemius muscle, respectively. Glucose clearance...

  4. Genetic modification of human mesenchymal stem cells helps to reduce adiposity and improve glucose tolerance in an obese diabetic mouse model.

    Science.gov (United States)

    Sen, Sabyasachi; Domingues, Cleyton C; Rouphael, Carol; Chou, Cyril; Kim, Chul; Yadava, Nagendra

    2015-12-09

    Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible. We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene expression. HG increased reactive superoxide (ROS) accumulation noted by day 7 both in cytosol and mitochondria. The OCR between the NG and HG exposed groups however did not change until 10 days at which point OCR of HG exposed cells were reduced significantly. We noted that HG exposure upregulated mRNA expression of adipogenic (PPARG, FABP-4, CREBP alpha and beta), inflammatory (IL-6 and TNF alpha) and antioxidant (SOD2 and Catalase) genes. Next, we used AdSOD2 to upregulate SOD2 prior to HG exposure and thereby noted reduction in superoxide generation. SOD2 upregulation helped reduce mRNA over-expression of PPARG, FABP-4, IL-6 and TNFα. In a series of separate experiments, we delivered the eGFP and SOD2 upregulated MSCs (5 days post ex-vivo transduction) and saline intra-peritoneally (IP) to obese diabetic (db/db) mice. We confirmed homing-in of eGFP labeled MSCs, delivered IP, to different inflamed fat pockets, particularly omental fat. Mice receiving SOD2-MSCs showed progressive reduction in body weight and improved glucose tolerance (GTT) at 4 weeks, post MSCs transplantation compared to the GFP-MSC group (control). High glucose evokes superoxide generation, OCR reduction and adipogenic differentiation. Mitochondrial superoxide dismutase upregulation quenches excess superoxide and reduces adipocyte

  5. Clinical use of continuous glucose monitoring in adults with type 1 diabetes

    OpenAIRE

    Slattery, David; Choudhary, Pratik

    2017-01-01

    With the emphasis on intensive management of type 1 diabetes, data from studies support frequent monitoring of glucose levels to improve glycemic control and reduce glucose variability, which can be related to an increase in macro and microvascular complications. However, few perform capillary blood glucose that frequently. There are currently two available alternatives that this review will discuss, continuous glucose monitoring (CGM) and flash glucose monitoring. CGM has become an important...

  6. Impaired insulin-stimulated nonoxidative glucose metabolism in pancreas-kidney transplant recipients. Dose-response effects of insulin on glucose turnover

    DEFF Research Database (Denmark)

    Christiansen, E; Vestergaard, H; Tibell, A

    1996-01-01

    -response curve for glucose disposal rates (Rd) was shifted to the right in the Px and Kx groups, and the maximal glucose disposal rate was reduced by 40% in the Px group (11.7 +/- 1.1 mg.kg-1 fat-free mass.min-1) and 30% in the Kx group (13.9 +/- 1.2 mg.kg-1 fat-free mass.min-1) compared with that in control...

  7. Influence of gastrointestinal factors on glucose metabolism in patients with cirrhosis

    DEFF Research Database (Denmark)

    Junker, Anders E; Gluud, Lise L; Holst, Jens Juul

    2015-01-01

    BACKGROUND AND AIMS: The impaired glucose tolerance in cirrhosis is poorly understood. We evaluated the influence of gastrointestinal-mediated glucose disposal and incretin effect in patients with cirrhosis. METHODS: Non-diabetic patients with Child Pugh A or B cirrhosis (n = 10) and matched...... of intravenous glucose in patients with cirrhosis compared to 24 ± 10 g in healthy controls (P = 0.003). The gastrointestinal-mediated glucose disposal was markedly lower in patients with cirrhosis (30 ± 23 vs. 52 ± 20%; P = 0.003). Despite higher levels of the incretin hormones glucagon-like peptide-1 (GLP-1......) and glucose-dependent insulinotropic peptide (GIP) patients with cirrhosis had reduced incretin effect (35 ± 44 vs. 55 ± 30%; P = 0.008). CONCLUSIONS: Impaired gastrointestinal-mediated glucose disposal and reduced incretin effect may contribute to the glucose intolerance seen in patients with cirrhosis....

  8. Impact of cereal fibre on glucose-regulating factors

    DEFF Research Database (Denmark)

    Weickert, M O; Mohlig, M; Koebnick, C

    2005-01-01

    postprandial glucose response on the following day subsequent to ingestion of a control meal (AUC(C-C) 4,140+/-401, AUC(C-WF) 2,850+/-331 [p=0.007], AUC(C-OF) 2,830+/-277 [p=0.011]), with no difference in maximal concentration and T(max) of glucose responses. No differences in insulin responses were observed......AIMS/HYPOTHESIS: Insoluble dietary fibre intake is associated, by unknown mechanisms, with a reduced risk of type 2 diabetes. We investigated whether a short-term dietary intervention with purified insoluble fibres influences acute and delayed responses of glucose, insulin, glucose...

  9. Continuous Glucose Monitoring in Patients with Abnormal Glucose Tolerance during Pregnancy: A Case Series

    Directory of Open Access Journals (Sweden)

    Mie Tonoike

    2016-01-01

    Full Text Available Abnormal glucose tolerance during pregnancy is associated with perinatal complications. We used continuous glucose monitoring (CGM in pregnant women with glucose intolerance to achieve better glycemic control and to evaluate the maternal glucose fluctuations. We also used CGM in women without glucose intolerance (the control cases. Furthermore, the standard deviation (SD and mean amplitude of glycemic excursions (MAGE were calculated for each case. For the control cases, the glucose levels were tightly controlled within a very narrow range; however, the SD and MAGE values in pregnant women with glucose intolerance were relativity high, suggesting postprandial hyperglycemia. Our results demonstrate that pregnant women with glucose intolerance exhibited greater glucose fluctuations compared with the control cases. The use of CGM may help to improve our understanding of glycemic patterns and may have beneficial effects on perinatal glycemic control, such as the detection of postprandial hyperglycemia in pregnant women.

  10. Glucose Control: non-insulin therapies* 9.1: Drug Summary ...

    African Journals Online (AJOL)

    Glucose Control: non-insulin therapies in 2017 SEMDSA Guideline for the Management of Type 2 Diabetes. Guideline ... Weight neutral or causes modest weight loss (-1.2kg). No weight ..... Older patients with multiple comorbidities. • Patients ...

  11. Bitter gourd reduces elevated fasting plasma glucose levels in an intervention study among prediabetics in Tanzania.

    Science.gov (United States)

    Krawinkel, Michael B; Ludwig, Christine; Swai, Mark E; Yang, Ray-Yu; Chun, Kwok Pan; Habicht, Sandra D

    2018-04-24

    Impaired glucose tolerance and diabetes mellitus have become major health issues even in non-industrialized countries. As access to clinical management is often poor, dietary interventions and alternative medicines are required. For bitter gourd, Momordica charantia L., antidiabetic properties have been claimed. The main objective of the intervention study was to assess antidiabetic effects of daily bitter gourd consumption of 2.5g powder over the course of eight weeks among prediabetic individuals. In a randomized placebo-controlled single blinded clinical trial, 52 individuals with prediabetes were studied after consuming a bitter gourd or a cucumber juice. For reducing the impact of between subject differences in the study population, a crossover design was chosen with eight weeks for each study period and four weeks washout in between. Fasting plasma glucose was chosen as the primary outcome variable. Comparing the different exposures, the CROS analysis (t=-2.23, p=0.031, r=0.326) revealed a significant difference in the change of FPG of 0.31mmol/L (5.6mg/dL) with a trend (R 2 =0,42387). The number of 44 finally complete data sets achieved a power of 0.82, with a medium-to-large effect size (Cohen's d 0.62). The effect was also proven by a general linear mixed model (estimate 0.31; SE: 0.12; p: 0.01; 95%CI: 0.08; 0.54). Not all participants responded, but the higher the initial blood glucose levels were, the more pronounced the effect was. No serious adverse effects were observed. Bitter gourd supplementation appeared to have benefits in lowering elevated fasting plasma glucose in prediabetes. The findings should be replicated in other intervention studies to further investigate glucose lowering effects and the opportunity to use bitter gourd for dietary self-management, especially in places where access to professional medical care is not easily assured. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Perception of difficulty and glucose control: Effects on academic performance in youth with type I diabetes.

    Science.gov (United States)

    Potts, Tiffany M; Nguyen, Jacqueline L; Ghai, Kanika; Li, Kathy; Perlmuter, Lawrence

    2015-04-15

    To investigate whether perceptions of task difficulty on neuropsychological tests predicted academic achievement after controlling for glucose levels and depression. Participants were type 1 diabetic adolescents, with a mean age = 12.5 years (23 females and 16 males), seen at a northwest suburban Chicago hospital. The sample population was free of co-morbid clinical health conditions. Subjects completed a three-part neuropsychological battery including the Digit Symbol Task, Trail Making Test, and Controlled Oral Word Association test. Following each task, individuals rated task difficulty and then completed a depression inventory. Performance on these three tests is reflective of neuropsychological status in relation to glucose control. Blood glucose levels were measured immediately prior to and after completing the neuropsychological battery using a glucose meter. HbA1c levels were obtained from medical records. Academic performance was based on self-reported grades in Math, Science, and English. Data was analyzed using multiple regression models to evaluate the associations between academic performance, perception of task difficulty, and glucose control. Perceptions of difficulty on a neuropsychological battery significantly predicted academic performance after accounting for glucose control and depression. Perceptions of difficulty on the neuropsychological tests were inversely correlated with academic performance (r = -0.48), while acute (blood glucose) and long-term glucose levels increased along with perceptions of task difficulty (r = 0.47). Additionally, higher depression scores were associated with poorer academic performance (r = -0.43). With the first regression analysis, perception of difficulty on the neuropsychological tasks contributed to 8% of the variance in academic performance after controlling for peripheral blood glucose and depression. In the second regression analysis, perception of difficulty accounted for 11% of the variance after

  13. Model-Based Closed-Loop Glucose Control in Type 1 Diabetes: The DiaCon Experience

    DEFF Research Database (Denmark)

    Schmidt, Signe; Boiroux, Dimitri; Duun-Henriksen, Anne Katrine

    2013-01-01

    Background: To improve type 1 diabetes mellitus (T1DM) management, we developed a model predictive control (MPC) algorithm for closed-loop (CL) glucose control based on a linear second-order deterministic-stochastic model. The deterministic part of the model is specified by three patient-specific......Background: To improve type 1 diabetes mellitus (T1DM) management, we developed a model predictive control (MPC) algorithm for closed-loop (CL) glucose control based on a linear second-order deterministic-stochastic model. The deterministic part of the model is specified by three patient...... crossover studies. Study 1 compared CL with open-loop (OL) control. Study 2 compared glucose control after CL initiation in the euglycemic (CL-Eu) and hyperglycemic (CL-Hyper) ranges, respectively. Patients were studied from 22:00–07:00 on two separate nights. Results: Each study included six T1DM patients...

  14. Blood glucose control in healthy subject and patients receiving intravenous glucose infusion or total parenteral nutrition using glucagon-like peptide 1

    DEFF Research Database (Denmark)

    Nauck, Michael A; Walberg, Jörg; Vethacke, Arndt

    2004-01-01

    It was the aim of the study to examine whether the insulinotropic gut hormone GLP-1 is able to control or even normalise glycaemia in healthy subjects receiving intravenous glucose infusions and in severely ill patients hyperglycaemic during total parenteral nutrition.......It was the aim of the study to examine whether the insulinotropic gut hormone GLP-1 is able to control or even normalise glycaemia in healthy subjects receiving intravenous glucose infusions and in severely ill patients hyperglycaemic during total parenteral nutrition....

  15. Correlation between pre-ramadan glycemic control and subsequent glucose fluctuation during fasting in adolescents with Type 1 diabetes.

    Science.gov (United States)

    Afandi, B; Kaplan, W; Al Hassani, N; Hadi, S; Mohamed, A

    2017-07-01

    Even though patients with type 1 diabetes mellitus (T1DM) are exempted from fasting, the vast majority elect to fast against the advice of their healthcare providers. We have previously reported the incidence of wide fluctuations in blood glucose (BG) along with "unrecognized" severe hypoglycemia during Ramadan fasting in adolescents with T1DM. This report compares the continuous glucose monitoring (CGM) data during fasting in adolescents with T1DM according to their Pre-Ramadan diabetes control. Children and adolescents with T1DM who intended to fast the month of Ramadan were asked to wear the CGM during fasting for a minimum of 3 days. Hypoglycemia, hyperglycemia, and severe hyperglycemia were identified as BG 300 mg/dL (16.7 mmol/L) respectively, while normoglycemia was identified as BG 70-200 mg/dL (3.9-11.1 mmol/L). Patients were categorized as well-controlled (Group 1) and poorly controlled (Group 2) if the pre-fasting HbA1C was ≤8% (64 mmol/mol) and >8%, respectively. We compared the mean BG and the percentages of time spent in hypoglycemia, hyperglycemia, and severe hyperglycemia between the two groups using Chi-square (significant difference when P value was fasting. Our data suggest that optimal glycemic control before Ramadan may reduce the potential risks associated with fasting and minimize glucose fluctuation.

  16. Glucagon-like peptide-1 reduces contractile function and fails to boost glucose utilization in normal hearts in the presence of fatty acids.

    Science.gov (United States)

    Nguyen, T Dung; Shingu, Yasushige; Amorim, Paulo A; Schwarzer, Michael; Doenst, Torsten

    2013-10-09

    GLP-1 and exendin-4, which are used as insulin sensitizers or weight reducing drugs, were shown to improve glucose uptake in the heart. However, the direct effects of GLP-1 or exendin-4 on normal hearts in the presence of fatty acids, the main cardiac substrates, have never been investigated. We therefore assessed the effects of GLP-1 or exendin-4 on myocardial glucose uptake (GU), glucose oxidation (GO) and cardiac performance (CP) under conditions of fatty acid utilization. Rat hearts were perfused with only glucose (5 mM) or glucose (5 mM) plus oleate (0.4 mM) as substrates for 60 min. After 30 min, GLP-1 or exendin-4 (0.5 nM or 5 nM) was added. In the absence of oleate, GLP-1 increased both GU and GO. Exendin-4 increased GO but showed no effect on GU. Neither GLP-1 nor exendin-4 affected CP. However, when oleate was present, GLP-1 failed to stimulate glucose utilization and exendin-4 even decreased GU. Furthermore, now GLP-1 reduced CP. In contrast to prior reports, this negative inotropic effect could not be blocked by the protein kinase A inhibitor H-89. We then measured myocardial GO and CP in rats receiving a 4-week GLP-1 infusion. Interestingly, this chronic treatment resulted in a significant reduction in both GO and CP. Under the influence of oleate, GLP-1 reduces contractile function and fails to stimulate glucose utilization in normal hearts. Exendin-4 may acutely reduce cardiac glucose uptake but not contractility. We suggest advanced investigation of heart function and metabolism in patients treating with these peptides. © 2013.

  17. Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Hou, Li-qiong; Liu, Yun-hui; Zhang, Yi-yi

    2015-01-01

    Garlic is a common spicy flavouring agent also used for certain therapeutic purposes. Garlic's effects on blood glucose have been the subject of many clinical and animal studies, however, studies reporting hypoglycemic effects of garlic in humans are conflicting. A comprehensive literature search was conducted to identify relevant trials of garlic or garlic extracts on markers of glycemic control [fasting blood glucose (FBG), postprandial glucose (PPG), glycosylated haemoglobin (HbA1c)]. A meta-analysis of the effect of garlic intake on human was done to assess garlic's effectiveness in lowering glucose levels. Two reviewers extracted data from each of the identified studies. Seven eligible randomized controlled trials with 513 subjects were identified. Pooled analyses showed that garlic intake results in a statistically significant lowering in FBG [SMD=-1.67; 95% CI (-2.80, -0.55), p=0.004]. Our pooled analyses did not include PPG control and HbA1c outcomes. Because only 1 study included in the meta-analysis reported PPG variables and only 2 studies reported HbA1c variables. In conclusion, the current meta-analysis showed that the administration of garlic resulted in a significant reduction in FBG concentrations. More trials are needed to investigate the effectiveness of garlic on HbA1c and PPG.

  18. Control of Hepatic Glucose Metabolism by Islet and Brain

    Science.gov (United States)

    Rojas, Jennifer M.; Schwartz, Michael W.

    2014-01-01

    Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP), both contribute to hyperglycemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver, but also via a mechanism involving the brain. Yet the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice investigating whether the direct hepatic action of insulin is necessary for normal HGP: when hepatic insulin signaling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients. PMID:25200294

  19. Plain to point network reduced graphene oxide - activated carbon composites decorated with platinum nanoparticles for urine glucose detection

    Science.gov (United States)

    Hossain, Mohammad Faruk; Park, Jae Y.

    2016-02-01

    In this study, a hydrothermal technique was applied to synthesize glucose-treated reduced graphene oxide-activated carbon (GRGO/AC) composites. Platinum nanoparticles (PtNP) were electrochemically deposited on the modified GRGO/AC surface, and chitosan-glucose oxidase (Chit-GOx) composites and nafion were integrated onto the modified surface of the working electrode to prepare a highly sensitive glucose sensor. The fabricated biosensor exhibited a good amperometric response to glucose in the detection range from 0.002 mM to 10 mM, with a sensitivity of 61.06 μA/mMcm2, a short response time (4 s) and a low detection limit of 2 μM (signal to noise ratio is 3). The glucose sensor exhibited a negligible response to interference and good stability. In addition, the glucose levels in human urine were tested in order to conduct a practical assessment of the proposed sensor, and the results indicate that the sensor had superior urine glucose recognition. These results thus demonstrate that the noble nano-structured electrode with a high surface area and electrocatalytic activity offers great promise for use in urine glucose sensing applications.

  20. Changes in blood glucose among trained normoglycemic adults during a mini-trampoline exercise session.

    Science.gov (United States)

    Martins Cunha, Raphael; Raiana Bentes, Mariana; Araújo, Victor H; DA Costa Souza, Mayara C; Vasconcelos Noleto, Marcelo; Azevedo Soares, Ademar; Machado Lehnen, Alexandre

    2016-12-01

    Blood glucose changes response during and after exercise are modulated by the postabsorptive state, intensity and duration of exercise, and the level of physical fitness as well. This study focused on the idea that high-intensity interval exercise, as mini-trampoline class, can reduce blood glucose. Thus, we examined acute changes in blood glucose among trained normoglycemic adults during a mini-trampoline exercise session. Twenty-four normoglycemic adult subjects were enrolled in the study. After physical assessment they were randomly assigned to either the experimental (N.=12) or the control group (N.=12). The experimental group performed a 50-minute session of moderate-to-high intensity (70 to 85% HRmax) exercise on a mini-trampoline commonly used in fitness classes. The control group did not perform any exercise, and all procedures were otherwise similar to the experimental group. Capillary blood glucose was measured before and every 15 minutes during the exercise session. The effects of exercise on blood glucose levels (group; time; and group interaction) were estimated using a generalized estimating equation (GEE) followed by Bonferroni's post-hoc Test (Ptrampoline can be used for reducing blood glucose levels and thus can potentially control blood glucose.

  1. A Hexose Transporter Homologue Controls Glucose Repression in the Methylotrophic Yeast Hansenula polymorpha

    NARCIS (Netherlands)

    Stasyk, Oleh V.; Stasyk, Olena G.; Komduur, Janet; Veenhuis, Marten; Cregg, James M.; Sibirny, Andrei A.

    2004-01-01

    Peroxisome biogenesis and synthesis of peroxisomal enzymes in the methylotrophic yeast Hansenula polymorpha are under the strict control of glucose repression. We identified an H. polymorpha glucose catabolite repression gene (HpGCR1) that encodes a hexose transporter homologue. Deficiency in GCR1

  2. The effect of a prenatal lifestyle intervention on glucose metabolism: results of the Norwegian Fit for Delivery randomized controlled trial.

    Science.gov (United States)

    Sagedal, Linda R; Vistad, Ingvild; Øverby, Nina C; Bere, Elling; Torstveit, Monica K; Lohne-Seiler, Hilde; Hillesund, Elisabet R; Pripp, Are; Henriksen, Tore

    2017-06-02

    The effectiveness of prenatal lifestyle intervention to prevent gestational diabetes and improve maternal glucose metabolism remains to be established. The Norwegian Fit for Delivery (NFFD) randomized, controlled trial studied the effect of a combined lifestyle intervention provided to a general population, and found significantly lower gestational weight gain among intervention participants but no improvement in obstetrical outcomes or the proportion of large infants. The aim of the present study is to examine the effect of the NFFD intervention on glucose metabolism, including an assessment of the subgroups of normal-weight and overweight/obese participants. Healthy, non-diabetic women expecting their first child, with pre-pregnancy body mass index (BMI) ≥19 kg/m 2 , age ≥ 18 years and a singleton pregnancy of ≤20 gestational-weeks were enrolled from healthcare clinics in southern Norway. Gestational weight gain was the primary endpoint. Participants (n = 606) were individually randomized to intervention (two dietary consultations and access to twice-weekly exercise groups) or control group (routine prenatal care). The effect of intervention on glucose metabolism was a secondary endpoint, measuring glucose (fasting and 2-h following 75-g glucose load), insulin, homeostatic assessment of insulin resistance (HOMA-IR) and leptin levels at gestational-week 30. Blood samples from 557 (91.9%) women were analyzed. For the total group, intervention resulted in reduced insulin (adj. Mean diff -0.91 mU/l, p = 0.045) and leptin levels (adj. Mean diff -207 pmol/l, p = 0.021) compared to routine care, while glucose levels were unchanged. However, the effect of intervention on both fasting and 2-h glucose was modified by pre-pregnancy BMI (interaction p = 0.030 and p = 0.039, respectively). For overweight/obese women (n = 158), intervention was associated with increased risk of at least one glucose measurement exceeding International Association of

  3. A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents.

    Directory of Open Access Journals (Sweden)

    Jian Luo

    Full Text Available Type 2 diabetes is characterized by impaired glucose homeostasis due to defects in insulin secretion, insulin resistance and the incretin response. GPR40 (FFAR1 or FFA1 is a G-protein-coupled receptor (GPCR, primarily expressed in insulin-producing pancreatic β-cells and incretin-producing enteroendocrine cells of the small intestine. Several GPR40 agonists, including AMG 837 and TAK-875, have been disclosed, but no GPR40 synthetic agonists have been reported that engage both the insulinogenic and incretinogenic axes. In this report we provide a molecular explanation and describe the discovery of a unique and potent class of GPR40 full agonists that engages the enteroinsular axis to promote dramatic improvement in glucose control in rodents. GPR40 full agonists AM-1638 and AM-6226 stimulate GLP-1 and GIP secretion from intestinal enteroendocrine cells and increase GSIS from pancreatic islets, leading to enhanced glucose control in the high fat fed, streptozotocin treated and NONcNZO10/LtJ mouse models of type 2 diabetes. The improvement in hyperglycemia by AM-1638 was reduced in the presence of the GLP-1 receptor antagonist Ex(9-39NH(2.

  4. Effects of blood glucose, blood lipids and blood pressure control on recovery of patients with gastric cancer complicated with metabolic syndrome after radical gastrectomy.

    Science.gov (United States)

    Sun, Li; Zhou, Pingping; Hua, Qingli; Jin, Changming; Guo, Chunling; Song, Bing

    2018-06-01

    This study aimed to investigate the effects of blood glucose, blood lipids and blood pressure control on recovery of patients with gastric cancer complicated with metabolic syndrome (MS) after radical gastrectomy. A total of 150 patients with gastric cancer, who were treated in Daqing Longnan Hospital from November, 2015 to May, 2017, were enrolled in this study. The patients were divided into the MS group (80 cases) and non-MS group (70 cases). Patients in the MS group were given corresponding drugs to control blood pressure, blood lipids and blood glucose, while patients in the non-MS group were not treated with those drugs. Patients in the MS group were divided into the normal and abnormal groups according to the levels of blood glucose, blood lipids and blood pressure. Moreover, occurrences of complications were compared between the normal and abnormal groups. Before surgery, blood glucose, blood lipids and blood pressure in the MS group were significantly higher than those in the non-MS group (pblood glucose, blood lipids and blood pressure of the MS group decreased significantly compared to those before operation (pblood glucose, 2 h postprandial blood glucose, glycosylated hemoglobin, total triglycerides (TGs), LDL, mean blood pressure and BMI (pblood glucose, blood lipids and blood pressure in patients with gastric cancer complicated with MS after radical gastrectomy can reduce the incidence of postoperative complications and promote postoperative recovery.

  5. Alteration patterns of brain glucose metabolism: comparisons of healthy controls, subjective memory impairment and mild cognitive impairment.

    Science.gov (United States)

    Song, In-Uk; Choi, Eun Kyoung; Oh, Jin Kyoung; Chung, Yong-An; Chung, Sung-Woo

    2016-01-01

    Some groups have focused on the detection and management of subjective memory impairment (SMI) as the stage that precedes mild cognitive impairment (MCI). However, there have been few clinical studies that have examined biomarkers of SMI to date. To investigate the differences in glucose metabolism as a prodromal marker of dementia in patients with SMI, MCI, and healthy controls using brain F-18 fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Sixty-eight consecutive patients with SMI, 47 patients with MCI, and 42 age-matched healthy subjects were recruited. All subjects underwent FDG-PET and detailed neuropsychological testing. FDG-PET images were analyzed using the statistical parametric mapping (SPM) program. FDG-PET analysis showed glucose hypometabolism in the periventricular regions of patients with SMI and in the parietal, precentral frontal, and periventricular regions of patients with MCI compared with healthy controls. Interestingly, hypometabolism on FDG-PET was noted in the parietal and precentral frontal regions in MCI patients compared to SMI patients. The results suggest that hypometabolism in the periventricular regions as seen on FDG-PET may play a role as a predictive biomarker of pre-dementia, and the extension of reduced glucose metabolism into parietal regions likely reflects progression of cognitive deterioration. © The Foundation Acta Radiologica 2014.

  6. Diabetter"T"M Reduces Post Meal Hyperglycemia Via Enhancement of Glucose Uptake Into Adipocytes and Muscles Cells

    International Nuclear Information System (INIS)

    Zainah Adam; Mohd Hishamudin Mohd Jinal; Alqarni Bader Ayed; Shafii Khamis

    2014-01-01

    There are lots of herbal products for diabetes mellitus treatment available in local market. Most of these products are not standardized and lack of efficacy and safety data. DiaBetter"T"M is one of the herbal products that have been used for diabetes treatment. This study was carried out to determine the efficacy of DiaBetter"T"M in reducing hyperglycemia and to elucidate the mechanisms by which hyperglycemia is reduced. The results showed that DiaBetter"T"M significantly reduced post meal hyperglycemia in normal and diabetic rats, and improved glucose tolerance activity in diabetic rats particularly after 4 and 6 hours of administration. Antihyperglycemic mechanisms elucidation revealed that the DiaBetter"T"M significantly enhanced insulin-stimulated glucose uptake into adipocytes and muscle cells, with the highest magnitude of enhancement were 1.54 fold (p<0.01) and 1.46 fold (p<0.001), respectively. Molecular mechanisms that responsible for this enhancement were the increment of insulin sensitivity at cells membrane. Cytotoxic evaluation was also done and confirmed that DiaBetter"T"M was toxicologically safe against muscle and adipocytes cells. In conclusion, post-meal antihyperglycemic and glucose tolerance activity of DiaBetter"T"M was mediated through the enhancement of glucose uptake into adipocytes and muscle cells. Insulin sensitizing activity showed by DiaBetter"T"M suggests that this product has the potential to ameliorate insulin resistance condition. Therefore, it is suggested that the DiaBetter"T"M can be used as dietary adjunct for the management of type 2 diabetes mellitus which related to insulin resistance. (Author)

  7. Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur.

    Science.gov (United States)

    Pifferi, Fabien; Dorieux, Olène; Castellano, Christian-Alexandre; Croteau, Etienne; Masson, Marie; Guillermier, Martine; Van Camp, Nadja; Guesnet, Philippe; Alessandri, Jean-Marc; Cunnane, Stephen; Dhenain, Marc; Aujard, Fabienne

    2015-08-01

    Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months' supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze. Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  8. Importance of the gut-brain axis in the control of glucose homeostasis.

    Science.gov (United States)

    Migrenne, Stéphanie; Marsollier, Nicolas; Cruciani-Guglielmacci, Céline; Magnan, Christophe

    2006-12-01

    Adult mammals finely match glucose production to glucose utilization, thus allowing glycaemia to be maintained in a physiological range of 0.8-1.2mg/dl whatever the energetic status of the mammal (i.e. fed or fasted, rested or exercised). To accomplish this, peripheral signals originating from the gut 'inform' the central nervous system, which in turn is able to monitor the status of both peripheral glucose stores and ongoing fuel availability. Indeed, both secretion and action of hormones regulating endogenous glucose production and utilization are regulated by the autonomic nervous system. These gut signals are either hormonal (e.g. glucagon-like peptide-1, ghrelin and cholecystokinine) or neuronal (e.g. afferent vagus nerve fibres). Recent data, combined with the development of incretin analogues for treatment of diabetes, highlight the importance of the gut-brain axis, especially glucagon-like peptide-1 and ghrelin, in the control of glucose homeostasis.

  9. Immediate Effect of Needling at CV-12 (Zhongwan) Acupuncture Point on Blood Glucose Level in Patients with Type 2 Diabetes Mellitus: A Pilot Randomized Placebo-Controlled Trial.

    Science.gov (United States)

    Kumar, Ranjan; Mooventhan, A; Manjunath, Nandi Krishnamurthy

    2017-08-01

    Diabetes mellitus is a major global health problem. Needling at CV-12 has reduced blood glucose level in diabetic rats. The aim of this study was to evaluate the effect of needling at CV-12 (Zhongwan) on blood glucose level in patients with type 2 diabetes mellitus (T2DM). Forty T2DM patients were recruited and randomized into either the acupuncture group or placebo control group. The participants in the acupuncture group were needled at CV-12 (4 cun above the center of the umbilicus), and those in the placebo control group were needled at a placebo point on the right side of the abdomen (1 cun beside the CV-12). For both groups, the needle was retained for 30 minutes. Assessments were performed prior to and after the intervention. Statistical analysis was performed using SPSS version 16. There was a significant reduction in random blood glucose level in the acupuncture group compared to baseline. No such significant change was observed in the placebo control group. The result of this study suggests that 30 minutes of needling at CV-12 might be useful in reducing blood glucose level in patients with T2DM. Copyright © 2017. Published by Elsevier B.V.

  10. Effect of a 26-month floorball training on male elderly's cardiovascular fitness, glucose control, body composition, and functional capacity

    DEFF Research Database (Denmark)

    Pedersen, Mogens Theisen; Vorup, Jacob; Bangsbo, Jens

    2018-01-01

    , the effect of long-term participation in floorball training among male elderly has not been investigated. The aim of the present study was to examine the effect of 26-month self-organized regular participation in floorball training on cardiovascular fitness, body composition, blood lipids, glucose control...... weekly floorball sessions with 40 min/session over 26-month appear to reduce age-related decline in cardiovascular fitness and glucose control and improve leg bone mineral density, suggesting that long-term participation in floorball training can be considered as a health-enhancing activity......Background: Floorball training offers a motivating and socially stimulating team activity for older adults, and 12 weeks of floorball training twice a week among men aged 65–76 years have been shown to have positive effects on a number of physiological parameters important for health. However...

  11. The CNS glucagon-like peptide-2 receptor in the control of energy balance and glucose homeostasis

    Science.gov (United States)

    2014-01-01

    The gut-brain axis plays a key role in the control of energy balance and glucose homeostasis. In response to luminal stimulation of macronutrients and microbiota-derived metabolites (secondary bile acids and short chain fatty acids), glucagon-like peptides (GLP-1 and -2) are cosecreted from endocrine L cells in the gut and coreleased from preproglucagonergic neurons in the brain stem. Glucagon-like peptides are proposed as key mediators for bariatric surgery-improved glycemic control and energy balance. Little is known about the GLP-2 receptor (Glp2r)-mediated physiological roles in the control of food intake and glucose homeostasis, yet Glp1r has been studied extensively. This review will highlight the physiological relevance of the central nervous system (CNS) Glp2r in the control of energy balance and glucose homeostasis and focuses on cellular mechanisms underlying the CNS Glp2r-mediated neural circuitry and intracellular PI3K signaling pathway. New evidence (obtained from Glp2r tissue-specific KO mice) indicates that the Glp2r in POMC neurons is essential for suppressing feeding behavior, gastrointestinal motility, and hepatic glucose production. Mice with Glp2r deletion selectively in POMC neurons exhibit hyperphagic behavior, accelerated gastric emptying, glucose intolerance, and hepatic insulin resistance. GLP-2 differentially modulates postsynaptic membrane excitability of hypothalamic POMC neurons in Glp2r- and PI3K-dependent manners. GLP-2 activates the PI3K-Akt-FoxO1 signaling pathway in POMC neurons by Glp2r-p85α interaction. Intracerebroventricular GLP-2 augments glucose tolerance, suppresses glucose production, and enhances insulin sensitivity, which require PI3K (p110α) activation in POMC neurons. Thus, the CNS Glp2r plays a physiological role in the control of food intake and glucose homeostasis. This review will also discuss key questions for future studies. PMID:24990862

  12. Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality.

    Science.gov (United States)

    Mieczkowska, Aleksandra; Irwin, Nigel; Flatt, Peter R; Chappard, Daniel; Mabilleau, Guillaume

    2013-10-01

    Bone is permanently remodeled by a complex network of local, hormonal and neuronal factors that affect osteoclast and osteoblast biology. In this context, a role for gastro-intestinal hormones has been proposed based on evidence that bone resorption dramatically falls after a meal. Glucose-dependent insulinotropic polypeptide (GIP) is one of the candidate hormones as its receptor, glucose-dependent insulinotropic polypeptide receptor (GIPR), is expressed in bone. In the present study we investigated bone strength and quality by three-point bending, quantitative x-ray microradiography, microCT, qBEI and FTIR in a GIPR knockout (GIPR KO) mouse model and compared with control wild-type (WT) animals. Animals with a deletion of the GIPR presented with a significant reduction in ultimate load (--11%), stiffness (-16%), total absorbed (-28%) and post-yield energies (-27%) as compared with WT animals. Furthermore, despite no change in bone outer diameter, the bone marrow diameter was significantly increased and as a result cortical thickness was significantly decreased by 20% in GIPR deficient animals. Bone resorption at the endosteal surface was significantly increased whilst bone formation was unchanged in GIPR deficient animals. Deficient animals also presented with a pronounced reduction in the degree of mineralization of bone matrix. Furthermore, the amount of mature cross-links of collagen matrix was significantly reduced in GIPR deficient animals and was associated with lowered intrinsic material properties. Taken together, these data support a positive effect of the GIPR on bone strength and quality. © 2013.

  13. Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats.

    Science.gov (United States)

    Oakes, Nicholas D; Thalén, Pia; Hultstrand, Therese; Jacinto, Severina; Camejo, Germán; Wallin, Boel; Ljung, Bengt

    2005-10-01

    Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor alpha/gamma agonist, tesaglitazar, 3 mumol.kg(-1).day(-1) for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.

  14. Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot.

    Science.gov (United States)

    Sarode, Bhagyesh R; Kover, Karen; Tong, Pei Y; Zhang, Chaoying; Friedman, Simon H

    2016-11-07

    In this work we demonstrate that blood glucose can be controlled remotely through light stimulated release of insulin from an injected cutaneous depot. Human insulin was tethered to an insoluble but injectable polymer via a linker, which was based on the light cleavable di-methoxy nitrophenyl ethyl (DMNPE) group. This material was injected into the skin of streptozotocin-treated diabetic rats. We observed insulin being released into the bloodstream after a 2 min trans-cutaneous irradiation of this site by a compact LED light source. Control animals treated with the same material, but in which light was blocked from the site, showed no release of insulin into the bloodstream. We also demonstrate that additional pulses of light from the light source result in additional pulses of insulin being absorbed into circulation. A significant reduction in blood glucose was then observed. Together, these results demonstrate the feasibility of using light to allow for the continuously variable control of insulin release. This in turn has the potential to allow for the tight control of blood glucose without the invasiveness of insulin pumps and cannulas.

  15. Green tea extract does not affect exogenous glucose appearance but reduces insulinemia with glucose ingestion in exercise recovery.

    Science.gov (United States)

    Martin, Brian J; McGlory, Chris; MacInnis, Martin J; Allison, Mary K; Phillips, Stuart M; Gibala, Martin J

    2016-12-01

    We reported that supplementation with green tea extract (GTE) lowered the glycemic response to an oral glucose load following exercise, but via an unknown mechanism (Martin BJ, MacInnis MJ, Gillen JB, Skelly LE, Gibala MJ. Appl Physiol Nutr Metab 41: 1057-1063, 2016. Here we examined the effect of supplementation with GTE on plasma glucose kinetics on ingestion of a glucose beverage during exercise recovery. Eleven healthy, sedentary men (21 ± 2 yr old; body mass index = 23 ± 4 kg/m 2 , peak O 2 uptake = 38 ± 7 ml·kg -1 ·min -1 ; means ± SD) ingested GTE (350 mg) or placebo (PLA) thrice daily for 7 days in a double-blind, crossover design. In the fasted state, a primed constant infusion of [U- 13 C 6 ]glucose was started, and 1 h later, subjects performed a graded exercise test (25 W/3 min) on a cycle ergometer. Immediately postexercise, subjects ingested a 75-g glucose beverage containing 2 g of [6,6- 2 H 2 ]glucose, and blood samples were collected every 10 min for 3 h of recovery. The rate of carbohydrate oxidation was lower during exercise after GTE vs. PLA (1.26 ± 0.34 vs. 1.48 ± 0.51 g/min, P = 0.04). Glucose area under the curve (AUC) was not different between treatments after drink ingestion (GTE = 1,067 ± 133 vs. PLA = 1,052 ± 91 mM/180 min, P = 0.91). Insulin AUC was lower after GTE vs. PLA (5,673 ± 2,153 vs. 7,039 ± 2,588 µIU/180 min, P = 0.05), despite similar rates of glucose appearance (GTE = 0.42 ± 0.16 vs. PLA = 0.43 ± 0.13 g/min, P = 0.74) and disappearance (GTE = 0.43 ± 0.14 vs. PLA = 0.44 ± 0.14 g/min, P = 0.57). We conclude that short-term GTE supplementation did not affect glucose kinetics following ingestion of an oral glucose load postexercise; however, GTE was associated with attenuated insulinemia. These findings suggest GTE lowers the insulin required for a given glucose load during postexercise recovery, which warrants further mechanistic studies in humans. Copyright © 2016 the American Physiological Society.

  16. Direct electrodeposition of a biocomposite consisting of reduced graphene oxide, chitosan and glucose oxidase on a glassy carbon electrode for direct sensing of glucose

    International Nuclear Information System (INIS)

    Yang, S.; Lu, Z.; Luo, S.; Liu, C.; Tang, Y.

    2013-01-01

    We have electrodeposited a composite film consisting of graphene oxide, chitosan and glucose oxidase directly on a glassy carbon electrode (GCE) through electrochemical reduction of a solution of the 3 components under controlled direct electrical potential. The procedure takes only several minutes, and the thickness of the resulting film is uniform and controllable. The GOx has uncompromised bioactivity and exhibits reversible 2-proton and 2-electron transfer in presence of glucose. It therefore can be used amperometric sensing of glucose. The biosensor has a fast response (<3 s), a detection limit of 0.4 μM (which is 50-fold lower compared to the biosensor prepared by drop-casting solutions of the same materials onto an GCE), and a linear response in the 0.4 μM to 2 mM concentration range (which again is much better than that of the biosensor prepared by the drop-casting method). Other features include high reproducibility, long-time storage stability, and satisfactory selectivity. We presume that the direct single-step electrodeposition of this nanocomposite offers a promising approach towards novel types of highly sensitive and stable electrochemical biosensors. (author)

  17. The effect of hydroxychloroquine on glucose control and insulin resistance in the prediabetes condition

    OpenAIRE

    Sheikhbahaie, Fahimeh; Amini, Masoud; Gharipour, Mojgan; Aminoroaya, Ashraf; Taheri, Nader

    2016-01-01

    Background: Hydroxychloroquine can improve most underlying coronary risk factors; however, there are a few studies on the effects of hydroxychloroquine on blood glucose and insulin resistance. The current study aimed to assess the effects of hydroxychloroquine on blood glucose control status as well as on level of lipid profile and inflammatory biomarkers in prediabetic patients. Materials and Methods: In a randomized, double-blinded, controlled trial, 39 consecutive patients who were suff...

  18. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review.

    Science.gov (United States)

    Manna, Prasenjit; Kalita, Jatin

    2016-01-01

    Micronutrients are gaining acceptance as an important nutritional therapy for the prevention and/or management of diabetes and its associated health risks. Although a very small quantity of micronutrients are required for specific functions in our bodies, moderate deficiencies can lead to serious health issues. Impaired insulin sensitivity and glucose intolerance play a major role in the development of diabetic pathophysiology. Vitamin K is well known for its function in blood coagulation. Moreover, several human studies reported the beneficial role of vitamin K supplementation in improving insulin sensitivity and glucose tolerance, preventing insulin resistance, and reducing the risk of type 2 diabetes (T2 D). Both animal and human studies have suggested that vitamin K-dependent protein (osteocalcin [OC]), regulation of adipokine levels, antiinflammatory properties, and lipid-lowering effects may mediate the beneficial function of vitamin K in insulin sensitivity and glucose tolerance. This review for the first time provides an overview of the currently available preclinical and clinical evidences on the effect of vitamin K supplementation in the management of insulin sensitivity and glucose tolerance. The outcome of this review will increase understanding for the development of a novel adjuvant therapy to achieve better control of glycemia and improve the lives of diabetic patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Adding glucose to food and solutions to enhance fructose absorption is not effective in preventing fructose-induced functional gastrointestinal symptoms: randomised controlled trials in patients with fructose malabsorption.

    Science.gov (United States)

    Tuck, C J; Ross, L A; Gibson, P R; Barrett, J S; Muir, J G

    2017-02-01

    In healthy individuals, the absorption of fructose in excess of glucose in solution is enhanced by the addition of glucose. The present study aimed to assess the effects of glucose addition to fructose or fructans on absorption patterns and genesis of gastrointestinal symptoms in patients with functional bowel disorders. Randomised, blinded, cross-over studies were performed in healthy subjects and functional bowel disorder patients with fructose malabsorption. The area-under-the-curve (AUC) was determined for breath hydrogen and symptom responses to: (i) six sugar solutions (fructose in solution) (glucose; sucrose; fructose; fructose + glucose; fructan; fructan + glucose) and (ii) whole foods (fructose in foods) containing fructose in excess of glucose given with and without additional glucose. Intake of fermentable short chain carbohydrates (FODMAPs; fermentable, oligo-, di-, monosaccharides and polyols) was controlled. For the fructose in solution study, in 26 patients with functional bowel disorders, breath hydrogen was reduced after glucose was added to fructose compared to fructose alone [mean (SD) AUC 92 (107) versus 859 (980) ppm 4 h -1 , respectively; P = 0.034). Glucose had no effect on breath hydrogen response to fructans (P = 1.000). The six healthy controls showed breath hydrogen patterns similar to those with functional bowel disorders. No differences in symptoms were experienced with the addition of glucose, except more nausea when glucose was added to fructose (P = 0.049). In the fructose in foods study, glucose addition to whole foods containing fructose in excess of glucose in nine patients with functional bowel disorders and nine healthy controls had no significant effect on breath hydrogen production or symptom response. The absence of a favourable response on symptoms does not support the concomitant intake of glucose with foods high in either fructose or fructans in patients with functional bowel disorders. © 2016 The British Dietetic

  20. Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin‐Stimulated Glucose Uptake

    Science.gov (United States)

    Mleczko, Justyna; Ortega, Francisco J.; Falcon‐Perez, Juan Manuel; Wabitsch, Martin; Fernandez‐Real, Jose Manuel

    2018-01-01

    Scope We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness. Methods and results EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin‐stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin‐stimulated 2‐deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin‐mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2‐deoxyglucose uptake in adipocytes (p = 0.0159). Conclusion EVs released by stressed adipocytes impair insulin action in neighboring adipocytes. PMID:29292863

  1. Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Xuemei Shi

    2017-11-01

    Conclusions: We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity.

  2. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

    Science.gov (United States)

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2016-01-01

    Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

  3. Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.

    Science.gov (United States)

    García-Cáceres, Cristina; Quarta, Carmelo; Varela, Luis; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Johansson, Pia; Ninkovic, Jovica; Yi, Chun-Xia; Le Thuc, Ophelia; Szigeti-Buck, Klara; Cai, Weikang; Meyer, Carola W; Pfluger, Paul T; Fernandez, Ana M; Luquet, Serge; Woods, Stephen C; Torres-Alemán, Ignacio; Kahn, C Ronald; Götz, Magdalena; Horvath, Tamas L; Tschöp, Matthias H

    2016-08-11

    We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Real-time continuous glucose monitoring during labour and delivery in women with Type 1 diabetes — observations from a randomized controlled trial

    DEFF Research Database (Denmark)

    Cordua, S; Secher, A L; Ringholm, L

    2013-01-01

    To explore whether real-time continuous glucose monitoring during labour and delivery supplementary to hourly self-monitored plasma glucose in women with Type 1 diabetes reduces the prevalence of neonatal hypoglycaemia.......To explore whether real-time continuous glucose monitoring during labour and delivery supplementary to hourly self-monitored plasma glucose in women with Type 1 diabetes reduces the prevalence of neonatal hypoglycaemia....

  5. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    International Nuclear Information System (INIS)

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82 Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

  6. Statistical transformation and the interpretation of inpatient glucose control data from the intensive care unit.

    Science.gov (United States)

    Saulnier, George E; Castro, Janna C; Cook, Curtiss B

    2014-05-01

    Glucose control can be problematic in critically ill patients. We evaluated the impact of statistical transformation on interpretation of intensive care unit inpatient glucose control data. Point-of-care blood glucose (POC-BG) data derived from patients in the intensive care unit for 2011 was obtained. Box-Cox transformation of POC-BG measurements was performed, and distribution of data was determined before and after transformation. Different data subsets were used to establish statistical upper and lower control limits. Exponentially weighted moving average (EWMA) control charts constructed from April, October, and November data determined whether out-of-control events could be identified differently in transformed versus nontransformed data. A total of 8679 POC-BG values were analyzed. POC-BG distributions in nontransformed data were skewed but approached normality after transformation. EWMA control charts revealed differences in projected detection of out-of-control events. In April, an out-of-control process resulting in the lower control limit being exceeded was identified at sample 116 in nontransformed data but not in transformed data. October transformed data detected an out-of-control process exceeding the upper control limit at sample 27 that was not detected in nontransformed data. Nontransformed November results remained in control, but transformation identified an out-of-control event less than 10 samples into the observation period. Using statistical methods to assess population-based glucose control in the intensive care unit could alter conclusions about the effectiveness of care processes for managing hyperglycemia. Further study is required to determine whether transformed versus nontransformed data change clinical decisions about the interpretation of care or intervention results. © 2014 Diabetes Technology Society.

  7. Reduced malonyl-CoA content in recovery from exercise correlates with improved insulin-stimulated glucose uptake in human skeletal muscle

    DEFF Research Database (Denmark)

    Frøsig, Christian; Roepstorff, Carsten; Brandt, Nina

    2009-01-01

    This study evaluated whether improved insulin-stimulated glucose uptake in recovery from acute exercise coincides with reduced malonyl-CoA (MCoA) content in human muscle. Furthermore, we investigated whether a high-fat diet [65 energy-% (Fat)] would alter the content of MCoA and insulin action...... to be compromised, although to a minor extent, by the Fat diet. Collectively, this study indicates that reduced muscle MCoA content in recovery from exercise may be part of the adaptive response leading to improved insulin action on glucose uptake after exercise in human muscle....

  8. Generalized decrease in brain glucose metabolism during fasting in humans studied by PET

    International Nuclear Information System (INIS)

    Redies, C.; Hoffer, L.J.; Beil, C.

    1989-01-01

    In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged

  9. Type-4 Resistant Starch in Substitution for Available Carbohydrate Reduces Postprandial Glycemic Response and Hunger in Acute, Randomized, Double-Blind, Controlled Study

    Directory of Open Access Journals (Sweden)

    Maria L. Stewart

    2018-01-01

    Full Text Available Resistant starch (RS is a type of dietary fiber that has been acknowledged for multiple physiological benefits. Resistant starch type 4 (RS4 is a subcategory of RS that has been more intensively studied as new types of RS4 emerge in the food supply. The primary aim of this randomized, double-blind, controlled study was to characterize the postprandial glucose response in healthy adults after consuming a high fiber scone containing a novel RS4 or a low fiber control scone without RS4. Secondary aims included assessment of postprandial insulin response, postprandial satiety, and gastrointestinal tolerance. The fiber scone significantly reduced postprandial glucose and insulin incremental areas under the curves (43–45% reduction, 35–40% reduction, respectively and postprandial glucose and insulin maximum concentrations (8–10% and 22% reduction, respectively. The fiber scone significantly reduced hunger and desire to eat during the 180 min following consumption and yielded no gastrointestinal side effects compared with the control scone. The results from this study demonstrate that a ready-to-eat baked-good, such as a scone, can be formulated with RS4 replacing refined wheat flour to yield statistically significant and clinically meaningful reductions in blood glucose and insulin excursions. This is the first study to report increased satiety after short-term RS4 intake, which warrants further investigation in long-term feeding studies.

  10. Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons.

    Science.gov (United States)

    Mounien, Lourdes; Marty, Nell; Tarussio, David; Metref, Salima; Genoux, David; Preitner, Frédéric; Foretz, Marc; Thorens, Bernard

    2010-06-01

    The physiological contribution of glucose in thermoregulation is not completely established nor whether this control may involve a regulation of the melanocortin pathway. Here, we assessed thermoregulation and leptin sensitivity of hypothalamic arcuate neurons in mice with inactivation of glucose transporter type 2 (Glut2)-dependent glucose sensing. Mice with inactivation of Glut2-dependent glucose sensors are cold intolerant and show increased susceptibility to food deprivation-induced torpor and abnormal hypothermic response to intracerebroventricular administration of 2-deoxy-d-glucose compared to control mice. This is associated with a defect in regulated expression of brown adipose tissue uncoupling protein I and iodothyronine deiodinase II and with a decreased leptin sensitivity of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons, as observed during the unfed-to-refed transition or following i.p. leptin injection. Sites of central Glut-2 expression were identified by a genetic tagging approach and revealed that glucose-sensitive neurons were present in the lateral hypothalamus, the dorsal vagal complex, and the basal medulla but not in the arcuate nucleus. NPY and POMC neurons were, however, connected to nerve terminals from Glut2-expressing neurons. Thus, our data suggest that glucose controls thermoregulation and the leptin sensitivity of NPY and POMC neurons through activation of Glut2-dependent glucose-sensing neurons located outside of the arcuate nucleus.

  11. Noninvasive glucose monitoring using saliva nano-biosensor

    Directory of Open Access Journals (Sweden)

    Wenjun Zhang

    2015-06-01

    Full Text Available Millions of people worldwide live with diabetes and several millions die from it each year. A noninvasive, painless method of glucose testing would highly improve compliance and glucose control while reducing complications and overall disease management costs. To provide accurate, low cost, and continuous glucose monitoring, we have developed a unique, disposable saliva nano-biosensor. More than eight clinical trials on real-time noninvasive salivary glucose monitoring were carried out on two healthy individuals (a 2–3 h-period for each trial, including both regular food and standard glucose beverage intake with more than 35 saliva samples obtained. Excellent clinical accuracy was revealed as compared to the UV Spectrophotometer. By measuring subjects’ salivary glucose and blood glucose in parallel, we found the two generated profiles share the same fluctuation trend but the correlation between them is individual dependent. There is a time lag between the peak glucose values from blood and from saliva. However, the correlation between the two glucose values at fasting is constant for each person enabling noninvasive diagnosis of diabetes through saliva instead of blood. Furthermore, a good correlation of glucose levels in saliva and in blood before and 2 h after glucose intake was observed. Glucose monitoring before and 2 h after meals is usually prescribed by doctors for diabetic patients. Thus, this disposable biosensor will be an alternative for real-time salivary glucose tracking at any time.

  12. USE OF A COMPUTER-GUIDED GLUCOSE MANAGEMENT SYSTEM TO IMPROVE GLYCEMIC CONTROL AND ADDRESS NATIONAL QUALITY MEASURES: A 7-YEAR, RETROSPECTIVE OBSERVATIONAL STUDY AT A TERTIARY CARE TEACHING HOSPITAL.

    Science.gov (United States)

    Tanenberg, Robert J; Hardee, Sandra; Rothermel, Caitlin; Drake, Almond J

    2017-03-01

    Inpatient hyperglycemia, hypoglycemia, and glucose variability are associated with increased mortality. The use of an electronic glucose management system (eGMS) to guide intravenous (IV) insulin infusion has been found to significantly improve blood glucose (BG) control. This retrospective observational study evaluated the 7-year (January 2009-December 2015) impact of the EndoTool ® eGMS in intensive and intermediate units at Vidant Medical Center, a 900-bed tertiary teaching hospital. Patients assigned to eGMS had indications for IV insulin infusion, including uncontrolled diabetes, stress hyperglycemia, and/or postoperative BG levels >140 mg/dL. This study evaluated time required to achieve BG control (180 mg/dL after control attained); and the impact of eGMS on hospital-acquired condition (HAC)-8 rates. Data were available for all treated patients (492,078 BG readings from 16,850 patients). With eGMS, BG levels were brought to target within 1.5 to 2.3 hours (4.5 to 4.8 hours for cardiovascular patients). Minimal hypoglycemia was observed (BG values 180 mg/dL once control was attained). HAC-8 rates were reduced from 0.083 per 1,000 patients (2008) to 0.032 per 1,000 patients (2011). The use of eGMS resulted in rapid, effective control of inpatient BG levels, including significantly reduced hypoglycemia rates. BG = blood glucose CMS = Centers for Medicare and Medicaid Services CV = coefficient of variation CV% = coefficient of variation percentage eGMS = electronic glucose management system GV = glycemic variability HAC = Hospital-Acquired Condition ICU = intensive care unit IU = intermediate unit IV = intravenous LOS = length of stay VMC = Vidant Medical Center.

  13. Pro-aging effects of glucose signaling through a G protein-coupled glucose receptor in fission yeast.

    Directory of Open Access Journals (Sweden)

    Antoine E Roux

    2009-03-01

    Full Text Available Glucose is the preferred carbon and energy source in prokaryotes, unicellular eukaryotes, and metazoans. However, excess of glucose has been associated with several diseases, including diabetes and the less understood process of aging. On the contrary, limiting glucose (i.e., calorie restriction slows aging and age-related diseases in most species. Understanding the mechanism by which glucose limits life span is therefore important for any attempt to control aging and age-related diseases. Here, we use the yeast Schizosaccharomyces pombe as a model to study the regulation of chronological life span by glucose. Growth of S. pombe at a reduced concentration of glucose increased life span and oxidative stress resistance as reported before for many other organisms. Surprisingly, loss of the Git3 glucose receptor, a G protein-coupled receptor, also increased life span in conditions where glucose consumption was not affected. These results suggest a role for glucose-signaling pathways in life span regulation. In agreement, constitutive activation of the Galpha subunit acting downstream of Git3 accelerated aging in S. pombe and inhibited the effects of calorie restriction. A similar pro-aging effect of glucose was documented in mutants of hexokinase, which cannot metabolize glucose and, therefore, are exposed to constitutive glucose signaling. The pro-aging effect of glucose signaling on life span correlated with an increase in reactive oxygen species and a decrease in oxidative stress resistance and respiration rate. Likewise, the anti-aging effect of both calorie restriction and the Deltagit3 mutation was accompanied by increased respiration and lower reactive oxygen species production. Altogether, our data suggest an important role for glucose signaling through the Git3/PKA pathway to regulate S. pombe life span.

  14. Age-related memory impairments due to reduced blood glucose responses to epinephrine.

    Science.gov (United States)

    Morris, Ken A; Chang, Qing; Mohler, Eric G; Gold, Paul E

    2010-12-01

    Increases in blood glucose levels are an important component of the mechanisms by which epinephrine enhances memory formation. The present experiments addressed the hypothesis that a dysfunction in the blood glucose response to circulating epinephrine contributes to age-related memory impairments. Doses of epinephrine and glucagon that significantly increased blood glucose levels in young adult rats were far less effective at doing so in 2-year-old rats. In young rats, epinephrine and glucose were about equally effective in enhancing memory and in prolonging post-training release of acetylcholine in the hippocampus. However, glucose was more effective than epinephrine in enhancing both memory and acetylcholine release in aged rats. These results suggest that an uncoupling between circulating epinephrine and glucose levels in old rats may lead to an age-related reduction in the provision of glucose to the brain during training. This in turn may contribute to age-related changes in memory and neural plasticity. Copyright © 2008 Elsevier Inc. All rights reserved.

  15. First Clinical Experience with Retrospective Flash Glucose Monitoring (FGM) Analysis in South Africa: Characterizing Glycemic Control with Ambulatory Glucose Profile.

    Science.gov (United States)

    Distiller, Larry A; Cranston, Iain; Mazze, Roger

    2016-11-01

    In 2014, an innovative blinded continuous glucose monitoring system was introduced with automated ambulatory glucose profile (AGP) reporting. The clinical use and interpretation of this new technology has not previously been described. Therefore we wanted to understand its use in characterizing key factors related to glycemic control: glucose exposure, variability, and stability, and risk of hypoglycemia in clinical practice. Clinicians representing affiliated diabetes centers throughout South Africa were trained and subsequently were given flash glucose monitoring readers and 2-week glucose sensors to use at their discretion. After patient use, sensor data were collected and uploaded for AGP reporting. Complete data (sensor AGP with corresponding clinical information) were obtained for 50 patients with type 1 (70%) and type 2 diabetes (30%), irrespective of therapy. Aggregated analysis of AGP data comparing patients with type 1 versus type 2 diabetes, revealed that despite similar HbA1c values between both groups (8.4 ± 2 vs 8.6 ± 1.7%, respectively), those with type 2 diabetes had lower mean glucose levels (9.2 ± 3 vs 10.3 mmol/l [166 ± 54 vs 185 mg/dl]) and lower indices of glucose variability (3.0 ± 1.5 vs 5.0 ± 1.9 mmol/l [54 ± 27 vs 90 ± 34.2 mg/dl]). This highlights key areas for future focus. Using AGP, the characteristics of glucose exposure, variability, stability, and hypoglycemia risk and occurrence were obtained within a short time and with minimal provider and patient input. In a survey at the time of the follow-up visit, clinicians indicated that aggregated AGP data analysis provided important new clinical information and insights. © 2016 Diabetes Technology Society.

  16. Dietary fructose and glucose differentially affect lipid and glucose homeostasis.

    Science.gov (United States)

    Schaefer, Ernst J; Gleason, Joi A; Dansinger, Michael L

    2009-06-01

    Absorbed glucose and fructose differ in that glucose largely escapes first-pass removal by the liver, whereas fructose does not, resulting in different metabolic effects of these 2 monosaccharides. In short-term controlled feeding studies, dietary fructose significantly increases postprandial triglyceride (TG) levels and has little effect on serum glucose concentrations, whereas dietary glucose has the opposite effects. When dietary glucose and fructose have been directly compared at approximately 20-25% of energy over a 4- to 6-wk period, dietary fructose caused significant increases in fasting TG and LDL cholesterol concentrations, whereas dietary glucose did not, but dietary glucose did increase serum glucose and insulin concentrations in the postprandial state whereas dietary fructose did not. When fructose at 30-60 g ( approximately 4-12% of energy) was added to the diet in the free-living state, there were no significant effects on lipid or glucose biomarkers. Sucrose and high-fructose corn syrup (HFCS) contain approximately equal amounts of fructose and glucose and no metabolic differences between them have been noted. Controlled feeding studies at more physiologic dietary intakes of fructose and glucose need to be conducted. In our view, to decrease the current high prevalence of obesity, dyslipidemia, insulin resistance, and diabetes, the focus should be on restricting the intake of excess energy, sucrose, HFCS, and animal and trans fats and increasing exercise and the intake of vegetables, vegetable oils, fish, fruit, whole grains, and fiber.

  17. Optimal blood glucose level control using dynamic programming based on minimal Bergman model

    Science.gov (United States)

    Rettian Anggita Sari, Maria; Hartono

    2018-03-01

    The purpose of this article is to simulate the glucose dynamic and the insulin kinetic of diabetic patient. The model used in this research is a non-linear Minimal Bergman model. Optimal control theory is then applied to formulate the problem in order to determine the optimal dose of insulin in the treatment of diabetes mellitus such that the glucose level is in the normal range for some specific time range. The optimization problem is solved using dynamic programming. The result shows that dynamic programming is quite reliable to represent the interaction between glucose and insulin levels in diabetes mellitus patient.

  18. Glucokinase, the pancreatic glucose sensor, is not the gut glucose sensor

    DEFF Research Database (Denmark)

    Murphy, R; Tura, A; Clark, P M

    2008-01-01

    AIMS/HYPOTHESIS: The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic peptide (GIP) are released from intestinal endocrine cells in response to luminal glucose. Glucokinase is present in these cells and has been proposed as a glucose sensor. The physiological...... role of glucokinase can be tested using individuals with heterozygous glucokinase gene (GCK) mutations. If glucokinase is the gut glucose sensor, GLP-1 and GIP secretion during a 75 g OGTT would be lower in GCK mutation carriers compared with controls. METHODS: We compared GLP-1 and GIP concentrations...... measured at five time-points during a 75 g OGTT in 49 participants having GCK mutations with those of 28 familial controls. Mathematical modelling of glucose, insulin and C-peptide was used to estimate basal insulin secretion rate (BSR), total insulin secretion (TIS), beta cell glucose sensitivity...

  19. Higher glucose levels associated with lower memory and reduced hippocampal microstructure.

    Science.gov (United States)

    Kerti, Lucia; Witte, A Veronica; Winkler, Angela; Grittner, Ulrike; Rujescu, Dan; Flöel, Agnes

    2013-11-12

    For this cross-sectional study, we aimed to elucidate whether higher glycosylated hemoglobin (HbA1c) and glucose levels exert a negative impact on memory performance and hippocampal volume and microstructure in a cohort of healthy, older, nondiabetic individuals without dementia. In 141 individuals (72 women, mean age 63.1 years ± 6.9 SD), memory was tested using the Rey Auditory Verbal Learning Test. Peripheral levels of fasting HbA1c, glucose, and insulin and 3-tesla MRI scans were acquired to assess hippocampal volume and microstructure, as indicated by gray matter barrier density. Linear regression and simple mediation models were calculated to examine associations among memory, glucose metabolism, and hippocampal parameters. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Moreover, mediation analyses indicated that beneficial effects of lower HbA1c on memory are in part mediated by hippocampal volume and microstructure. Our results indicate that even in the absence of manifest type 2 diabetes mellitus or impaired glucose tolerance, chronically higher blood glucose levels exert a negative influence on cognition, possibly mediated by structural changes in learning-relevant brain areas. Therefore, strategies aimed at lowering glucose levels even in the normal range may beneficially influence cognition in the older population, a hypothesis to be examined in future interventional trials.

  20. Layer-by-layer assembly of functionalized reduced graphene oxide for direct electrochemistry and glucose detection.

    Science.gov (United States)

    Mascagni, Daniela Branco Tavares; Miyazaki, Celina Massumi; da Cruz, Nilson Cristino; de Moraes, Marli Leite; Riul, Antonio; Ferreira, Marystela

    2016-11-01

    We report an electrochemical glucose biosensor made with layer-by-layer (LbL) films of functionalized reduced graphene oxide (rGO) and glucose oxidase (GOx). The LbL assembly using positively and negatively charged rGO multilayers represents a simple approach to develop enzymatic biosensors. The electron transport properties of graphene were combined with the specificity provided by the enzyme. rGO was obtained and functionalized using chemical methods, being positively charged with poly(diallyldimethylammonium chloride) to form GPDDA, and negatively charged with poly(styrene sulfonate) to form GPSS. Stable aqueous dispersions of GPDDA and GPSS are easily obtained, enabling the growth of LbL films on various solid supports. The use of graphene in the immobilization of GOx promoted Direct Electron Transfer, which was evaluated by Cyclic Voltammetry. Amperometric measurements indicated a detection limit of 13.4μmol·L(-1) and sensitivity of 2.47μA·cm(-2)·mmol(-1)·L for glucose with the (GPDDA/GPSS)1/(GPDDA/GOx)2 architecture, whose thickness was 19.80±0.28nm, as determined by Surface Plasmon Resonance (SPR). The sensor may be useful for clinical analysis since glucose could be detected even in the presence of typical interfering agents and in real samples of a lactose-free milk and an electrolyte solution to prevent dehydration. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Brain glucose content in fetuses of ethanol-fed rats

    Energy Technology Data Exchange (ETDEWEB)

    Pullen, G.; Singh, S.P.; Snyder, A.K.; Hoffen, B.

    1986-03-01

    The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4 and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.

  2. A Controlled Trial of CPAP Therapy on Metabolic Control in Individuals with Impaired Glucose Tolerance and Sleep Apnea

    Science.gov (United States)

    Weinstock, Tanya G.; Wang, Xuelei; Rueschman, Michael; Ismail-Beigi, Faramarz; Aylor, Joan; Babineau, Denise C.; Mehra, Reena; Redline, Susan

    2012-01-01

    Study Objectives: To address whether treatment of sleep apnea improves glucose tolerance. Design: Randomized, double-blind crossover study. Setting: Sleep clinic referrals. Patients: 50 subjects with moderate to severe sleep apnea (AHI > 15) and impaired glucose tolerance. Interventions: Subjects were randomized to 8 weeks of CPAP or sham CPAP, followed by the alternate therapy after a one-month washout. After each treatment, subjects underwent 2-hour OGTT, polysomnography, actigraphy, and measurements of indices of glucose control. Measurements and Results: The primary outcome was normalization of the mean 2-h OGTT; a secondary outcome was improvement in the Insulin Sensitivity Index (ISI (0,120). Subjects were 42% men, mean age of 54 (10), BMI of 39 (8), and AHI of 44 (27). Baseline fasting glucose was 104 (12), and mean 2-h OGTT was 110 (57) mg/dL. Seven subjects normalized their mean 2-h OGTT after CPAP but not after sham CPAP, while 5 subjects normalized after sham CPAP but not after CPAP. Overall, there was no improvement in ISI (0,120) between CPAP and sham CPAP (3.6%; 95% CI: [-2.2%, 9.7%]; P = 0.22). However, in those subjects with baseline AHI ≥ 30 (n = 25), there was a 13.3% (95% CI: [5.2%, 22.1%]; P CPAP compared to sham CPAP. Conclusions: This study did not show that IGT normalizes after CPAP in subjects with moderate sleep apnea and obesity. However, insulin sensitivity improved in those with AHI ≥ 30, suggesting beneficial metabolic effects of CPAP in severe sleep apnea. Clinical Trials Information: ClinicalTrials.gov Identifier: NCT01385995. Citation: Weinstock TG; Wang X; Rueschman M; Ismail-Beigi F; Aylor J; Babineau DC; Mehra R; Redline S. A controlled trial of CPAP therapy on metabolic control in individuals with impaired glucose tolerance and sleep apnea. SLEEP 2012;35(5):617-625. PMID:22547887

  3. A Novel EPO Receptor Agonist Improves Glucose Tolerance via Glucose Uptake in Skeletal Muscle in a Mouse Model of Diabetes

    Directory of Open Access Journals (Sweden)

    Michael S. Scully

    2011-01-01

    Full Text Available Patients treated with recombinant human Epo demonstrate an improvement in insulin sensitivity. We aimed to investigate whether CNTO 530, a novel Epo receptor agonist, could affect glucose tolerance and insulin sensitivity. A single administration of CNTO 530 significantly and dose-dependently reduced the area under the curve in a glucose tolerance test in diet-induced obese and diabetic mice after 14, 21, and 28 days. HOMA analysis suggested an improvement in insulin sensitivity, and this effect was confirmed by a hyperinsulinemic-euglycemic clamp. Uptake of 14C-2-deoxy-D-glucose indicated that animals dosed with CNTO 530 transported more glucose into skeletal muscle and heart relative to control animals. In conclusion, CNTO530 has a profound effect on glucose tolerance in insulin-resistant rodents likely because of improving peripheral insulin sensitivity. This effect was observed with epoetin-α and darbepoetin-α, suggesting this is a class effect, but the effect with these compounds relative to CNTO530 was decreased in duration and magnitude.

  4. Dysregulation of glucose metabolism even in Chinese PCOS women with normal glucose tolerance.

    Science.gov (United States)

    Li, Weiping; Li, Qifu

    2012-01-01

    To clarify the necessity of improving glucose metabolism in polycystic ovary syndrome (PCOS) women as early as possible, 111 PCOS women with normal glucose tolerance and 92 healthy age-matched controls were recruited to investigate glucose levels distribution, insulin sensitivity and β cell function. 91 PCOS women and 33 controls underwent hyperinsulinemic-euglycemic clamp to assess their insulin sensitivity, which was expressed as M value. β cell function was estimated by homeostatic model assessment (HOMA)-β index after adjusting insulin sensitivity (HOMA-βad index). Compared with lean controls, lean PCOS women had similar fasting plasma glucose (FPG), higher postprandial plasma glucose (PPG) (6.03±1.05 vs. 5.44±0.97 mmol/L, PPCOS women had higher levels of both FPG (5.24±0.58 vs. 4.90±0.39, PPCOS women separately, and the cutoff of BMI indicating impaired β cell function of PCOS women was 25.545kg/m². In conclusion, insulin resistance and dysregulation of glucose metabolism were common in Chinese PCOS women with normal glucose tolerance. BMI ≥ 25.545kg/m² indicated impaired β cell function in PCOS women with normal glucose tolerance.

  5. Factors Affecting Accuracy and Time Requirements of a Glucose Oxidase-Peroxidase Assay for Determination of Glucose

    Science.gov (United States)

    Accurate and rapid assays for glucose are desirable for analysis of glucose and starch in food and feedstuffs. An established colorimetric glucose oxidase-peroxidase method for glucose was modified to reduce analysis time, and evaluated for factors that affected accuracy. Time required to perform t...

  6. Optical detection of glucose and glycated hemoglobin using etched fiber Bragg gratings coated with functionalized reduced graphene oxide.

    Science.gov (United States)

    Sridevi, S; Vasu, K S; Sampath, S; Asokan, S; Sood, A K

    2016-07-01

    An enhanced optical detection of D-glucose and glycated hemoglobin (HbA1c ) has been established in this study using etched fiber Bragg gratings (eFBG) coated with aminophenylboronic acid (APBA)-functionalized reduced graphene oxide (RGO). The read out, namely the shift in Bragg wavelength (ΔλB ) is highly sensitive to changes that occur due to the adsorption of glucose (or HbA1c ) molecules on the eFBG sensor coated with APBA-RGO complex through a five-membered cyclic ester bond formation between glucose and APBA molecules. A limit of detection of 1 nM is achieved with a linear range of detection from 1 nM to 10 mM in the case of D-glucose detection experiments. For HbA1c , a linear range of detection varying from 86 nM to 0.23 mM is achieved. The observation of only 4 pm (picometer) change in ΔλB even for the 10 mM lactose solution confirms the specificity of the APBA-RGO complex coated eFBG sensors to glucose molecules. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. AJS1669, a novel small-molecule muscle glycogen synthase activator, improves glucose metabolism and reduces body fat mass in mice

    Science.gov (United States)

    Nakano, Kazuhiro; Takeshita, Sen; Kawasaki, Noriko; Miyanaga, Wataru; Okamatsu, Yoriko; Dohi, Mizuki; Nakagawa, Tadakiyo

    2017-01-01

    Impaired glycogen synthesis and turnover are common in insulin resistance and type 2 diabetes. As glycogen synthase (GS) is a key enzyme involved in the synthetic process, it presents a promising therapeutic target for the treatment of type 2 diabetes. In the present study, we identified a novel, potent and orally available GS activator AJS1669 {sodium 2-[[5-[[4-(4,5-difluoro-2-methylsulfanyl-phenyl) phenoxy] methyl]furan-2-carbonyl]-(2-furylmethyl)amino] acetate}. In vitro, we performed a glycogen synthase 1 (GYS1) activation assay for screening GS activators and identified that the activity of AJS1669 was further potentiated in the presence of glucose-6-phosphate (G6P). In vivo, we used ob/ob mice to evaluate the novel anti-diabetic effects of AJS1669 by measuring basal blood glucose levels, glucose tolerance and body fat mass index. Repeated administration of AJS1669 over 4 weeks reduced blood glucose and hemoglobin A1c (HbA1c) levels in ob/ob mice. AJS1669 also improved glucose tolerance in a dose-dependent manner, and decreased body fat mass. The mRNA levels of genes involved in mitochondrial fatty acid oxidation and mitochondrial biogenesis were elevated in skeletal muscle tissue following AJS1669 treatment. Hepatic tissue of treated mice also exhibited elevated expression of genes associated with fatty acid oxidation. In contrast to ob/ob mice, in C57Bl/6 mice AJS1669 administration did not alter body weight or reduce glucose levels. These results demonstrate that pharmacological agents that activate GYS1, the main GS subtype found in skeletal muscle, have potential for use as novel treatments for diabetes that improve glucose metabolism in skeletal muscle. PMID:28290602

  8. Developmental, gustatory, and behavioral responses of leafroller larvae, Choristoneura rosaceana, to tannic acid and glucose.

    Science.gov (United States)

    Panzuto, M; Mauffette, Y; Alber, P J

    2002-01-01

    Soluble sugars are essential nutrients generally perceived as phagostimulants to most insects studied. However, tannins are known as digestibility reducers, hence deleterious to caterpillar development, and as deterrents as well. Previous work demonstrated that larvae of the polyphagous oblique-banded leafroller, Choristoneura rosaceana, performed better when reared on a control + 0.5% tannic acid diet than on the standard control diet and that larvae reared on a control + 5% glucose diet had slower development and reduced survival. This study was designed to elucidate the behavioral and neurophysiological components of the larval responses to tannic acid and glucose. C. rosaceana larvae were reared individually from the first to the sixth instar on one of four different artificial diets: (1) control; (2) control + 5% glucose; (3) control + 0.5% tannic acid; (4) control + 5% glucose + 0.5% tannic acid. After 14 days, larvae reared on the control + 5% glucose diet had not developed past the fourth instar, whereas a considerable proportion of larvae reared on the control + 0.5% tannic acid diet had already attained the pupal stage. Insects reared on the control or the control + 5% glucose + 0.5% tannic acid diet had intermediate development. with most larvae in the fifth instar. In addition, once the mid-sixth instar was reached, the feeding preferences to 25 and 300 mM glucose, 25 mM tannic acid, and 25 mM glucose + 25 mM tannic acid over water were assessed in two-choice tests. Feeding affected preference. Control-reared insects preferred feeding on treatments containing glucose and were not deterred by tannic acid. However, larvae that had been exposed to tannic acid during their development were deterred by tannic acid and their glucose discrimination was impaired. The sensitivity to glucose was also examined from neurophysiological recordings by stimulating the sugar-sensitive cell (cell 1) on the lateral styloconic sensillum of the maxillary galea with

  9. Knowledge, attitude and practice of exercise for plasma blood glucose control among patients with type-2 diabetes.

    Science.gov (United States)

    Awotidebe, Taofeek O; Adedoyin, Rufus A; Afolabi, Mubaraq A; Opiyo, Rose

    2016-01-01

    Exercise plays significant role in the health outcomes of patients with diabetes, however, little is known about patients' knowledge of exercise for plasma blood glucose control among patients with type-2 diabetes (T2D). This study investigated knowledge, attitude and practice (KAP) of exercise for plasma blood glucose control among patients with T2D. This cross-sectional study recruited 299 patients with T2D (male=105; female=194) from selected government hospitals in Osun State, Nigeria using purposive sampling technique. Validated questionnaires were used to assess of exercise for plasma blood glucose control and socioeconomic status (SES) of the patients. Data were analysed using descriptive and inferential statistics. Alpha level was set at exercise whilst 269(90.0%) had negative attitude to exercise practice. Less than a third, 82(27.4%) engaged in exercise practice for plasma blood glucose control. There was significant association between knowledge and practice of exercise ((2)=12.535; p=0.002). Furthermore, significant associations were found between knowledge and gender ((2)=11.453; p=0.003), and socioeconomic status ((2)=29.127, p=0.001) but not associated with attitude towards exercise (p>0.05). Patients with demonstrated good knowledge of exercise for plasma blood glucose control but reported negative attitude and poor practice of exercise. Copyright © 2016. Published by Elsevier Ltd.

  10. Sleep Control, GPCRs, and Glucose Metabolism.

    Science.gov (United States)

    Tsuneki, Hiroshi; Sasaoka, Toshiyasu; Sakurai, Takeshi

    2016-09-01

    Modern lifestyles prolong daily activities into the nighttime, disrupting circadian rhythms, which may cause sleep disturbances. Sleep disturbances have been implicated in the dysregulation of blood glucose levels and reported to increase the risk of type 2 diabetes (T2D) and diabetic complications. Sleep disorders are treated using anti-insomnia drugs that target ionotropic and G protein-coupled receptors (GPCRs), including γ-aminobutyric acid (GABA) agonists, melatonin agonists, and orexin receptor antagonists. A deeper understanding of the effects of these medications on glucose metabolism and their underlying mechanisms of action is crucial for the treatment of diabetic patients with sleep disorders. In this review we focus on the beneficial impact of sleep on glucose metabolism and suggest a possible strategy for therapeutic intervention against sleep-related metabolic disorders. Copyright © 2016. Published by Elsevier Ltd.

  11. Reduced viscosity Barley β-Glucan versus placebo: a randomized controlled trial of the effects on insulin sensitivity for individuals at risk for diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Schmelzer Wade

    2011-08-01

    Full Text Available Abstract Background Prior studies suggest soluble fibers may favorably affect glucose/insulin metabolism. Methods This prospective, randomized, placebo controlled, double blind, parallel group trial evaluated 50 generally healthy subjects without prior diagnosis of diabetes mellitus (44 completers, who were administered beverages containing placebo (control, lower dose (3 g/d, or higher dose (6 g/d reduced viscosity barley β-glucan (BBG extract. Subjects (68% women mean age 56 years, Body Mass Index (BMI 32 kg/m2 and baseline fasting plasma glucose 102 mg/dl were instructed to follow a weight-maintaining Therapeutic Lifestyle Changes (TLC diet and consumed three 11 oz study beverages daily with meals for 12 weeks. The four primary study endpoint measures were plasma glucose and insulin [each fasting and post-Oral Glucose Tolerance Testing (OGTT]. Results Compared to placebo, administration of 3 g/d BBG over 12 weeks significantly reduced glucose incremental Area Under the Curve (iAUC measures during OGTT and 6 g/d BBG over 12 weeks significantly reduced fasting insulin as well as the related homeostasis model assessment of insulin resistance (HOMA-IR. Beverages were generally well tolerated with no serious adverse experiences and no significant differences between groups for adverse experiences. Per protocol instruction, subjects maintained body weight. Conclusions These findings suggest 6 g/d BBG consumed in a beverage over 12 weeks may improve insulin sensitivity among hyperglycemic individuals with no prior diagnosis of diabetes mellitus, and who experience no change in body weight. Trial Registration ClinicalTrials.gov Identifier: NCT01375803.

  12. Circadian control of the daily plasma glucose rhythm: an interplay of GABA and glutamate.

    Science.gov (United States)

    Kalsbeek, Andries; Foppen, Ewout; Schalij, Ingrid; Van Heijningen, Caroline; van der Vliet, Jan; Fliers, Eric; Buijs, Ruud M

    2008-09-15

    The mammalian biological clock, located in the hypothalamic suprachiasmatic nuclei (SCN), imposes its temporal structure on the organism via neural and endocrine outputs. To further investigate SCN control of the autonomic nervous system we focused in the present study on the daily rhythm in plasma glucose concentrations. The hypothalamic paraventricular nucleus (PVN) is an important target area of biological clock output and harbors the pre-autonomic neurons that control peripheral sympathetic and parasympathetic activity. Using local administration of GABA and glutamate receptor (ant)agonists in the PVN at different times of the light/dark-cycle we investigated whether daily changes in the activity of autonomic nervous system contribute to the control of plasma glucose and plasma insulin concentrations. Activation of neuronal activity in the PVN of non-feeding animals, either by administering a glutamatergic agonist or a GABAergic antagonist, induced hyperglycemia. The effect of the GABA-antagonist was time dependent, causing increased plasma glucose concentrations only when administered during the light period. The absence of a hyperglycemic effect of the GABA-antagonist in SCN-ablated animals provided further evidence for a daily change in GABAergic input from the SCN to the PVN. On the other hand, feeding-induced plasma glucose and insulin responses were suppressed by inhibition of PVN neuronal activity only during the dark period. These results indicate that the pre-autonomic neurons in the PVN are controlled by an interplay of inhibitory and excitatory inputs. Liver-dedicated sympathetic pre-autonomic neurons (responsible for hepatic glucose production) and pancreas-dedicated pre-autonomic parasympathetic neurons (responsible for insulin release) are controlled by inhibitory GABAergic contacts that are mainly active during the light period. Both sympathetic and parasympathetic pre-autonomic PVN neurons also receive excitatory inputs, either from the

  13. Glucose effectiveness in nondiabetic relatives

    DEFF Research Database (Denmark)

    Egede, M B; Henriksen, J-E; Durck, T T

    2014-01-01

    AIMS: Reduced glucose effectiveness is a predictor of future glucose tolerance in individuals with a family history of type 2 diabetes. We examined retrospectively at 10 years in normoglycemic relatives of diabetic subjects (RELs) the pathophysiological role of glucose effectiveness in the develo...

  14. Optimizing insulin injection technique and its effect on blood glucose control

    Directory of Open Access Journals (Sweden)

    Giorgio Grassi, MD

    2014-12-01

    Conclusions: Targeted individualized training in IT, including the switch to a 4 mm needle, is associated with improved glucose control, greater satisfaction with therapy, better and simpler injection practices and possibly lower consumption of insulin after only a three month period.

  15. miR-182 Regulates Metabolic Homeostasis by Modulating Glucose Utilization in Muscle

    Directory of Open Access Journals (Sweden)

    Duo Zhang

    2016-07-01

    Full Text Available Understanding the fiber-type specification and metabolic switch in skeletal muscle provides insights into energy metabolism in physiology and diseases. Here, we show that miR-182 is highly expressed in fast-twitch muscle and negatively correlates with blood glucose level. miR-182 knockout mice display muscle loss, fast-to-slow fiber-type switching, and impaired glucose metabolism. Mechanistic studies reveal that miR-182 modulates glucose utilization in muscle by targeting FoxO1 and PDK4, which control fuel selection via the pyruvate dehydrogenase complex (PDHC. Short-term high-fat diet (HFD feeding reduces muscle miR-182 levels by tumor necrosis factor α (TNFα, which contributes to the upregulation of FoxO1/PDK4. Restoration of miR-182 expression in HFD-fed mice induces a faster muscle phenotype, decreases muscle FoxO1/PDK4 levels, and improves glucose metabolism. Together, our work establishes miR-182 as a critical regulator that confers robust and precise controls on fuel usage and glucose homeostasis. Our study suggests that a metabolic shift toward a faster and more glycolytic phenotype is beneficial for glucose control.

  16. The Diabetes Assistant: A Smartphone-Based System for Real-Time Control of Blood Glucose

    Directory of Open Access Journals (Sweden)

    Patrick Keith-Hynes

    2014-11-01

    Full Text Available Type 1 Diabetes Mellitus (T1DM is an autoimmune disease in which the insulin-producing beta cells of the pancreas are destroyed and insulin must be injected daily to enable the body to metabolize glucose. Standard therapy for T1DM involves self-monitoring of blood glucose (SMBG several times daily with a blood glucose meter and injecting insulin via a syringe, pen or insulin pump. An “Artificial Pancreas” (AP is a closed-loop control system that uses a continuous glucose monitor (CGM, an insulin pump and an internal algorithm to automatically manage insulin infusion to keep the subject’s blood glucose within a desired range. Although no fully closed-loop AP systems are currently commercially available there are intense academic and commercial efforts to produce safe and effective AP systems. In this paper we present the Diabetes Assistant (DiAs, an ultraportable AP research platform designed to enable home studies of Closed Loop Control (CLC of blood glucose in subjects with Type 1 Diabetes Mellitus. DiAs consists of an Android (Google Inc., Mountain View, CA, USA smartphone equipped with communication, control and user interface software wirelessly connected to a continuous glucose monitor and insulin pump. The software consists of a network of mobile applications with well-defined Application Programming Interfaces (APIs running atop an enhanced version of Android with non-essential elements removed. CLC and safety applications receive real-time data from the CGM and pump, estimate the patient’s metabolic state and risk of hypo- and hyperglycemia, adjust the insulin infusion rate, raise alarms as needed and transmit de-identified data to a secure remote server. Some applications may be replaced by researchers wishing to conduct outpatient ambulatory studies of novel Closed Loop Control, Safety or User Interface modules. Over the past three years the DiAs platform has been used in a series of AP clinical trials sponsored by the National

  17. TCPTP Regulates Insulin Signalling in AgRP Neurons to Coordinate Glucose Metabolism with Feeding.

    Science.gov (United States)

    Dodd, Garron T; Lee-Young, Robert S; Brüning, Jens C; Tiganis, Tony

    2018-04-30

    Insulin regulates glucose metabolism by eliciting effects on peripheral tissues as well as the brain. Insulin receptor (IR) signalling inhibits AgRP-expressing neurons in the hypothalamus to contribute to the suppression of hepatic glucose production (HGP) by insulin, whereas AgRP neuronal activation attenuates brown adipose tissue (BAT) glucose uptake. The tyrosine phosphatase TCPTP suppresses IR signalling in AgRP neurons. Hypothalamic TCPTP is induced by fasting and degraded after feeding. Here we assessed the influence of TCPTP in AgRP neurons in the control of glucose metabolism. TCPTP deletion in AgRP neurons ( Agrp -Cre; Ptpn2 fl/fl ) enhanced insulin sensitivity as assessed by the increased glucose infusion rates and reduced HGP during hyperinsulinemic-euglycemic clamps, accompanied by increased [ 14 C]-2-deoxy-D-glucose uptake in BAT and browned white adipose tissue. TCPTP deficiency in AgRP neurons promoted the intracerebroventricular insulin-induced repression of hepatic gluconeogenesis in otherwise unresponsive food-restricted mice yet had no effect in fed/satiated mice where hypothalamic TCPTP levels are reduced. The improvement in glucose homeostasis in Agrp -Cre; Ptpn2 fl/fl mice was corrected by IR heterozygosity ( Agrp -Cre; Ptpn2 fl/fl ; Insr fl/+ ), causally linking the effects on glucose metabolism with the IR signalling in AgRP neurons. Our findings demonstrate that TCPTP controls IR signalling in AgRP neurons to coordinate HGP and brown/beige adipocyte glucose uptake in response to feeding/fasting. © 2018 by the American Diabetes Association.

  18. Impaired insulin-stimulated nonoxidative glucose metabolism in pancreas-kidney transplant recipients

    DEFF Research Database (Denmark)

    Christiansen, Erik; Vestergaard, Henrik; Tibell, Annika

    1996-01-01

    -response curve for glucose disposal rates (Rd) was shifted to the right in the Px and Kx groups, and the maximal glucose disposal rate was reduced by 40% in the Px group (11.7 +/- 1.1 mg.kg-1 fat-free mass.min-1) and 30% in the Kx group (13.9 +/- 1.2 mg.kg-1 fat-free mass.min-1) compared with that in control...

  19. Cerebral glucose utilization in pediatric neurological disorders determined by positron emission tomography

    International Nuclear Information System (INIS)

    Yanai, Kazuhiko; Tohoku Univ., Sendai; Iinuma, Kazuie; Miyabayashi, Shigeaki; Narisawa, Kuniaki; Tada, Keiya; Matsuzawa, Taiju; Tohoku Univ., Sendai; Ito, Masatoshi; Yamada, Kenji

    1987-01-01

    We measured local cerebral glucose utilization in 19 patients with Lennox-Gastaut syndrome (LG), partial seizures (PS), atypical and classical phenylketonuria (PKU), Leigh disease, and subacute sclerosing panencephalitis (SSPE), using positron emission tomography (PET). The mean values of regional glucose utilization in interictal scans of LG were significantly reduced in all brain regions when compared with that of PS (P<0.005). PET studies of glucose utilization in LG revealed more widespread hypometabolism than in PS. Two sibling with dihydropteridine reductase deficiency, a patient with classical PKU, and a boy with cytochrome c oxidase deficiency showed reduced glucose utilization in the caudate and putamen. A marked decrease in glucose utilization was found in the cortical gray matter of a patient with rapidly progressive SSPE, despite relatively preserved utilization in the caudate and putamen. The PET study of a patient with slowly progressive SSPE revealed patterns and values of glucose utilization similar to those of the control. Thus, PET provided a useful clue toward understanding brain dysfunction in LG, PS, PKU, Leigh disease, and SSPE. (orig.)

  20. Cerebral glucose utilization in pediatric neurological disorders determined by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yanai, Kazuhiko; Iinuma, Kazuie; Miyabayashi, Shigeaki; Narisawa, Kuniaki; Tada, Keiya; Matsuzawa, Taiju; Ito, Masatoshi; Yamada, Kenji

    1987-09-01

    We measured local cerebral glucose utilization in 19 patients with Lennox-Gastaut syndrome (LG), partial seizures (PS), atypical and classical phenylketonuria (PKU), Leigh disease, and subacute sclerosing panencephalitis (SSPE), using positron emission tomography (PET). The mean values of regional glucose utilization in interictal scans of LG were significantly reduced in all brain regions when compared with that of PS (P<0.005). PET studies of glucose utilization in LG revealed more widespread hypometabolism than in PS. Two sibling with dihydropteridine reductase deficiency, a patient with classical PKU, and a boy with cytochrome c oxidase deficiency showed reduced glucose utilization in the caudate and putamen. A marked decrease in glucose utilization was found in the cortical gray matter of a patient with rapidly progressive SSPE, despite relatively preserved utilization in the caudate and putamen. The PET study of a patient with slowly progressive SSPE revealed patterns and values of glucose utilization similar to those of the control. Thus, PET provided a useful clue toward understanding brain dysfunction in LG, PS, PKU, Leigh disease, and SSPE.

  1. Optimal blood glucose control in diabetes mellitus treatment using dynamic programming based on Ackerman’s linear model

    Science.gov (United States)

    Pradanti, Paskalia; Hartono

    2018-03-01

    Determination of insulin injection dose in diabetes mellitus treatment can be considered as an optimal control problem. This article is aimed to simulate optimal blood glucose control for patient with diabetes mellitus. The blood glucose regulation of diabetic patient is represented by Ackerman’s Linear Model. This problem is then solved using dynamic programming method. The desired blood glucose level is obtained by minimizing the performance index in Lagrange form. The results show that dynamic programming based on Ackerman’s Linear Model is quite good to solve the problem.

  2. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-05-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.

  3. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    International Nuclear Information System (INIS)

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-01-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions

  4. [Metabolic control in the critically ill patient an update: hyperglycemia, glucose variability hypoglycemia and relative hypoglycemia].

    Science.gov (United States)

    Pérez-Calatayud, Ángel Augusto; Guillén-Vidaña, Ariadna; Fraire-Félix, Irving Santiago; Anica-Malagón, Eduardo Daniel; Briones Garduño, Jesús Carlos; Carrillo-Esper, Raúl

    Metabolic changes of glucose in critically ill patients increase morbidity and mortality. The appropriate level of blood glucose has not been established so far and should be adjusted for different populations. However concepts such as glucose variability and relative hypoglycemia of critically ill patients are concepts that are changing management methods and achieving closer monitoring. The purpose of this review is to present new data about the management and metabolic control of patients in critical areas. Currently glucose can no longer be regarded as an innocent element in critical patients; both hyperglycemia and hypoglycemia increase morbidity and mortality of patients. Protocols and better instruments for continuous measurement are necessary to achieve the metabolic control of our patients. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  5. Glucose turnover, gluconeogenesis from glycerol, and estimation of net glucose cycling in cancer patients

    International Nuclear Information System (INIS)

    Lundholm, K.; Edstroem, S.; Karlberg, I.; Ekman, L.; Schersten, T.

    1982-01-01

    A double isotope method was used in patients with progressive malignancy and in control patients to measure: glucose turnover, conversion rate of carbon skeleton of glycerol into glucose, and the interorgan cycling of glucose carbons (Cori-cycle plus alanine-glucose cycle). [U- 14 C]glycerol and [6- 3 H]glucose were given intravenously as a single dose injection. The time course of the specific radioactivities of [6- 3 H] and [U- 14 C]glucose was followed in blood. The pool size and the turnover rate of glucose were increased in the cancer group as compared with the control patients. The net recycling of glucose carbons was not increased in the cancer group, despite the increased turnover of glucose. The alterations in the metabolism of glucose did not correlate with the plasma levels of insulin or thyroid hormones (T4, T3, rT3) neither in the entire cancer group nor in those cancer patients who were repeatedly investigated at different intervals of time. The turnover rate of glucose in the cancer patients correlated inversely to their body weight index. The gluconeogenesis rate, given as the fractional conversion rate of the injected radioactive dose of [ 14 C]glycerol, or as mol glucose . kg body weight-1 . day-1, was increased in the cancer group, but still contributed only 3% of the glucose turnover rate in both cancer and control patients. We conclude that an increased gluconeogenesis from glycerol is not significant in terms of energy expenditure in patients with progressive malignancy, as has previously been concluded for the gluconeogenesis from alanine. It seems that increased turnover of glucose may contribute to inappropriately high energy expenditure in cancer patients

  6. Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Cedric Cortijo

    2012-12-01

    Full Text Available Planar cell polarity (PCP refers to the collective orientation of cells within the epithelial plane. We show that progenitor cells forming the ducts of the embryonic pancreas express PCP proteins and exhibit an active PCP pathway. Planar polarity proteins are acquired at embryonic day 11.5 synchronously to apicobasal polarization of pancreas progenitors. Loss of function of the two PCP core components Celsr2 and Celsr3 shows that they control the differentiation of endocrine cells from polarized progenitors, with a prevalent effect on insulin-producing beta cells. This results in a decreased glucose clearance. Loss of Celsr2 and 3 leads to a reduction of Jun phosphorylation in progenitors, which, in turn, reduces beta cell differentiation from endocrine progenitors. These results highlight the importance of the PCP pathway in cell differentiation in vertebrates. In addition, they reveal that tridimensional organization and collective communication of cells are needed in the pancreatic epithelium in order to generate appropriate numbers of endocrine cells.

  7. Effect of adding the novel fiber, PGX®, to commonly consumed foods on glycemic response, glycemic index and GRIP: a simple and effective strategy for reducing post prandial blood glucose levels - a randomized, controlled trial

    Directory of Open Access Journals (Sweden)

    Lyon Michael

    2010-11-01

    Full Text Available Abstract Background Reductions in postprandial glycemia have been demonstrated previously with the addition of the novel viscous polysaccharide (NVP, PolyGlycopleX® (PGX®, to an OGTT or white bread. This study explores whether these reductions are sustained when NVP is added to a range of commonly consumed foods or incorporated into a breakfast cereal. Methods Ten healthy subjects (4M, 6F; age 37.3 ± 3.6 y; BMI 23.8 ± 1.3 kg/m2, participated in an acute, randomized controlled trial. The glycemic response to cornflakes, rice, yogurt, and a frozen dinner with and without 5 g of NVP sprinkled onto the food was determined. In addition, 3 granolas with different levels of NVP and 3 control white breads and one white bread and milk were also consumed. All meals contained 50 g of available carbohydrate. Capillary blood samples were taken fasting and at 15, 30, 45, 60, 90 and 120 min after the start of the meal. The glycemic index (GI and the glycemic reduction index potential (GRIP were calculated. The blood glucose concentrations at each time and the iAUC values were subjected to repeated-measures analysis of variance (ANOVA examining for the effect of test meal. After demonstration of significant heterogeneity, differences between individual means was assessed using GLM ANOVA with Tukey test to adjust for multiple comparisons. Results Addition of NVP reduced blood glucose response irrespective of food or dose (p Conclusion Sprinkling or incorporation of NVP into a variety of different foods is highly effective in reducing postprandial glycemia and lowering the GI of a food. Clinical Trial registration NCT00935350.

  8. Comparison of the effects on insulin resistance and glucose tolerance of 6-mo high-monounsaturated-fat, low-fat, and control diets

    DEFF Research Database (Denmark)

    Due, Anette; Larsen, Thomas M; Hermansen, Kjeld

    2008-01-01

    and after the 6-mo dietary intervention. All foods were provided by a purpose-built supermarket. RESULTS: After 6 mo, the MUFA diet reduced fasting glucose (-3.0%), insulin (-9.4%), and the homeostasis model assessment of insulin resistance score (-12.1%). Compared with the MUFA diet, the control diet......BACKGROUND: The effect of dietary fat and carbohydrate on glucose metabolism has been debated for decades. OBJECTIVE: The objective was to compare the effect of 3 ad libitum diets, different in type and amount of fat and carbohydrate, on insulin resistance and glucose tolerance subsequent to weight...... loss. DESIGN: Forty-six nondiabetic, obese [mean (+/-SEM) body mass index (in kg/m(2)): 31.2 +/- 0.3] men (n = 20) and premenopausal women (n = 26) aged 28.0 +/- 0.7 y were randomly assigned to 1 of 3 diets after > or = 8% weight loss: 1) MUFA diet (n = 16): moderate in fat (35-45% of energy) and high...

  9. Effects of self-monitoring of blood glucose on diabetes control in a ...

    African Journals Online (AJOL)

    Methods:This study assessed the effect on diabetes control in patients who received glucometers and education ... Self-monitoring of blood glucose (SMBG) helps patients make ..... unhealthy eating habits could possibly be related to the low.

  10. Parathyroidectomy Ameliorates Glucose and Blood Pressure Control in a Patient with Primary Hyperparathyroidism, Type 2 Diabetes, and Hypertension

    Directory of Open Access Journals (Sweden)

    Alok Kumar

    2015-01-01

    Full Text Available Effect of parathyroidectomy on glucose control and hypertension is controversial. Here, we report a case of a patient with primary hyperparathyroidism, type 2 diabetes mellitus, and hypertension in whom parathyroidectomy ameliorated both glucose control and blood pressure. Once high serum calcium levels were noticed, ultrasonography of neck confirmed a well-defined oval hypoechoic mass posterior to the right lobe of the thyroid, confirmed by scintiscan. Parathyroidectomy resulted in improvement of blood pressure and blood glucose. We could stop insulin and antihypertensive medications. We conclude that in patients with type 2 diabetes with vague complaints like fatigue, body ache, and refractory hypertension, as a part of the diagnostic workup, clinicians should also check serum calcium levels and parathyroid hormone to rule out hyperparathyroidism. Correction of hyperparathyroidism may result in improvement of hypertension and glucose control.

  11. Evaluation of salivary glucose, IgA and flow rate in diabetic patients: a case-control study.

    Science.gov (United States)

    Bakianian Vaziri, P; Vahedi, M; Mortazavi, H; Abdollahzadeh, Sh; Hajilooi, M

    2010-01-01

    An association between diabetes mellitus and alterations in the oral cavity has been noted. In this study, we evaluated differences between salivary IgA, glucose and flow rate in diabetic patients compared with healthy controls. Forty patients with type 1 diabetes, 40 patients with type 2 diabetes and 40 healthy controls were selected. Whole unstimulated saliva samples were collected by the standard method and the salivary flow rate was determined. Nephelometric and Pars method were used to measure salivary IgA and salivary glucose concentrations, respectively. Statistical analysis was performed by Chi-square and t test. There were no significant differences in salivary IgA and glucose concentrations between type 1 and type 2 diabetic patients and their matched control subjects (P>0.05). Salivary flow rate was significantly lower in diabetic patients (Pdiabetic patients than the controls. Determination of salivary constituents may be useful in the description and management of oral findings in diabetic patients.

  12. Model-based closed-loop glucose control in type 1 diabetes

    DEFF Research Database (Denmark)

    Schmidt, Signe; Boiroux, Dimitri; Duun-Henriksen, Anne Katrine

    2013-01-01

    To improve type 1 diabetes mellitus (T1DM) management, we developed a model predictive control (MPC) algorithm for closed-loop (CL) glucose control based on a linear second-order deterministic-stochastic model. The deterministic part of the model is specified by three patient-specific parameters......: insulin sensitivity factor, insulin action time, and basal insulin infusion rate. The stochastic part is identical for all patients but identified from data from a single patient. Results of the first clinical feasibility test of the algorithm are presented....

  13. Systematic review of randomised controlled trials of the effects of caffeine or caffeinated drinks on blood glucose concentrations and insulin sensitivity in people with diabetes mellitus.

    Science.gov (United States)

    Whitehead, N; White, H

    2013-04-01

    Compounds other than macronutrients have been shown to influence blood glucose concentrations and insulin sensitivity in people with diabetes, with caffeine being one such substance. The present study systematically reviewed the evidence of the effects of caffeine on blood glucose concentrations and/or insulin sensitivity in people with diabetes. Four databases, including MEDLINE and EMBASE, were searched up to 1 February 2012. Randomised controlled trials (RCTs) investigating the effects of caffeine on blood glucose and/or insulin sensitivity in humans, diagnosed with type I, type II or gestational diabetes mellitus (GDM), were included. Quality assessment and data extraction were conducted and agreed by both authors. Of 253 articles retrieved, nine trials (134 participants) were identified. Trials in people with type II diabetes demonstrated that the ingestion of caffeine (approximately 200-500 mg) significantly increased blood glucose concentrations by 16-28% of the area under the curve (AUC) and insulin concentrations by 19-48% of the AUC when taken prior to a glucose load, at the same time as decreasing insulin sensitivity by 14-37%. In type I diabetes, trials indicated enhanced recognition and a reduced duration of hypoglycaemic episodes following ingestion of 400-500 mg caffeine, without altering glycated haemoglobin. In GDM, a single trial demonstrated that approximately 200 mg of caffeine induced a decrease in insulin sensitivity by 18% and a subsequent increase in blood glucose concentrations by 19% of the AUC. Evidence indicates a negative effect of caffeine intake on blood glucose control in individuals with type II diabetes, as replicated in a single trial in GDM. Larger-scale RCTs of longer duration are needed to determine the effects of timing and dose. Early indications of a reduced duration and an improved awareness of hypoglycaemia in type I diabetes require further confirmation. © 2013 The Authors Journal of Human Nutrition and Dietetics

  14. Involvement of the Niacin Receptor GPR109a in the LocalControl of Glucose Uptake in Small Intestine of Type 2Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Tung Po Wong

    2015-09-01

    Full Text Available Niacin is a popular nutritional supplement known to reduce the risk of cardiovascular diseases by enhancing high-density lipoprotein levels. Despite such health benefits, niacin impairs fasting blood glucose. In type 2 diabetes (T2DM, an increase in jejunal glucose transport has been well documented; however, this is intriguingly decreased during niacin deficient state. In this regard, the role of the niacin receptor GPR109a in T2DM jejunal glucose transport remains unknown. Therefore, the effects of diabetes and high-glucose conditions on GPR109a expression were studied using jejunal enterocytes of 10-week-old m+/db and db/db mice, as well as Caco-2 cells cultured in 5.6 or 25.2 mM glucose concentrations. Expression of the target genes and proteins were quantified using real-time polymerase chain reaction (RT-PCR and Western blotting. Glucose uptake in Caco-2 cells and everted mouse jejunum was measured using liquid scintillation counting. 10-week T2DM increased mRNA and protein expression levels of GPR109a in jejunum by 195.0% and 75.9%, respectively, as compared with the respective m+/db control; high-glucose concentrations increased mRNA and protein expression of GPR109a in Caco-2 cells by 130.2% and 69.0%, respectively, which was also confirmed by immunohistochemistry. In conclusion, the enhanced GPR109a expression in jejunal enterocytes of T2DM mice and high-glucose treated Caco-2 cells suggests that GPR109a is involved in elevating intestinal glucose transport observed in diabetes.

  15. Peculiarities of the Continuous Glucose Monitoring Data Stream and Their Impact on Developing Closed-Loop Control Technology

    OpenAIRE

    Kovatchev, Boris; Clarke, William

    2008-01-01

    Therapeutic advances in type 1 diabetes (T1DM) are currently focused on developing a closed-loop control system using a continuous glucose monitor (CGM), subcutaneous insulin delivery, and a control algorithm. Because a CGM assesses blood glucose indirectly (and therefore often inaccurately), it limits the effectiveness of the controller. In order to improve the quality of CGM data, a series of analyses are suggested. These analyses evaluate and compensate for CGM errors, assess risks associa...

  16. Growth and enzymatic responses of phytopathogenic fungi to glucose in culture media and soil

    Directory of Open Access Journals (Sweden)

    Beatriz de Oliveira Costa

    2012-03-01

    Full Text Available The effect of inoculation of Aspergillus flavus, Fusarium verticillioides, and Penicillium sp. in Dystrophic Red Latosol (DRL and Eutroferric Red Latosol (ERL soils with or without glucose on the total carbohydrate content and the dehydrogenase and amylase activities was studied. The fungal growth and spore production in culture medium with and without glucose were also evaluated. A completely randomized design with factorial arrangement was used. The addition of glucose in the culture medium increased the growth rate of A. flavus and Penicillium sp. but not of F. verticillioides. The number of spores increased 1.2 for F. verticillioides and 8.2 times for A. flavus in the medium with glucose, but was reduced 3.5 times for Penicillium sp. The total carbohydrates contents reduced significantly according to first and second degree equations. The consumption of total carbohydrates by A. flavus and Penicillium sp. was higher than the control or soil inoculated with F. verticillioides. The addition of glucose to soils benefited the use of carbohydrates, probably due to the stimulation of fungal growth. Dehydrogenase activity increased between 1.5 to 1.8 times (p <0.05 in soils with glucose and inoculated with the fungi (except F. verticillioides, in relation to soil without glucose. Amylase activity increased 1.3 to 1.5 times due to the addition of glucose in the soil. Increased amylase activity was observed in the DRL soil with glucose and inoculated with A. flavus and Penicillium sp. when compared to control.

  17. Dietary Fructose and Glucose Differentially Affect Lipid and Glucose Homeostasis1–3

    OpenAIRE

    Schaefer, Ernst J.; Gleason, Joi A.; Dansinger, Michael L.

    2009-01-01

    Absorbed glucose and fructose differ in that glucose largely escapes first-pass removal by the liver, whereas fructose does not, resulting in different metabolic effects of these 2 monosaccharides. In short-term controlled feeding studies, dietary fructose significantly increases postprandial triglyceride (TG) levels and has little effect on serum glucose concentrations, whereas dietary glucose has the opposite effects. When dietary glucose and fructose have been directly compared at ∼20–25% ...

  18. Impact of flash glucose monitoring on hypoglycaemia in adults with type 1 diabetes managed with multiple daily injection therapy: a pre-specified subgroup analysis of the IMPACT randomised controlled trial.

    Science.gov (United States)

    Oskarsson, Per; Antuna, Ramiro; Geelhoed-Duijvestijn, Petronella; Krӧger, Jens; Weitgasser, Raimund; Bolinder, Jan

    2018-03-01

    staff were not masked to group allocation. The primary outcome was the change in time in hypoglycaemia (blood glucose tests performed per day reduced from 5.5 ± 2.0 (median 5.4) at baseline to 0.5 ± 1.0 (median 0.1). The baseline frequency of self-monitored blood glucose tests by control participants was maintained (from 5.6 ± 1.9 [median 5.2] to 5.5 ± 2.6 [median 5.1] per day). Treatment satisfaction and perception of hypo/hyperglycaemia were improved compared with control. No device-related hypoglycaemia or safety-related issues were reported. Nine serious adverse events were reported for eight participants (four in each group), none related to the device. Eight adverse events for six of the participants in the intervention group were also reported, which were related to sensor insertion/wear; four of these participants withdrew because of the adverse event. Use of flash glucose technology in type 1 diabetes controlled with MDI therapy significantly reduced time in hypoglycaemia without deterioration of HbA 1c , and improved treatment satisfaction. ClinicalTrials.gov NCT02232698 FUNDING: Abbott Diabetes Care, Witney, UK.

  19. The Type 2 Diabetes Associated Minor Allele of rs2237895 KCNQ1 Associates with Reduced Insulin Release Following an Oral Glucose Load

    DEFF Research Database (Denmark)

    Brunak, Søren; Holmkvist, J; Banasik, K

    2009-01-01

    , and rs2237897) on estimates of glucose stimulated insulin release. METHODOLOGY/PRINCIPAL FINDINGS: Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT) in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin...... release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses. Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean......,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified...

  20. [Blood-sugar self control. A means for the diabetic of controlling his metabolic management. Quality control of a battery-run pocket size reflectometer (glucose-meter)].

    Science.gov (United States)

    Leidinger, F; Jörgens, V; Chantelau, E; Berchtold, P; Berger, M

    1980-07-26

    Home blood glucose monitoring by diabetic patients has recently been advocated as an effective means to improve metabolic control. The Glucocheck apparatus, a pocket-size battery-driven reflectance-meter (in Germany commercially available under the name Glucose-meter), has been evaluated for accuracy and practicability. In 450 blood glucose measurements, the variance between the values obtained using the Glucocheck apparatus and routine clinical laboratory procedures was +/- 11.7%. Especially in the low range of blood glucose concentrations, the Glucocheck method was very reliable. The quantitative precision of the Glucocheck method depends, however, quite considerably on the ability of the patient to use the apparatus correctly. In order to profit from Glucocheck in clinical practice, particular efforts to educate the patients in its use are necessary.

  1. Glucose deficit triggers tau pathology and synaptic dysfunction in a tauopathy mouse model.

    Science.gov (United States)

    Lauretti, E; Li, J-G; Di Meco, A; Praticò, D

    2017-01-31

    Clinical investigations have highlighted a biological link between reduced brain glucose metabolism and Alzheimer's disease (AD). Previous studies showed that glucose deprivation may influence amyloid beta formation in vivo but no data are available on the effect that this condition might have on tau protein metabolism. In the current paper, we investigated the effect of glucose deficit on tau phosphorylation, memory and learning, and synaptic function in a transgenic mouse model of tauopathy, the h-tau mice. Compared with controls, h-tau mice with brain glucose deficit showed significant memory impairments, reduction of synaptic long-term potentiation, increased tau phosphorylation, which was mediated by the activation of P38 MAPK Kinase pathway. We believe our studies demonstrate for the first time that reduced glucose availability in the central nervous system directly triggers behavioral deficits by promoting the development of tau neuropathology and synaptic dysfunction. Since restoring brain glucose levels and metabolism could afford the opportunity to positively influence the entire AD phenotype, this approach should be considered as a novel and viable therapy for preventing and/or halting the disease progression.

  2. Glucose kinetics in infants of diabetic mothers

    International Nuclear Information System (INIS)

    Cowett, R.M.; Susa, J.B.; Giletti, B.; Oh, W.; Schwartz, R.

    1983-01-01

    Glucose kinetic studies were performed to define the glucose turnover rate with 78% enriched D-[U-13C] glucose by the prime constant infusion technique at less than or equal to 6 hours of age in nine infants of diabetic mothers (four insulin-dependent and five chemical diabetic patients) at term. Five normal infants were studied as control subjects. All infants received 0.9% saline intravenously during the study with the tracer. Fasting plasma glucose, insulin, and glucose13/12C ratios were measured during the steady state, and the glucose turnover rate was derived. The average plasma glucose concentration was similar during the steady state in the infants of the diabetic mothers and in the control infants, and the glucose turnover rate was not significantly different among the groups: 2.3 +/- 0.6 mg . kg-1 min-1 in infants of insulin-dependent diabetic patients; 2.4 +/- 0.4 mg . kg-1 min-1 in infants of chemical diabetic patients; and 3.2 +/- 0.3 mg . kg-1 min-1 in the control subjects. Good control of maternal diabetes evidenced by the normal maternal hemoglobin A1c and plasma glucose concentration at delivery and cord plasma glucose concentration resulted in glucose kinetic values in the infants of diabetic mothers that were indistinguishable from those of control subjects. The data further support the importance of good control of the diabetic state in the pregnant woman to minimize or prevent neonatal hypoglycemia

  3. Reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet impairs the incretin effect in healthy subjects

    DEFF Research Database (Denmark)

    Hansen, K B; Vilsbøll, T; Bagger, J I

    2010-01-01

    The loss of incretin effect in patients with type 2 diabetes mellitus may be secondary to impaired glucose homeostasis. We investigated whether reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet in healthy young males...

  4. A data driven nonlinear stochastic model for blood glucose dynamics.

    Science.gov (United States)

    Zhang, Yan; Holt, Tim A; Khovanova, Natalia

    2016-03-01

    The development of adequate mathematical models for blood glucose dynamics may improve early diagnosis and control of diabetes mellitus (DM). We have developed a stochastic nonlinear second order differential equation to describe the response of blood glucose concentration to food intake using continuous glucose monitoring (CGM) data. A variational Bayesian learning scheme was applied to define the number and values of the system's parameters by iterative optimisation of free energy. The model has the minimal order and number of parameters to successfully describe blood glucose dynamics in people with and without DM. The model accounts for the nonlinearity and stochasticity of the underlying glucose-insulin dynamic process. Being data-driven, it takes full advantage of available CGM data and, at the same time, reflects the intrinsic characteristics of the glucose-insulin system without detailed knowledge of the physiological mechanisms. We have shown that the dynamics of some postprandial blood glucose excursions can be described by a reduced (linear) model, previously seen in the literature. A comprehensive analysis demonstrates that deterministic system parameters belong to different ranges for diabetes and controls. Implications for clinical practice are discussed. This is the first study introducing a continuous data-driven nonlinear stochastic model capable of describing both DM and non-DM profiles. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  5. A glassy carbon electrode modified with a composite consisting of reduced graphene oxide, zinc oxide and silver nanoparticles in a chitosan matrix for studying the direct electron transfer of glucose oxidase and for enzymatic sensing of glucose

    International Nuclear Information System (INIS)

    Li, Zhenjiang; Sheng, Liying; Xie, Cuicui; Meng, Alan; Zhao, Kun

    2016-01-01

    The authors describe the fabrication of a nanocomposite consisting of reduced graphene oxide, zinc oxide and silver nanoparticles by microwave-assisted synthesis. The composite was further reduced in-situ with hydrazine hydrate and then placed, along with the enzyme glucose oxidase, on a glassy carbon electrode. The synergistic effect of the materials employed in the nanocomposite result in excellent electrocatalytic activity. The Michaelis-Menten constant of the adsorbed GOx is 0.25 mM, implying a remarkable affinity of the GOx for glucose. The amperometric response of the modified GCE is linearly proportional to the concentration of glucose in 0.1 to 12.0 mM concentration range, and the detection limit is 10.6 µM. The biosensor is highly selective, well reproducible and stable. (author)

  6. The Phytocomplex from Fucus vesiculosus and Ascophyllum nodosum Controls Postprandial Plasma Glucose Levels: An In Vitro and In Vivo Study in a Mouse Model of NASH

    Directory of Open Access Journals (Sweden)

    Daniela Gabbia

    2017-02-01

    Full Text Available Edible seaweeds have been consumed by Asian coastal communities since ancient times. Fucus vesiculosus and Ascophyllum nodosum extracts have been traditionally used for the treatment of obesity and several gastrointestinal diseases. We evaluated the ability of extracts obtained from these algae to inhibit the digestive enzymes α-amylase and α-glucosidase in vitro, and control postprandial plasma glucose levels in a mouse model of non-alcoholic steatohepatitis (NASH; a liver disease often preceding the development of Type 2 diabetes (T2DM. This model was obtained by the administration of a high-fat diet. Our results demonstrate that these algae only delayed and reduced the peak of blood glucose (p < 0.05 in mice fed with normal diet, without changing the area under the blood glucose curve (AUC. In the model of NASH, the phytocomplex was able to reduce both the postprandial glycaemic peak, and the AUC. The administration of the extract in a diet particularly rich in fat is associated with a delay in carbohydrate digestion, but also with a decrease in its assimilation. In conclusion, our results indicate that this algal extract may be useful in the control of carbohydrate digestion and absorption. This effect may be therapeutically exploited to prevent the transition of NASH to T2DM.

  7. PENGARUH KONSUMSI KAPPA-KARAGENAN TERHADAP GLUKOSA DARAH TIKUS WISTAR (Ratus norvegicus DIABETES [The Effect of Kappa-Carrageenan Consumption on Blood Glucose Level of Diabetic Wistar Rat (Ratus norwegicus

    Directory of Open Access Journals (Sweden)

    Hardoko

    2006-04-01

    Full Text Available The effect of kappa-carrageenan consumption on blood glucose level were studied on diabetic male wistar rat (Ratus norvegicus.The rats were made diabetic by aloxan injection, and then were given that a ration contains 5, 10, 15, 20% (w/w kappa-carrageenan, standard ration (negative control, and parental glibenklamid (positive control. The results showed that the standard ration could not reduce blood glucose from hyperglycemic to normal level, while the ration contained kappacarrageenan could. The higher kappa-carrageenan seaweed level in the ration has higher capacity to decrease blood glucose level. The ration containing 20% and 15% kappa-carrageenan could reduce blood glucose in 18 and 21 days, respectively.The effect of this ration was similar to that of glibenklamid which reduced blood glucose to normal level in 18 days. The ration containing 5 and 10% kappa-carrageenan could reduce blood glucose level; Blood glucose leve return to normal on the 21st day.

  8. Pulsatile hyperglucagonemia fails to increase hepatic glucose production in normal man

    International Nuclear Information System (INIS)

    Paolisso, G.; Scheen, A.J.; Luyckx, A.S.; Lefebvre, P.J.

    1987-01-01

    To study the metabolic effects of pulsatile glucagon administration, six male volunteers were submitted to a 260-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of the pancreatic hormones was inhibited by somatostatin, basal insulin secretion was replaced by a continuous insulin infusion, and glucagon was infused intravenously in two conditions at random: either continuously or intermittently. Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classical methodology using a D-[3- 3 H]glucose infusion allowed the authors to study glucose turnover. While basal plasma glucagon levels were similar in both conditions, they plateaued at 189 +/- 38 pg ml -1 during continuous infusion and varied between 95 and 501 pg x ml -1 during pulsatile infusion. When compared with continuous administration, pulsatile glucagon infusion 1) initially induced a similar increase in endogenous (hepatic) glucose production and blood glucose, 2) did not prevent the so-called evanescent effect of glucagon on blood glucose, and 3) after 3 h tended to reduce rather than increase hepatic glucose production. In conclusion, in vivo pulsatile hyperglucanemia in normal man fails to increase hepatic glucose production

  9. Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet.

    Science.gov (United States)

    Vickers, Steven P; Cheetham, Sharon C; Headland, Katie R; Dickinson, Keith; Grempler, Rolf; Mayoux, Eric; Mark, Michael; Klein, Thomas

    2014-01-01

    The present study assessed the potential of the sodium glucose-linked transporter (SGLT)-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg) for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg) with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes.

  10. [Blood glucose self monitoring].

    Science.gov (United States)

    Wascher, Thomas C; Stechemesser, Lars

    2016-04-01

    Self monitoring of blood glucose contributes to the integrated management of diabetes mellitus. It, thus, should be available for all patients with diabetes mellitus type-1 and type-2. Self monitoring of blood glucose improves patients safety, quality of life and glucose control. The current article represents the recommendations of the Austrian Diabetes Association for the use of blood glucose self monitoring according to current scientific evidence.

  11. Bihormonal model predictive control of blood glucose in people with type 1 diabetes

    DEFF Research Database (Denmark)

    Batora, Vladimir; Tarnik, Marian; Murgas, Jan

    2014-01-01

    In this paper we present a bihormonal control system that controls blood glucose in people with type 1 diabetes (T1D). We use insulin together with glucagon to mitigate the negative effects of hyper- and hypoglycemia. The system consists of a Kalman filter, a micro-bolus insulin and glucagon...

  12. What goes up must come down: glucose variability and glucose control in diabetes and critical illness

    NARCIS (Netherlands)

    Siegelaar, S.E.

    2011-01-01

    The central question of this thesis is whether it is necessary to curb all glucose peaks. From the studies presented in this thesis we conclude that this is not always the case. In diabetes it is important to lower mean glucose while avoiding hypoglycaemia, but we found that lowering of glucose to

  13. The Effect of Metformine on Glucose Control in Patients with Diabetes Type 1

    Directory of Open Access Journals (Sweden)

    A. Ziaee

    2010-07-01

    Full Text Available Introduction & Objective: Metabolic control in adolescents with type 1 DM who are in pubertal period will be impaired, thus finding a therapeutic strategy such as adding metformin to insulin to reduce insulin resistance will be useful in blood glucose control and metabolic state improvement.Materials & Methods: This was a randomized double blind placebo controlled 3-month trial metformin therapy in 32 adolescents with type 1 DM. These patients were divided in two groups of metformin and placebo and treated with metformin and placebo for 3-months. Their HbA1C, FBS, Insulin dosage, TG, Cholesterol, and LDL were measured at the initiation and end of the treatment.Results: After the study there was a significant improvement of FBS and TG in metformin group versus placebo group (P=0.02 and P=0.028 in order. But, there was not significant difference in other variables such as BMI, insulin dosage, HbA1C, Cholesterol and LDL between the two groups.Conclusion: Metformin treatment in teenagers with type1 DM who are in pubertal period will improve the control of FBS and lowers TG but has not any significant effect on HbA1C, BMI, insulin dosage, Cholesterol and LDL.

  14. Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response.

    Science.gov (United States)

    Helseth, R; Carlsen, S M; Bollerslev, J; Svartberg, J; Øksnes, M; Skeie, S; Fougner, S L

    2016-02-01

    In acromegaly, high GH/IGF-1 levels associate with abnormal glucose metabolism. Somatostatin analogs (SSAs) reduce GH and IGF-1 but inhibit insulin secretion. We studied glucose homeostasis in de novo patients with acromegaly and changes in glucose metabolism after treatment with SSA and surgery. In this post hoc analysis from a randomized controlled trial, 55 de novo patients with acromegaly, not using antidiabetic medication, were included. Before surgery, 26 patients received SSAs for 6 months. HbA1c, fasting glucose, and oral glucose tolerance test were performed at baseline, after SSA pretreatment and at 3 months postoperative. Area under curve of glucose (AUC-G) was calculated. Glucose homeostasis was compared to baseline levels of GH and IGF-1, change after SSA pretreatment, and remission both after SSA pretreatment and 3 months postoperative. In de novo patients, IGF-1/GH levels did not associate with baseline glucose parameters. After SSA pretreatment, changes in GH/IGF-1 correlated positively to change in HbA1c levels (both p acromegaly, disease activity did not correlate with glucose homeostasis. Surgical treatment of acromegaly improved glucose metabolism in both cured and not cured patients, while SSA pretreatment led to deterioration in glucose homeostasis in patients not achieving biochemical control.

  15. Validity of the reduced-sample insulin modified frequently-sampled intravenous glucose tolerance test using the nonlinear regression approach.

    Science.gov (United States)

    Sumner, Anne E; Luercio, Marcella F; Frempong, Barbara A; Ricks, Madia; Sen, Sabyasachi; Kushner, Harvey; Tulloch-Reid, Marshall K

    2009-02-01

    The disposition index, the product of the insulin sensitivity index (S(I)) and the acute insulin response to glucose, is linked in African Americans to chromosome 11q. This link was determined with S(I) calculated with the nonlinear regression approach to the minimal model and data from the reduced-sample insulin-modified frequently-sampled intravenous glucose tolerance test (Reduced-Sample-IM-FSIGT). However, the application of the nonlinear regression approach to calculate S(I) using data from the Reduced-Sample-IM-FSIGT has been challenged as being not only inaccurate but also having a high failure rate in insulin-resistant subjects. Our goal was to determine the accuracy and failure rate of the Reduced-Sample-IM-FSIGT using the nonlinear regression approach to the minimal model. With S(I) from the Full-Sample-IM-FSIGT considered the standard and using the nonlinear regression approach to the minimal model, we compared the agreement between S(I) from the Full- and Reduced-Sample-IM-FSIGT protocols. One hundred African Americans (body mass index, 31.3 +/- 7.6 kg/m(2) [mean +/- SD]; range, 19.0-56.9 kg/m(2)) had FSIGTs. Glucose (0.3 g/kg) was given at baseline. Insulin was infused from 20 to 25 minutes (total insulin dose, 0.02 U/kg). For the Full-Sample-IM-FSIGT, S(I) was calculated based on the glucose and insulin samples taken at -1, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 minutes. For the Reduced-Sample-FSIGT, S(I) was calculated based on the time points that appear in bold. Agreement was determined by Spearman correlation, concordance, and the Bland-Altman method. In addition, for both protocols, the population was divided into tertiles of S(I). Insulin resistance was defined by the lowest tertile of S(I) from the Full-Sample-IM-FSIGT. The distribution of subjects across tertiles was compared by rank order and kappa statistic. We found that the rate of failure of resolution of S(I) by

  16. Glucose de-repression by yeast AMP-activated protein kinase SNF1 is controlled via at least two independent steps.

    Science.gov (United States)

    García-Salcedo, Raúl; Lubitz, Timo; Beltran, Gemma; Elbing, Karin; Tian, Ye; Frey, Simone; Wolkenhauer, Olaf; Krantz, Marcus; Klipp, Edda; Hohmann, Stefan

    2014-04-01

    The AMP-activated protein kinase, AMPK, controls energy homeostasis in eukaryotic cells but little is known about the mechanisms governing the dynamics of its activation/deactivation. The yeast AMPK, SNF1, is activated in response to glucose depletion and mediates glucose de-repression by inactivating the transcriptional repressor Mig1. Here we show that overexpression of the Snf1-activating kinase Sak1 results, in the presence of glucose, in constitutive Snf1 activation without alleviating glucose repression. Co-overexpression of the regulatory subunit Reg1 of the Glc-Reg1 phosphatase complex partly restores glucose regulation of Snf1. We generated a set of 24 kinetic mathematical models based on dynamic data of Snf1 pathway activation and deactivation. The models that reproduced our experimental observations best featured (a) glucose regulation of both Snf1 phosphorylation and dephosphorylation, (b) determination of the Mig1 phosphorylation status in the absence of glucose by Snf1 activity only and (c) a regulatory step directing active Snf1 to Mig1 under glucose limitation. Hence it appears that glucose de-repression via Snf1-Mig1 is regulated by glucose via at least two independent steps: the control of activation of the Snf1 kinase and directing active Snf1 to inactivating its target Mig1. © 2014 FEBS.

  17. Reduced glutathione and glutathione disulfide in the blood of glucose-6-phosphate dehydrogenase-deficient newborns.

    Science.gov (United States)

    Gong, Zhen-Hua; Tian, Guo-Li; Huang, Qi-Wei; Wang, Yan-Min; Xu, Hong-Ping

    2017-07-20

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency. The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard. G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 μmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 μmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.

  18. Higher Endogenous Glucose Production during OGTT vs Isoglycemic Intravenous Glucose Infusion

    DEFF Research Database (Denmark)

    Lund, Asger; Bagger, Jonatan I; Christensen, Mikkel Bring

    2016-01-01

    CONTEXT: Oral glucose ingestion elicits a larger insulin response and delayed suppression of glucagon compared to isoglycemic intravenous (iv) glucose infusion (IIGI). OBJECTIVE: We studied whether these differences translate into effects on endogenous glucose production (EGP) and glucose disposal......); HbA1c 53.8 ± 11.0 mmol/mol; duration of diabetes 9.2 ± 5.0 years) and 10 matched non-diabetic control subjects (age 56.0±10.7 years; BMI 29.8 ± 2.9 kg/m(2); HbA1c 33.8 ± 5.5 mmol/mol) Interventions: Three experimental days: 75 g-oral glucose tolerance test (OGTT), IIGI and IIGI+glucagon (IIGI...

  19. Role of SUMO-specific protease 2 in reprogramming cellular glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Shuang Tang

    Full Text Available Most cancer cells exhibit a shift in glucose metabolic strategy, displaying increased glycolysis even with adequate oxygen supply. SUMO-specific proteases (SENPs de-SUMOylate substrates including HIF1α and p53,two key regulators in cancer glucose metabolism, to regulate their activity, stability and subcellular localization. However, the role of SENPs in tumor glucose metabolism remains unclear. Here we report that SUMO-specific protease 2 (SENP2 negatively regulates aerobic glycolysis in MCF7 and MEF cells. Over-expression of SENP2 reduces the glucose uptake and lactate production, increasing the cellular ATP levels in MCF7 cells, while SENP2 knockout MEF cells show increased glucose uptake and lactate production along with the decreased ATP levels. Consistently, the MCF7 cells over-expressing SENP2 exhibit decreased expression levels of key glycolytic enzymes and an increased rate of glucose oxidation compared with control MCF7 cells, indicating inhibited glycolysis but enhanced oxidative mitochondrial respiration. Moreover, SENP2 over-expressing MCF7 cells demonstrated a reduced amount of phosphorylated AKT, whereas SENP2 knockout MEFs exhibit increased levels of phosphorylated AKT. Furthermore, inhibiting AKT phosphorylation by LY294002 rescued the phenotype induced by SENP2 deficiency in MEFs. In conclusion, SENP2 represses glycolysis and shifts glucose metabolic strategy, in part through inhibition of AKT phosphorylation. Our study reveals a novel function of SENP2 in regulating glucose metabolism.

  20. Molecular Weight Dependent Glucose Lowering Effect of Low Molecular Weight Chitosan Oligosaccharide (GO2KA1 on Postprandial Blood Glucose Level in SD Rats Model

    Directory of Open Access Journals (Sweden)

    Emmanouil Apostolidis

    2013-07-01

    Full Text Available This research investigated the effect of enzymatically digested low molecular weight (MW chitosan oligosaccharide on type 2 diabetes prevention. Three different chitosan oligosaccharide samples with varying MW were evaluated in vitro for inhibition of rat small intestinal α-glucosidase and porcine pancreatic α-amylase (GO2KA1; 10,000 Da. The in vitro results showed that all tested samples had similar rat α-glucosidase inhibitory and porcine α-amylase inhibitory activity. Based on these observations, we decided to further investigate the effect of all three samples at a dose of 0.1 g/kg, on reducing postprandial blood glucose levels in Sprague-Dawley (SD rat model after sucrose loading test. In the animal trial, all tested samples had postprandial blood glucose reduction effect, when compared to control, however GO2KA1 supplementation had the strongest effect. The glucose peak (Cmax for GO2KA1 and control was 152 mg/dL and 193 mg/dL, respectively. The area under the blood glucose-time curve (AUC for GO2KA1 and control was 262 h mg/dL and 305 h mg/dL, respectively. Furthermore, the time of peak plasma concentration of blood glucose (Tmax for GO2KA1 was significantly delayed (0.9 h compared to control (0.5 h. These results suggest that GO2KA1 could have a beneficial effect for blood glucose management relevant to diabetes prevention in normal and pre-diabetic individuals. The suggested mechanism of action is via inhibition of the carbohydrate hydrolysis enzyme α-glucosidase and since GO2KA1 (MW < 1000 Da had higher in vivo effect, we hypothesize that it is more readily absorbed and might exert further biological effect once it is absorbed in the blood stream, relevant to blood glucose management.

  1. Evidence for brain glucose dysregulation in Alzheimer's disease.

    Science.gov (United States)

    An, Yang; Varma, Vijay R; Varma, Sudhir; Casanova, Ramon; Dammer, Eric; Pletnikova, Olga; Chia, Chee W; Egan, Josephine M; Ferrucci, Luigi; Troncoso, Juan; Levey, Allan I; Lah, James; Seyfried, Nicholas T; Legido-Quigley, Cristina; O'Brien, Richard; Thambisetty, Madhav

    2018-03-01

    It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. Copyright © 2017 the Alzheimer's Association. All rights reserved.

  2. Evaluation of Salivary Glucose, IgA and Flow Rate in Diabetic Patients: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    P. Bakianian Vaziri

    2010-03-01

    Full Text Available Objective: An association between diabetes mellitus and alterations in the oral cavity has been noted. In this study, we evaluated differences between salivary IgA, glucose and flow rate in diabetic patients compared with healthy controls.Materials and Methods: Forty patients with type 1 diabetes, 40 patients with type 2 diabetes and 40 healthy controls were selected. Whole unstimulated saliva samples were collected by the standard method and the salivary flow rate was determined. Nephelometricand Pars method were used to measure salivary IgA and salivary glucose concentrations,respectively. Statistical analysis was performed by Chi-square and t test.Results: There were no significant differences in salivary IgA and glucose concentrations between type 1 and type 2 diabetic patients and their matched control subjects (P>0.05.Salivary flow rate was significantly lower in diabetic patients (P<0.05. In addition,DMFT was higher in diabetic patients than the controls.Conclusion: Determination of salivary constituents may be useful in the description and management of oral findings in diabetic patients.

  3. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder

    International Nuclear Information System (INIS)

    Swedo, S.E.; Schapiro, M.B.; Grady, C.L.; Cheslow, D.L.; Leonard, H.L.; Kumar, A.; Friedland, R.; Rapoport, S.I.; Rapoport, J.L.

    1989-01-01

    The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system

  4. Regional cerebral glucose metabolism in patients with alcoholic Korsakoff's syndrome

    International Nuclear Information System (INIS)

    Kessler, R.M.; Parker, E.S.; Clark, C.M.; Martin, P.R.; George, D.T.; Weingartner, H.; Sokoloff, L.; Ebert, M.H.; Mishkin, M.

    1985-01-01

    Seven alcoholic male subjects diagnosed as having Korsakoff's syndrome and eight age-matched male normal volunteers were studied with /sup 18/F 2-fluoro-2-deoxy-D-glucose (2/sup 18/FDG). All subjects were examined at rest with eyes covered in a quiet, darkened room. Serial plasma samples were obtained following injection of 4 to 5 mCi of 2/sup 18/FDG. Tomographic slices spaced at 10mm axial increments were obtained (in-plane resolution = 1.75 cm, axial resolution = 1.78 cm). Four planes were selected from each subject, and a total of 46 regions of interest were sampled and glucose metabolic rates for each region calculated. The mean glucose metalbolic rate for the 46 regions in the Korsakoff subjects was significantly lower than that in the normal controls (5.17 +- .43 versus 6.6 +- 1.31). A Q-component analysis, which examined each subject's regional rates relative to his mean rate, revealed two distinct patterns in the Korsakoff group. Glucose metabolism was significantly reduced in 37 of the 46 regions sampled. Reduced cerebral glucose metabolism in a nondemented group of subjects has not previously been reported. The reduction in cortical metabolism may be the result of damage to sub-cortical projecting systems. The differing patterns of cerebral metabolism in Korsakoff's syndrome suggests subgroups with differing neuropathology. Regions implicated in memory function, medial temporal, thalamic and medial prefrontal were among the regions reduced in metabolism

  5. Impact of taurine depletion on glucose control and insulin secretion in mice.

    Science.gov (United States)

    Ito, Takashi; Yoshikawa, Natsumi; Ito, Hiromi; Schaffer, Stephen W

    2015-09-01

    Taurine, an endogenous sulfur-containing amino acid, is found in millimolar concentrations in mammalian tissue, and its tissue content is altered by diet, disease and aging. The effectiveness of taurine administration against obesity and its related diseases, including type 2 diabetes, has been well documented. However, the impact of taurine depletion on glucose metabolism and fat deposition has not been elucidated. In this study, we investigated the effect of taurine depletion (in the taurine transporter (TauT) knockout mouse model) on blood glucose control and high fat diet-induced obesity. TauT-knockout (TauTKO) mice exhibited lower body weight and abdominal fat mass when maintained on normal chow than wild-type (WT) mice. Blood glucose disposal after an intraperitoneal glucose injection was faster in TauTKO mice than in WT mice despite lower serum insulin levels. Islet beta-cells (insulin positive area) were also decreased in TauTKO mice compared to WT mice. Meanwhile, overnutrition by high fat (60% fat)-diet could lead to obesity in TauTKO mice despite lower body weight under normal chow diet condition, indicating nutrition in normal diet is not enough for TauTKO mice to maintain body weight comparable to WT mice. In conclusion, taurine depletion causes enhanced glucose disposal despite lowering insulin levels and lower body weight, implying deterioration in tissue energy metabolism. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  6. Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2015-03-01

    The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats.

  7. Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects

    International Nuclear Information System (INIS)

    Wajngot, A.; Khan, A.; Giacca, A.; Vranic, M.; Efendic, S.

    1990-01-01

    We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with [2-3H]glucose and HGP with [6-3H]glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). [2-3H]- minus [6-3H]glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP

  8. The association between estimated average glucose levels and fasting plasma glucose levels

    Directory of Open Access Journals (Sweden)

    Giray Bozkaya

    2010-01-01

    Full Text Available OBJECTIVE: The level of hemoglobin A1c (HbA1c, also known as glycated hemoglobin, determines how well a patient's blood glucose level has been controlled over the previous 8-12 weeks. HbA1c levels help patients and doctors understand whether a particular diabetes treatment is working and whether adjustments need to be made to the treatment. Because the HbA1c level is a marker of blood glucose for the previous 120 days, average blood glucose levels can be estimated using HbA1c levels. Our aim in the present study was to investigate the relationship between estimated average glucose levels, as calculated by HbA1c levels, and fasting plasma glucose levels. METHODS: The fasting plasma glucose levels of 3891 diabetic patient samples (1497 male, 2394 female were obtained from the laboratory information system used for HbA1c testing by the Department of Internal Medicine at the Izmir Bozyaka Training and Research Hospital in Turkey. These samples were selected from patient samples that had hemoglobin levels between 12 and 16 g/dL. The estimated glucose levels were calculated using the following formula: 28.7 x HbA1c - 46.7. Glucose and HbA1c levels were determined using hexokinase and high performance liquid chromatography (HPLC methods, respectively. RESULTS: A strong positive correlation between fasting plasma glucose levels and estimated average blood glucose levels (r=0.757, p<0.05 was observed. The difference was statistically significant. CONCLUSION: Reporting the estimated average glucose level together with the HbA1c level is believed to assist patients and doctors determine the effectiveness of blood glucose control measures.

  9. Direct electrochemistry and electrocatalysis of glucose oxidase immobilized on reduced graphene oxide and silver nanoparticles nanocomposite modified electrode.

    Science.gov (United States)

    Palanisamy, Selvakumar; Karuppiah, Chelladurai; Chen, Shen-Ming

    2014-02-01

    The direct electrochemistry of glucose oxidase (GOx) was successfully realized on electrochemically reduced graphene oxide and silver nanoparticles (RGO/Ag) nanocomposite modified electrode. The fabricated nanocomposite was characterized by field emission scanning electron microscope and energy dispersive spectroscopy. The GOx immobilized nanocomposite modified electrode showed a pair of well-defined redox peaks with a formal potential (E°) of -0.422 V, indicating that the bioactivity of GOx was retained. The heterogeneous electron transfer rate constant (Ks) of GOx at the nanocomposite was calculated to be 5.27 s(-1), revealing a fast direct electron transfer of GOx. The GOx immobilized RGO/Ag nanocomposite electrode exhibited a good electrocatalytic activity toward glucose over a linear concentration range from 0.5 to 12.5 mM with a detection limit of 0.16 mM. Besides, the fabricated biosensor showed an acceptable sensitivity and selectivity for glucose. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Differential cognitive effects of energy drink ingredients: caffeine, taurine, and glucose.

    Science.gov (United States)

    Giles, Grace E; Mahoney, Caroline R; Brunyé, Tad T; Gardony, Aaron L; Taylor, Holly A; Kanarek, Robin B

    2012-10-01

    Energy drinks containing caffeine, taurine, and glucose may improve mood and cognitive performance. However, there are no studies assessing the individual and interactive effects of these ingredients. We evaluated the effects of caffeine, taurine, and glucose alone and in combination on cognitive performance and mood in 24-hour caffeine-abstained habitual caffeine consumers. Using a randomized, double-blind, mixed design, 48 habitual caffeine consumers (18 male, 30 female) who were 24-hour caffeine deprived received one of four treatments (200 mg caffeine/0 mg taurine, 0 mg caffeine/2000 mg taurine, 200 mg caffeine/2000 mg taurine, 0 mg caffeine/0 mg taurine), on each of four separate days, separated by a 3-day wash-out period. Between-participants treatment was a glucose drink (50 g glucose, placebo). Salivary cortisol, mood and heart rate were measured. An attention task was administered 30-minutes post-treatment, followed by a working memory and reaction time task 60-minutes post-treatment. Caffeine enhanced executive control and working memory, and reduced simple and choice reaction time. Taurine increased choice reaction time but reduced reaction time in the working memory tasks. Glucose alone slowed choice reaction time. Glucose in combination with caffeine, enhanced object working memory and in combination with taurine, enhanced orienting attention. Limited glucose effects may reflect low task difficulty relative to subjects' cognitive ability. Caffeine reduced feelings of fatigue and increased tension and vigor. Taurine reversed the effects of caffeine on vigor and caffeine-withdrawal symptoms. No effects were found for salivary cortisol or heart rate. Caffeine, not taurine or glucose, is likely responsible for reported changes in cognitive performance following consumption of energy drinks, especially in caffeine-withdrawn habitual caffeine consumers. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Near infrared radiation rescues mitochondrial dysfunction in cortical neurons after oxygen-glucose deprivation.

    Science.gov (United States)

    Yu, Zhanyang; Liu, Ning; Zhao, Jianhua; Li, Yadan; McCarthy, Thomas J; Tedford, Clark E; Lo, Eng H; Wang, Xiaoying

    2015-04-01

    Near infrared radiation (NIR) is known to penetrate and affect biological systems in multiple ways. Recently, a series of experimental studies suggested that low intensity NIR may protect neuronal cells against a wide range of insults that mimic diseases such as stroke, brain trauma and neurodegeneration. However, the potential molecular mechanisms of neuroprotection with NIR remain poorly defined. In this study, we tested the hypothesis that low intensity NIR may attenuate hypoxia/ischemia-induced mitochondrial dysfunction in neurons. Primary cortical mouse neuronal cultures were subjected to 4 h oxygen-glucose deprivation followed by reoxygenation for 2 h, neurons were then treated with a 2 min exposure to 810-nm NIR. Mitochondrial function markers including MTT reduction and mitochondria membrane potential were measured at 2 h after treatment. Neurotoxicity was quantified 20 h later. Our results showed that 4 h oxygen-glucose deprivation plus 20 h reoxygenation caused 33.8 ± 3.4 % of neuron death, while NIR exposure significantly reduced neuronal death to 23.6 ± 2.9 %. MTT reduction rate was reduced to 75.9 ± 2.7 % by oxygen-glucose deprivation compared to normoxic controls, but NIR exposure significantly rescued MTT reduction to 87.6 ± 4.5 %. Furthermore, after oxygen-glucose deprivation, mitochondria membrane potential was reduced to 48.9 ± 4.39 % of normoxic control, while NIR exposure significantly ameliorated this reduction to 89.6 ± 13.9 % of normoxic control. Finally, NIR significantly rescued OGD-induced ATP production decline at 20 min after NIR. These findings suggest that low intensity NIR can protect neurons against oxygen-glucose deprivation by rescuing mitochondrial function and restoring neuronal energetics.

  12. How Effective is Swedish Massage on Blood Glucose Level in Children with Diabetes Mellitus?

    Directory of Open Access Journals (Sweden)

    Firoozeh Sajedi

    2011-09-01

    Full Text Available "nThis study was conducted to determine the effect of Swedish massage on blood glucose level in children with diabetes mellitus (DM. It was prospective randomized controlled trial study that conducted on 36 children, 6-12 years old with DM, recruited from a hospital in Qom City, Iran. The children were randomly assigned to intervention and control groups. Swedish massage was performed 15 minutes, 3 times a week, for 3 months in intervention group. The blood glucose levels were evaluated immediately after every session of massage in two groups. The mean ages of children in the intervention (n=18 and control (n=18 groups were 9.05 ± 1.55 and 9.83 ±2.03 years respectively. There was statistically no significant difference in blood glucose levels before intervention between two groups (P=0.586, but the blood glucose levels were lower significantly in intervention group in comparison with control group after intervention (P<0.0001. Addition of Swedish massage to daily routines; exercise, diet and medication regimens, is an effective intervention to reduce blood glucose level in diabetic children.

  13. Circulating Betatrophin Correlates with Triglycerides and Postprandial Glucose among Different Glucose Tolerance Statuses--A Case-Control Study.

    Science.gov (United States)

    Gao, Ting; Jin, Kairui; Chen, Peihong; Jin, Hua; Yang, Lili; Xie, Xinmiao; Yang, Meili; Hu, Cheng; Yu, Xuemei

    2015-01-01

    Previous researches of betatrophin on glucose and lipids metabolism under insulin-resistant condition have reached controversial conclusions. To further identify the possible impact of betatrophin, we measured the circulating betatrophin levels in newly diagnosed type 2 diabetes (T2DM) patients, and in subjects with both impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) and investigated the relationship between serum betatrophin and other clinical parameters in these patients with different glucose tolerance statuses. A total of 460 permanent residents of the Fengxian District, aged 40-60 years, were enrolled. Based on the results of a 75 g oral glucose tolerance test, we selected newly diagnosed T2DM (n = 50) patients and subjects with IGT (n = 51) and NGT (n = 50) according to their age, gender and body mass index (18-28 kg/m2). Anthropometric parameters, glycosylated haemoglobin, blood lipids and fasting insulin were measured. Serum betatrophin concentrations were determined via ELISA. Serum betatrophin levels in T2DM patients were increased significantly compared with IGT and NGT groups, and decreased in subjects with better islet beta cell function. Serum betatrophin was positively correlated with triglyceride, 2-hour postprandial glucose, alanine aminotransferase and aspartate transaminase after adjusting for age, sex and body mass index in all subjects. Multiple regression analysis showed that 2-hour postprandial glucose was independently associated with serum betatrophin significantly. Circulating betatrophin is increased in newly-diagnosed T2DM patients and positively correlated with the triglycerides and postprandial glucose levels. The results suggest that betatrophin may participate in glucose and triglycerides metabolism.

  14. Effects of self-monitoring of glucose in non-insulin treated patients with type 2 diabetes: design of the IN CONTROL-trial

    Directory of Open Access Journals (Sweden)

    Kostense Piet J

    2009-04-01

    Full Text Available Abstract Background Diabetes specific emotional problems interfere with the demanding daily management of living with type 2 diabetes mellitus (T2DM. Possibly, offering direct feedback on diabetes management may diminish the presence of diabetes specific emotional problems and might enhance the patients' belief they are able to manage their illness. It is hypothesized that self-monitoring of glucose in combination with an algorithm how and when to act will motivate T2DM patients to become more active participants in their own care leading to a decrease in diabetes related distress and an increased self-efficacy. Methods and design Six hundred patients with T2DM (45 ≤ 75 years who receive care in a structured diabetes care system, HbA1c ≥ 7.0%, and not using insulin will be recruited and randomized into 3 groups; Self-monitoring of Blood Glucose (SMBG, Self-monitoring of Urine Glucose (SMUG and usual care (n = 200 per group. Participants are eligible if they have a known disease duration of over 1 year and have used SMBG or SMUG less than 3 times in the previous year. All 3 groups will receive standardized diabetes care. The intervention groups will receive additional instructions on how to perform self-monitoring of glucose and how to interpret the results. Main outcome measures are changes in diabetes specific emotional distress and self-efficacy. Secondary outcome measures include difference in HbA1c, patient satisfaction, occurrence of hypoglycaemia, physical activity, costs of direct and indirect healthcare and changes in illness beliefs. Discussion The IN CONTROL-trial is designed to explore whether feedback from self-monitoring of glucose in T2DM patients who do not require insulin can affect diabetes specific emotional distress and increase self-efficacy. Based on the self-regulation model it is hypothesized that glucose self-monitoring feedback changes illness perceptions, guiding the patient to reduce emotional responses to

  15. Reduced gluconeogenesis and lactate clearance in Huntington's disease

    DEFF Research Database (Denmark)

    Josefsen, Knud; Nielsen, Signe M B; Campos, André

    2010-01-01

    We studied systemic and brain glucose and lactate metabolism in Huntington's disease (HD) patients in response to ergometer cycling. Following termination of exercise, blood glucose increased abruptly in control subjects, but no peak was seen in any of the HD patients (2.0 ± 0.5 vs. 0.0 ± 0.2mM, P...... HD mouse model R6/2 following a lactate challenge, combined with reduced phosphoenolpyruvate carboxykinase and increased pyruvate kinase activity in the mouse liver suggest a reduced capacity...... for gluconeogenesis in HD, possibly contributing to the clinical symptoms of HD. We propose that blood glucose concentration in the recovery from exercise can be applied as a liver function test in HD patients....

  16. CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

    Science.gov (United States)

    Kim, Hyunbae; Zheng, Ze; Walker, Paul D; Kapatos, Gregory; Zhang, Kezhong

    2017-07-15

    Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. Copyright © 2017 American Society for Microbiology.

  17. High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats

    Science.gov (United States)

    Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.

    2013-01-01

    Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (−9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

  18. Fabrication of Glucose-Sensitive Layer-by-Layer Films for Potential Controlled Insulin Release Applications

    Directory of Open Access Journals (Sweden)

    Talusan Timothy Jemuel E.

    2015-01-01

    Full Text Available Self-regulated drug delivery systems (DDS are potential alternative to the conventional method of introducing insulin to the body due to their controlled drug release mechanism. In this study, Layer-by-Layer technique was utlized to manufacture drug loaded, pH responsive thin films. Insulin was alternated with pH-sensitive, [2-(dimethyl amino ethyl aminoacrylate] (PDMAEMA and topped of with polymer/glucose oxidase (GOD layers. Similarly, films using a different polymer, namely Poly(Acrylic Acid (PAA were also fabricated. Exposure of the films to glucose solutions resulted to the production of gluconic acid causing a polymer conformation change due to protonation, thus releasing the embedded insulin. The insulin release was monitored by subjecting the dipping glucose solutions to Bradford Assay. Films exhibited a reversal in drug release profile in the presence of glucose as compared to without glucose. PAA films were also found out to release more insulin compared to that of the PDMAEMA films.The difference in the profile of the two films were due to different polymer-GOD interactions, since both films exhibited almost identical profiles when embedded with Poly(sodium 4-styrenesulfonate (PSS instead of GOD.

  19. Evidence for dual control mechanism regulating hepatic glucose output in nondiabetic men

    International Nuclear Information System (INIS)

    Clore, J.N.; Glickman, P.S.; Helm, S.T.; Nestler, J.E.; Blackard, W.G.

    1991-01-01

    The authors previously reported a fall in hepatic glucose output (HGO) during sleep accompanied by reductions in glucose utilization (Rd) and free fatty acids (FFAs). This study was undertaken to determine the potential role of changes in Rd and FFA on HGO in nondiabetic men. To determine if the fall in HGO during sleep could be reversed by FFA elevation, seven nondiabetic men underwent [3-3H]glucose infusions from 2200 to 0800, with heparin (90 mU.kg-1.min-1) added at 0200. Glucose appearance (Ra) fell from 11.7 ± 1.1 at 2430 to 8.9 ± 0.8 mumol.kg-1.min-1 (P less than 0.05) at 0200. The fall in Ra was associated with decreases in FFA (0.57 ± 0.10 to 0.48 ± 0.07 mM) and glycerol (0.08 ± 0.01 to 0.06 ± 0.01 mM). Infusion of heparin significantly increased FFA and glycerol (1.09 ± 0.21 and 0.11 ± 0.01 mM, respectively, P less than 0.01) and resulted in a significant fall in plasma alanine, suggesting that gluconeogenesis had been increased. However, rates of glucose turnover were indistinguishable from overnight studies without heparin. In additional studies (n = 6), intralipid and heparin-induced FFA elevation (from 0.61 ± 0.07 to 0.95 ± 0.05 mM, P less than 0.01) stimulated gluconeogenesis ([U-14C]alanine to glucose) twofold (188 ± 22% increase compared to 114 ± 6% in saline control studies, P less than 0.01). However, despite increasing gluconeogenesis, overall HGO did not change (10.6 ± 0.5 vs. 10.7 ± 0.6 mumol.kg-1.min-1) during lipid infusion

  20. Reduced circulating stem cells associate with excess fasting and post-load NEFA exposure in healthy adults with normal glucose tolerance.

    Science.gov (United States)

    Fadini, Gian Paolo; Tura, Andrea; Pacini, Giovanni; Avogaro, Angelo; Vigili de Kreutzenberg, Saula

    2017-06-01

    Reduced levels of circulating stem cells (CSCs) predict cardiovascular events and death, but the factors underlying variability of CSCs in healthy adults are mostly unknown. Previous studies detected associations of CSCs with glucose tolerance or insulin resistance, while the role of fatty acids has been overlooked. We herein aimed to describe in better detail the metabolic abnormalities associated with a reduced CSC level. This was a cross-sectional study on 94 healthy male and female individuals with normal glucose tolerance, aged 18-65 years. All participants underwent an oral glucose tolerance test (OGTT) with blood samples collected at 0, 10, 20, 30, 60, 90 and 120 min. Mathematical models were applied to plasma glucose, insulin, C-peptide and non-esterified fatty acids (NEFA) concentrations. CSCs were defined as CD34 + or CD133 + . Participants (mean ± SEM age 43.8 ± 0.7; 41% males) were divided according to CSC levels below (low) or above (high) the median value and metabolic parameters were compared. There was no significant baseline difference between groups except for higher concentrations of fasting NEFA in subjects with low CSCs. Upon OGTT, individuals with low CSCs had higher area under curve (AUC) of NEFA (p glucose, insulin and C-peptide. Several insulin sensitivity and beta cell function indexes were not significantly different, except for a decrease in the disposition index (DI) in subjects with low CSCs. CSCs were associated with excess NEFA levels independently from age and DI. We show for the first time that, in healthy adults with normal glucose tolerance, low CSCs are strongly associated with excess NEFA exposure. The pathophysiological consequence of this association needs to be interpreted in view of the prognostic role of CSCs. Future studies should explore whether excess NEFA and low CSCs and are causally interconnected. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. pH-switchable electrochemical sensing platform based on chitosan-reduced graphene oxide/concanavalin a layer for assay of glucose and urea.

    Science.gov (United States)

    Song, Yonghai; Liu, Hongyu; Tan, Hongliang; Xu, Fugang; Jia, Jianbo; Zhang, Lixue; Li, Zhuang; Wang, Li

    2014-02-18

    A facile and effective electrochemical sensing platform for the detection of glucose and urea in one sample without separation was developed using chitosan-reduced graphene oxide (CS-rGO)/concanavalin A (Con A) as a sensing layer. The CS-rGO/Con A with pH-dependent surface net charges exhibited pH-switchable response to negatively charged Fe(CN)6(3-). The principle for glucose and urea detection was essentially based on in situ pH-switchable enzyme-catalyzed reaction in which the oxidation of glucose catalyzed by glucose oxidase or the hydrolyzation of urea catalyzed by urease resulted in a pH change of electrolyte solution to give different electrochemical responses toward Fe(CN)6(3-). It was verified by cyclic voltammograms, differential pulse voltammograms, and electrochemical impedance spectroscopy. The resistance to charge transfer or amperometric current changed proportionally toward glucose concentration from 1.0 to 10.0 mM and urea concentration from 1.0 to 7.0 mM. On the basis of human serum experiments, the sensing platform was proved to be suitable for simultaneous assay of glucose and urea in a practical biosystem. This work not only gives a way to detect glucose and urea in one sample without separation but also provides a potential strategy for the detection of nonelectroactive species based on the enzyme-catalyzed reaction and pH-switchable biosensor.

  2. Brain glucose metabolism in an animal model of depression.

    Science.gov (United States)

    Detka, J; Kurek, A; Kucharczyk, M; Głombik, K; Basta-Kaim, A; Kubera, M; Lasoń, W; Budziszewska, B

    2015-06-04

    An increasing number of data support the involvement of disturbances in glucose metabolism in the pathogenesis of depression. We previously reported that glucose and glycogen concentrations in brain structures important for depression are higher in a prenatal stress model of depression when compared with control animals. A marked rise in the concentrations of these carbohydrates and glucose transporters were evident in prenatally stressed animals subjected to acute stress and glucose loading in adulthood. To determine whether elevated levels of brain glucose are associated with a change in its metabolism in this model, we assessed key glycolytic enzymes (hexokinase, phosphofructokinase and pyruvate kinase), products of glycolysis, i.e., pyruvate and lactate, and two selected enzymes of the tricarboxylic acid cycle (pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) in the hippocampus and frontal cortex. Additionally, we assessed glucose-6-phosphate dehydrogenase activity, a key enzyme in the pentose phosphate pathway (PPP). Prenatal stress increased the levels of phosphofructokinase, an important glycolytic enzyme, in the hippocampus and frontal cortex. However, prenatal stress had no effect on hexokinase or pyruvate kinase levels. The lactate concentration was elevated in prenatally stressed rats in the frontal cortex, and pyruvate levels remained unchanged. Among the tricarboxylic acid cycle enzymes, prenatal stress decreased the level of pyruvate dehydrogenase in the hippocampus, but it had no effect on α-ketoglutarate dehydrogenase. Like in the case of glucose and its transporters, also in the present study, differences in markers of glucose metabolism between control animals and those subjected to prenatal stress were not observed under basal conditions but in rats subjected to acute stress and glucose load in adulthood. Glucose-6-phosphate dehydrogenase activity was not reduced by prenatal stress but was found to be even higher in animals exposed to

  3. Circulating Betatrophin Correlates with Triglycerides and Postprandial Glucose among Different Glucose Tolerance Statuses—A Case-Control Study

    Science.gov (United States)

    Chen, Peihong; Jin, Hua; Yang, Lili; Xie, Xinmiao; Yang, Meili; Hu, Cheng; Yu, Xuemei

    2015-01-01

    Purpose Previous researches of betatrophin on glucose and lipids metabolism under insulin-resistant condition have reached controversial conclusions. To further identify the possible impact of betatrophin, we measured the circulating betatrophin levels in newly diagnosed type 2 diabetes (T2DM) patients, and in subjects with both impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) and investigated the relationship between serum betatrophin and other clinical parameters in these patients with different glucose tolerance statuses. Methods A total of 460 permanent residents of the Fengxian District, aged 40–60 years, were enrolled. Based on the results of a 75 g oral glucose tolerance test, we selected newly diagnosed T2DM (n = 50) patients and subjects with IGT (n = 51) and NGT (n = 50) according to their age, gender and body mass index (18–28 kg/m2). Anthropometric parameters, glycosylated haemoglobin, blood lipids and fasting insulin were measured. Serum betatrophin concentrations were determined via ELISA. Results Serum betatrophin levels in T2DM patients were increased significantly compared with IGT and NGT groups, and decreased in subjects with better islet beta cell function. Serum betatrophin was positively correlated with triglyceride, 2-hour postprandial glucose, alanine aminotransferase and aspartate transaminase after adjusting for age, sex and body mass index in all subjects. Multiple regression analysis showed that 2-hour postprandial glucose was independently associated with serum betatrophin significantly. Conclusions Circulating betatrophin is increased in newly-diagnosed T2DM patients and positively correlated with the triglycerides and postprandial glucose levels. The results suggest that betatrophin may participate in glucose and triglycerides metabolism. PMID:26247824

  4. Low-protein, high-carbohydrate diet increases glucose uptake and fatty acid synthesis in brown adipose tissue of rats.

    Science.gov (United States)

    Aparecida de França, Suélem; Pavani Dos Santos, Maísa; Nunes Queiroz da Costa, Roger Vinícius; Froelich, Mendalli; Buzelle, Samyra Lopes; Chaves, Valéria Ernestânia; Giordani, Morenna Alana; Pereira, Mayara Peron; Colodel, Edson Moleta; Marlise Balbinotti Andrade, Cláudia; Kawashita, Nair Honda

    2014-04-01

    The aim of this study was to evaluate glucose uptake and the contribution of glucose to fatty acid (FA) synthesis and the glycerol-3-phosphate (G3P) of triacylglycerol synthesis by interscapular brown adipose tissue (IBAT) of low-protein, high-carbohydrate (LPHC) diet-fed rats. LPHC (6% protein; 74% carbohydrate) or control (17% protein; 63% carbohydrate) diets were administered to rats (∼ 100 g) for 15 d. Total FA and G3P synthesis and the synthesis of FA and G3P from glucose were evaluated in vivo by (3)H2O and (14)C-glucose. Sympathetic neural contribution for FA synthesis was evaluated by comparing the synthesis in denervated (7 d before) IBAT with that of the contralateral innervated side. The insulin signaling and β3 adrenergic receptor (β3-AR) contents, as well as others, were determined by Western blot (Student's t test or analysis of variance; P ≤ 0.05). Total FA synthesis in IBAT was 133% higher in the LPHC group and was reduced 85% and 70% by denervation for the LPHC and control groups, respectively. Glucose uptake was 3.5-fold higher in the IBAT of LPHC rats than in that of the control rats, and the contribution of glucose to the total FA synthesis increased by 12% in control rats compared with 18% in LPHC rats. The LPHC diet increased the G3P generation from glucose by 270% and the insulin receptor content and the p-AKT insulin stimulation in IBAT by 120% and reduced the β3-AR content by 50%. The LPHC diet stimulated glucose uptake, both the total rates and the rates derived from glucose-dependent FA and G3P synthesis, by increasing the insulin sensitivity and the sympathetic flux, despite a reduction in the β3-AR content. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity.

    Science.gov (United States)

    Shi, Xuemei; Chacko, Shaji; Li, Feng; Li, Depei; Burrin, Douglas; Chan, Lawrence; Guan, Xinfu

    2017-11-01

    Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose homeostasis. The objective of this study was to determine whether activation of PPG neurons per se modulates glucose homeostasis and insulin sensitivity in vivo. We generated glucagon (Gcg) promoter-driven Cre transgenic mice and injected excitatory hM3Dq-mCherry AAV into their brainstem NTS. We characterized the metabolic impact of PPG neuron activation on glucose homeostasis and insulin sensitivity using stable isotopic tracers coupled with hyperinsulinemic euglycemic clamp. We showed that after ip injection of clozapine N-oxide, Gcg-Cre lean mice transduced with hM3Dq in the brainstem NTS downregulated basal endogenous glucose production and enhanced glucose tolerance following ip glucose tolerance test. Moreover, acute activation of PPG neurons NTS enhanced whole-body insulin sensitivity as indicated by increased glucose infusion rate as well as augmented insulin-suppression of endogenous glucose production and gluconeogenesis. In contrast, insulin-stimulation of glucose disposal was not altered significantly. We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  6. Assessment of insulin resistance in fructose-fed rats with 125I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport

    International Nuclear Information System (INIS)

    Perret, Pascale; Slimani, Lotfi; Briat, Arnaud; Villemain, Daniele; Fagret, Daniel; Ghezzi, Catherine; Halimi, Serge; Demongeot, Jacques

    2007-01-01

    Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using 125 I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p < 0.05; heart, p < 0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p < 0.001; muscle, p < 0.001; heart, p < 0.01) whereas no significant changes were observed in fructose-fed rats. This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging. (orig.)

  7. Assessment of insulin resistance in fructose-fed rats with 125I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport

    Science.gov (United States)

    Perret, Pascale; Slimani, Lotfi; Briat, Arnaud; Villemain, Danièle; Halimi, Serge; Demongeot, Jacques; Fagret, Daniel; Ghezzi, Catherine

    2007-01-01

    Purpose Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state and it has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats with 125I-6-Deoxy-6-Iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. Methods Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood were assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. Results Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady-state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p<0.01; muscle, p<0.05; heart, p<0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p<0.001; muscle, p<0.001; heart, p<0.01) and whereas no significant changes were observed in fructose-fed rats. Conclusion This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging. PMID:17171359

  8. Loss of arylformamidase with reduced thymidine kinase expression leads to impaired glucose tolerance

    Directory of Open Access Journals (Sweden)

    Alison J. Hugill

    2015-11-01

    Full Text Available Tryptophan metabolites have been linked in observational studies with type 2 diabetes, cognitive disorders, inflammation and immune system regulation. A rate-limiting enzyme in tryptophan conversion is arylformamidase (Afmid, and a double knockout of this gene and thymidine kinase (Tk has been reported to cause renal failure and abnormal immune system regulation. In order to further investigate possible links between abnormal tryptophan catabolism and diabetes and to examine the effect of single Afmid knockout, we have carried out metabolic phenotyping of an exon 2 Afmid gene knockout. These mice exhibit impaired glucose tolerance, although their insulin sensitivity is unchanged in comparison to wild-type animals. This phenotype results from a defect in glucose stimulated insulin secretion and these mice show reduced islet mass with age. No evidence of a renal phenotype was found, suggesting that this published phenotype resulted from loss of Tk expression in the double knockout. However, despite specifically removing only exon 2 of Afmid in our experiments we also observed some reduction of Tk expression, possibly due to a regulatory element in this region. In summary, our findings support a link between abnormal tryptophan metabolism and diabetes and highlight beta cell function for further mechanistic analysis.

  9. Clinical Observations of Abnormal Glucose Tolerance in Hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Ja; Lee, Hong Kyu [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1969-09-15

    Plasma glucose levels before and after oral glucose administration have been compared in g group of 76 thyrotoxic subjects and a group of 8 normal control subjects in order to study the effect of glucose loading in thyrotoxicosis. Following were the results: 1) The mean fasting plasma glucose level was elevated in thyrotoxic group (95.5 mg%) compared to normal control group (88 mg%). 2) The peak of glucose tolerance curve is at 30 minutes after glucose administration in both groups, but its mean value was 44 mg% higher in thyrotoxic group than in control group. 3) The plasma glucose levels returned towards the fasting level in the later stage of the test more rapidly in thyrotoxic group than in control group. 4) 69.6% of oral glucose tolerance tests were impaired in the thyrotoxic group, and the occurrence of abnormal glucose tolerance could be related to the degree of thyrotoxicity, sex and age. 5) The mechanisms of the impaired glucose tolerance in thyrotoxicosis are thought to be related to an increased rate of glucose absorption from gastrointestinal tract, abnormal liver function with decreased hepatic glycogenesis, increased glucose oxidation, decreased pancreatic release of insulin, and genetic relationship between diabetes and thyrotoxicosis.

  10. Differential facilitative effects of glucose administration on Stroop task conditions.

    Science.gov (United States)

    Brandt, Karen R; Gibson, E Leigh; Rackie, James M

    2013-12-01

    Previous research has demonstrated that glucose administration improves memory performance. These glucose facilitation effects have been most reliably demonstrated in medial temporal lobe tasks with the greatest effects found for cognitively demanding tasks. The aim of the proposed research was to first explore whether such effects might be demonstrated in a frontal lobe task. A second aim was to investigate whether any beneficial effects of glucose may arise more prominently under tasks of increasing cognitive demand. To achieve these aims, the Stroop Task was administered to participants and effects of a drink of glucose (25 g) were compared with an aspartame-sweetened control drink on performance in young adults. Results demonstrated that glucose ingestion significantly reduced RTs in the congruent and incongruent conditions. No effect on error rates was observed. Of most importance was the finding that this glucose facilitative effect was significantly greatest in the most cognitively demanding task, that is, the incongruent condition. The present results support the contention that the glucose facilitation effect is most robust under conditions of enhanced task difficulty and demonstrate that such benefits extend to frontal lobe function.

  11. GLP-1 Response to Oral Glucose is Reduced in Pre-diabetes, Screen-detected Type 2 Diabetes, and Obesity and Influenced by Sex

    DEFF Research Database (Denmark)

    Færch, Kristine; Torekov, Signe S; Vistisen, Dorte

    2015-01-01

    concentrations of glucose, insulin and GLP-1 during an oral glucose tolerance test (OGTT) were analyzed in individuals with normal glucose tolerance (NGT, n=774), pre-diabetes (n=523) or screen-detected type 2 diabetes (n=163) who attended the Danish ADDITION-PRO study (n=1,462). Compared with individuals...... with NGT, women with pre-diabetes or type 2 diabetes had 25% lower GLP-1 response to an OGTT, and both men and women with pre-diabetes or type 2 diabetes had 16-21% lower 120-min GLP-1 concentrations independent of age and obesity. Obese and overweight individuals had 20% reduced GLP-1 response to oral...

  12. Postmeal exercise blunts postprandial glucose excursions in people on metformin monotherapy.

    Science.gov (United States)

    Erickson, Melissa L; Little, Jonathan P; Gay, Jennifer L; McCully, Kevin K; Jenkins, Nathan T

    2017-08-01

    Metformin is used clinically to reduce fasting glucose with minimal effects on postprandial glucose. Postmeal exercise reduces postprandial glucose and may offer additional glucose-lowering benefit beyond that of metformin alone, yet controversy exists surrounding exercise and metformin interactions. It is currently unknown how postmeal exercise and metformin monotherapy in combination will affect postprandial glucose. Thus, we examined the independent and combined effects of postmeal exercise and metformin monotherapy on postprandial glucose. A randomized crossover design was used to assess the influence of postmeal exercise on postprandial glucose excursions in 10 people treated with metformin monotherapy (57 ± 10 yr, HbA 1C  = 6.3 ± 0.6%). Each participant completed the following four conditions: sedentary and postmeal exercise (5 × 10-min bouts of treadmill walking at 60% V̇o 2max ) with metformin and sedentary and postmeal exercise without metformin. Peak postprandial glucose within a 2-h time window and 2-h total area under the curve was assessed after a standardized breakfast meal, using continuous glucose monitoring. Postmeal exercise significantly blunted 2-h peak ( P = 0.001) and 2-h area under the curve ( P = 0.006), with the lowest peak postprandial glucose excursion observed with postmeal exercise and metformin combined ( P exercise: 9.7 ± 2.3, washout/sedentary: 13.3 ± 3.2, washout/exercise: 11.1 ± 3.4 mmol/l). Postmeal exercise and metformin in combination resulted in the lowest peak postprandial glucose excursion compared with either treatment modality alone. Exercise timed to the postprandial phase may be important for optimizing glucose control during metformin monotherapy. NEW & NOTEWORTHY The interactive effects of metformin and exercise on key physiological outcomes remain an area of controversy. Findings from this study show that the combination of metformin monotherapy and moderate-intensity postmeal exercise led to

  13. Correlation of salivary glucose level with blood glucose level in diabetes mellitus.

    Science.gov (United States)

    Gupta, Shreya; Nayak, Meghanand T; Sunitha, J D; Dawar, Geetanshu; Sinha, Nidhi; Rallan, Neelakshi Singh

    2017-01-01

    Saliva is a unique fluid, which is important for normal functioning of the oral cavity. Diabetes mellitus (DM) is a disease of absolute or relative insulin deficiency characterized by insufficient secretion of insulin by pancreatic beta-cells. The diagnosis of diabetes through blood is difficult in children, older adults, debilitated and chronically ill patients, so diagnosis by analysis of saliva can be potentially valuable as collection of saliva is noninvasive, easier and technically insensitive, unlike blood. The aim of the study was to correlate blood glucose level (BGL) and salivary glucose level (SGL) in DM patients. A cross-sectional study was conducted in 120 patients, who were categorized as 40 controlled diabetics, 40 uncontrolled diabetics and 40 healthy, age- and sex-matched individuals constituted the controls. The blood and unstimulated saliva samples were collected from the patients at the different intervals for fasting, random and postprandial levels. These samples were then subjected for analysis of glucose in blood and saliva using glucose oxidase/peroxidase reagent in HITACHI 902 (R) Automatic analyzer, and the results were recorded. The mean SGLs were higher in uncontrolled and controlled diabetic groups than in nondiabetic group. A highly statistically significant correlation was found between fasting saliva glucose and fasting blood glucose in all the groups. With increase in BGL, increase in SGL was observed in patients with diabetes suggesting that SGL can be used for monitoring glycemic level in DM.

  14. Chronic Electrical Stimulation at Acupoints Reduces Body Weight and Improves Blood Glucose in Obese Rats via Autonomic Pathway.

    Science.gov (United States)

    Liu, Jiemin; Jin, Haifeng; Foreman, Robert D; Lei, Yong; Xu, Xiaohong; Li, Shiying; Yin, Jieyun; Chen, Jiande D Z

    2015-07-01

    The aim of this study was to investigate effects and mechanisms of chronic electrical stimulation at acupoints (CEA) using surgically implanted electrodes on food intake, body weight, and metabolisms in diet-induced obese (DIO) rats. Thirty-six DIO rats were chronically implanted with electrodes at acupoints ST-36 (Zusanli). Three sets of parameters were tested: electrical acupuncture (EA) 1 (2-s on, 3-s off, 0.5 ms, 15 Hz, 6 mA), EA2 (same as EA1 but continuous pulses), and EA3 (same as EA2 but 10 mA). A chronic study was then performed to investigate the effects of CEA on body weight and mechanisms involving gastrointestinal hormones and autonomic functions. EA2 significantly reduced food intake without uncomfortable behaviors. CEA at EA2 reduced body weight and epididymal fat pad weight (P fasting plasma level of glucagon-like peptide-1 (GLP-1) and peptide YY (P < 0.05); the increase of GLP-1 was inversely correlated with postprandial blood glucose (R (2) = 0.89, P < 0.05); and the plasma ghrelin level remained unchanged. EA increased sympathetic activity (P < 0.01) and reduced vagal activity (P < 0.01). CEA at ST-36 reduces body weight and improves blood glucose possibly attributed to multiple mechanisms involving gastrointestinal motility and hormones via the autonomic pathway.

  15. EFFECT OF SAPPAN WOOD (Caesalpinnia sappan L EXTRACT ON BLOOD GLUCOSE LEVEL IN WHITE RATS

    Directory of Open Access Journals (Sweden)

    Saefudin Saefudin

    2016-05-01

    Full Text Available Sappan wood or kayu secang (Caesalpinia sappan L. was reported of having medicinal properties, such as natural antioxidant, relieve vomiting of blood, and mix of ingredients for malaria drugs. The research was conducted to study the influence of ethanol extract from sappan wood on blood glucose level of white rats. The study of the blood glucose level in rats was carried out by using glucose tolerance method. It was measured by Refloluxs (Accutrend GC with Chloropropamide 50 mg/200 g BW (Body weight as positive control. The ethanol extracts were used in various concentrations 10, 20, 30, 40 and 50 mg/200 g BW per-oral and was observed every hour, beginning one hour before to 7 hours after the extract being administered. The results showed that treatment of ethanol extract of sappan wood by administer doses gave remarkable effect on the blood glucose level in white rat. It reduced the glucose level in the blood compared to the negative and positive control. Treatment of dose 30 mg/200 g BW gave similar effect to positive controls, while a dose of 50 mg/200 g BW gave lower blood glucose level (93 mg/dl than the positive controls.

  16. Glucose in vaginal secretions before and after oral glucose tolerance testing in women with and without recurrent vulvovaginal candidiasis.

    Science.gov (United States)

    Ehrström, Sophia; Yu, Anna; Rylander, Eva

    2006-12-01

    To measure the change of glucose in vaginal secretions during glucose tolerance testing in women with recurrent vulvovaginal candidiasis and in healthy control subjects. Thirty-eight women with recurrent vulvovaginal candidiasis and 45 healthy, age-matched controls completed a health questionnaire regarding general and gynecologic health and food and alcohol habits. They all underwent an oral glucose tolerance test and a vaginal examination. Vaginal secretion was collected from the proximal part of the vagina. Glucose in plasma and in vaginal secretions were measured at fasting and after 2 hours and analyzed with the hexokinase method. A sample size analysis showed that the number of subjects included in the study was sufficient for a beta value of 0.80, at the significance level of alpha=.05, at a difference in glucose in vaginal secretions of 30% after oral glucose tolerance test. In healthy women, the median level of glucose in vaginal secretions was 5.2 mM before and 3.7 mM after oral glucose tolerance test, and plasma glucose was 5.0 mM before and 5.8 mM after oral glucose tolerance test. No significant difference was seen regarding change of glucose level in vaginal secretions and plasma glucose after testing, compared with before oral glucose tolerance testing. There were no differences between women with recurrent vulvovaginal candidiasis and control subjects regarding change in glucose level in vaginal secretions or in plasma during oral glucose tolerance test. II-2.

  17. Arsenate-induced maternal glucose intolerance and neural tube defects in a mouse model

    International Nuclear Information System (INIS)

    Hill, Denise S.; Wlodarczyk, Bogdan J.; Mitchell, Laura E.; Finnell, Richard H.

    2009-01-01

    Background: Epidemiological studies have linked environmental arsenic (As) exposure to increased type 2 diabetes risk. Periconceptional hyperglycemia is a significant risk factor for neural tube defects (NTDs), the second most common structural birth defect. A suspected teratogen, arsenic (As) induces NTDs in laboratory animals. Objectives: We investigated whether maternal glucose homeostasis disruption was responsible for arsenate-induced NTDs in a well-established dosing regimen used in studies of arsenic's teratogenicity in early neurodevelopment. Methods: We evaluated maternal intraperitoneal (IP) exposure to As 9.6 mg/kg (as sodium arsenate) in LM/Bc/Fnn mice for teratogenicity and disruption of maternal plasma glucose and insulin levels. Selected compounds (insulin pellet, sodium selenate (SS), N-acetyl cysteine (NAC), L-methionine (L-Met), N-tert-Butyl-α-phenylnitrone (PBN)) were investigated for their potential to mitigate arsenate's effects. Results: Arsenate caused significant glucose elevation during an IP glucose tolerance test (IPGTT). Insulin levels were not different between arsenate and control dams before (arsenate, 0.55 ng/dl; control, 0.48 ng/dl) or after glucose challenge (arsenate, 1.09 ng/dl; control, 0.81 ng/dl). HOMA-IR index was higher for arsenate (3.9) vs control (2.5) dams (p = 0.0260). Arsenate caused NTDs (100%, p < 0.0001). Insulin pellet and NAC were the most successful rescue agents, reducing NTD rates to 45% and 35%. Conclusions: IPGTT, insulin assay, and HOMA-IR results suggest a modest failure of glucose stimulated insulin secretion and insulin resistance characteristic of glucose intolerance. Insulin's success in preventing arsenate-induced NTDs provides evidence that these arsenate-induced NTDs are secondary to elevated maternal glucose. The NAC rescue, which did not restore maternal glucose or insulin levels, suggests oxidative disruption plays a role.

  18. Long-term high-physiological-dose growth hormone reduces intra-abdominal fat in HIV-infected patients with a neutral effect on glucose metabolism

    DEFF Research Database (Denmark)

    Hansen, B R; Haugaard, S B; Jensen, Frank Krieger

    2010-01-01

    , glucose tolerance, and total plasma cholesterol and triglycerides did not significantly change during intervention. CONCLUSIONS: Daily 0.7 mg rhGH treatment for 40 weeks reduced abdominal visceral fat and trunk fat mass in HIV-infected patients. This treatment appeared to be safe with respect to glucose......OBJECTIVES: The aim of the study was to investigate the effect of long-term high-physiological-dose recombinant human growth hormone (rhGH) therapy on fat distribution and glucose metabolism in HIV-infected patients. METHODS: Forty-six HIV-infected Caucasian men on highly active antiretroviral...... between 1 and 3 pm for 40 weeks. Endpoints included changes in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), limb fat mass, percentage of limb fat, plasma lipids, insulin resistance and glucose tolerance. RESULTS: VAT and trunk fat mass decreased significantly in the GH group compared...

  19. Continuous glucose profiles in obese and normal-weight pregnant women on a controlled diet: metabolic determinants of fetal growth.

    Science.gov (United States)

    Harmon, Kristin A; Gerard, Lori; Jensen, Dalan R; Kealey, Elizabeth H; Hernandez, Teri L; Reece, Melanie S; Barbour, Linda A; Bessesen, Daniel H

    2011-10-01

    We sought to define 24-h glycemia in normal-weight and obese pregnant women using continuous glucose monitoring (CGM) while they consumed a habitual and controlled diet both early and late in pregnancy. Glycemia was prospectively measured in early (15.7 ± 2.0 weeks' gestation) and late (27.7 ± 1.7 weeks' gestation) pregnancy in normal-weight (n = 22) and obese (n = 16) pregnant women on an ad libitum and controlled diet. Fasting glucose, triglycerides (early pregnancy only), nonesterified fatty acids (FFAs), and insulin also were measured. The 24-h glucose area under the curve was higher in obese women than in normal-weight women both early and late in pregnancy despite controlled diets. Nearly all fasting and postprandial glycemic parameters were higher in the obese women later in pregnancy, as were fasting insulin, triglycerides, and FFAs. Infants born to obese mothers had greater adiposity. Maternal BMI (r = 0.54, P = 0.01), late average daytime glucose (r = 0.48, P fasting insulin (r = 0.49, P fasting triglycerides (r = 0.67, P fasting FFAs (r = 0.54, P obese women without diabetes have higher daytime and nocturnal glucose profiles than normal-weight women despite a controlled diet both early and late in gestation. Body fat in infants, not birth weight, was related to maternal BMI, glucose, insulin, and FFAs, but triglycerides were the strongest predictor. These metabolic findings may explain higher rates of infant macrosomia in obese women, which might be targeted in trials to prevent excess fetal growth.

  20. Impaired incretin effect is an early sign of glucose dysmetabolism in nondiabetic patients with psoriasis

    DEFF Research Database (Denmark)

    Gyldenløve, M; Lauritsen, Tina Vilsbøll; Zachariae, Claus

    2015-01-01

    BACKGROUND: Patients with psoriasis have an increased risk of type 2 diabetes. The gastrointestinal system plays a major role in normal glucose metabolism, and in healthy individuals, postprandial insulin secretion is largely mediated by the gut incretin hormones. This potentiation is termed...... the incretin effect and is reduced in type 2 diabetes. The impact of psoriasis on gastrointestinal factors involved in glucose metabolism has not previously been examined. OBJECTIVE: To investigate whether the incretin effect, gastrointestinal-mediated glucose disposal (GIGD) and/or secretion of glucagon...... and gut incretin hormones are impaired in normal glucose-tolerant patients with psoriasis. METHODS: Oral glucose tolerance tests and intravenous isoglycaemic glucose infusions were performed in 12 patients with moderate-to-severe psoriasis and 12 healthy matched control subjects. RESULTS: In patients...

  1. Effect of Guava in Blood Glucose and Lipid Profile in Healthy Human Subjects: A Randomized Controlled Study

    Science.gov (United States)

    Rakavi, R; Mangaraj, Manaswini

    2016-01-01

    Introduction The fruit of Psidium guajava (P.guajava) is known to contain free sugars yet the fruit juice showed hypoglycaemic effect. Hypoglycaemic activity of guava leaves has been well documented but not for guava fruit. Aim So we aimed to evaluate the effect of ripe guava (with peel and without peel) fruit supplementation on blood glucose and lipid profile in healthy human subjects. Materials and Methods Randomized Controlled study undertaken in: 1) Baseline; 2) 6 weeks supplementation phase. Forty five healthy MBBS students were included and randomly enrolled into Group A, Group B and Group C. In Baseline phase: Fasting Plasma Glucose (FPG) and serum lipid profile was done in all 3 groups. Group A were supplemented with 400g of ripe guava with peel and group B without peel, for 6 weeks. Rest 15 treated as control i.e., Group C. Result Supplementation of ripe guava fruit with peel reduced BMI as well as blood pressure (pguava pulp supplementation was not significant. Serum Total cholesterol, Triglycerides and Low Density Lipoprotein Cholesterol (LDLc) levels decreased significantly (pguava pulp without peel may have a favourable effect on lipid levels and blood sugar as well. Conclusion Guava fruit without peel is more effective in lowering blood sugar as well as serum total cholesterol, triglycerides and LDLc. It increases HDLc levels also. PMID:27790420

  2. The woven fiber organic electrochemical transistors based on polypyrrole nanowires/reduced graphene oxide composites for glucose sensing.

    Science.gov (United States)

    Wang, Yuedan; Qing, Xing; Zhou, Quan; Zhang, Yang; Liu, Qiongzhen; Liu, Ke; Wang, Wenwen; Li, Mufang; Lu, Zhentan; Chen, Yuanli; Wang, Dong

    2017-09-15

    Novel woven fiber organic electrochemical transistors based on polypyrrole (PPy) nanowires and reduced graphene oxide (rGO) have been prepared. SEM revealed that the introduction of rGO nanosheets could induce the growth and increase the amount of PPy nanowires. Moreover, it could enhance the electrical performance of fiber transistors. The hybrid transistors showed high on/off ratio of 10 2 , fast switch speed, and long cycling stability. The glucose sensors based on the fiber organic electrochemical transistors have also been investigated, which exhibited outstanding sensitivity, as high as 0.773 NCR/decade, with a response time as fast as 0.5s, a linear range of 1nM to 5μM, a low detection concentration as well as good repeatability. In addition, the glucose could be selectively detected in the presence of ascorbic acid and uric acid interferences. The reliability of the proposed glucose sensor was evaluated in real samples of rabbit blood. All the results indicate that the novel fiber transistors pave the way for portable and wearable electronics devices, which have a promising future for healthcare and biological applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Predicting Plasma Glucose From Interstitial Glucose Observations Using Bayesian Methods

    DEFF Research Database (Denmark)

    Hansen, Alexander Hildenbrand; Duun-Henriksen, Anne Katrine; Juhl, Rune

    2014-01-01

    One way of constructing a control algorithm for an artificial pancreas is to identify a model capable of predicting plasma glucose (PG) from interstitial glucose (IG) observations. Stochastic differential equations (SDEs) make it possible to account both for the unknown influence of the continuous...... glucose monitor (CGM) and for unknown physiological influences. Combined with prior knowledge about the measurement devices, this approach can be used to obtain a robust predictive model. A stochastic-differential-equation-based gray box (SDE-GB) model is formulated on the basis of an identifiable...

  4. Impact of Glucose Tolerance Status, Sex, and Body Size on Glucose Absorption Patterns During OGTTs

    DEFF Research Database (Denmark)

    Faerch, K.; Pacini, G.; Nolan, J. J.

    2013-01-01

    OBJECTIVEWe studied whether patterns of glucose absorption during oral glucose tolerance tests (OGTTs) were abnormal in individuals with impaired glucose regulation and whether they were related to sex and body size (height and fat-free mass). We also examined how well differences in insulin......, reflected the differences for these parameters between those with normal and impaired glucose regulation as measured by gold-standard tests.CONCLUSIONSGlucose absorption patterns during an OGTT are significantly related to plasma glucose levels and body size, which should be taken into account when.......RESULTSMore rapid glucose absorption (P 0.036) and reduced late glucose absorption (P 0.039) were observed in the i-IFG group relative to NGT and i-IGT groups. Women with i-IGT had a lower early glucose absorption than did men with i-IGT (P = 0.041); however, this difference did not persist when differences in body...

  5. Tofogliflozin, a potent and highly specific sodium/glucose cotransporter 2 inhibitor, improves glycemic control in diabetic rats and mice.

    Science.gov (United States)

    Suzuki, Masayuki; Honda, Kiyofumi; Fukazawa, Masanori; Ozawa, Kazuharu; Hagita, Hitoshi; Kawai, Takahiro; Takeda, Minako; Yata, Tatsuo; Kawai, Mio; Fukuzawa, Taku; Kobayashi, Takamitsu; Sato, Tsutomu; Kawabe, Yoshiki; Ikeda, Sachiya

    2012-06-01

    Sodium/glucose cotransporter 2 (SGLT2) is the predominant mediator of renal glucose reabsorption and is an emerging molecular target for the treatment of diabetes. We identified a novel potent and selective SGLT2 inhibitor, tofogliflozin (CSG452), and examined its efficacy and pharmacological properties as an antidiabetic drug. Tofogliflozin competitively inhibited SGLT2 in cells overexpressing SGLT2, and K(i) values for human, rat, and mouse SGLT2 inhibition were 2.9, 14.9, and 6.4 nM, respectively. The selectivity of tofogliflozin toward human SGLT2 versus human SGLT1, SGLT6, and sodium/myo-inositol transporter 1 was the highest among the tested SGLT2 inhibitors under clinical development. Furthermore, no interaction with tofogliflozin was observed in any of a battery of tests examining glucose-related physiological processes, such as glucose uptake, glucose oxidation, glycogen synthesis, hepatic glucose production, glucose-stimulated insulin secretion, and glucosidase reactions. A single oral gavage of tofogliflozin increased renal glucose clearance and lowered the blood glucose level in Zucker diabetic fatty rats. Tofogliflozin also improved postprandial glucose excursion in a meal tolerance test with GK rats. In db/db mice, 4-week tofogliflozin treatment reduced glycated hemoglobin and improved glucose tolerance in the oral glucose tolerance test 4 days after the final administration. No blood glucose reduction was observed in normoglycemic SD rats treated with tofogliflozin. These findings demonstrate that tofogliflozin inhibits SGLT2 in a specific manner, lowers blood glucose levels by increasing renal glucose clearance, and improves pathological conditions of type 2 diabetes with a low hypoglycemic potential.

  6. Systematic review and meta-analysis of the effectiveness of continuous glucose monitoring (CGM) on glucose control in diabetes

    OpenAIRE

    Poolsup, Nalinee; Suksomboon, Naeti; Kyaw, Aye Mon

    2013-01-01

    Diabetes mellitus is a chronic disease that necessitates continuing treatment and patient self-care education. Monitoring of blood glucose to near normal level without hypoglycemia becomes a challenge in the management of diabetes. Although self monitoring of blood glucose (SMBG) can provide daily monitoring of blood glucose level and help to adjust therapy, it cannot detect hypoglycemic unawareness and nocturnal hypoglycemia which occurred mostly in T1DM pediatrics. Continuous glucose monito...

  7. Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System.

    Science.gov (United States)

    Daniele, Giuseppe; Iozzo, Patricia; Molina-Carrion, Marjorie; Lancaster, Jack; Ciociaro, Demetrio; Cersosimo, Eugenio; Tripathy, Devjit; Triplitt, Curtis; Fox, Peter; Musi, Nicolas; DeFronzo, Ralph; Gastaldelli, Amalia

    2015-10-01

    Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMRglu) was measured by positron emission tomography after an injection of [(18)F]2-fluoro-2-deoxy-d-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO0-60 min (4.6 ± 1.4 vs. 13.1 ± 1.7 μmol/min ⋅ kg) and decreased the rise in mean glucose0-60 min (107 ± 6 vs. 138 ± 8 mg/dL) and insulin0-60 min (17.3 ± 3.1 vs. 24.7 ± 3.8 mU/L). Exenatide increased CMRglu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO0-60 min after exenatide was inversely correlated to CMRglu. In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  8. Glucose phosphorylation rate in rat parietal cortex during normoglycemia, hypoglycemia, acute hyperglycemia, and in diabetes-prone rats

    Energy Technology Data Exchange (ETDEWEB)

    Broendsted, H.E.; Gjedde, A. (Department of General Physiology and Biophysics, Panum Institute, University of Copenhagen (Denmark))

    1990-01-01

    Cerebral metabolic rate for glucose (CMRglc) was studied in rats using (6-{sup 14}C)glucose. After intravenous injection the radioactivity of the parietal cortex was corrected for loss of labeled CO{sub 2} and divided by the integral of the arterial plasma glucose concentration, determined during tracer circulation. Treatment with insulin, resulting in plasma glucose concentrations less than 2.6 mmol/l, reduced CMRglc to 64% of the values found in control animals. CMRglc did not change in animals with acute hyper-glycemia produced by intraperiotoneal injection of a glucose solution or in diabetes-prone rats with or withour insulin treatment. (author).

  9. Glucose phosphorylation rate in rat rarietal cortex during normoglycemia, hypoglycemia, acute hyperglycemia, and in diabetes-prone rats

    International Nuclear Information System (INIS)

    Broendsted, H.E.; Gjedde, A.

    1990-01-01

    Cerebral metabolic rate for glucose (CMRglc) was studied in rats using [6- 14 C]glucose. After intravenous injection the radioactivity of the parietal cortex was corrected for loss of labeled CO 2 and divided by the integral of the arterial plasma glucose concentration, determined during tracer circulation. Treatment with insulin, resulting in plasma glucose concentrations less than 2.6 mmol/l, reduced CMRglc to 64% of the values found in control animals. CMRglc did not change in animals with acute hyper-glycemia produced by intraperiotoneal injection of a glucose solution or in diabetes-prone rats with or withour insulin treatment. (author)

  10. Assessment of insulin resistance in fructose-fed rats with {sup 125}I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport

    Energy Technology Data Exchange (ETDEWEB)

    Perret, Pascale; Slimani, Lotfi; Briat, Arnaud; Villemain, Daniele; Fagret, Daniel; Ghezzi, Catherine [INSERM, E340, 38000 Grenoble, (France); Univ Grenoble, 38000 Grenoble, (France); Halimi, Serge [CHRU Grenoble, Hopital Michallon, Service de Diabetologie, 38000 Grenoble, (France); Demongeot, Jacques [Univ Grenoble, 38000 Grenoble, (France); CNRS, UMR 5525, 38000 Grenoble, (France)

    2007-05-15

    Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using {sup 125}I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p < 0.05; heart, p < 0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p < 0.001; muscle, p < 0.001; heart, p < 0.01) whereas no significant changes were observed in fructose-fed rats. This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging. (orig.)

  11. The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity.

    Science.gov (United States)

    Kelly, Karen R; Brooks, Latina M; Solomon, Thomas P J; Kashyap, Sangeeta R; O'Leary, Valerie B; Kirwan, John P

    2009-06-01

    Aging and obesity are characterized by decreased beta-cell sensitivity and defects in the potentiation of nutrient-stimulated insulin secretion by GIP. Exercise and diet are known to improve glucose metabolism and the pancreatic insulin response to glucose, and this effect may be mediated through the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% Vo(2 max)) combined with a eucaloric (EX, n = 10) or hypocaloric (EX-HYPO, pre: 1,945 +/- 190, post: 1,269 +/- 70, kcal/day; n = 9) diet on the GIP response to glucose in older (66.8 +/- 1.5 yr), obese (34.4 +/- 1.7 kg/m(2)) adults with impaired glucose tolerance. In addition to GIP, plasma PYY(3-36), insulin, and glucose responses were measured during a 3-h, 75-g oral glucose tolerance test. Both interventions led to a significant improvement in Vo(2 max) (P HYPO (-8.3 +/- 1.1 vs. -2.8 +/- 0.5, P = 0.002). The glucose-stimulated insulin response was reduced after EX-HYPO (P = 0.02), as was the glucose-stimulated GIP response (P caloric restriction and exercise reduces the GIP response to ingested glucose, 2) GIP may mediate the attenuated glucose-stimulated insulin response after exercise/diet interventions, and 3) the increased PYY(3-36) response represents an improved capacity to regulate satiety and potentially body weight in older, obese, insulin-resistant adults.

  12. In vitro antioxidant, hypoglycemic and oral glucose tolerance test of banana peels

    Directory of Open Access Journals (Sweden)

    V.V. Navghare

    2017-08-01

    Full Text Available Banana fruit is claimed to have antidiabetic effects despite its high calorie content, and its peels also contain vital phytoconstituents including gallocatechin. Previously banana pulp has been studied for antihyperglycemic effects, and in the present investigation antihyperglycemic effect of ethanolic extract of inner peels of Musa sapientum (EMS, Musa paradisiaca (EMP, Musa cavendish (EMC and Musa acuminata (EMA fruit was evaluated using oral glucose tolerance test in normoglycemic rats. In vitro antioxidant study was conducted using DPPH, H2O2 radical scavenging assay and ferric reducing power assay. Wistar rats were divided into fourteen groups and twelve groups received different doses of aforementioned extracts, while control group received gum acacia solution and remaining group received standard drug, glimepiride. All the rats received glucose load at a dose of 2 g/kg body weight. Groups treated with EMC and EMA showed significant decrease in glucose level (p < 0.01 at 150 min as compared to control group. In hypoglycemic study, only EMP 500 mg/kg, p.o. treated group revealed a significant decrease (p < 0.05 in glucose level at 120 min, while other groups did not show any sign of hypoglycemia. In glucose tolerance test, animals treated with EMC and EMA depicted dose dependent antihyperglycemic effect at 150 min while EMS and EMP showed significant reduction in plasma glucose at higher doses. In a similar fashion, EMA i.e. M. acuminata demonstrated highest antioxidant activity followed by EMC against DPPH radical. In ferric reducing power and H2O2 scavenging assay, EMA demonstrated maximal antioxidant activity when compared with other extracts.

  13. Glucose metabolism disorder in obese children assessed by continuous glucose monitoring system.

    Science.gov (United States)

    Zou, Chao-Chun; Liang, Li; Hong, Fang; Zhao, Zheng-Yan

    2008-02-01

    Continuous glucose monitoring system (CGMS) can measure glucose levels at 5-minute intervals over a few days, and may be used to detect hypoglycemia, guide insulin therapy, and control glucose levels. This study was undertaken to assess the glucose metabolism disorder by CGMS in obese children. Eighty-four obese children were studied. Interstitial fluid (ISF) glucose levels were measured by CGMS for 24 hours covering the time for oral glucose tolerance test (OGTT). Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), type 2 diabetic mellitus (T2DM) and hypoglycemia were assessed by CGMS. Five children failed to complete CGMS test. The glucose levels in ISF measured by CGMS were highly correlated with those in capillary samples (r=0.775, Pobese children who finished the CGMS, 2 children had IFG, 2 had IGT, 3 had IFG + IGT, and 2 had T2DM. Nocturnal hypoglycemia was noted during the overnight fasting in 11 children (13.92%). Our data suggest that glucose metabolism disorder including hyperglycemia and hypoglycemia is very common in obese children. Further studies are required to improve the precision of the CGMS in children.

  14. Facile and controllable preparation of glucose biosensor based on Prussian blue nanoparticles hybrid composites.

    Science.gov (United States)

    Li, Lei; Sheng, Qinglin; Zheng, Jianbin; Zhang, Hongfang

    2008-11-01

    A glucose biosensor based on polyvinylpyrrolidone (PVP) protected Prussian blue nanoparticles (PBNPs)-polyaniline/multi-walled carbon nanotubes hybrid composites was fabricated by electrochemical method. A novel route for PBNPs preparation was applied in the fabrication with the help of PVP, and from scanning electron microscope images, Prussian blue particles on the electrode were found nanoscaled. The biosensor exhibits fast current response (<6 s) and a linearity in the range from 6.7x10(-6) to 1.9x10(-3) M with a high sensitivity of 6.28 microA mM(-1) and a detection limit of 6x10(-7) M (S/N=3) for the detection of glucose. The apparent activation energy of enzyme-catalyzed reaction and the apparent Michaelis-Menten constant are 23.9 kJ mol(-1) and 1.9 mM respectively, which suggests a high affinity of the enzyme-substrate. This easy and controllable construction method of glucose biosensor combines the characteristics of the components of the hybrid composites, which favors the fast and sensitive detection of glucose with improved analytical capabilities. In addition, the biosensor was examined in human serum samples for glucose determination with a recovery between 95.0 and 104.5%.

  15. Current concepts in blood glucose monitoring

    OpenAIRE

    Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

    2013-01-01

    Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on t...

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose ... glucose) Dawn Phenomenon Checking for Ketones Tight Diabetes Control donate en -- A Future Without Diabetes - a-future- ...

  17. Combining insulins for optimal blood glucose control in type 1 and 2 diabetes: focus on insulin glulisine

    Directory of Open Access Journals (Sweden)

    Heather Ulrich

    2007-07-01

    Full Text Available Heather Ulrich1,4, Benjamin Snyder1,Satish K Garg1,2,31Barbara Davis Center for Childhood Diabetes; 2Department of Medicine; 3Pediatrics; 4Department of Clinical Pharmacy, School of Pharmacy, University of Colorado at Denver and Health Sciences Center, Denver, CO, USAAbstract: Normalization of blood glucose is essential for the prevention of diabetes mellitus (DM-related microvascular and macrovascular complications. Despite substantial literature to support the benefits of glucose lowering and clear treatment targets, glycemic control remains suboptimal for most people with DM in the United States. Pharmacokinetic limitations of conventional insulins have been a barrier to achieving treatment targets secondary to adverse effects such as hypoglycemia and weight gain. Recombinant DNA technology has allowed modification of the insulin molecule to produce insulin analogues that overcome these pharmacokinetic limitations. With time action profiles that more closely mimic physiologic insulin secretion, rapid acting insulin analogues (RAAs reduce post-prandial glucose excursions and hypoglycemia when compared to regular human insulin (RHI. Insulin glulisine (Apidra® is a rapid-acting insulin analogue created by substituting lysine for asparagine at position B3 and glutamic acid for lysine at position B29 on the B chain of human insulin. The quick absorption of insulin glulisine more closely reproduces physiologic first-phase insulin secretion and its rapid acting profile is maintained across patient subtypes. Clinical trials have demonstrated comparable or greater efficacy of insulin glulisine versus insulin lispro or RHI, respectively. Efficacy is maintained even when insulin glulisine is administered post-meal. In addition, glulisine appears to have a more rapid time action profile compared with insulin lispro across various body mass indexes (BMIs. The safety and tolerability profile of insulin glulisine is also comparable to that of insulin

  18. Orexins control intestinal glucose transport by distinct neuronal, endocrine and direct epithelial pathways. : Orexins regulate intestinal glucose absorption

    OpenAIRE

    Ducroc, Robert; Voisin, Thierry; El Firar, Aadil; Laburthe, Marc

    2007-01-01

    International audience; Objective : Orexins are neuropeptides involved in energy homeostasis. We investigated the effect of orexin A (OxA) and OxB on intestinal glucose transport in the rat. Research Design and Methods : Injection of orexins led to a decrease in the blood glucose level in OGTT. Effects of orexins on glucose entry were analysed in Ussing chamber using the Na+-dependent increase in short-circuit current to quantify jejunal glucose transport. Results & Conclusions : The rapid an...

  19. Which evidence-based strategies reduce perioperative morbidity ...

    African Journals Online (AJOL)

    adopted to reduce serious complications after surgery. There is ... postoperative pain after major surgery. • Epidural ... major abdominal surgery, and should be given before skin ... There is no evidence that intraoperative tight glucose control.

  20. Abnormal transient rise in hepatic glucose production after oral glucose in non-insulin-dependent diabetic subjects.

    Science.gov (United States)

    Thorburn, A; Litchfield, A; Fabris, S; Proietto, J

    1995-05-01

    A transient rise in hepatic glucose production (HGP) after an oral glucosa load has been reported in some insulin-resistant states such as in obese fa/fa Zucker rats. The aim of this study was to determine whether this rise in HGP also occurs in subjects with established non-insulin-dependent diabetes mellitus (NIDDM). Glucose kinetics were measured basally and during a double-label oral glucose tolerance test (OGTT) in 12 NIDDM subjects and 12 non-diabetic 'control' subjects. Twenty minutes after the glucose load, HGP had increased 73% above basal in the NIDDM subjects (7.29 +/- 0.52 to 12.58 +/- 1.86 mumol/kg/min, P < 0.02). A transient rise in glucagon (12 pg/ml above basal, P < 0.004) occurred at a similar time. In contrast, the control subjects showed no rise in HGP or plasma glucagon. HGP began to suppress 40-50 min after the OGTT in both the NIDDM and control subjects. A 27% increase in the rate of gut-derived glucose absorption was also observed in the NIDDM group, which could be the result of increased gut glucose absorption or decreased first pass extraction of glucose by the liver. Therefore, in agreement with data in animal models of NIDDM, a transient rise in HGP partly contributes to the hyperglycemia observed after an oral glucose load in NIDDM subjects.

  1. Effects of Higher Dietary Protein and Fiber Intakes at Breakfast on Postprandial Glucose, Insulin, and 24-h Interstitial Glucose in Overweight Adults.

    Science.gov (United States)

    Amankwaah, Akua F; Sayer, R Drew; Wright, Amy J; Chen, Ningning; McCrory, Megan A; Campbell, Wayne W

    2017-04-02

    Dietary protein and fiber independently influence insulin-mediated glucose control. However, potential additive effects are not well-known. Men and women ( n = 20; age: 26 ± 5 years; body mass index: 26.1 ± 0.2 kg/m²; mean ± standard deviation) consumed normal protein and fiber (NPNF; NP = 12.5 g, NF = 2 g), normal protein and high fiber (NPHF; NP = 12.5 g, HF = 8 g), high protein and normal fiber (HPNF; HP = 25 g, NF = 2 g), or high protein and fiber (HPHF; HP = 25 g, HF = 8 g) breakfast treatments during four 2-week interventions in a randomized crossover fashion. On the last day of each intervention, meal tolerance tests were completed to assess postprandial (every 60 min for 240 min) serum glucose and insulin concentrations. Continuous glucose monitoring was used to measure 24-h interstitial glucose during five days of the second week of each intervention. Repeated-measures ANOVA was applied for data analyses. The HPHF treatment did not affect postprandial glucose and insulin responses or 24-h glucose total area under the curve (AUC). Higher fiber intake reduced 240-min insulin AUC. Doubling the amount of protein from 12.5 g to 25 g/meal and quadrupling fiber from 2 to 8 g/meal at breakfast was not an effective strategy for modulating insulin-mediated glucose responses in these young, overweight adults.

  2. Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet

    Directory of Open Access Journals (Sweden)

    Vickers SP

    2014-07-01

    Full Text Available Steven P Vickers,1 Sharon C Cheetham,1 Katie R Headland,1 Keith Dickinson,1 Rolf Grempler,2 Eric Mayoux,2 Michael Mark,2 Thomas Klein2 1RenaSci, BioCity Nottingham, Nottingham, UK; 2Boehringer Ingelheim Pharma, Biberach an der Riss, Germany Abstract: The present study assessed the potential of the sodium glucose-linked transporter (SGLT-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes. Keywords

  3. Modulation of memory with septal injections of morphine and glucose: effects on extracellular glucose levels in the hippocampus.

    Science.gov (United States)

    McNay, Ewan C; Canal, Clinton E; Sherwin, Robert S; Gold, Paul E

    2006-02-28

    The concentration of glucose in the extracellular fluid (ECF) of the hippocampus decreases substantially during memory testing on a hippocampus-dependent memory task. Administration of exogenous glucose, which enhances task performance, prevents this decrease, suggesting a relationship between hippocampal glucose availability and memory performance. In the present experiment, spontaneous alternation performance and task-related changes in hippocampal ECF glucose were assessed in rats after intraseptal administration of morphine, which impairs memory on a spontaneous alternation task, and after co-administration of intraseptal glucose, which attenuates that impairment. Consistent with previous findings, spontaneous alternation testing resulted in a decrease in hippocampal ECF glucose levels in control rats. However, rats that received intraseptal morphine prior to testing showed memory impairments and an absence of the task-related decrease in hippocampal ECF glucose levels. Intraseptal co-administration of glucose with morphine attenuated the memory impairment, and ECF glucose levels in the hippocampus decreased in a manner comparable to that seen in control rats. These data suggest that fluctuations in hippocampal ECF glucose levels may be a marker of mnemonic processing and support the view that decreases in extracellular glucose during memory testing reflect increased glucose demand during memory processing.

  4. Glucose oxidase probe as a surface-enhanced Raman scattering sensor for glucose.

    Science.gov (United States)

    Qi, Guohua; Wang, Yi; Zhang, Biying; Sun, Dan; Fu, Cuicui; Xu, Weiqing; Xu, Shuping

    2016-10-01

    Glucose oxidase (GOx) possessing a Raman-active chromophore (flavin adenine dinucleotide) is used as a signal reporter for constructing a highly specific "turn off" surface-enhanced Raman scattering (SERS) sensor for glucose. This sensing chip is made by the electrostatic assembly of GOx over silver nanoparticle (Ag NP)-functionalized SERS substrate through a positively charged polyelectrolyte linker under the pH of 6.86. To trace glucose in blood serum, owing to the reduced pH value caused by the production of gluconic acid in the GOx-catalyzed oxidation reaction, the bonding force between GOx and polyelectrolyte weakens, making GOx drop off from the sensing chip. As a result, the SERS intensity of GOx on the chip decreases along with the concentration of glucose. This glucose SERS sensor exhibits excellent selectivity based on the specific GOx/glucose catalysis reaction and high sensitivity to 1.0 μM. The linear sensing range is 2.0-14.0 mM, which also meets the requirement on the working range of the human blood glucose detection. Using GOx as a probe shows superiority over other organic probes because GOx almost has no toxicity to the biological system. This sensing mechanism can be applied for intracellular in vivo SERS monitoring of glucose in the future. Graphical abstract Glucose oxidase is used as a Raman signal reporter for constructing a highly specific glucose surface-enhanced Raman scattering (SERS) sensor.

  5. Continuous tissue glucose monitoring correlates with measurement of intermittent capillary glucose in patients with distributive shock.

    Science.gov (United States)

    Ballesteros, D; Martínez, Ó; Blancas Gómez-Casero, R; Martín Parra, C; López Matamala, B; Estébanez, B; Chana, M

    2015-10-01

    Intermittent glycemic measurements in patients admitted to the intensive care unit (ICU) can result in episodes of severe hypoglycemia or in a poor control of glycemia range. We designed a study to assess accuracy and reliability of continuous monitoring of tissue glucose for patients with distributive shock. Consecutive patients admitted to the ICU with a diagnosis of distributive shock and the need of insulin infusion for glycemic control were included in the study. These patients were implanted a Continuous Glucose Control Monitoring System (CGMS) with the sensor inserted subcutaneously into the abdominal wall. CGMS values were recorded every 5min. Capillary glucose (CG) was monitored for adjusting insulin perfusion according to the ICU protocol. Correlation between both methods was assessed. A total of 11,673 CGMS and 348 CG values were recorded. In five patients, CGMS failed to detect tissue glucose. A glucose value <3.33mmol/l (<60mg/dl) was observed in 3.6% of CGMS and in 0.29% CG values. 295 pairs of measurements were included in the statistical analysis for correlation assessment. The intraclass correlation coefficient was 0.706. The Pearson correlation coefficient was 0.71 (p<0.0001, 95% CI 0.65-0.76). The mean of differences between both measurement methods was 0.22mmol/l (3.98mg/dl) (95% CI 0.66-7.31). When the Continuous Glucose Control Monitoring System (CGMS) is able to obtain data (75% of the patients), there is correlation between the values obtained by this method and capillary blood glucose in patients with distributive shock. CGMS can detect more episodes of glycemic excursions outside the normal range than intermittent capillary glucose monitoring. Variables that may impair glucose metabolism and peripheral soft tissues perfusion could impair CGMS measurements. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  6. Central control of glucose homeostasis: the brain--endocrine pancreas axis.

    Science.gov (United States)

    Thorens, B

    2010-10-01

    A large body of data gathered over the last decades has delineated the neuronal pathways that link the central nervous system with the autonomic innervation of the endocrine pancreas, which controls alpha- and beta-cell secretion activity and mass. These are important regulatory functions that are certainly keys for preserving the capacity of the endocrine pancreas to control glucose homeostasis over a lifetime. Identifying the cells involved in controlling the autonomic innervation of the endocrine pancreas, in response to nutrient, hormonal and environmental cues and how these cues are detected to activate neuronal activity are important goals of current research. Elucidation of these questions may possibly lead to new means for preserving or restoring defects in insulin and glucagon secretion associated with type 2 diabetes. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  7. A mathematical model of brain glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Kimura Hidenori

    2009-11-01

    Full Text Available Abstract Background The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. Methods In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.

  8. Response to dexamethasone is glucose-sensitive in multiple myeloma cell lines

    Directory of Open Access Journals (Sweden)

    Turturro Francesco

    2011-09-01

    Full Text Available Abstract Background Hyperglycemia is among the major side effects of dexamethasone (DEX. Glucose or glucocorticoid (GC regulates the expression of thioredoxin-interacting protein (TXNIP that controls the production of reactive oxygen species (ROS through the modulation of thioredoxin (TRX activity. Methods Multiple myeloma (MM cells were grown in 5 or 20 mM/L glucose with or without 25 μM DEX. Semiquantitative reverse transcription-PCR (RT-PCR was used to assess TXNIP RNA expression in response to glucose and DEX. ROS were detected by 5-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA. TRX activity was assayed by the insulin disulfide-reducing assay. Proliferation was evaluated using CellTiter96 reagent with 490-nm absorbtion and used to calculate the DEX IC50 in 20 mM/L glucose using the Chou's dose effect equation. Results TXNIP RNA level responded to glucose or DEX with the same order of magnitude ARH77 > NCIH929 > U266B1 in these cells. MC/CAR cells were resistant to the regulation. ROS level increased concurrently with reduced TRX activity. Surprisingly glucose increased TRX activity in MC/CAR cells keeping ROS level low. DEX and glucose were lacking the expected additive effect on TXNIP RNA regulation when used concurrently in sensitive cells. ROS level was significantly lower when DEX was used in conditions of hyperglycemia in ARH77/NCIH9292 cells but not in U266B1 cells. Dex-IC50 increased 10-fold when the dose response effect of DEX was evaluated with glucose in ARH && and MC/Car cells Conclusions Our study shows for the first time that glucose or DEX regulates important components of ROS production through TXNIP modulation or direct interference with TRX activity in MM cells. We show that glucose modulates the activity of DEX through ROS regualtion in MM cells. A better understanding of these pathways may help in improving the efficacy and reducing the toxicity of DEX, a drug still highly used in the treatment of

  9. Increased glucose dependence in resting, iron-deficient rats

    International Nuclear Information System (INIS)

    Brooks, G.A.; Henderson, S.A.; Dallman, P.R.

    1987-01-01

    Rates of blood glucose and lactate turnover were assessed in resting iron-deficient and iron-sufficient (control) rats to test the hypothesis that dependence on glucose metabolism is increased in iron deficiency. Male Sprague-Dawley rats, 21 days old, were fed a diet containing either 6 mg iron/kg feed (iron-deficient group) or 50 mg iron/kg feed (iron-sufficient group) for 3-4 wk. The iron-deficient group became anemic, with hemoglobin levels of 6.4 ± 0.2 compared with 13.8 ± 0.3 g/dl for controls. Rats received a 90-min primed continuous infusion of D-[6- 3 H]glucose and sodium L-[U- 14 C]lactate via a jugular catheter. Serial samples were taken from a carotid catheter for concentration and specific activity determinations. Iron-deficient rats had significantly higher blood glucose and lactate concentrations than controls. The iron-deficient group had a significantly higher glucose turnover rate than the control group. Significantly more metabolite recycling in iron-deficient rats was indicated by greater incorporation of 14 C into blood glucose. Assuming a carbon crossover correction factor of 2, half of blood glucose arose from lactate in deficient animals. By comparison, only 25% of glucose arose from lactate in controls. Lack of a difference in lactate turnover rates between deficient rats and controls was attributed to 14 C recycling. The results indicate a greater dependence on glucose metabolism in iron-deficient rats

  10. Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis.

    Science.gov (United States)

    Mir-Coll, Joan; Duran, Jordi; Slebe, Felipe; García-Rocha, Mar; Gomis, Ramon; Gasa, Rosa; Guinovart, Joan J

    2016-05-01

    Glycogen accumulation occurs in beta cells of diabetic patients and has been proposed to partly mediate glucotoxicity-induced beta cell dysfunction. However, the role of glycogen metabolism in beta cell function and its contribution to diabetes pathophysiology remain poorly understood. We investigated the function of beta cell glycogen by studying glucose homeostasis in mice with (1) defective glycogen synthesis in the pancreas; and (2) excessive glycogen accumulation in beta cells. Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using pancreas-specific Cre lines. Glucose homeostasis was assessed by determining fasting glycaemia, insulinaemia and glucose tolerance. Beta cell mass was determined by morphometry. Glycogen was detected histologically by periodic acid-Schiff's reagent staining. Isolated islets were used for the determination of glycogen and insulin content, insulin secretion, immunoblots and gene expression assays. Gys1 knockout (Gys1 (KO)) mice did not exhibit differences in glucose tolerance or basal glycaemia and insulinaemia relative to controls. Insulin secretion and gene expression in isolated islets was also indistinguishable between Gys1 (KO) and controls. Conversely, despite effective glycogen overaccumulation in islets, mice with PTG overexpression (PTG(OE)) presented similar glucose tolerance to controls. However, under fasting conditions they exhibited lower glycaemia and higher insulinaemia. Importantly, neither young nor aged PTG(OE) mice showed differences in beta cell mass relative to age-matched controls. Finally, a high-fat diet did not reveal a beta cell-autonomous phenotype in either model. Glycogen metabolism is not required for the maintenance of beta cell function. Glycogen accumulation in beta cells alone is not sufficient to trigger the dysfunction or loss of these cells, or progression to diabetes.

  11. Current concepts in blood glucose monitoring.

    Science.gov (United States)

    Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

    2013-12-01

    Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus.

  12. Current concepts in blood glucose monitoring

    Science.gov (United States)

    Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

    2013-01-01

    Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus. PMID:24910827

  13. Current concepts in blood glucose monitoring

    Directory of Open Access Journals (Sweden)

    Kranti Shreesh Khadilkar

    2013-01-01

    Full Text Available Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG and continuous glucose monitoring system (CGMS. It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus.

  14. Rice (Oryza sativa japonica) Albumin Suppresses the Elevation of Blood Glucose and Plasma Insulin Levels after Oral Glucose Loading.

    Science.gov (United States)

    Ina, Shigenobu; Ninomiya, Kazumi; Mogi, Takashi; Hase, Ayumu; Ando, Toshiki; Matsukaze, Narumi; Ogihara, Jun; Akao, Makoto; Kumagai, Hitoshi; Kumagai, Hitomi

    2016-06-22

    The suppressive effect of rice albumin (RA) of 16 kDa on elevation of blood glucose level after oral loading of starch or glucose and its possible mechanism were examined. RA suppressed the increase in blood glucose levels in both the oral starch tolerance test and the oral glucose tolerance test. The blood glucose concentrations 15 min after the oral administration of starch were 144 ± 6 mg/dL for control group and 127 ± 4 mg/dL for RA 200 mg/kg BW group, while those after the oral administration of glucose were 157 ± 7 mg/dL for control group and 137 ± 4 mg/dL for RA 200 mg/kg BW group. However, in the intraperitoneal glucose tolerance test, no significant differences in blood glucose level were observed between RA and the control groups, indicating that RA suppresses the glucose absorption from the small intestine. However, RA did not inhibit the activity of mammalian α-amylase. RA was hydrolyzed to an indigestible high-molecular-weight peptide (HMP) of 14 kDa and low-molecular-weight peptides by pepsin and pancreatin. Furthermore, RA suppressed the glucose diffusion rate through a semipermeable membrane like dietary fibers in vitro. Therefore, the indigestible HMP may adsorb glucose and suppress its absorption from the small intestine.

  15. Tattoo-based noninvasive glucose monitoring: a proof-of-concept study.

    Science.gov (United States)

    Bandodkar, Amay J; Jia, Wenzhao; Yardımcı, Ceren; Wang, Xuan; Ramirez, Julian; Wang, Joseph

    2015-01-06

    We present a proof-of-concept demonstration of an all-printed temporary tattoo-based glucose sensor for noninvasive glycemic monitoring. The sensor represents the first example of an easy-to-wear flexible tattoo-based epidermal diagnostic device combining reverse iontophoretic extraction of interstitial glucose and an enzyme-based amperometric biosensor. In-vitro studies reveal the tattoo sensor's linear response toward physiologically relevant glucose levels with negligible interferences from common coexisting electroactive species. The iontophoretic-biosensing tattoo platform is reduced to practice by applying the device on human subjects and monitoring variations in glycemic levels due to food consumption. Correlation of the sensor response with that of a commercial glucose meter underscores the promise of the tattoo sensor to detect glucose levels in a noninvasive fashion. Control on-body experiments demonstrate the importance of the reverse iontophoresis operation and validate the sensor specificity. This preliminary investigation indicates that the tattoo-based iontophoresis-sensor platform holds considerable promise for efficient diabetes management and can be extended toward noninvasive monitoring of other physiologically relevant analytes present in the interstitial fluid.

  16. Glucose-dependent insulinotropic polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel Bring

    2016-01-01

    was to investigate how the blood glucose level affects the glucagon and insulin responses to GIP in healthy subjects (Study 1) and patients with Type 2 diabetes (Study 2), and more specifically to investigate the effects of GIP and GLP-1 at low blood glucose in patients with Type 1 diabetes without endogenous...... as his own control. Interventions were intravenous administration of hormones GIP, GLP-1 and placebo (saline) during different blood glucose levels maintained (clamped) at a certain level. The end-points were plasma concentrations of glucagon and insulin as well as the amount of glucose used to clamp...... the blood glucose levels. In Study 3, we also used stable glucose isotopes to estimate the endogenous glucose production and assessed symptoms and cognitive function during hypoglycaemia. The results from the three studies indicate that GIP has effects on insulin and glucagon responses highly dependent upon...

  17. Spexin peptide is expressed in human endocrine and epithelial tissues and reduced after glucose load in type 2 diabetes.

    Science.gov (United States)

    Gu, Liping; Ma, Yuhang; Gu, Mingyu; Zhang, Ying; Yan, Shuai; Li, Na; Wang, Yufan; Ding, Xiaoying; Yin, Jiajing; Fan, Nengguang; Peng, Yongde

    2015-09-01

    Spexin mRNA and protein are widely expressed in rat tissues and associate with weight loss in rodents of diet-induced obesity. Its location in endocrine and epithelial cells has also been suggested. Spexin is a novel peptide that involves weight loss in rodents of diet-induced obesity. Therefore, we aimed to examine its expression in human tissues and test whether spexin could have a role in glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). The expression of the spexin gene and immunoreactivity in the adrenal gland, skin, stomach, small intestine, liver, thyroid, pancreatic islets, visceral fat, lung, colon, and kidney was higher than that in the muscle and connective tissue. Immunoreactive serum spexin levels were reduced in T2DM patients and correlated with fasting blood glucose (FBG, r=-0.686, Pepithelial tissues, indicating that spexin may be involved in physiological functions of endocrine and in several other tissues. Circulating spexin levels are low in T2DM patients and negatively related to blood glucose and lipids suggesting that the peptide may play a role in glucose and lipid metabolism in T2DM. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients

    DEFF Research Database (Denmark)

    Toft-Nielsen, M B; Madsbad, Sten; Holst, J J

    1999-01-01

    OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefo....... CONCLUSIONS: We conclude that 48-h continuous subcutaneous infusion of GLP-1 in type 2 diabetic patients 1) lowers fasting as well as meal-related plasma glucose, 2) reduces appetite, 3) has no gastrointestinal side effects, and 4) has no negative effect on blood pressure.......OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefore......, previously shown to lower blood glucose effectively in type 2 diabetic patients. Fasting plasma glucose (day 2) decreased from 14.1 +/- 0.9 (saline) to 12.2 +/- 0.7 mmol/l (GLP-1), P = 0.009, and 24-h mean plasma glucose decreased from 15.4 +/- 1.0 to 13.0 +/- 1.0 mmol/l, P = 0.0009. Fasting and total area...

  19. The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load.

    Directory of Open Access Journals (Sweden)

    Johan Holmkvist

    Full Text Available BACKGROUND: Polymorphisms in the potassium channel, voltage-gated, KQT-like subfamily, member 1 (KCNQ1 have recently been reported to associate with type 2 diabetes. The primary aim of the present study was to investigate the putative impact of these KCNQ1 polymorphisms (rs2283228, rs2237892, rs2237895, and rs2237897 on estimates of glucose stimulated insulin release. METHODOLOGY/PRINCIPAL FINDINGS: Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses. Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean+/-SD: (CC 277+/-160 vs. (AC 280+/-164 vs. (AA 299+/-200 pmol/l, p = 0.008 after an oral glucose load, insulinogenic index (29.6+/-17.4 vs. 30.2+/-18.7vs. 32.2+/-22.1, p = 0.007, incremental area under the insulin curve (20,477+/-12,491 vs. 20,503+/-12,386 vs. 21,810+/-14,685, p = 0.02 among the 4,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified for the less common diabetes risk alleles of rs2237892, rs2237897, or rs2283228. CONCLUSION: The minor C-allele of rs2237895 of KCNQ1, which has a prevalence of about 42% among Caucasians was associated with reduced measures of insulin release following an oral glucose load suggesting that the increased risk of type 2 diabetes, previously reported for this variant, likely is mediated through an impaired beta cell function.

  20. Regional cerebral glucose metabolism in patients with alcoholic Korsakoff's syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, R.M.; Parker, E.S.; Clark, C.M.; Martin, P.R.; George, D.T.; Weingartner, H.; Sokoloff, L.; Ebert, M.H.; Mishkin, M.

    1985-05-01

    Seven alcoholic male subjects diagnosed as having Korsakoff's syndrome and eight age-matched male normal volunteers were studied with /sup 18/F 2-fluoro-2-deoxy-D-glucose (2/sup 18/FDG). All subjects were examined at rest with eyes covered in a quiet, darkened room. Serial plasma samples were obtained following injection of 4 to 5 mCi of 2/sup 18/FDG. Tomographic slices spaced at 10mm axial increments were obtained (in-plane resolution = 1.75 cm, axial resolution = 1.78 cm). Four planes were selected from each subject, and a total of 46 regions of interest were sampled and glucose metabolic rates for each region calculated. The mean glucose metalbolic rate for the 46 regions in the Korsakoff subjects was significantly lower than that in the normal controls (5.17 +- .43 versus 6.6 +- 1.31). A Q-component analysis, which examined each subject's regional rates relative to his mean rate, revealed two distinct patterns in the Korsakoff group. Glucose metabolism was significantly reduced in 37 of the 46 regions sampled. Reduced cerebral glucose metabolism in a nondemented group of subjects has not previously been reported. The reduction in cortical metabolism may be the result of damage to sub-cortical projecting systems. The differing patterns of cerebral metabolism in Korsakoff's syndrome suggests subgroups with differing neuropathology. Regions implicated in memory function, medial temporal, thalamic and medial prefrontal were among the regions reduced in metabolism.

  1. Sodium-glucose co-transporter 2 (SGLT2 inhibitors: a growing class of anti-diabetic agents

    Directory of Open Access Journals (Sweden)

    Eva M Vivian

    2014-12-01

    Full Text Available Although several treatment options are available to reduce hyperglycemia, only about half of individuals with diagnosed diabetes mellitus (DM achieve recommended glycemic targets. New agents that reduce blood glucose concentrations by novel mechanisms and have acceptable safety profiles are needed to improve glycemic control and reduce the complications associated with type 2 diabetes mellitus (T2DM. The renal sodium-glucose co-transporter 2 (SGLT2 is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors of SGLT2 lower blood glucose independent of the secretion and action of insulin by inhibiting renal reabsorption of glucose, thereby promoting the increased urinary excretion of excess glucose. Canagliflozin, dapagliflozin, and empagliflozin are SGLT2 inhibitors approved as treatments for T2DM in the United States, Europe, and other countries. Canagliflozin, dapagliflozin, and empagliflozin increase renal excretion of glucose and improve glycemic parameters in patients with T2DM when used as monotherapy or in combination with other antihyperglycemic agents. Treatment with SGLT2 inhibitors is associated with weight reduction, lowered blood pressure, and a low intrinsic propensity to cause hypoglycemia. Overall, canagliflozin, dapagliflozin, and empagliflozin are well tolerated. Cases of genital infections and, in some studies, urinary tract infections have been more frequent in canagliflozin-, dapagliflozin-, and empagliflozin-treated patients compared with those receiving placebo. Evidence from clinical trials suggests that SGLT2 inhibitors are a promising new treatment option for T2DM.

  2. Nanomaterials in glucose sensing

    CERN Document Server

    Burugapalli, Krishna

    2013-01-01

    The smartness of nano-materials is attributed to their nanoscale and subsequently unique physicochemical properties and their use in glucose sensing has been aimed at improving performance, reducing cost and miniaturizing the sensor and its associated instrumentation. So far, portable (handheld) glucose analysers were introduced for hospital wards, emergency rooms and physicians' offices; single-use strip systems achieved nanolitre sampling for painless and accurate home glucose monitoring; advanced continuous monitoring devices having 2 to 7 days operating life are in clinical and home use; and continued research efforts are being made to develop and introduce increasingly advanced glucose monitoring systems for health as well as food, biotechnology, cell and tissue culture industries. Nanomaterials have touched every aspect of biosensor design and this chapter reviews their role in the development of advanced technologies for glucose sensing, and especially for diabetes. Research shows that overall, nanomat...

  3. Association between blood glucose level derived using the oral glucose tolerance test and glycated hemoglobin level.

    Science.gov (United States)

    Kim, Hyoung Joo; Kim, Young Geon; Park, Jin Soo; Ahn, Young Hwan; Ha, Kyoung Hwa; Kim, Dae Jung

    2016-05-01

    Glycated hemoglobin (HbA1c) is widely used as a marker of glycemic control. Translation of the HbA1c level to an average blood glucose level is useful because the latter figure is easily understood by patients. We studied the association between blood glucose levels revealed by the oral glucose tolerance test (OGTT) and HbA1c levels in a Korean population. A total of 1,000 subjects aged 30 to 64 years from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort were included. Fasting glucose levels, post-load glucose levels at 30, 60, and 120 minutes into the OGTT, and HbA1c levels were measured. Linear regression of HbA1c with mean blood glucose levels derived using the OGTT revealed a significant correlation between these measures (predicted mean glucose [mg/dL] = 49.4 × HbA1c [%] - 149.6; R (2) = 0.54, p Glucose (ADAG) study and Diabetes Control and Complications Trial (DCCT) cohort. Discrepancies between our results and those of the ADAG study and DCCT cohort may be attributable to differences in the test methods used and the extent of insulin secretion. More studies are needed to evaluate the association between HbA1c and self monitoring blood glucose levels.

  4. Brain glucose sensing, counterregulation, and energy homeostasis.

    Science.gov (United States)

    Marty, Nell; Dallaporta, Michel; Thorens, Bernard

    2007-08-01

    Neuronal circuits in the central nervous system play a critical role in orchestrating the control of glucose and energy homeostasis. Glucose, beside being a nutrient, is also a signal detected by several glucose-sensing units that are located at different anatomical sites and converge to the hypothalamus to cooperate with leptin and insulin in controlling the melanocortin pathway.

  5. Positive sliding mode control for blood glucose regulation

    Science.gov (United States)

    Menani, Karima; Mohammadridha, Taghreed; Magdelaine, Nicolas; Abdelaziz, Mourad; Moog, Claude H.

    2017-11-01

    Biological systems involving positive variables as concentrations are some examples of so-called positive systems. This is the case of the glycemia-insulinemia system considered in this paper. To cope with these physical constraints, it is shown that a positive sliding mode control (SMC) can be designed for glycemia regulation. The largest positive invariant set (PIS) is obtained for the insulinemia subsystem in open and closed loop. The existence of a positive SMC for glycemia regulation is shown here for the first time. Necessary conditions to design the sliding surface and the discontinuity gain are derived to guarantee a positive SMC for the insulin dynamics. SMC is designed to be positive everywhere in the largest closed-loop PIS of plasma insulin system. Two-stage SMC is employed; the last stage SMC2 block uses the glycemia error to design the desired insulin trajectory. Then the plasma insulin state is forced to track the reference via SMC1. The resulting desired insulin trajectory is the required virtual control input of the glycemia system to eliminate blood glucose (BG) error. The positive control is tested in silico on type-1 diabetic patients model derived from real-life clinical data.

  6. Microwave Deposition of Palladium Catalysts on Graphite Spheres and Reduced Graphene Oxide Sheets for Electrochemical Glucose Sensing.

    Science.gov (United States)

    Xie, Jian-De; Gu, Siyong; Zhang, Houan

    2017-09-21

    This work outlines a synthetic strategy inducing the microwave-assisted synthesis of palladium (Pd) nanocrystals on a graphite sphere (GS) and reduced graphene oxide (rGO) supports, forming the Pd catalysts for non-enzymatic glucose oxidation reaction (GOR). The pulse microwave approach takes a short period (i.e., 10 min) to fast synthesize Pd nanocrystals onto a carbon support at 150 °C. The selection of carbon support plays a crucial role in affecting Pd particle size and dispersion uniformity. The robust design of Pd-rGO catalyst electrode displays an enhanced electrocatalytic activity and sensitivity toward GOR. The enhanced performance is mainly attributed to the synergetic effect that combines small crystalline size and two-dimensional conductive support, imparting high accessibility to non-enzymatic GOR. The rGO sheets serve as a conductive scaffold, capable of fast conducting electron. The linear plot of current response versus glucose concentration exhibits good correlations within the range of 1-12 mM. The sensitivity of the Pd-rGO catalyst is significantly enhanced by 3.7 times, as compared to the Pd-GS catalyst. Accordingly, the Pd-rGO catalyst electrode can be considered as a potential candidate for non-enzymatic glucose biosensor.

  7. Coping with an exogenous glucose overload: glucose kinetics of rainbow trout during graded swimming.

    Science.gov (United States)

    Choi, Kevin; Weber, Jean-Michel

    2016-03-15

    This study examines how chronically hyperglycemic rainbow trout modulate glucose kinetics in response to graded exercise up to critical swimming speed (Ucrit), with or without exogenous glucose supply. Our goals were 1) to quantify the rates of hepatic glucose production (Ra glucose) and disposal (Rd glucose) during graded swimming, 2) to determine how exogenous glucose affects the changes in glucose fluxes caused by exercise, and 3) to establish whether exogenous glucose modifies Ucrit or the cost of transport. Results show that graded swimming causes no change in Ra and Rd glucose at speeds below 2.5 body lengths per second (BL/s), but that glucose fluxes may be stimulated at the highest speeds. Excellent glucoregulation is also achieved at all exercise intensities. When exogenous glucose is supplied during exercise, trout suppress hepatic production from 16.4 ± 1.6 to 4.1 ± 1.7 μmol·kg(-1)·min(-1) and boost glucose disposal to 40.1 ± 13 μmol·kg(-1)·min(-1). These responses limit the effects of exogenous glucose to a 2.5-fold increase in glycemia, whereas fish showing no modulation of fluxes would reach dangerous levels of 114 mM of blood glucose. Exogenous glucose reduces metabolic rate by 16% and, therefore, causes total cost of transport to decrease accordingly. High glucose availability does not improve Ucrit because the fish are unable to take advantage of this extra fuel during maximal exercise and rely on tissue glycogen instead. In conclusion, trout have a remarkable ability to adjust glucose fluxes that allows them to cope with the cumulative stresses of a glucose overload and graded exercise. Copyright © 2016 the American Physiological Society.

  8. Effect of inulin-type fructans on blood lipid profile and glucose level: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Liu, F; Prabhakar, M; Ju, J; Long, H; Zhou, H-W

    2017-01-01

    This systematic review and meta-analysis was performed to assess the effects of inulin-type fructans (ITF) on human blood lipids and glucose homeostasis associated with metabolic abnormalities, including dyslipidemia, overweight or obesity, and type-2 diabetes mellitus (T2DM). The MEDLINE, EMBASE and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) before January 2016. Human trials that investigated the effects of ITF supplementation on the lipid profile, fasting glucose and insulin were included using Review Manager 5.3. Twenty RCTs with 607 adult participants were included in this systematic review and meta-analysis. In the overall analysis, the supplementation of ITF reduced only the low density lipoprotein-cholesterol (LDL-c) (mean difference (MD): -0.15; 95% confidence interval (CI): -0.29, -0.02; P=0.03) without affecting the other endpoints. Within the T2DM subgroup analysis, ITF supplementation was positively associated with a decreased fasting insulin concentration (MD: -4.01; 95% CI: -5.92, -2.09; Pglucose tendency was identified only in the T2DM subgroup (MD: -0.42; 95% CI: -0.90, 0.06; P=0.09). There was a potential publication bias, and few trials were available for the T2DM subgroup analysis. In summary, the use of ITF may have benefits for LDL-c reduction across all study populations, whereas HDL-c improvement and glucose control were demonstrated only in the T2DM subgroup. Thus, additional, well-powered, long-term, randomized clinical trials are required for a definitive conclusion. Overall, ITF supplementation may provide a novel direction for improving the lipid profile and glucose metabolism.

  9. Pregnancy induces molecular alterations reflecting impaired insulin control over glucose oxidative pathways that only in women with a family history of Type 2 diabetes last beyond pregnancy.

    Science.gov (United States)

    Piccinini, M; Mostert, M; Seardo, M A; Bussolino, S; Alberto, G; Lupino, E; Ramondetti, C; Buccinnà, B; Rinaudo, M T

    2009-01-01

    In circulating lymphomonocytes (CLM) of patients with Type 2 diabetes (DM2) pyruvate dehydrogenase (PDH), the major determinant of glucose oxidative breakdown, is affected by a cohort of alterations reflecting impaired insulin stimulated glucose utilization. The cohort is also expressed, although incompletely, in 40% of healthy young subjects with a DM2-family history (FH). Pregnancy restrains glucose utilization in maternal peripheral tissues to satisfy fetal requirements. Here we explore whether pregnant women develop the PDH alterations and, if so, whether there are differences between women with and without FH (FH+, FH-). Ten FH+ and 10 FH- were evaluated during pregnancy (12-14, 24-26, and 37-39 weeks) and 1 yr after (follow-up) for fasting plasma glucose and insulin as well as body mass index (BMI), and for the PDH alterations. Twenty FH- and 20 FH+ non-pregnant women served as controls. All FH+ and FH- controls exhibited normal clinical parameters and 8 FH+ had an incomplete cohort of PDH alterations. In FH- and FH+ pregnant women at 12-14 weeks clinical parameters were normal; from 24-26 weeks, with unvaried glucose, insulin and BMI rose more in FH- and only in the latter recovered the 12-14 weeks values at follow-up. In all FH-, the cohort of PDH alterations was incomplete at 24-26 weeks, complete at 37-39 weeks, and absent at follow-up but complete from 12-14 weeks including follow-up in all FH+. In FH-, the cohort is an acquired trait restricted to pregnancy signaling transiently reduced insulin-stimulated glucose utilization; in FH+, instead, it unveils the existence of an inherited DM2-related background these women all have, that is awakened by pregnancy and as such lastingly impairs insulin-stimulated glucose utilization.

  10. Reduced brain/serum glucose ratios predict cerebral metabolic distress and mortality after severe brain injury.

    Science.gov (United States)

    Kurtz, Pedro; Claassen, Jan; Schmidt, J Michael; Helbok, Raimund; Hanafy, Khalid A; Presciutti, Mary; Lantigua, Hector; Connolly, E Sander; Lee, Kiwon; Badjatia, Neeraj; Mayer, Stephan A

    2013-12-01

    The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury. We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80-120 mg/dL (4.4-6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality. A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2-1.7], P brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2-38.9], P brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.

  11. Mitochondrial Pyruvate Carrier 2 Hypomorphism in Mice Leads to Defects in Glucose-Stimulated Insulin Secretion

    Directory of Open Access Journals (Sweden)

    Patrick A. Vigueira

    2014-06-01

    Full Text Available Carrier-facilitated pyruvate transport across the inner mitochondrial membrane plays an essential role in anabolic and catabolic intermediary metabolism. Mitochondrial pyruvate carrier 2 (Mpc2 is believed to be a component of the complex that facilitates mitochondrial pyruvate import. Complete MPC2 deficiency resulted in embryonic lethality in mice. However, a second mouse line expressing an N-terminal truncated MPC2 protein (Mpc2Δ16 was viable but exhibited a reduced capacity for mitochondrial pyruvate oxidation. Metabolic studies demonstrated exaggerated blood lactate concentrations after pyruvate, glucose, or insulin challenge in Mpc2Δ16 mice. Additionally, compared with wild-type controls, Mpc2Δ16 mice exhibited normal insulin sensitivity but elevated blood glucose after bolus pyruvate or glucose injection. This was attributable to reduced glucose-stimulated insulin secretion and was corrected by sulfonylurea KATP channel inhibitor administration. Collectively, these data are consistent with a role for MPC2 in mitochondrial pyruvate import and suggest that Mpc2 deficiency results in defective pancreatic β cell glucose sensing.

  12. In Vitro Evaluation of Fluorescence Glucose Biosensor Response

    OpenAIRE

    Aloraefy, Mamdouh; Pfefer, T. Joshua; Ramella-Roman, Jessica C.; Sapsford, Kim E.

    2014-01-01

    Rapid, accurate, and minimally-invasive glucose biosensors based on Förster Resonance Energy Transfer (FRET) for glucose measurement have the potential to enhance diabetes control. However, a standard set of in vitro approaches for evaluating optical glucose biosensor response under controlled conditions would facilitate technological innovation and clinical translation. Towards this end, we have identified key characteristics and response test methods, fabricated FRET-based glucose biosensor...

  13. Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Yeow, Toh Peng; Pacini, Giovanni; Tura, Andrea

    2017-01-01

    are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. RESEARCH DESIGN AND METHODS: This case-control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum......OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect...... glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS...

  14. Multilevel control of glucose homeostasis by adenylyl cyclase 8

    NARCIS (Netherlands)

    Raoux, Matthieu; Vacher, Pierre; Papin, Julien; Picard, Alexandre; Kostrzewa, Elzbieta; Devin, Anne; Gaitan, Julien; Limon, Isabelle; Kas, Martien J.; Magnan, Christophe; Lang, Jochen

    2015-01-01

    Aims/hypothesis: Nutrient homeostasis requires integration of signals generated by glucose metabolism and hormones. Expression of the calcium-stimulated adenylyl cyclase ADCY8 is regulated by glucose and the enzyme is capable of integrating signals from multiple pathways. It may thus have an

  15. Valsartan improves adipose tissue function in humans with impaired glucose metabolism: a randomized placebo-controlled double-blind trial.

    Directory of Open Access Journals (Sweden)

    Gijs H Goossens

    Full Text Available BACKGROUND: Blockade of the renin-angiotensin system (RAS reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans. Therefore, we examined whether 26-wks treatment with the angiotensin II type 1 receptor blocker valsartan affects AT function in humans with impaired glucose metabolism (IGM. METHODOLOGY/PRINCIPAL FINDINGS: We performed a randomized, double-blind, placebo-controlled parallel-group study, in which 38 subjects with IGM were treated with valsartan (VAL, 320 mg/d or placebo (PLB for 26 weeks. Before and after treatment, an abdominal subcutaneous AT biopsy was collected for measurement of adipocyte size and AT gene/protein expression of angiogenesis/capillarization, adipogenesis, lipolytic and inflammatory cell markers. Furthermore, we evaluated fasting and postprandial AT blood flow (ATBF ((133Xe wash-out, systemic inflammation and insulin sensitivity (hyperinsulinemic-euglycemic clamp. VAL treatment markedly reduced adipocyte size (P<0.001, with a shift toward a higher proportion of small adipocytes. In addition, fasting (P = 0.043 and postprandial ATBF (P = 0.049 were increased, whereas gene expression of angiogenesis/capillarization, adipogenesis and macrophage infiltration markers in AT was significantly decreased after VAL compared with PLB treatment. Interestingly, the change in adipocyte size was associated with alterations in insulin sensitivity and reduced AT gene expression of macrophage infiltration markers. VAL did not alter plasma monocyte-chemoattractant protein (MCP-1, TNF-α, adiponectin and leptin concentrations. CONCLUSIONS/SIGNIFICANCE: 26-wks VAL treatment markedly reduced abdominal subcutaneous adipocyte size and AT macrophage infiltration markers, and increased ATBF in IGM subjects. The VAL

  16. The Phytocomplex from Fucus vesiculosus and Ascophyllum nodosum Controls Postprandial Plasma Glucose Levels: An In Vitro and In Vivo Study in a Mouse Model of NASH.

    Science.gov (United States)

    Gabbia, Daniela; Dall'Acqua, Stefano; Di Gangi, Iole Maria; Bogialli, Sara; Caputi, Valentina; Albertoni, Laura; Marsilio, Ilaria; Paccagnella, Nicola; Carrara, Maria; Giron, Maria Cecilia; De Martin, Sara

    2017-02-15

    Edible seaweeds have been consumed by Asian coastal communities since ancient times. Fucus vesiculosus and Ascophyllum nodosum extracts have been traditionally used for the treatment of obesity and several gastrointestinal diseases. We evaluated the ability of extracts obtained from these algae to inhibit the digestive enzymes α-amylase and α-glucosidase in vitro, and control postprandial plasma glucose levels in a mouse model of non-alcoholic steatohepatitis (NASH); a liver disease often preceding the development of Type 2 diabetes (T2DM). This model was obtained by the administration of a high-fat diet. Our results demonstrate that these algae only delayed and reduced the peak of blood glucose ( p NASH, the phytocomplex was able to reduce both the postprandial glycaemic peak, and the AUC. The administration of the extract in a diet particularly rich in fat is associated with a delay in carbohydrate digestion, but also with a decrease in its assimilation. In conclusion, our results indicate that this algal extract may be useful in the control of carbohydrate digestion and absorption. This effect may be therapeutically exploited to prevent the transition of NASH to T2DM.

  17. [Effect of a dehydrated extract of nopal (Opuntia ficus indica Mill.) on blood glucose].

    Science.gov (United States)

    Frati-Munari, A C; de León, C; Ariza-Andraca, R; Bañales-Ham, M B; López-Ledesma, R; Lozoya, X

    1989-01-01

    To assess if a dehydrated extract of nopal stems retains the effect on glycemia of the entire nopal stems two experiments were performed. A. Six patients with type II diabetes mellitus in fasting condition received 30 capsules containing 10.1 +/- 0.3 g of the extract, and serum glucose levels were measured hourly from 0 to 180 minutes. B. Six healthy volunteers received 30 capsules with the extract followed by 74 g of dextrose orally. Serum glucose measurements were made in a similar fashion. In each experiment a control test with empty capsules was performed. Nopal extract did not reduce fasting glycemia in diabetic subjects. Nevertheless, the extract diminished the increase of serum glucose which followed a dextrose load. Peak serum glucose was 20.3 +/- 18.2 mg/dl (X +/- SD) lower in the test with nopal than in the control one (P less than 0.025). Dehydrated extract of nopal (Opuntia ficus-indica Mill) did not show acute hypoglycemic effect, although could attenuate postprandial hyperglycemia.

  18. A randomized trial of a home system to reduce nocturnal hypoglycemia in type 1 diabetes.

    Science.gov (United States)

    Maahs, David M; Calhoun, Peter; Buckingham, Bruce A; Chase, H Peter; Hramiak, Irene; Lum, John; Cameron, Fraser; Bequette, B Wayne; Aye, Tandy; Paul, Terri; Slover, Robert; Wadwa, R Paul; Wilson, Darrell M; Kollman, Craig; Beck, Roy W

    2014-07-01

    Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels. Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred. Overnight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43-0.64]; P 2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P 250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm. Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis. © 2014 by the American Diabetes Association.

  19. Starfruit Leaves as Glucose Absorption Inhibitor in Mice’s Small Intestinal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Rifqi Y Muhammad

    2016-12-01

    Full Text Available Background: Starfruit (Averrhoa carambola leaves contain flavone derivatives that exhibit anti-hyperglycemic effects. This study aims to determine the effect of starfruit leaves in reducing glucose absorption in intestinal epithelial cells of mice. Methods: This study was done by performing perfusion on the small intestines of mice. The mice that were used in this study were divided into four groups. The control group was given glucose solution without infused starfruit leaves whereas, the remaining 3 groups were given 3 mmol (540 mg/dL glucose solution with infused starfruit leaves of varying concentrations; 200, 400, and 600 mg/kg. Samples were collected at 0, 15th, 30th, 45th, and 60th minute. The sample was tested for glucose levels using spectrophotometry. Results: Test of significance showed a significant difference between the control group and the test group with p < 0.05. Conclusions: Starfruit leaves have a reduction effect towards glucose absorption in the small intestines in Wistar strains where the group using 600 mg/kg of infused starfruit leaves have the most significant effect as compared to other groups.

  20. Hepatitis C virus eradication by direct antiviral agents improves glucose tolerance and reduces post-load insulin resistance in nondiabetic patients with genotype 1.

    Science.gov (United States)

    Salomone, Federico; Catania, Maurizio; Montineri, Arturo; Bertino, Gaetano; Godos, Justyna; Rizzo, Leonardo; Magrì, Giovanni; Li Volti, Giovanni

    2017-12-19

    Genotype 1 chronic hepatitis C is associated with an impairment of glucose homoeostasis, especially in the advanced stages of the disease. Glucose tolerance is an independent predictor of liver-related mortality in patients with cirrhosis because of chronic hepatitis C. However, no study has demonstrated so far weather hepatitis C virus clearance affects glucose tolerance. To this aim, we performed a prospective study assessing the effects of direct antiviral agents treatment in nondiabetic cirrhotic patients with genotypes 1a/1b and impaired glucose tolerance based on a 75-g oral glucose tolerance test. Impaired glucose tolerance was diagnosed by a 2-hour plasma glucose between 140 and 199 mg/dL. Insulin resistance was estimated by the oral glucose insulin sensitivity index, an oral glucose tolerance test-derived measure. After meeting the inclusion criteria, the study population included 32 outpatients (26/6 genotypes 1b/1a; age 62 ± 7.4 years; 18 males) with compensated Child-A cirrhosis. All patients achieved a sustained virological response following direct antiviral agents treatment. After viral eradication, we did not observe change in fasting plasma glucose (103.5 ± 7.1 vs 102.8 ± 7.2 mg/dL, P = .15) but 2-hour plasma glucose was reduced (165.2 ± 22.7 vs 138.5 ± 21.3 mg/dL, P Hepatitis C virus eradication led also to a significant reduction in HbA1c (6.1 ± 0.2% vs 5.7 ± 0.3%, P resistance as assessed by the oral glucose insulin sensitivity index (6.92 ± 1.56 vs 9.52 ± 1.39 mg/kg/min, P  .5). Our results indicate that hepatitis C virus eradication may early improve glucose tolerance in patients with hepatitis C virus-related cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Green Chemistry Glucose Biosensor Development using Etlingera elatior Extract

    Science.gov (United States)

    Fatoni, A.; Anggraeni, M. D.; Zusfahair; Iqlima, H.

    2018-01-01

    Glucose biosensor development is one of the important strategies for early detection of diabetes mellitus disease. This study was aimed to explore the flower extract of Etlingera elatior for a green-analysis method of glucose biosensor. Flowers were extracted using ethanol: HCl and tested its performances as an indicator of glucose biosensor using glucose oxidase enzyme. The glucose oxidase react with glucose resulted hydrogen peroxide that would change the color of the flower extract. Furthermore, the extract was also studied including their stability to pH, oxidizing and reducing, temperature, and storage. The results showed that the Etlingera elatior extract had high correlation between color change and glucose concentration with regression equation of y = -0.0005x + 0.4724 and R2 of 0.9965. The studied biosensor showed a wide linear range to detect glucose sample of 0 to 500 mM. The extract characterization showed a more stable in low pH (acid), reducing agent addition, heating treatment and storage.

  2. Mapping glucose-mediated gut-to-brain signalling pathways in humans.

    Science.gov (United States)

    Little, Tanya J; McKie, Shane; Jones, Richard B; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G; McLaughlin, John T

    2014-08-01

    Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250ml) of: 1M glucose+predosing with dexloxiglumide (CCK1 receptor antagonist), 1M glucose+placebo, or 0.9% saline (control)+placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose+dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. Copyright © 2014. Published by Elsevier Inc.

  3. Mapping glucose-mediated gut-to-brain signalling pathways in humans☆

    Science.gov (United States)

    Little, Tanya J.; McKie, Shane; Jones, Richard B.; D'Amato, Massimo; Smith, Craig; Kiss, Orsolya; Thompson, David G.; McLaughlin, John T.

    2014-01-01

    Objectives Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Experimental design Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250 ml) of: 1 M glucose + predosing with dexloxiglumide (CCK1 receptor antagonist), 1 M glucose + placebo, or 0.9% saline (control) + placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Principal observations Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose + dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Conclusions Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. PMID:24685436

  4. Assessment of Blood Glucose Regulation and Safety of Resistant Starch Formula-Based Diet in Healthy Normal and Subjects With Type 2 Diabetes.

    Science.gov (United States)

    Lin, Chia-Hung; Chang, Daw-Ming; Wu, Da-Jen; Peng, Hui-Yu; Chuang, Lee-Ming

    2015-08-01

    To evaluate the effects of the new resistant starch (RS) formula, PPB-R-203, on glucose homeostasis in healthy subjects and subjects with type 2 diabetes.A cohort consisting of 40 healthy participants received test and control diets and was checked for up to 3 hours post-meal. A randomized, 2-regimen, cross-over, comparative study was conducted in 44 subjects with type 2 diabetes and glycemic control was assessed with a continuous glucose monitoring system.In healthy participants, serum glucose values and incremental areas under the glucose curves (AUC) were significantly lower in the PPB-R-203 than the control group (P blood glucose concentrations for subjects on the control regimen were higher than those for subjects on the PPB-R-203-based regimen (7.9 ± 1.7, 95% confidence interval [CI] 7.4-8.4 vs 7.4 ± 1.6, 95% CI 6.9-7.9 mmol/L, respectively; P = 0.023). AUCs for total blood glucose and hyperglycemia (glucose >10 mmol/L) were also reduced for subjects on the PPB-R-203-based regimen as compared with those on control regimen (total blood glucose: 16.2 ± 4.0, 95% CI 14.9-17.4 vs 18.7 ± 4.0, 95% CI 17.6-20.1, P AUC measurements for hypoglycemia (glucose glucose excursion.

  5. Increased muscle glucose uptake after exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Ploug, Thorkil; Galbo, Henrik

    1985-01-01

    responsiveness of glucose uptake was noted only in controls. Analysis of intracellular glucose-6-phosphate, glucose, glycogen synthesis, and glucose transport suggested that the exercise effect on responsiveness might be due to enhancement of glucose disposal. After electrical stimulation of diabetic...... of glucose. At maximal insulin concentrations, the enhancing effect of exercise on glucose uptake may involve enhancement of glucose disposal, an effect that is probably less in muscle from diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)......It has recently been shown that insulin sensitivity of skeletal muscle glucose uptake and glycogen synthesis is increased after a single exercise session. The present study was designed to determine whether insulin is necessary during exercise for development of these changes found after exercise...

  6. The acute effect of coffee on endothelial function and glucose metabolism following a glucose load in healthy human volunteers.

    Science.gov (United States)

    Boon, Evan A J; Croft, Kevin D; Shinde, Sujata; Hodgson, Jonathan M; Ward, Natalie C

    2017-09-20

    A diet rich in plant polyphenols has been suggested to reduce the incidence of cardiovascular disease and type 2 diabetes mellitus, in part, via improvements in endothelial function. Coffee is a rich source of phenolic compounds including the phenolic acid, chlorogenic acid (CGA). The aim of the study was to investigate the effect of coffee as a whole beverage on endothelial function, blood pressure and blood glucose concentration. Twelve healthy men and women were recruited to a randomised, placebo-controlled, cross-over study, with three treatments tested: (i) 18 g of ground caffeinated coffee containing 300 mg CGA in 200 mL of hot water, (ii) 18 g of decaffeinated coffee containing 287 mg CGA in 200 mL of hot water, and (iii) 200 mL of hot water (control). Treatment beverages were consumed twice, two hours apart, with the second beverage consumed simultaneously with a 75 g glucose load. Blood pressure was recorded and the finger prick glucose test was performed at time = 0 and then every 30 minutes up to 2 hours. Endothelial function, assessed using flow-mediated dilatation (FMD) of the brachial artery, was measured at 1 hour and a blood sample taken at 2 hours to measure plasma nitrate/nitrite and 5-CGA concentrations. The FMD response was significantly higher in the caffeinated coffee group compared to both decaffeinated coffee and water groups (P coffee and water. Blood glucose concentrations and blood pressure were not different between the three treatment groups. In conclusion, the consumption of caffeinated coffee resulted in a significant improvement in endothelial function, but there was no evidence for benefit regarding glucose metabolism or blood pressure. Although the mechanism has yet to be elucidated the results suggest that coffee as a whole beverage may improve endothelial function, or that caffeine is the component of coffee responsible for improving FMD.

  7. Intensive glucose control and risk of cancer in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Stefansdottir, G; Zoungas, S; Chalmers, J

    2011-01-01

    AIMS/HYPOTHESIS: Type 2 diabetes has been associated with an increased risk of cancer. This study examines the effect of more vs less intensive glucose control on the risk of cancer in patients with type 2 diabetes. METHODS: All 11,140 participants from the Action in Diabetes and Vascular Disease...

  8. Hypothalamic control of energy and glucose metabolism.

    Science.gov (United States)

    Sisley, Stephanie; Sandoval, Darleen

    2011-09-01

    The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

  9. Predictive Control of the Blood Glucose Level in Type I Diabetic Patient Using Delay Differential Equation Wang Model.

    Science.gov (United States)

    Esna-Ashari, Mojgan; Zekri, Maryam; Askari, Masood; Khalili, Noushin

    2017-01-01

    Because of increasing risk of diabetes, the measurement along with control of blood sugar has been of great importance in recent decades. In type I diabetes, because of the lack of insulin secretion, the cells cannot absorb glucose leading to low level of glucose. To control blood glucose (BG), the insulin must be injected to the body. This paper proposes a method for BG level regulation in type I diabetes. The control strategy is based on nonlinear model predictive control. The aim of the proposed controller optimized with genetics algorithms is to measure BG level each time and predict it for the next time interval. This merit causes a less amount of control effort, which is the rate of insulin delivered to the patient body. Consequently, this method can decrease the risk of hypoglycemia, a lethal phenomenon in regulating BG level in diabetes caused by a low BG level. Two delay differential equation models, namely Wang model and Enhanced Wang model, are applied as controller model and plant, respectively. The simulation results exhibit an acceptable performance of the proposed controller in meal disturbance rejection and robustness against parameter changes. As a result, if the nutrition of the person decreases instantly, the hypoglycemia will not happen. Furthermore, comparing this method with other works, it was shown that the new method outperforms previous studies.

  10. Intensive perioperative glucose control does not improve outcomes of patients submitted to open-heart surgery: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Raquel Pei Chen Chan

    2009-01-01

    Full Text Available BACKGROUND: The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: We designed a prospective study in a university hospital where 109 consecutive patients were enrolled during a six-month period. All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass. Patients were randomly allocated into two groups. One group consisted of 55 patients and had a target glucose level of 80-130 mg/dl, while the other contained 54 patients and had a target glucose level of 160-200 mg/dl. These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit. Primary outcomes were clinical outcomes, including time of mechanical ventilation, length of stay in the intensive care unit, infection, hypoglycemia, renal or neurological dysfunction, blood transfusion and length of stay in the hospital. The secondary outcome was a combined end-point (mortality at 30 days, infection or length of stay in the intensive care unit of more than 3 days. A p-value of 0.05. CONCLUSIONS: In 109 patients undergoing cardiac surgery with cardiopulmonary bypass, both protocols of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe, easily achieved and not to differentially affect clinical outcomes.

  11. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Herman, Gary A; Bergman, Arthur; Stevens, Catherine

    2006-01-01

    CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglyce......CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral...... antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated. OBJECTIVE: The objective of the study was to examine...... concentrations; and sitagliptin pharmacokinetics. RESULTS: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25...

  12. Educational intervention together with an on-line quality control program achieve recommended analytical goals for bedside blood glucose monitoring in a 1200-bed university hospital.

    Science.gov (United States)

    Sánchez-Margalet, Víctor; Rodriguez-Oliva, Manuel; Sánchez-Pozo, Cristina; Fernández-Gallardo, María Francisca; Goberna, Raimundo

    2005-01-01

    Portable meters for blood glucose concentrations are used at the patients bedside, as well as by patients for self-monitoring of blood glucose. Even though most devices have important technological advances that decrease operator error, the analytical goals proposed for the performance of glucose meters have been recently changed by the American Diabetes Association (ADA) to reach nurses in a 1200-bed University Hospital to achieve recommended analytical goals, so that we could improve the quality of diabetes care. We used portable glucose meters connected on-line to the laboratory after an educational program for nurses with responsibilities in point-of-care testing. We evaluated the system by assessing total error of the glucometers using high- and low-level glucose control solutions. In a period of 6 months, we collected data from 5642 control samples obtained by 14 devices (Precision PCx) directly from the control program (QC manager). The average total error for the low-level glucose control (2.77 mmol/l) was 6.3% (range 5.5-7.6%), and even lower for the high-level glucose control (16.66 mmol/l), at 4.8% (range 4.1-6.5%). In conclusion, the performance of glucose meters used in our University Hospital with more than 1000 beds not only improved after the intervention, but the meters achieved the analytical goals of the suggested ADA/National Academy of Clinical Biochemistry criteria for total error (<7.9% in the range 2.77-16.66 mmol/l glucose) and optimal total error for high glucose concentrations of <5%, which will improve the quality of care of our patients.

  13. Regulation of intracellular glucose and polyol pathway by thiamine and benfotiamine in vascular cells cultured in high glucose.

    Science.gov (United States)

    Berrone, Elena; Beltramo, Elena; Solimine, Carmela; Ape, Alessandro Ubertalli; Porta, Massimo

    2006-04-07

    Hyperglycemia is a causal factor in the development of the vascular complications of diabetes. One of the biochemical mechanisms activated by excess glucose is the polyol pathway, the key enzyme of which, aldose reductase, transforms d-glucose into d-sorbitol, leading to imbalances of intracellular homeostasis. We aimed at verifying the effects of thiamine and benfotiamine on the polyol pathway, transketolase activity, and intracellular glucose in endothelial cells and pericytes under high ambient glucose. Human umbilical vein endothelial cells and bovine retinal pericytes were cultured in normal (5.6 mmol/liter) or high (28 mmol/liter) glucose, with or without thiamine or benfotiamine 50 or 100 mumol/liter. Transketolase and aldose reductase mRNA expression was determined by reverse transcription-PCR, and their activity was measured spectrophotometrically; sorbitol concentrations were quantified by gas chromatography-mass spectrometry and intracellular glucose concentrations by fluorescent enzyme-linked immunosorbent assay method. Thiamine and benfotiamine reduce aldose reductase mRNA expression, activity, sorbitol concentrations, and intracellular glucose while increasing the expression and activity of transketolase, for which it is a coenzyme, in human endothelial cells and bovine retinal pericytes cultured in high glucose. Thiamine and benfotiamine correct polyol pathway activation induced by high glucose in vascular cells. Activation of transketolase may shift excess glycolytic metabolites into the pentose phosphate cycle, accelerate the glycolytic flux, and reduce intracellular free glucose, thereby preventing its conversion to sorbitol. This effect on the polyol pathway, together with other beneficial effects reported for thiamine in high glucose, could justify testing thiamine as a potential approach to the prevention and/or treatment of diabetic complications.

  14. Colorimetric Glucose Assay Based on Magnetic Particles Having Pseudo-peroxidase Activity and Immobilized Glucose Oxidase.

    Science.gov (United States)

    Martinkova, Pavla; Opatrilova, Radka; Kruzliak, Peter; Styriak, Igor; Pohanka, Miroslav

    2016-05-01

    Magnetic particles (MPs) are currently used as a suitable alternative for peroxidase in the construction of novel biosensors, analytic and diagnostic methods. Their better chemical and thermal stabilities predestine them as appropriate pseudo-enzymatic catalysts. In this point of view, our research was focused on preparation of simply and fast method for immobilization of glucose oxidase onto surface of MPs with peroxidase-like activity. Spectrophotometric method (wavelength 450 nm) optimized for glucose determination using modified MPs has been successfully developed. Concentration curve for optimization of method was assayed, and Michaelis-Menten constant (K m) calculated, maximum reaction rate (V max), limit of detection, and correlation coefficient were determined to be 0.13 mmol/l (2.34 mg/dl), 1.79 pkat, 3.74 µmol/l (0.067 mg/dl), and 0.996, respectively. Interferences of other sugars such as sucrose, sorbitol, deoxyribose, maltose, and fructose were determined as well as effect of substances presenting in plasma (ascorbic acid, reduced glutathione, trolox, and urea). Results in comparison with positive and negative controls showed no interferences of the other sugars and no influence of plasma substances to measuring of glucose. The constructed method showed corresponding results with linear dependence and a correlation coefficient of 0.997. Possibility of repeated use of modified MPs was successfully proved.

  15. Autonomic regulation of hepatic glucose production

    NARCIS (Netherlands)

    Bisschop, Peter H.; Fliers, Eric; Kalsbeek, Andries

    2015-01-01

    Glucose produced by the liver is a major energy source for the brain. Considering its critical dependence on glucose, it seems only natural that the brain is capable of monitoring and controlling glucose homeostasis. In addition to neuroendocrine pathways, the brain uses the autonomic nervous system

  16. Renal glucose handling in diabetes and sodium glucose cotransporter 2 inhibition

    Directory of Open Access Journals (Sweden)

    Resham Raj Poudel

    2013-01-01

    Full Text Available The kidneys play a major role in glucose homeostasis through its utilization, gluconeogenesis, and reabsorption via sodium glucose cotransporters (SGLTs. The defective renal glucose handling from upregulation of SGLTs, mainly the SGLT2, plays a fundamental role in the pathogenesis of type 2 diabetes mellitus. Genetic mutations in a SGLT2 isoform that results in benign renal glycosuria, as well as clinical studies with SGLT2 inhibitors in type 2 diabetes support the potential of this approach. These studies indicate that inducing glycosuria by suppressing SGLT2 can reduce plasma glucose and A1c levels, as well as decrease weight, resulting in improved β-cell function and enhanced insulin sensitivity in liver and muscle. Because the mechanism of SGLT2 inhibition is independent of insulin secretion and sensitivity, these agents can be combined with other antidiabetic agents, including exogenous insulin. This class represents a novel therapeutic approach with potential for the treatment of both type 2 and type 1 diabetes.

  17. Glucose-ABL1-TOR Signaling Modulates Cell Cycle Tuning to Control Terminal Appressorial Cell Differentiation.

    Science.gov (United States)

    Marroquin-Guzman, Margarita; Sun, Guangchao; Wilson, Richard A

    2017-01-01

    The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia). WT appressorial development is accompanied by one round of mitosis followed by autophagic cell death of the conidium. In contrast, Δabl1 mutant strains undergo multiple rounds of accelerated mitosis in elongated germ tubes, produce few appressoria, and are abolished for autophagy. Treating WT spores with glucose or 2-deoxyglucose phenocopied Δabl1. Inactivating TOR in Δabl1 mutants or glucose-treated WT strains restored appressorium formation by promoting mitotic arrest at G1/G0 via an appressorium- and autophagy-inducing cell cycle delay at G2/M. Collectively, this work uncovers a novel glucose-ABL1-TOR signaling axis and shows it engages two metabolic checkpoints in order to modulate cell cycle tuning and mediate terminal appressorial cell differentiation. We thus provide new molecular insights into TOR regulation and cell development in response to glucose.

  18. [Designing and implementation of a web-based quality monitoring system for plasma glucose measurement in multicenter population study].

    Science.gov (United States)

    Liu, Yong; Wang, Limin; Pang, Richard; Mo, Nanxun; Hu, Yan; Deng, Qian; Hu, Zhaohui

    2015-05-01

    The aim of this paper is to describe the designing and implementation of a web-based plasma glucose measurement quality monitoring system to assess the analytical quality of plasma glucose measurements in multicenter population study and provide evidence for the future studies. In the chronic non-communicable disease and related factor surveillance in China, a web based quality monitoring system for plasma glucose measurement was established to conduct evaluation on plasma glucose monitoring quality and effectiveness in 302 surveillance centers, including quality control data entry, transmission and feedback. The majority of the surveillance centers met the quality requirements and passed the evaluation of reproducibility and precision of plasma glucose measurement, only a few centers required intensive training and re-assessment. In order to ensure the completeness and reliability of plasma glucose measurement in the surveillance centers, the establishment of web-based plasma glucose measurement quality control system can facilitate the identification of the qualified surveillance centers and evaluation of plasma glucose measurement quality in different regions. Communication and training are important in ensuring plasma glucose measurement quality. It is necessary to further improve this web-based plasma glucose measurement quality monitoring system in the future to reduce the method specific plasma glucose measurement bias.

  19. N-Methyl-D aspartate receptor-mediated effect on glucose transporter-3 levels of high glucose exposed-SH-SY5Y dopaminergic neurons.

    Science.gov (United States)

    Engin, Ayse Basak; Engin, Evren Doruk; Karakus, Resul; Aral, Arzu; Gulbahar, Ozlem; Engin, Atilla

    2017-11-01

    High glucose and insulin lead to neuronal insulin resistance. Glucose transport into the neurons is achieved by regulatory induction of surface glucose transporter-3 (GLUT3) instead of the insulin. N-methyl-D aspartate (NMDA) receptor activity increases GLUT3 expression. This study explored whether an endogenous NMDA receptor antagonist, kynurenic acid (KynA) affects the neuronal cell viability at high glucose concentrations. SH-SY5Y neuroblastoma cells were exposed to 150-250 mg/dL glucose and 40 μU/mL insulin. In KynA and N-nitro-l-arginine methyl ester (L-NAME) supplemented cultures, oxidative stress, mitochondrial metabolic activity (MTT), nitric oxide as nitrite+nitrate (NOx) and GLUT3 were determined at the end of 24 and 48-h incubation periods. Viable cells were counted by trypan blue dye. High glucose-exposed SH-SY5Y cells showed two-times more GLUT3 expression at second 24-h period. While GLUT3-stimulated glucose transport and oxidative stress was increased, total mitochondrial metabolic activity was significantly reduced. Insulin supplementation to high glucose decreased NOx synthesis and GLUT3 levels, in contrast oxidative stress increased three-fold. KynA significantly reduced oxidative stress, and increased MTT by regulating NOx production and GLUT3 expression. KynA is a noteworthy compound, as an endogenous, specific NMDA receptor antagonist; it significantly reduces oxidative stress, while increasing cell viability at high glucose and insulin concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Central insulin and leptin-mediated autonomic control of glucose homeostasis

    OpenAIRE

    Marino, Joseph S.; Xu, Yong; Hill, Jennifer W.

    2011-01-01

    Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular...

  1. AMPKα1: a glucose sensor that controls CD8 T-cell memory.

    Science.gov (United States)

    Rolf, Julia; Zarrouk, Marouan; Finlay, David K; Foretz, Marc; Viollet, Benoit; Cantrell, Doreen A

    2013-04-01

    The adenosine monophosphate-activated protein kinase (AMPK) is activated by antigen receptor signals and energy stress in T cells. In many cell types, AMPK can maintain energy homeostasis and can enforce quiescence to limit energy demands. We consequently evaluated the importance of AMPK for controlling the transition of metabolically active effector CD8 T lymphocytes to the metabolically quiescent catabolic memory T cells during the contraction phase of the immune response. We show that AMPKα1 activates rapidly in response to the metabolic stress caused by glucose deprivation of CD8 cytotoxic T lymphocytes (CTLs). Moreover, AMPKα1 restrains mammalian target of rapamycin complex 1 activity under conditions of glucose stress. AMPKα1 activity is dispensable for proliferation and differentiation of CTLs. However, AMPKα1 is required for in vivo survival of CTLs following withdrawal of immune stimulation. AMPKα1(null) T cells also show a striking defect in their ability to generate memory CD8 T-cell responses during Listeria monocytogenes infection. These results show that AMPKα1 monitors energy stress in CTLs and controls CD8 T-cell memory. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling.

    Science.gov (United States)

    Na, Ha-Na; Hegde, Vijay; Dubuisson, Olga; Dhurandhar, Nikhil V

    2016-01-01

    Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR), and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1). In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown) with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling.

  3. E4orf1 Enhances Glucose Uptake Independent of Proximal Insulin Signaling.

    Directory of Open Access Journals (Sweden)

    Ha-Na Na

    Full Text Available Impaired proximal insulin signaling is often present in diabetes. Hence, approaches to enhance glucose disposal independent of proximal insulin signaling are desirable. Evidence indicates that Adenovirus-derived E4orf1 protein may offer such an approach. This study determined if E4orf1 improves insulin sensitivity and downregulates proximal insulin signaling in vivo and enhances cellular glucose uptake independent of proximal insulin signaling in vitro. High fat fed mice were injected with a retrovirus plasmid expressing E4orf1, or a null vector. E4orf1 significantly improved insulin sensitivity in response to a glucose load. Yet, their proximal insulin signaling in fat depots was impaired, as indicated by reduced tyrosine phosphorylation of insulin receptor (IR, and significantly increased abundance of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1. In 3T3-L1 pre-adipocytes E4orf1 expression impaired proximal insulin signaling. Whereas, treatment with rosiglitazone reduced ENPP1 abundance. Unaffected by IR-KD (insulin receptor knockdown with siRNA, E4orf1 significantly up-regulated distal insulin signaling pathway and enhanced cellular glucose uptake. In vivo, E4orf1 impairs proximal insulin signaling in fat depots yet improves glycemic control. This is probably explained by the ability of E4orf1 to promote cellular glucose uptake independent of proximal insulin signaling. E4orf1 may provide a therapeutic template to enhance glucose disposal in the presence of impaired proximal insulin signaling.

  4. The Relationship Between a Balanced Time Perspective and Self-monitoring of Blood Glucose Among People With Type 1 Diabetes.

    Science.gov (United States)

    Baird, Harriet M; Webb, Thomas L; Martin, Jilly; Sirois, Fuschia M

    2018-05-10

    Self-monitoring of blood glucose helps people with type 1 diabetes to maintain glycemic control and reduce the risk of complications. However, adherence to blood glucose monitoring is often suboptimal. Like many health behaviors, self-monitoring of blood glucose involves exerting effort in the present to achieve future benefits. As such, the present research explored whether individual differences in time perspective-specifically, the extent to which people have a balanced time perspective-are associated with the frequency with which people with type 1 diabetes monitor their blood glucose and, thus, maintain glycemic control. Adults with type 1 diabetes completed measures of time perspective, feelings associated with monitoring, attitudes toward monitoring, and trait self-control. Objective data regarding the frequency with which participants monitored their blood glucose levels and their long-term glycemic control were extracted from their medical records. Hierarchical regression analyses and tests of indirect effects (N = 129) indicated that having a more balanced time perspective was associated with more frequent monitoring of blood glucose and, as a result, better glycemic control. Further analyses (N = 158) also indicated that there was an indirect relationship between balanced time perspective and monitoring of blood glucose via the feelings that participants associated with monitoring and their subsequent attitudes toward monitoring. These findings point to the importance and relevance of time perspective for understanding health-related behavior and may help to inform interventions designed to promote self-monitoring of blood glucose in people with type 1 diabetes.

  5. "Learning" Can Improve the Blood Glucose Control Performance for Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Wang, Youqing; Zhang, Jinping; Zeng, Fanmao; Wang, Na; Chen, Xiaoping; Zhang, Bo; Zhao, Dong; Yang, Wenying; Cobelli, Claudio

    2017-01-01

    A learning-type artificial pancreas has been proposed to exploit the repetitive nature in the blood glucose dynamics. We clinically evaluated the efficacy of the learning-type artificial pancreas. We conducted a pilot clinical study in 10 participants of mean age 36.1 years (standard deviation [SD] 12.7; range 16-58) with type 1 diabetes. Each trial was conducted for eight consecutive mornings. The first two mornings were open-loop to obtain the individualized parameters. Then, the following six mornings were closed-loop, during which a learning-type model predictive control algorithm was employed to calculate the insulin infusion rate. To evaluate the algorithm's robustness, each participant took exercise or consumed alcohol on the fourth or sixth closed-loop day and the order was determined randomly. The primary outcome was the percentage of time spent in the target glucose range of 3.9-8.0 mmol/L between 0900 and 1200 h. The percentage of time with glucose spent in target range was significantly improved from 51.6% on day 1 to 71.6% on day 3 (mean difference between groups 17.9%, confidence interval [95% CI] 3.6-32.1; P = 0.020). There were no hypoglycemic episodes developed on day 3 compared with two episodes on day 1. There was no difference in the percentage of time with glucose spent in target range between exercise day versus day 5 and alcohol day versus day 5. The learning-type artificial pancreas system achieved good glycemic regulation and provided increased effectiveness over time. It showed a satisfactory performance even when the blood glucose was challenged by exercise or alcohol.

  6. St. John's wort impairs glucose tolerance by reducing insulin response in healthy men

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Damkier, Per; Christensen, Mette Marie Hougaard

    2015-01-01

    The purpose of this study was to examine if the over-the-counter herbal medicinal plant St. John's wort affects glucose tolerance in healthy men. To do this, we included 10 healthy men who were examined by a 2-hr oral glucose tolerance test on three occasions; A: Baseline, B: After 21 days...

  7. Depressed glucose utilization in lungs of BB wistar spontaneously diabetic rats

    International Nuclear Information System (INIS)

    Uhal, B.D.; Moxley, M.A.; Longmore, W.J.

    1986-01-01

    Lungs of BB wistar spontaneously diabetic rats were perfused with [ 14 C(U)]glucose in modified Krebs Ringer bicarbonate medium for 1.5 hours. Lungs from non-diabetic BB Wistar rats were perfused simultaneously and served as controls. The perfusions were terminated by rapid freezing of the tissue in liquid N 2 followed by separation of surfactant and residual lung fractions. The rates of glucose incorporation into surfactant DSPC, PG, and PE were decreased 4.7, 2.4 and 2.5-fold, respectively, in lungs of spontaneously diabetic rats when expressed as final product specific activities. The rate of glucose incorporation into residual PC was also reduced by 2.3-fold. Expressed as moles incorporated per gram wet weight of lung, incorporations into surfactant DSPC, PG and residual PC were also reduced by 4.1, 6.3 and 3.8-fold respectively. These data; (1) agree with previous studies of the lungs of streptozotocin and alloxan-diabetic rats; (2) show that the depressed glucose utilization for lipid synthesis observed previously is not due to streptozotocin or alloxan toxicity; (3) suggest that the BB Wistar rat will provide a useful model for the study of the effects of insulin-dependent diabetes on lung metabolism

  8. Low GDP Solution and Glucose-Sparing Strategies for Peritoneal Dialysis.

    Science.gov (United States)

    Szeto, Cheuk Chun; Johnson, David W

    2017-01-01

    Long-term exposure to a high glucose concentration in conventional peritoneal dialysis (PD) solution has a number of direct and indirect (via glucose degradation products [GDP]) detrimental effects on the peritoneal membrane, as well as systemic metabolism. Glucose- or GDP-sparing strategies often are hypothesized to confer clinical benefits to PD patients. Icodextrin (glucose polymer) solution improves peritoneal ultrafiltration and reduces the risk of fluid overload, but these beneficial effects are probably the result of better fluid removal rather than being glucose sparing. Although frequently used for glucose sparing, the role of amino acid-based solution in this regard has not been tested thoroughly. When glucose-free solutions are used in a combination regimen, published studies showed that glycemic control was improved significantly in diabetic PD patients, and there probably are beneficial effects on peritoneal function. However, the long-term effects of glucose-free solutions, used either alone or as a combination regimen, require further studies. On the other hand, neutral pH-low GDP fluids have been shown convincingly to preserve residual renal function and urine volume. The cost effectiveness of these solutions supports the regular use of neutral pH-low GDP solutions. Nevertheless, further studies are required to determine whether neutral pH-low GDP solutions exert beneficial effects on patient-level outcomes, such as peritonitis, technique survival, and patient survival. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The Role of Pre-Operative and Post-Operative Glucose Control in Surgical-Site Infections and Mortality

    OpenAIRE

    Jeon, Christie Y.; Furuya, E. Yoko; Berman, Mitchell F.; Larson, Elaine L.

    2012-01-01

    Background and Objective The impact of glucose control on surgical-site infection (SSI) and death remains unclear. We examined how pre- and post-operative glucose levels and their variability are associated with the risk of SSI or in-hospital death. Methods This retrospective cohort study employed data on 13,800 hospitalized patients who underwent a surgical procedure at a large referral hospital in New York between 2006 and 2008. Over 20 different sources of electronic data were used to anal...

  10. Central insulin and leptin-mediated autonomic control of glucose homeostasis.

    Science.gov (United States)

    Marino, Joseph S; Xu, Yong; Hill, Jennifer W

    2011-07-01

    Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Clofibrate improves glucose tolerance in fat-fed rats but decreases hepatic glucose consumption capacity

    NARCIS (Netherlands)

    Gustafson, LA; Kuipers, F; Wiegman, C; Sauerwein, HP; Romijn, JA; Meijer, AJ

    2002-01-01

    Background/Aims: High-fat (HF) diets cause glucose intolerance. Fibrates improve glucose tolerance. We have tried to obtain information on possible hepatic mechanisms contributing to this effect. Methods: Rats were fed a HF diet, isocaloric with the control diet, for 3 weeks without or with

  12. Antilipolytic drug boosts glucose metabolism in prostate cancer

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Divilov, Vadim; Koziorowski, Jacek

    2013-01-01

    The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts.......The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts....

  13. Glucose-mediated control of ghrelin release from primary cultures of gastric mucosal cells

    Science.gov (United States)

    Sakata, Ichiro; Park, Won-Mee; Walker, Angela K.; Piper, Paul K.; Chuang, Jen-Chieh; Osborne-Lawrence, Sherri

    2012-01-01

    The peptide hormone ghrelin is released from a distinct group of gastrointestinal cells in response to caloric restriction, whereas its levels fall after eating. The mechanisms by which ghrelin secretion is regulated remain largely unknown. Here, we have used primary cultures of mouse gastric mucosal cells to investigate ghrelin secretion, with an emphasis on the role of glucose. Ghrelin secretion from these cells upon exposure to different d-glucose concentrations, the glucose antimetabolite 2-deoxy-d-glucose, and other potential secretagogues was assessed. The expression profile of proteins involved in glucose transport, metabolism, and utilization within highly enriched pools of mouse ghrelin cells and within cultured ghrelinoma cells was also determined. Ghrelin release negatively correlated with d-glucose concentration. Insulin blocked ghrelin release, but only in a low d-glucose environment. 2-Deoxy-d-glucose prevented the inhibitory effect of high d-glucose exposure on ghrelin release. mRNAs encoding several facilitative glucose transporters, hexokinases, the ATP-sensitive potassium channel subunit Kir6.2, and sulfonylurea type 1 receptor were expressed highly within ghrelin cells, although neither tolbutamide nor diazoxide exerted direct effects on ghrelin secretion. These findings suggest that direct exposure of ghrelin cells to low ambient d-glucose stimulates ghrelin release, whereas high d-glucose and glucose metabolism within ghrelin cells block ghrelin release. Also, low d-glucose sensitizes ghrelin cells to insulin. Various glucose transporters, channels, and enzymes that mediate glucose responsiveness in other cell types may contribute to the ghrelin cell machinery involved in regulating ghrelin secretion under these different glucose environments, although their exact roles in ghrelin release remain uncertain. PMID:22414807

  14. Effects of Berberine on Amelioration of Hyperglycemia and Oxidative Stress in High Glucose and High Fat Diet-Induced Diabetic Hamsters In Vivo

    Directory of Open Access Journals (Sweden)

    Cong Liu

    2015-01-01

    Full Text Available This study investigated the effects of berberine on amelioration of hyperglycemia and hyperlipidemia and the mechanism involved in high glucose and high fat diet-induced diabetic hamsters. Golden hamsters fed with high glucose and high fat diet were medicated with metformin, simvastatin, and low or high dose of berberine (50 and 100 mg·kg−1 for 6 weeks. The results showed that the body weights were significantly lower in berberine-treated groups than control group. Histological analyses revealed that the treatment of berberine inhibited hepatic fat accumulation. Berberine significantly reduced plasma total cholesterol, triglyceride, free fatty acid, low density lipoprotein cholesterol, malondialdehyde, thiobarbituric acid-reactive substance, and 8-isoprostane level but significantly increased plasma superoxide dismutase activity. Glucose and insulin levels were significantly reduced in metformin and berberine-treated groups. Glucose tolerance tests documented that berberine-treated mice were more glucose tolerant. Berberine treatment increased expression of skeletal muscle glucose transporter 4 mRNA and significantly decreased liver low density lipoprotein receptor mRNA expression. The study suggested that berberine was effective in lowering blood glucose and lipids levels, reducing the body weight, and alleviating the oxidative stress in diabetic hamsters, which might be beneficial in reducing the cardiovascular risk factors in diabetes.

  15. Glucagon-like peptide-1 inhibits blood-brain glucose transfer in humans

    DEFF Research Database (Denmark)

    Lerche, Susanne; Brock, Birgitte; Rungby, Jørgen

    2008-01-01

    OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has many effects on glucose homeostasis, and GLP-1 receptors are broadly represented in many tissues including the brain. Recent research in rodents suggests a protective effect of GLP-1 on brain tissue. The mechanism is unknown. We therefore tested......-independent effect of GLP-1 on unidirectional glucose transport into the brain during a pituitary-pancreatic normoglycemic (plasma glucose approximately 4.5 mmol/l) clamp with 18-fluoro-deoxy-glucose as tracer. RESULTS: On average, GLP-1 reduced cerebral glucose transport by 27% in total cerebral gray matter (P = 0...... that a hormone involved in postprandial glucose regulation also limits glucose delivery to brain tissue and hence provides a possible regulatory mechanism for the link between plasma glucose and brain glucose. Because GLP-1 reduces glucose uptake across the intact blood-brain barrier at normal glycemia, GLP-1...

  16. The global regulatory system Csr senses glucose through the phosphoenolpyruvate: carbohydrate phosphotransferase system.

    Science.gov (United States)

    Pérez-Morales, Deyanira; Bustamante, Víctor H

    2016-02-01

    A novel connection between two regulatory systems controlling crucial biological processes in bacteria, the carbon storage regulator (Csr) system and the glucose-specific phosphotransferase system (PTS), is reported by Leng et al. in this issue. This involves the interaction of unphosphorylated EIIA(Glc), a component of the glucose-specific PTS, with the CsrD protein, which accelerates the decay of the CsrB and CsrC small RNAs via RNase E in Escherichia coli. As unphosphorylated EIIA(G) (lc) is generated in the presence of glucose, the PTS thus acts as a sensor of glucose for the Csr system. Interestingly, another pathway can operate for communication between the Csr system and the glucose-specific PTS. The absence of glucose generates phosphorylated EIIA(Glc) , which activates the enzyme adenylate cyclase to produce cyclic adenosine monophosphate (cAMP) that, in turn, binds to the regulator cAMP receptor protein (CRP). Leng et al. show that the complex cAMP-CRP modestly reduces CsrB decay independently of CsrD. On the other hand, a previous study indicates that the complex cAMP-CRP positively regulates the transcription of CsrB and CsrC in Salmonella enterica. Therefore, EIIA(G) (lc) could work as a molecular switch that regulates the activity of the Csr system, in response to its phosphorylation state determined by the presence or absence of glucose, in order to control gene expression. © 2015 John Wiley & Sons Ltd.

  17. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors in pharmacokinetics, pharmacodynamics, and pharmacologic effects

    Directory of Open Access Journals (Sweden)

    Atsuo Tahara

    2016-03-01

    Full Text Available The sodium-glucose cotransporter (SGLT 2 offer a novel approach to treating type 2 diabetes by reducing hyperglycaemia via increased urinary glucose excretion. In the present study, the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six SGLT2 inhibitors commercially available in Japan were investigated and compared. Based on findings in normal and diabetic mice, the six drugs were classified into two categories, long-acting: ipragliflozin and dapagliflozin, and intermediate-acting: tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin. Long-acting SGLT2 inhibitors exerted an antihyperglycemic effect with lower variability of blood glucose level via a long-lasting increase in urinary glucose excretion. In addition, ipragliflozin and luseogliflozin exhibited superiority over the others with respect to fast onset of pharmacological effect. Duration and onset of the pharmacologic effects seemed to be closely correlated with the pharmacokinetic properties of each SGLT2 inhibitor, particularly with respect to high distribution and long retention in the target organ, the kidney. While all six SGLT2 inhibitors were significantly effective in increasing urinary glucose excretion and reducing hyperglycemia, our findings suggest that variation in the quality of daily blood glucose control associated with duration and onset of pharmacologic effects of each SGLT2 inhibitor might cause slight differences in rates of improvement in type 2 diabetes.

  18. Effects of Taurine Supplementation on Neuronal Excitability and Glucose Homeostasis.

    Science.gov (United States)

    El Idrissi, Abdeslem; El Hilali, Fatiha; Rotondo, Salvatore; Sidime, Francoise

    2017-01-01

    In this study we examined the role of chronic taurine supplementation on plasma glucose homeostasis and brain excitability through activation of the insulin receptor. FVB/NJ male mice were supplemented with taurine in drinking water (0.05% w/v) for 4 weeks and subjected to a glucose tolerance test (7.5 mg/kg BW) after 12 h fasting. We found that taurine-fed mice were slightly hypoglycemic prior to glucose injection and showed significantly reduced plasma glucose at 30 and 60 min post-glucose injection when compared to control mice. Previously, we reported that taurine supplementation induces biochemical changes that target the GABAergic system. Those studies show that taurine-fed mice are hyperexcitable, have reduced GABA A receptors expression and increased GAD and somatostatin expression in the brain. In this study, we found that taurine-fed mice had a significant increase in insulin receptor (IR) immuno-reactivity in the pancreas and all brain regions examined. At the mRNA level, we found that the IR showed differential regional expression. Surprisingly, we found that neurons express the gene for insulin and that taurine had a significant role in regulating insulin gene expression. We propose that increased insulin production and secretion in taurine-fed mice cause an increase activation of the central IR and may be partially responsible for the increased neuronal excitability observed in taurine supplemented mice. Furthermore, the high levels of neuronal insulin expression and its regulation by taurine implicates taurine in the regulation of metabolic homeostasis.

  19. Toward an injectable continuous osmotic glucose sensor.

    Science.gov (United States)

    Johannessen, Erik; Krushinitskaya, Olga; Sokolov, Andrey; Philipp, Häfliger; Hoogerwerf, Arno; Hinderling, Christian; Kautio, Kari; Lenkkeri, Jaakko; Strömmer, Esko; Kondratyev, Vasily; Tønnessen, Tor Inge; Mollnes, Tom Eirik; Jakobsen, Henrik; Zimmer, Even; Akselsen, Bengt

    2010-07-01

    The growing pandemic of diabetes mellitus places a stringent social and economic burden on the society. A tight glycemic control circumvents the detrimental effects, but the prerogative is the development of new more effective tools capable of longterm tracking of blood glucose (BG) in vivo. Such discontinuous sensor technologies will benefit from an unprecedented marked potential as well as reducing the current life expectancy gap of eight years as part of a therapeutic regime. A sensor technology based on osmotic pressure incorporates a reversible competitive affinity assay performing glucose-specific recognition. An absolute change in particles generates a pressure that is proportional to the glucose concentration. An integrated pressure transducer and components developed from the silicon micro- and nanofabrication industry translate this pressure into BG data. An in vitro model based on a 3.6 x 8.7 mm large pill-shaped implant is equipped with a nanoporous membrane holding 4-6 nm large pores. The affinity assay offers a dynamic range of 36-720 mg/dl with a resolution of +/-16 mg/dl. An integrated 1 x 1 mm(2) large control chip samples the sensor signals for data processing and transmission back to the reader at a total power consumption of 76 microW. Current studies have demonstrated the design, layout, and performance of a prototype osmotic sensor in vitro using an affinity assay solution for up to four weeks. The small physical size conforms to an injectable device, forming the basis of a conceptual monitor that offers a tight glycemic control of BG. 2010 Diabetes Technology Society.

  20. Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism ★

    OpenAIRE

    Marcelin, Geneviève; Jo, Young-Hwan; Li, Xiaosong; Schwartz, Gary J.; Zhang, Ying; Dun, Nae J.; Lyu, Rong-Ming; Blouet, Clémence; Chang, Jaw K.; Chua, Streamson

    2013-01-01

    Tight control of glucose excursions has been a long-standing goal of treatment for patients with type 2 diabetes mellitus in order to ameliorate the morbidity and mortality associated with hyperglycemia. Fibroblast growth factor (FGF) 19 is a hormone-like enterokine released postprandially that emerged as a potential therapeutic agent for metabolic disorders, including diabetes and obesity. Remarkably, FGF19 treatment has hypoglycemic actions that remain potent in models of genetic and acquir...

  1. Glucose-reducing effect of the ORMD-0801 oral insulin preparation in patients with uncontrolled type 1 diabetes: a pilot study.

    Directory of Open Access Journals (Sweden)

    Roy Eldor

    Full Text Available The unpredictable behavior of uncontrolled type 1 diabetes often involves frequent swings in blood glucose levels that impact maintenance of a daily routine. An intensified insulin regimen is often unsuccessful, while other therapeutic options, such as amylin analog injections, use of continuous glucose sensors, and islet or pancreas transplantation are of limited clinical use. In efforts to provide patients with a more compliable treatment method, Oramed Pharmaceuticals tested the capacity of its oral insulin capsule (ORMD-0801, 8 mg insulin in addressing this resistant clinical state. Eight Type I diabetes patients with uncontrolled diabetes (HbA1c: 7.5-10% were monitored throughout the 15-day study period by means of a blind continuous glucose monitoring device. Baseline patient blood glucose behavior was monitored and recorded over a five-day pretreatment screening period. During the ensuing ten-day treatment phase, patients were asked to conduct themselves as usual and to self-administer an oral insulin capsule three times daily, just prior to meal intake. CGM data sufficient for pharmacodynamics analyses were obtained from 6 of the 8 subjects. Treatment with ORMD-0801 was associated with a significant 24.4% reduction in the frequencies of glucose readings >200 mg/dL (60.1 ± 7.9% pretreatment vs. 45.4 ± 4.9% during ORMD-0801 treatment; p = 0.023 and a significant mean 16.6% decrease in glucose area under the curve (AUC (66055 ± 5547 mg/dL/24 hours vs. 55060 ± 3068 mg/dL/24 hours, p = 0.023, with a greater decrease during the early evening hours. In conclusion, ORMD-0801 oral insulin capsules in conjunction with subcutaneous insulin injections, well tolerated and effectively reduced glycemia throughout the day.Clinicaltrials.gov NCT00867594.

  2. E4orf1: a novel ligand that improves glucose disposal in cell culture.

    Directory of Open Access Journals (Sweden)

    Emily J Dhurandhar

    Full Text Available Reducing dietary fat intake and excess adiposity, the cornerstones of behavioral treatment of insulin resistance (IR, are marginally successful over the long term. Ad36, a human adenovirus, offers a template to improve IR, independent of dietary fat intake or adiposity. Ad36 increases cellular glucose uptake via a Ras-mediated activation of phosphatidyl inositol 3-kinase(PI3K, and improves hyperglycemia in mice, despite a high-fat diet and without reducing adiposity. Ex-vivo studies suggest that Ad36 improves hyperglycemia in mice by increasing glucose uptake by adipose tissue and skeletal muscle, and by reducing hepatic glucose output. It is impractical to use Ad36 for therapeutic action. Instead, we investigated if the E4orf1 protein of Ad36, mediates its anti-hyperglycemic action. Such a candidate protein may offer an attractive template for therapeutic development. Experiment-1 determined that Ad36 'requires' E4orf1 protein to up-regulate cellular glucose uptake. Ad36 significantly increased glucose uptake in 3T3-L1 preadipocytes, which was abrogated by knocking down E4orf1 with siRNA. Experiment-2 identified E4orf1 as 'sufficient' to up-regulate glucose uptake. 3T3-L1 cells that inducibly express E4orf1, increased glucose uptake in an induction-dependent manner, compared to null vector control cells. E4orf1 up-regulated PI3K pathway and increased abundance of Ras--the obligatory molecule in Ad36-induced glucose uptake. Experiment-3: Signaling studies of cells transiently transfected with E4orf1 or a null vector, revealed that E4orf1 may activate Ras/PI3K pathway by binding to Drosophila discs-large (Dlg1 protein. E4orf1 activated total Ras and, particularly the H-Ras isoform. By mutating the PDZ domain binding motif (PBM of E4orf1, Experiment-4 showed that E4orf1 requires its PBM to increase Ras activation or glucose uptake. Experiment-5: In-vitro, a transient transfection by E4orf1 significantly increased glucose uptake in preadipocytes

  3. E4orf1: a novel ligand that improves glucose disposal in cell culture.

    Science.gov (United States)

    Dhurandhar, Emily J; Dubuisson, Olga; Mashtalir, Nazar; Krishnapuram, Rashmi; Hegde, Vijay; Dhurandhar, Nikhil V

    2011-01-01

    Reducing dietary fat intake and excess adiposity, the cornerstones of behavioral treatment of insulin resistance (IR), are marginally successful over the long term. Ad36, a human adenovirus, offers a template to improve IR, independent of dietary fat intake or adiposity. Ad36 increases cellular glucose uptake via a Ras-mediated activation of phosphatidyl inositol 3-kinase(PI3K), and improves hyperglycemia in mice, despite a high-fat diet and without reducing adiposity. Ex-vivo studies suggest that Ad36 improves hyperglycemia in mice by increasing glucose uptake by adipose tissue and skeletal muscle, and by reducing hepatic glucose output. It is impractical to use Ad36 for therapeutic action. Instead, we investigated if the E4orf1 protein of Ad36, mediates its anti-hyperglycemic action. Such a candidate protein may offer an attractive template for therapeutic development. Experiment-1 determined that Ad36 'requires' E4orf1 protein to up-regulate cellular glucose uptake. Ad36 significantly increased glucose uptake in 3T3-L1 preadipocytes, which was abrogated by knocking down E4orf1 with siRNA. Experiment-2 identified E4orf1 as 'sufficient' to up-regulate glucose uptake. 3T3-L1 cells that inducibly express E4orf1, increased glucose uptake in an induction-dependent manner, compared to null vector control cells. E4orf1 up-regulated PI3K pathway and increased abundance of Ras--the obligatory molecule in Ad36-induced glucose uptake. Experiment-3: Signaling studies of cells transiently transfected with E4orf1 or a null vector, revealed that E4orf1 may activate Ras/PI3K pathway by binding to Drosophila discs-large (Dlg1) protein. E4orf1 activated total Ras and, particularly the H-Ras isoform. By mutating the PDZ domain binding motif (PBM) of E4orf1, Experiment-4 showed that E4orf1 requires its PBM to increase Ras activation or glucose uptake. Experiment-5: In-vitro, a transient transfection by E4orf1 significantly increased glucose uptake in preadipocytes, adipocytes, or

  4. Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses.

    Science.gov (United States)

    Rendle, D I; Rutledge, F; Hughes, K J; Heller, J; Durham, A E

    2013-11-01

    Metformin is a potential therapeutic agent for the treatment of insulin resistance (IR). In laboratory animals, orally administered metformin reduces intestinal glucose absorption and may therefore affect insulinaemic responses to oral carbohydrate ingestion. To determine whether pretreatment with metformin reduces plasma glucose concentration and insulin responses following consumption of dextrose in horses. Therapeutic cross-over study. Seven healthy Standardbred and Thoroughbred geldings were subjected to an oral dextrose challenge test on 4 occasions: with and without metformin, before and after induction of IR with dexamethasone. Metformin was administered by nasogastric tube at 30 mg/kg bwt 1 h before administration of dextrose. Glucose and insulin concentrations in plasma/serum were measured at regular intervals during each test. Linear mixed models were specified for each predetermined outcome variable, and for each model the 'treatment' was included as a fixed effect with 4 categorical levels (none, metformin, dexamethasone and dexamethasone with metformin) and horse accounted for as a random effect. In healthy horses, the administration of metformin resulted in a statistically significant reduction in peak glucose concentration (P = 0.002), area under the glucose curve (Pdextrose administration (P = 0.011). Following the induction of IR, administration of metformin was associated with significant differences in peak glucose concentration (Pdextrose administration (P = 0.014). Metformin resulted in reduced glycaemic and insulinaemic responses both in healthy horses and in horses with experimentally induced IR. Metformin may benefit horses with naturally acquired IR by reducing glycaemic and insulinaemic responses to dietary nonstructural carbohydrates. Further investigations into the mechanisms of action of metformin in horses and controlled clinical trials are warranted. © 2013 EVJ Ltd.

  5. Pyruvate incubation enhances glycogen stores and sustains neuronal function during subsequent glucose deprivation.

    Science.gov (United States)

    Shetty, Pavan K; Sadgrove, Matthew P; Galeffi, Francesca; Turner, Dennis A

    2012-01-01

    The use of energy substrates, such as lactate and pyruvate, has been shown to improve synaptic function when administered during glucose deprivation. In the present study, we investigated whether prolonged incubation with monocarboxylate (pyruvate or lactate) prior rather than during glucose deprivation can also sustain synaptic and metabolic function. Pyruvate pre-incubation(3-4h) significantly prolonged (>25 min) the tolerance of rat hippocampal slices to delayed glucose deprivation compared to control and lactate pre-incubated slices, as revealed by field excitatory post synaptic potentials (fEPSPs); pre-incubation with pyruvate also reduced the marked decrease in NAD(P)H fluorescence resulting from glucose deprivation. Moreover, pyruvate exposure led to the enhancement of glycogen stores with time, compared to glucose alone (12 μmol/g tissue at 4h vs. 3.5 μmol/g tissue). Prolonged resistance to glucose deprivation following exogenous pyruvate incubation was prevented by glycogenolysis inhibitors, suggesting that enhanced glycogen mediates the delay in synaptic activity failure. The application of an adenosine A1 receptor antagonist enhanced glycogen utilization and prolonged the time to synaptic failure, further confirming this hypothesis of the importance of glycogen. Moreover, tissue levels of ATP were also significantly maintained during glucose deprivation in pyruvate pretreated slices compared to control and lactate. In summary, these experiments indicate that pyruvate exposure prior to glucose deprivation significantly increased the energy buffering capacity of hippocampal slices, particularly by enhancing internal glycogen stores, delaying synaptic failure during glucose deprivation by maintaining ATP levels, and minimizing the decrease in the levels of NAD(P)H. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Pancreatic α-Amylase Controls Glucose Assimilation by Duodenal Retrieval through N-Glycan-specific Binding, Endocytosis, and Degradation*

    Science.gov (United States)

    Date, Kimie; Satoh, Ayano; Iida, Kaoruko; Ogawa, Haruko

    2015-01-01

    α-Amylase, a major pancreatic protein and starch hydrolase, is essential for energy acquisition. Mammalian pancreatic α-amylase binds specifically to glycoprotein N-glycans in the brush-border membrane to activate starch digestion, whereas it significantly inhibits glucose uptake by Na+/glucose cotransporter 1 (SGLT1) at high concentrations (Asanuma-Date, K., Hirano, Y., Le, N., Sano, K., Kawasaki, N., Hashii, N., Hiruta, Y., Nakayama, K., Umemura, M., Ishikawa, K., Sakagami, H., and Ogawa, H. (2012) Functional regulation of sugar assimilation by N-glycan-specific interaction of pancreatic α-amylase with glycoproteins of duodenal brush border membrane. J. Biol. Chem. 287, 23104–23118). However, how the inhibition is stopped was unknown. Here, we show a new mechanism for the regulation of intestinal glucose absorption. Immunohistochemistry revealed that α-amylase in the duodena of non-fasted, but not fasted, pigs was internalized from the pancreatic fluid and immunostained. We demonstrated that after N-glycan binding, pancreatic α-amylase underwent internalization into lysosomes in a process that was inhibited by α-mannoside. The internalized α-amylase was degraded, showing low enzymatic activity and molecular weight at the basolateral membrane. In a human intestinal Caco-2 cell line, Alexa Fluor 488-labeled pancreatic α-amylase bound to the cytomembrane was transported to lysosomes through the endocytic pathway and then disappeared, suggesting degradation. Our findings indicate that N-glycan recognition by α-amylase protects enterocytes against a sudden increase in glucose concentration and restores glucose uptake by gradual internalization, which homeostatically controls the postprandial blood glucose level. The internalization of α-amylase may also enhance the supply of amino acids required for the high turnover of small intestine epithelial cells. This study provides novel and significant insights into the control of blood sugar during the absorption

  7. Self-reported discrimination, diabetes distress, and continuous blood glucose in women with type 2 diabetes.

    Science.gov (United States)

    Wagner, Julie A; Tennen, Howard; Feinn, Richard; Osborn, Chandra Y

    2015-04-01

    We investigated whether self-reported racial discrimination was associated with continuous glucose levels and variability in individuals with diabetes, and whether diabetes distress mediated these associations. Seventy-four Black and White women with type 2 diabetes completed the Experience of Discrimination scale, a measure of lifetime racial discrimination, and the Problem Areas in Diabetes, a measure of diabetes distress. Participants wore a continuous glucose monitor for 24 h after 8 h of fasting, a standard meal, and a 4-h run in period. Higher discrimination predicted higher continuous mean glucose and higher standard deviation of glucose. For both mean and standard deviation of glucose, a race × discrimination interaction indicated a stronger relationship between discrimination and glucose for Whites than for Blacks. Diabetes distress mediated the discrimination-mean glucose relationship. Whites who report discrimination may be uniquely sensitive to distress. These preliminary findings suggest that racial discrimination adversely affects glucose control in women with diabetes, and does so indirectly through diabetes distress. Diabetes distress may be an important therapeutic target to reduce the ill effects of racial discrimination in persons with diabetes.

  8. Co{sub 3}O{sub 4}-reduced graphene oxide nanocomposite as an effective peroxidase mimetic and its application in visual biosensing of glucose

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Jianxin [The Key Laboratory of Luminescence and Real-time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); College of Resources and Environment, Yuxi Normal University, Yunnan 653100 (China); Cao, Haiyan; Jiang, Huan; Chen, Yujin [The Key Laboratory of Luminescence and Real-time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Shi, Wenbing [College of Chemistry and Chemical Engineering, Yangtze Normal University, Chongqing 408003 (China); Zheng, Huzhi [The Key Laboratory of Luminescence and Real-time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Huang, Yuming, E-mail: yuminghuang2000@yahoo.com [The Key Laboratory of Luminescence and Real-time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)

    2013-09-24

    Graphical abstract: -- Highlights: •The well-dispersed Co{sub 3}O{sub 4} NPs on rGO surfaces were successfully synthesized. •The as-obtained Co{sub 3}O{sub 4}/rGO nanocomposites exhibit an effective peroxidase-like activity. •They can catalyze the oxidation of TMB by H{sub 2}O{sub 2} to produce an intensified blue reaction. •The Co{sub 3}O{sub 4}/rGO-based colorimetric and visual biosensing of glucose was developed. -- Abstract: The well-dispersed Co{sub 3}O{sub 4} nanoparticles on reduced graphene oxide (rGO) surfaces were successfully prepared by in situ controlled nucleation of Co{sub 3}O{sub 4} NPs on GO sheets and subsequent in situ reduction of GO by low temperature hydrothermal reaction in ethanol media. The as-prepared Co{sub 3}O{sub 4}/rGO nanocomposites were characterized by transmission electron microscopy (TEM), scanning electron microscope (SEM), thermogravimetry (TG), X-ray diffraction (XRD) and FT-IR spectra. It was found that the Co{sub 3}O{sub 4} NPs were successfully decorated and well dispersed on the surface of rGO sheet without agglomeration. We discovered that the Co{sub 3}O{sub 4}/rGO nanocomposites possess intrinsic peroxidase-like activity and catalase-like activity, and could catalytically oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) by hydrogen peroxide (H{sub 2}O{sub 2}) to produce a intensified colour reaction. Results of electron spin resonance (ESR) experiments demonstrated that the Co{sub 3}O{sub 4}/rGO nanocomposites showed catalytic ability to H{sub 2}O{sub 2} decomposition into ·OH radicals. On this basis, a simple and selective method for glucose detection was developed by coupling the oxidation of glucose catalyzed by glucose oxidase (GOx). As low as 1 × 10{sup −6} mol L{sup −1} glucose could be detected with a linear range from 1 × 10{sup −6} to 1 × 10{sup −4} mol L{sup −1}. The visual detection of glucose can be realized easily through the observable color change from colorless to blue by the naked

  9. Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation

    Science.gov (United States)

    Sobieski, Courtney; Shu, Hong-Jin

    2018-01-01

    Neurons require a nearly constant supply of ATP. Glucose is the predominant source of brain ATP, but the direct effects of prolonged glucose deprivation on neuronal viability and function remain unclear. In sparse rat hippocampal microcultures, neurons were surprisingly resilient to 16 h glucose removal in the absence of secondary excitotoxicity. Neuronal survival and synaptic transmission were unaffected by prolonged removal of exogenous glucose. Inhibition of lactate transport decreased microculture neuronal survival during concurrent glucose deprivation, suggesting that endogenously released lactate is important for tolerance to glucose deprivation. Tandem depolarization and glucose deprivation also reduced neuronal survival, and trace glucose concentrations afforded neuroprotection. Mass cultures, in contrast to microcultures, were insensitive to depolarizing glucose deprivation, a difference attributable to increased extracellular lactate levels. Removal of local astrocyte support did not reduce survival in response to glucose deprivation or alter evoked excitatory transmission, suggesting that on-demand, local lactate shuttling is not necessary for neuronal tolerance to prolonged glucose removal. Taken together, these data suggest that endogenously produced lactate available globally in the extracellular milieu sustains neurons in the absence of glucose. A better understanding of resilience mechanisms in reduced preparations could lead to therapeutic strategies aimed to bolster these mechanisms in vulnerable neuronal populations. PMID:29617444

  10. Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity.

    Science.gov (United States)

    Reay, Jonathon L; Kennedy, David O; Scholey, Andrew B

    2005-07-01

    Single doses of the traditional herbal treatment Panax ginseng have recently been shown to elicit cognitive improvements in healthy young volunteers. The mechanisms by which ginseng improves cognitive performance are not known. However, they may be related to the glycaemic properties of some Panax species. Using a double-blind, placebo-controlled, balanced crossover design, 30 healthy young adults completed a 10 min test battery at baseline, and then six times in immediate succession commencing 60 min after the day's treatment (placebo, 200mg G115 or 400mg G115). The 10 min battery comprised a Serial Threes subtraction task (2 min); a Serial Sevens task (2 min); a Rapid Visual Information Processing task (5 min); then a 'mental fatigue' visual analogue scale. Blood glucose was measured prior to each day's treatment, and before, during and after the post-dose completions of the battery. Both the 200mg and 400mg treatments led to significant reductions in blood glucose levels at all three post-treatment measurements (p 0.005 in all cases). The most notable behavioural effects were associated with 200mg of ginseng and included significantly improved Serial Sevens subtraction task performance and significantly reduced subjective mental fatigue throughout all (with the exception of one time point in each case) of the post-dose completions of the 10 min battery (p 0.05). Overall these data suggest that Panax ginseng can improve performance and subjective feelings of mental fatigue during sustained mental activity. This effect may be related to the acute gluco-regulatory properties of the extract.

  11. Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

    2016-12-01

    The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC 50  = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU 50  = 2.68 ± 0.75 %) or without (GU 50  = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

  12. Glucose-responsive neurons of the paraventricular thalamus control sucrose-seeking behavior.

    Science.gov (United States)

    Labouèbe, Gwenaël; Boutrel, Benjamin; Tarussio, David; Thorens, Bernard

    2016-08-01

    Feeding behavior is governed by homeostatic needs and motivational drive to obtain palatable foods. Here, we identify a population of glutamatergic neurons in the paraventricular thalamus of mice that express the glucose transporter Glut2 (encoded by Slc2a2) and project to the nucleus accumbens. These neurons are activated by hypoglycemia and, in freely moving mice, their activation by optogenetics or Slc2a2 inactivation increases motivated sucrose-seeking but not saccharin-seeking behavior. These neurons may control sugar overconsumption in obesity and diabetes.

  13. Hydroethanolic extract of the inner stem bark of Cedrela odorata has low toxicity and reduces hyperglycemia induced by an overload of sucrose and glucose.

    Science.gov (United States)

    Giordani, Morenna Alana; Collicchio, Thiago Carvalho Mamede; Ascêncio, Sergio Donizeti; Martins, Domingos Tabajara de Oliveira; Balogun, Sikiru Olaitan; Bieski, Isanete Geraldini Costa; da Silva, Leilane Aparecida; Colodel, Edson Moleta; de Souza, Roberto Lopes; de Souza, Damiana Luiza Pereira; de França, Suélem Aparecida; Andrade, Claudia Marlise Balbinotti; Kawashita, Nair Honda

    2015-03-13

    animals that received glucose overload by 36.7% and 24.1% in the area under the glucose curve (AUC). When the overload was sucrose, HeECo reduced the blood glucose level by 44.4% without affecting AUC. Treatment with HeECo of the blood glucose of the diabetic animals for 21 days did not lead to improvement in weight gain and regularization of the blood glucose level, but reduced the triacylglycerol and malondialdehyde levels by 36.6% and 48.1%, respectively. The activity of the antioxidant enzymes, superoxide dismutase and glutathione peroxidase were significantly increased when compared to diabetic control rats. HPLC analysis showed the presence of polyphenols, such as gallic acid, (-)- gallocatechin and (+)- catechin, the latter is present in higher quantity. Collectively, these data showed that HeECo could blunt the postprandial glycemic surge in rats; possibly through inhibition of alpha-glucosidase and positive modulation of antioxidant enzymes. Our findings confirmed the anti-hiperglycemic activity of HeECo in STZ- diabetic rats. Cedrela odorata is effective in diminishing glucose levels in vitro and in vivo and in ameliorating oxidative damage that occurs in diabetes and/or due to hyperglycemia in rats. According to our results, the efficacy of Cedrela odorata preparation could be due to the presence of active principles with different mode of actions at the molecular level, including α-glycosidases and glucose transporter inhibitors and antioxidant property. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides

    Science.gov (United States)

    McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin

    2014-01-01

    Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of β-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6 Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain. PMID:24169853

  15. Exercise Training Reduces Intrathoracic Fat Regardless of Defective Glucose Tolerance.

    Science.gov (United States)

    Honkala, Sanna M; Motiani, Kumail K; Eskelinen, Jari-Joonas; Savolainen, Anna; Saunavaara, Virva; Virtanen, Kirsi A; Löyttyniemi, Eliisa; Kapanen, Jukka; Knuuti, Juhani; Kalliokoski, Kari K; Hannukainen, Jarna C

    2017-07-01

    Epicardial (EAT) and pericardial (PAT) fat masses and myocardial triglyceride content (MTC) are enlarged in obesity and insulin resistance. We studied whether the high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) similarly decrease ectopic fat in and around the heart and whether the decrease is similar in healthy subjects and subjects with defective glucose tolerance (DGT). A total of 28 healthy men (body mass index = 20.7-30.0 kg·m, age = 40-55 yr) and 16 men with DGT (body mass index = 23.8-33.5 kg·m, age = 43-53 yr) were randomized into HIIT and MICT interventions for 2 wk. EAT and PAT were determined by computed tomography and MTC by H-MRS. At baseline, DGT subjects had impaired aerobic capacity and insulin sensitivity and higher levels of whole body fat, visceral fat, PAT, and EAT (P < 0.05, all) compared with healthy subjects. In the whole group, HIIT increased aerobic capacity (HIIT = 6%, MICT = 0.3%; time × training P = 0.007) and tended to improve insulin sensitivity (HIIT = 24%, MICT = 8%) as well as reduce MTC (HIIT = -42%, MICT = +23%) (time × training P = 0.06, both) more efficiently compared with MICT, and without differences in the training response between the healthy and the DGT subjects. However, both training modes decreased EAT (-5%) and PAT (-6%) fat (time P < 0.05) and not differently between the healthy and the DGT subjects. Whole body fat, visceral fat, PAT, and EAT masses are enlarged in DGT. Both HIIT and MICT effectively reduce EAT and PAT in healthy and DGT subjects, whereas HIIT seems to be superior as regards improving aerobic capacity, whole-body insulin sensitivity, and MTC.

  16. Electron-transfer mediator for a NAD-glucose dehydrogenase-based glucose sensor.

    Science.gov (United States)

    Kim, Dong-Min; Kim, Min-yeong; Reddy, Sanapalli S; Cho, Jaegeol; Cho, Chul-ho; Jung, Suntae; Shim, Yoon-Bo

    2013-12-03

    A new electron-transfer mediator, 5-[2,5-di (thiophen-2-yl)-1H-pyrrol-1-yl]-1,10-phenanthroline iron(III) chloride (FePhenTPy) oriented to the nicotinamide adenine dinucleotide-dependent-glucose dehydrogenase (NAD-GDH) system was synthesized through a Paal-Knorr condensation reaction. The structure of the mediator was confirmed by Fourier-transform infrared spectroscopy, proton and carbon nucler magnetic resonance spectroscopy, and mass spectroscopy, and its electron-transfer characteristic for a glucose sensor was investigated using voltammetry and impedance spectroscopy. A disposable amperometric glucose sensor with NAD-GDH was constructed with FePhenTPy as an electron-transfer mediator on a screen printed carbon electrode (SPCE) and its performance was evaluated, where the addition of reduces graphene oxide (RGO) to the mediator showed the enhanced sensor performance. The experimental parameters to affect the analytical performance and the stability of the proposed glucose sensor were optimized, and the sensor exhibited a dynamic range between 30 mg/dL and 600 mg/dL with the detection limit of 12.02 ± 0.6 mg/dL. In the real sample experiments, the interference effects by acetaminophen, ascorbic acid, dopamine, uric acid, caffeine, and other monosaccharides (fructose, lactose, mannose, and xylose) were completely avoided through coating the sensor surface with the Nafion film containing lead(IV) acetate. The reliability of proposed glucose sensor was evaluated by the determination of glucose in artificial blood and human whole blood samples.

  17. Brain glucose sensing in homeostatic and hedonic regulation.

    Science.gov (United States)

    Steinbusch, Laura; Labouèbe, Gwenaël; Thorens, Bernard

    2015-09-01

    Glucose homeostasis as well as homeostatic and hedonic control of feeding is regulated by hormonal, neuronal, and nutrient-related cues. Glucose, besides its role as a source of metabolic energy, is an important signal controlling hormone secretion and neuronal activity, hence contributing to whole-body metabolic integration in coordination with feeding control. Brain glucose sensing plays a key, but insufficiently explored, role in these metabolic and behavioral controls, which when deregulated may contribute to the development of obesity and diabetes. The recent introduction of innovative transgenic, pharmacogenetic, and optogenetic techniques allows unprecedented analysis of the complexity of central glucose sensing at the molecular, cellular, and neuronal circuit levels, which will lead to a new understanding of the pathogenesis of metabolic diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Resistant starch lowers postprandial glucose and leptin in overweight adults consuming a moderate-to-high-fat diet: a randomized-controlled trial.

    Science.gov (United States)

    Maziarz, Mindy Patterson; Preisendanz, Sara; Juma, Shanil; Imrhan, Victorine; Prasad, Chandan; Vijayagopal, Parakat

    2017-02-21

    High-amylose maize resistant starch type 2 (HAM-RS2) stimulates gut-derived satiety peptides and reduces adiposity in animals. Human studies have not supported these findings despite improvements in glucose homeostasis and insulin sensitivity after HAM-RS2 intake which can lower adiposity-related disease risk. The primary objective of this study was to evaluate the impact of HAM-RS2 consumption on blood glucose homeostasis in overweight, healthy adults. We also examined changes in biomarkers of satiety (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], and leptin) and body composition determined by anthropometrics and dual-energy x-ray absorptiometry, dietary intake, and subjective satiety measured by a visual analogue scale following HAM-RS2 consumption. Using a randomized-controlled, parallel-arm, double-blind design, 18 overweight, healthy adults consumed either muffins enriched with 30 g HAM-RS2 (n = 11) or 0 g HAM-RS2 (control; n = 7) daily for 6 weeks. The HAM-RS2 and control muffins were similar in total calories and available carbohydrate. At baseline, total PYY concentrations were significantly higher 120 min following the consumption of study muffins in the HAM-RS2 group than control group (P = 0.043). Within the HAM-RS2 group, the area under the curve (AUC) glucose (P = 0.028), AUC leptin (P = 0.022), and postprandial 120-min leptin (P = 0.028) decreased independent of changes in body composition or overall energy intake at the end of 6 weeks. Fasting total PYY increased (P = 0.033) in the HAM-RS2 group, but changes in insulin or total GLP-1 were not observed. Mean overall change in subjective satiety score did not correlate with mean AUC biomarker changes suggesting the satiety peptides did not elicit a satiation response or change in overall total caloric intake. The metabolic response from HAM-RS2 occurred despite the habitual intake of a moderate-to-high-fat diet (mean range 34.5% to 39.4% of total calories). Consuming 30

  19. One-pot synthesis of reduced graphene oxide supported gold-based nanomaterials as robust nanocatalysts for glucose electrooxidation

    International Nuclear Information System (INIS)

    Ghosh, Srabanti; Holade, Yaovi; Remita, Hynd; Servat, Karine; Beaunier, Patricia; Hagège, Agnès; Kokoh, K. Boniface

    2016-01-01

    Highlights: • Fast preparation of graphene nanosheets by one-pot radiolytic reduction of GO. • One-pot synthesis of graphene nanosheets supported Au-Pt-Pd nanoparticles. • Radiolysis enables to engineer highly active Metal/rGO nanocomposites. • Ternary Au_5_0Pt_2_5Pd_2_5/rGO electrocatalyst is 5-fold higher effective than Pt/rGO. • Selective glucose oxidation reaction in a 2-electron process leads to gluconate. - Abstract: We report a novel “one-pot”, convenient and efficient method based on radiolysis to synthesize gold-based nanoparticles finely dispersed on reduced graphene oxide (rGO) nanosheets obtained from reductive transformation of graphene oxide (GO). Extensive characterizations of the metal/rGO nanocomposites were performed and revealed that the optimized bimetallic Au_9_0Pd_1_0 and trimetallic Au_5_0Pd_2_5Pt_2_5 materials were mostly nano-alloyed. Not only the multimetallic catalysts demonstrate high electrocatalytic performances towards glucose in alkaline medium, but they also surpass the majority of the reported noble metals based nanocatalysts. The spectroelectrochemical investigations have highlighted a 2-electron reaction process leading to gluconate, a high added-value chemical used in various industries. Definitely, the strategies developed herein pave new rational pathways for the design of effective anode catalysts for glucose-based electrochemical energy converters and the scalability in the catalyst composition opens up new avenues in the efficient application of graphene-based nanocomposites as promising electrode materials in the electrocatalysis of carbohydrates.

  20. Hypothalamic neurones governing glucose homeostasis.

    Science.gov (United States)

    Coppari, R

    2015-06-01

    The notion that the brain directly controls the level of glucose in the blood (glycaemia) independent of its known action on food intake and body weight has been known ever since 1849. That year, the French physiologist Dr Claude Bernard reported that physical puncture of the floor of the fourth cerebral ventricle rapidly leads to an increased level of sugar in the blood (and urine) in rabbits. Despite this important discovery, it took approximately 150 years before significant efforts aimed at understanding the underlying mechanism of brain-mediated control of glucose metabolism were made. Technological developments allowing for genetically-mediated manipulation of selected molecular pathways in a neurone-type-specific fashion unravelled the importance of specific molecules in specific neuronal populations. These neuronal pathways govern glucose metabolism in the presence and even in the absence of insulin. Also, a peculiarity of these pathways is that certain biochemically-defined neurones govern glucose metabolism in a tissue-specific fashion. © 2015 British Society for Neuroendocrinology.

  1. Impact of PTBP1 rs11085226 on glucose-stimulated insulin release in adult Danes

    DEFF Research Database (Denmark)

    Hansen, Tue Haldor; Vestergaard, Henrik; Jørgensen, Torben

    2015-01-01

    ,641 glucose tolerant controls, respectively. Quantitative trait analyses were performed in up to 13,605 individuals subjected to an OGTT or blood samples obtained after an overnight fast, as well as in 596 individuals subjected to an IVGTT. Results: Analyses of fasting and OGTT-derived quantitative traits did.......024; P=0.01) assuming a dominant model of inheritance, but failed to replicate a previously reported association with area under the curve (AUC) for insulin. Case control analysis did not show an association of the PTBP1 rs11085226 variant with type 2 diabetes. Conclusions: Despite failure to replicate......Background: The variant rs11085226 (G) within the gene encoding polypyrimidine tract binding protein 1 (PTBP1) was reported to associate with reduced insulin release determined by an oral glucose tolerance test (OGTT) as well as an intravenous glucose tolerance test (IVGTT). The aim of the present...

  2. Long-term feeding of red algae (Gelidium amansii ameliorates glucose and lipid metabolism in a high fructose diet-impaired glucose tolerance rat model

    Directory of Open Access Journals (Sweden)

    Hshuan-Chen Liu

    2017-07-01

    Full Text Available This study was designed to investigate the effect of Gelidium amansii (GA on carbohydrate and lipid metabolism in rats with high fructose (HF diet (57.1% w/w. Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1 control diet group (Con; (2 HF diet group (HF; and (3 HF with GA diet group (HF + 5% GA. The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation of GA caused a decrease in plasma glucose, insulin, tumor necrosis factor-α, and leptin. HF diet increased hepatic lipid content. However, intake of GA reduced the accumulation of hepatic lipids including total cholesterol (TC and triglyceride contents. GA elevated the excretion of fecal lipids and bile acid in HF diet-fed rats. Furthermore, GA significantly decreased plasma TC, triglyceride, low density lipoprotein plus very low density lipoprotein cholesterol, and TC/high density lipoprotein cholesterol ratio in HF diet-fed rats. HF diet induced an in plasma glucose and an impaired glucose tolerance, but GA supplementation decreased homeostasis model assessment equation-insulin resistance and improved impairment of glucose tolerance. Taken together, these results indicate that supplementation of GA can improve the impairment of glucose and lipid metabolism in an HF diet-fed rat model.

  3. Age differences in intercorrelations between regional cerebral metabolic rates for glucose

    International Nuclear Information System (INIS)

    Horwitz, B.; Duara, R.; Rapoport, S.I.

    1986-01-01

    Patterns of cerebral metabolic intercorrelations were compared in the resting state in 15 healthy young men (ages 20 to 32 years) and 15 healthy elderly men (ages 64 to 83 years). Controlling for whole-brain glucose metabolism, partial correlation coefficients were determined between pairs of regional cerebral metabolic rates for glucose determined by positron emission tomography using [18F]fluorodeoxyglucose and obtained in 59 brain regions. Compared with the young men, the elderly men had fewer statistically significant correlations, with the most notable reductions observed between the parietal lobe regions, and between the parietal and frontal lobe regions. These results suggest that cerebral functional interactions are reduced in healthy elderly men

  4. Zinc Status Affects Glucose Homeostasis and Insulin Secretion in Patients with Thalassemia

    Directory of Open Access Journals (Sweden)

    Ellen B. Fung

    2015-06-01

    Full Text Available Up to 20% of adult patients with Thalassemia major (Thal live with diabetes, while 30% may be zinc deficient. The objective of this study was to explore the relationship between zinc status, impaired glucose tolerance and insulin sensitivity in Thal patients. Charts from thirty subjects (16 male, 27.8 ± 9.1 years with Thal were reviewed. Patients with low serum zinc had significantly lower fasting insulin, insulinogenic and oral disposition indexes (all p < 0.05 and elevated glucose response curve, following a standard 75 g oral load of glucose compared to those with normal serum zinc after controlling for baseline (group × time interaction p = 0.048. Longitudinal data in five patients with a decline in serum zinc over a two year follow up period (−19.0 ± 9.6 μg/dL, showed consistent increases in fasting glucose (3.6 ± 3.2 mg/dL and insulin to glucose ratios at 120 min post glucose dose (p = 0.05. Taken together, these data suggest that the frequently present zinc deficiency in Thal patients is associated with decreased insulin secretion and reduced glucose disposal. Future zinc trials will require modeling of oral glucose tolerance test data and not simply measurement of static indices in order to understand the complexities of pancreatic function in the Thal patient.

  5. The association between estimated average glucose levels and fasting plasma glucose levels in a rural tertiary care centre

    Directory of Open Access Journals (Sweden)

    Raja Reddy P

    2013-01-01

    Full Text Available The level of hemoglobin A1c (HbA1c, also known as glycated hemoglobin, determines how well a patient’s blood glucose level has been controlled over the previous 8-12 weeks. HbA1c levels help patients and doctors understand whether a particular diabetes treatment is working and whether adjustments need to be made to the treatment. Because the HbA1c level is a marker of blood glucose for the previous 60- 90 days, average blood glucose levels can be estimated using HbA1c levels. Aim in the present study was to investigate the relationship between estimated average glucose levels, as calculated by HbA1c levels, and fasting plasma glucose levels. Methods: Type 2 diabetes patients attending medicine outpatient department of RL Jalappa hospital, Kolar between March 2010 and July 2012 were taken. The estimated glucose levels (mg/dl were calculated using the following formula: 28.7 x HbA1c-46.7. Glucose levels were determined using the hexokinase method. HbA1c levels were determined using an HPLC method. Correlation and independent t- test was the test of significance for quantitative data. Results: A strong positive correlation between fasting plasma glucose level and estimated average blood glucose levels (r=0.54, p=0.0001 was observed. The difference was statistically significant. Conclusion: Reporting the estimated average glucose level together with the HbA1c level is believed to assist patients and doctors determine the effectiveness of blood glucose control measures.

  6. Glucose Synthesis in a Protein-Based Artificial Photosynthesis System.

    Science.gov (United States)

    Lu, Hao; Yuan, Wenqiao; Zhou, Jack; Chong, Parkson Lee-Gau

    2015-09-01

    The objective of this study was to understand glucose synthesis of a protein-based artificial photosynthesis system affected by operating conditions, including the concentrations of reactants, reaction temperature, and illumination. Results from non-vesicle-based glyceraldehyde-3-phosphate (GAP) and glucose synthesis showed that the initial concentrations of ribulose-1,5-bisphosphate (RuBP) and adenosine triphosphate (ATP), lighting source, and temperature significantly affected glucose synthesis. Higher initial concentrations of RuBP and ATP significantly enhanced GAP synthesis, which was linearly correlated to glucose synthesis, confirming the proper functions of all catalyzing enzymes in the system. White fluorescent light inhibited artificial photosynthesis and reduced glucose synthesis by 79.2 % compared to in the dark. The reaction temperature of 40 °C was optimum, whereas lower or higher temperature reduced glucose synthesis. Glucose synthesis in the vesicle-based artificial photosynthesis system reconstituted with bacteriorhodopsin, F 0 F 1 ATP synthase, and polydimethylsiloxane-methyloxazoline-polydimethylsiloxane triblock copolymer was successfully demonstrated. This system efficiently utilized light-induced ATP to drive glucose synthesis, and 5.2 μg ml(-1) glucose was synthesized in 0.78-ml reaction buffer in 7 h. Light-dependent reactions were found to be the bottleneck of the studied artificial photosynthesis system.

  7. Continuous glucose monitoring systems for type 1 diabetes mellitus

    NARCIS (Netherlands)

    Langendam, Miranda; Luijf, Yoeri M.; Hooft, Lotty; DeVries, J. Hans; Mudde, Aart H.; Scholten, Rob J. P. M.

    2012-01-01

    Background Self-monitoring of blood glucose is essential to optimise glycaemic control in type 1 diabetes mellitus. Continuous glucose monitoring (CGM) systems measure interstitial fluid glucose levels to provide semi-continuous information about glucose levels, which identifies fluctuations that

  8. A glucose-centric perspective of hyperglycemia.

    Science.gov (United States)

    Ramasarma, T; Rafi, M

    2016-02-01

    Digestion of food in the intestines converts the compacted storage carbohydrates, starch and glycogen, to glucose. After each meal, a flux of glucose (> 200 g) passes through the blood pool (4-6 g) in a short period of 2 h, keeping its concentration ideally in the range of 80-120 mg/100 mL. Tissue-specific glucose transporters (GLUTs) aid in the distribution of glucose to all tissues. The balance glucose after meeting the immediate energy needs is converted into glycogen and stored in liver (up to 100 g) and skeletal muscle (up to 300 g) for later use. High blood glucose gives the signal for increased release of insulin from pancreas. Insulin binds to insulin receptor on the plasma membrane and activates its autophosphorylation. This initiates the post-insulin-receptor signal cascade that accelerates synthesis of glycogen and triglyceride. Parallel control by phos-dephos and redox regulation of proteins exists for some of these steps. A major action of insulin is to inhibit gluconeogensis in the liver decreasing glucose output into blood. Cases with failed control of blood glucose have alarmingly increased since 1960 coinciding with changed life-styles and large scale food processing. Many of these turned out to be resistant to insulin, usually accompanied by dysfunctional glycogen storage. Glucose has an extended stay in blood at 8 mM and above and then indiscriminately adds on to surface protein-amino groups. Fructose in common sugar is 10-fold more active. This random glycation process interferes with the functions of many proteins (e.g., hemoglobin, eye lens proteins) and causes progressive damage to heart, kidneys, eyes and nerves. Some compounds are known to act as insulin mimics. Vanadium-peroxide complexes act at post-receptor level but are toxic. The fungus-derived 2,5-dihydroxybenzoquinone derivative is the first one known to act on the insulin receptor. The safe herbal products in use for centuries for glucose control have multiple active principles and

  9. 6-Paradol and 6-Shogaol, the Pungent Compounds of Ginger, Promote Glucose Utilization in Adipocytes and Myotubes, and 6-Paradol Reduces Blood Glucose in High-Fat Diet-Fed Mice

    Directory of Open Access Journals (Sweden)

    Chien-Kei Wei

    2017-01-01

    Full Text Available The anti-diabetic activity of ginger powder (Zingiber officinale has been recently promoted, with the recommendation to be included as one of the dietary supplements for diabetic patients. However, previous studies presented different results, which may be caused by degradation and metabolic changes of ginger components, gingerols, shogaols and paradols. Therefore, we prepared 10 ginger active components, namely 6-, 8-, 10-paradols, 6-, 8-, 10-shogaols, 6-, 8-, 10-gingerols and zingerone, and evaluated their anti-hyperglycemic activity. Among the tested compounds, 6-paradol and 6-shogaol showed potent activity in stimulating glucose utilization by 3T3-L1 adipocytes and C2C12 myotubes. The effects were attributed to the increase in 5′ adenosine monophosphate-activated protein kinase (AMPK phosphorylation in 3T3-L1 adipocytes. 6-Paradol, the major metabolite of 6-shogaol, was utilized in an in vivo assay and significantly reduced blood glucose, cholesterol and body weight in high-fat diet-fed mice.

  10. Hypothalamic glucose sensing: making ends meet

    Directory of Open Access Journals (Sweden)

    Vanessa eRouth

    2014-12-01

    Full Text Available The neuroendocrine system governs essential survival and homeostatic functions. For example, growth is needed for development. Thermoregulation maintains optimal core temperature in a changing environment. Reproduction ensures species survival. Stress and immune responses enable an organism to overcome external and internal threats. The circadian system regulates arousal and sleep such that vegetative and active functions do not overlap. All of these functions require a significant portion of the body’s energy. As the integrator of the neuroendocrine system, the hypothalamus carefully assesses the energy status of the body in order to appropriately partition resources to provide for each system without compromising the others. While doing so the hypothalamus must ensure that adequate glucose levels are preserved for brain function since glucose is the primary fuel of the brain. To this end, the hypothalamus contains specialized glucose sensing neurons which are scattered throughout the nuclei controlling distinct neuroendocrine functions. We hypothesize that these neurons play a key role in enabling the hypothalamus to partition energy to meet these peripheral survival needs without endangering the brain’s glucose supply. The goal of this review is to describe the varied mechanisms underlying glucose sensing in neurons within discrete hypothalamic nuclei. We will then evaluate the way in which peripheral energy status regulates glucose sensitivity. For example, during energy deficit such as fasting specific hypothalamic glucose sensing neurons become sensitized to decreased glucose. This increases the gain of the information relay when glucose availability is a greater concern for the brain. Finally, changes in glucose sensitivity under pathological conditions (e.g., recurrent insulin-hypoglycemia, diabetes will be addressed. The overall goal of this review is to place glucose sensing neurons within the context of hypothalamic control of

  11. Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents.

    Science.gov (United States)

    Jastreboff, Ania M; Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A; Santoro, Nicola; Savoye, Mary; Duran, Elvira J; Pierpont, Bridget; Cline, Gary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia

    2016-07-01

    Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  12. High Glucose Promotes Aβ Production by Inhibiting APP Degradation

    Science.gov (United States)

    Zhang, Shuting; Song, Weihong

    2013-01-01

    Abnormal deposition of neuriticplaques is the uniqueneuropathological hallmark of Alzheimer’s disease (AD).Amyloid β protein (Aβ), the major component of plaques, is generated from sequential cleavage of amyloidβ precursor protein (APP) by β-secretase and γ-secretase complex. Patients with diabetes mellitus (DM), characterized by chronic hyperglycemia,have increased risk of AD development.However, the role of high blood glucose in APP processing and Aβ generation remains elusive. In this study, we investigated the effect of high glucose on APP metabolism and Aβ generation in cultured human cells. We found that high glucose treatment significantly increased APP protein level in both neuronal-like and non-neuronal cells, and promoted Aβ generation. Furthermore, we found that high glucose-induced increase of APP level was not due to enhancement of APP gene transcription but resulted from inhibition of APP protein degradation. Taken together, our data indicated that hyperglycemia could promote AD pathogenesis by inhibiting APP degradation and enhancing Aβ production. More importantly, the elevation of APP level and Aβ generation by high glucose was caused by reduction of APP turnover rate.Thus,our study provides a molecular mechanism of increased risk of developing AD in patients withDMand suggests thatglycemic control might be potentially beneficial for reducing the incidence of AD in diabetic patients and delaying the AD progression. PMID:23894546

  13. Fluorometric determination of free glucose and glucose 6-phosphate in cows' milk and other opaque matrices

    DEFF Research Database (Denmark)

    Larsen, Torben

    2015-01-01

    Analyses of free glucose and glucose 6-phosphate in milk have until now been dependent upon several time consuming and troublesome procedures. This has limited investigations in the area. The present article presents a new, reliable, analytical procedure, based on enzymatic degradation and fluoro......Analyses of free glucose and glucose 6-phosphate in milk have until now been dependent upon several time consuming and troublesome procedures. This has limited investigations in the area. The present article presents a new, reliable, analytical procedure, based on enzymatic degradation...... and fluorometric detection. Standards and control materials were based on milk that was stripped of intrinsic glucose and glucose 6-phosphate in order to obtain standards and samples based on the same matrix. The analysis works without pre-treatment of the samples, e.g. without centrifugation and precipitation...

  14. Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes.

    Science.gov (United States)

    Jabbour, S A; Goldstein, B J

    2008-08-01

    The kidney plays a central role in the regulation of plasma glucose levels, although until recently this has not been widely appreciated or considered a target for therapeutic intervention. The sodium glucose co-transporter type 2 (SGLT2) located in the plasma membrane of cells lining the proximal tubule mediates the majority of renal glucose reabsorption from the tubular fluid, which normally prevents the loss of glucose in the urine. Competitive inhibitors of SGLT2 that provoke the renal excretion of glucose have been discovered, thereby providing a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. To explore the physiology of SGLT2 action and discuss several SGLT2 inhibitors that have entered early clinical development. All publicly available data were identified by searching the internet for 'SGLT2' and 'SGLT2 inhibitor' through 1 November 2007. Published articles, press releases and abstracts presented at national and international meetings were considered. Sodium glucose co-transporter type 2 inhibition is a novel treatment option for diabetes, which has been studied in preclinical models and a few potent and selective SGLT2 inhibitors have been reported and are currently in clinical development. These agents appear to be safe and generally well tolerated, and will potentially be a beneficial addition to the growing battery of oral antihyperglycaemic agents.

  15. A randomized controlled trial: branched-chain amino acid levels and glucose metabolism in patients with obesity and sleep apnea.

    Science.gov (United States)

    Barceló, Antonia; Morell-Garcia, Daniel; Salord, Neus; Esquinas, Cristina; Pérez, Gerardo; Pérez, Antonio; Monasterio, Carmen; Gasa, Merce; Fortuna, Ana Maria; Montserrat, Josep Maria; Mayos, Mercedes

    2017-12-01

    There is evidence that changes in branched-chain amino acid (BCAA) levels may correlate with the efficacy of therapeutic interventions for affecting improvement in metabolic control. The objective of this study was to evaluate whether serum concentrations of BCAAs (leucine, isoleucine, valine) could mediate in insulin sensitivity and glucose tolerance after continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). A prospective randomized controlled trial of OSA patients with morbid obesity was conducted. Eighty patients were randomized into two groups: 38 received conservative treatment and 42 received CPAP treatment for 12 weeks. Plasma levels of BCAA, glucose tolerance and insulin resistance were evaluated at baseline and after treatment. After treatment, significant decreases of leucine levels were observed in both groups when compared with baseline levels (P fasting plasma glucose and glycosylated haemoglobin values only in the conservative group (P < 0.05). In summary, we found that the treatment with CPAP for 12 weeks caused similar changes in circulating BCAAs concentrations to conservative treatment and a differential metabolic response of CPAP and conservative treatment was observed between the relationship of BCAAs and glucose homeostasis. Additional studies are needed to determine the interplay between branched-chain amino acids and glucose metabolism in patients with sleep apnea. © 2017 European Sleep Research Society.

  16. Impact of control of blood glucose level during treatment of sudden deafness in diabetics: relationship with prognosis.

    Science.gov (United States)

    Min, Sang-Ki; Shin, Ji-Ho; Chang, Mun-Young; Min, Hyun-Jin; Kim, Kyung-Soo; Lee, Sei-Young; Yang, Hoon-Shik; Hong, Young-Ho; Mun, Seog-Kyun

    2017-03-01

    The objective of this study is to investigate the impact of control of blood glucose level during treatment of sudden deafness. A retrospective study was performed involving 197 patients from January, 2011 to September, 2015. All patients were administrated prednisolone (Pharmaprednisolone tab ® , 5 mg/T; KoreaPharma) p.o under the following regimen: 60 mg/day for 4 days, 40 mg/day for 2 days, 30 mg/day for 1 day, 20 mg/day for 1 day, and 10 mg/day for 2 days. During treatment, pure tone audiometry and blood glucose level were investigated for each patient and the results were statistically analyzed. Mean hearing improvement was 19.2 dB for the non-diabetes group and 24.8 dB for the diabetes group. The greater improvement for diabetics was not statistically significant (p = 0.146). Hearing improvement was 25.1 dB for subjects with mean blood glucose blood glucose >200 mg/dl; the difference was not statistically significant (p = 0.267). Mean blood glucose level was 200.8 mg/dl for subjects with hearing improvement >20 dB and 181.8 mg/dl for subjects with hearing improvement blood glucose level during treatment of sudden deafness does not have a direct effect on prognosis.

  17. Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

    DEFF Research Database (Denmark)

    Caillaud, Corinne; Mechta, Mie; Ainge, Heidi

    2015-01-01

    Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose levels...... and glucose tolerance, without altering total body weight or retroperitoneal fat mass. Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced markers of oxidative stress, and restored heat-shock protein 72 expression in soleus muscles from HFD-fed rats. Incubation of skeletal muscle...... not directly activate the phosphorylation of AKT in muscle cells. We propose that the reduced systemic inflammation or oxidative stress that we observed after treatment with EPO could contribute to the improvement of whole-body glucose metabolism....

  18. Short-term effect of add on bell pepper (Capsicum annuum var. grossum) juice with integrated approach of yoga therapy on blood glucose levels and cardiovascular functions in patients with type 2 diabetes mellitus: A randomized controlled study.

    Science.gov (United States)

    Nagasukeerthi, Padakandla; Mooventhan, A; Manjunath, N K

    2017-10-01

    Type 2 diabetes mellitus (T2DM) is a major global health problem. Though various studies have reported the beneficial effect of Yoga in patient with T2DM, there is a lack of study in combination with bell pepper and yoga. Hence, the present study aims at evaluating short-term effect of add on bell pepper juice with integrated approach of yoga therapy (IAYT) on blood glucose levels and cardiovascular variables in patients with T2DM. Fifty T2DM subjects with the age varied from 34 to 69-years were recruited and randomly divided into either study group or control group. The study group received 100-ml of bell pepper juice (twice/day) along with IAYT while the control group received only IAYT for 4-consecutive days. Baseline and post-test assessments were taken before and after the intervention. Statistical analysis was performed using statistical package for the social sciences, version-16. Results of this study showed no significant difference in overall (fasting and post prandial) blood glucose level in the study group compared with control group. However, a significant reduction in Post prandial blood glucose (PPBG), systolic blood pressure (SBP), pulse pressure (PP), rate pressure product (RPP) and Double product (Do-P) was observed in the study group compared with control group. Results of this study suggest that though an addition of 100-ml of bell pepper juice (twice/day) along with IAYT is not more effective in reducing fasting blood glucose, it may be more effective in reducing PPBG, SBP, PP, RPP and Do-P than IAYT alone. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Detection of glutathione based on MnO2 nanosheet-gated mesoporous silica nanoparticles and target induced release of glucose measured with a portable glucose meter.

    Science.gov (United States)

    Tan, Qingqing; Zhang, Ruirui; Kong, Rongmei; Kong, Weisu; Zhao, Wenzhi; Qu, Fengli

    2017-12-08

    The authors describe a novel method for the determination of glutathione (GSH). Detection is based on target induced release of glucose from MnO 2 nanosheet-gated aminated mesoporous silica nanoparticles (MSNs). In detail, glucose is loaded into the pores of MSNs. Negatively charged MnO 2 nanosheets are assembled on the MSNs through electrostatic interactions. The nanosheets are reduced by GSH, and this results in the release of glucose which is quantified by using a commercial electrochemical glucose meter. GSH can be quantified by this method in the 100 nM to 10 μM concentration range, with a 34 nM limit of detection. Graphical abstract Glucose is loaded into the pores of mesoporous silica nanoparticles (MSNs). MnO 2 nanosheets are assembled on MSNs through electrostatic interactions. Glutathione (GSH) can reduce the nanosheets, and this results in the release of glucose which is quantified by using a commercial glucose meter.

  20. Overexpression of the ped/pea-15 Gene Causes Diabetes by Impairing Glucose-Stimulated Insulin Secretion in Addition to Insulin Action

    OpenAIRE

    Vigliotta, Giovanni; Miele, Claudia; Santopietro, Stefania; Portella, Giuseppe; Perfetti, Anna; Maitan, Maria Alessandra; Cassese, Angela; Oriente, Francesco; Trencia, Alessandra; Fiory, Francesca; Romano, Chiara; Tiveron, Cecilia; Tatangelo, Laura; Troncone, Giancarlo; Formisano, Pietro

    2004-01-01

    Overexpression of the ped/pea-15 gene is a common feature of type 2 diabetes. In the present work, we show that transgenic mice ubiquitously overexpressing ped/pea-15 exhibited mildly elevated random-fed blood glucose levels and decreased glucose tolerance. Treatment with a 60% fat diet led ped/pea-15 transgenic mice to develop diabetes. Consistent with insulin resistance in these mice, insulin administration reduced glucose levels by only 35% after 45 min, compared to 70% in control mice. In...

  1. Regulation of Blood Glucose Concentration in Type 1 Diabetics Using Single Order Sliding Mode Control Combined with Fuzzy On-line Tunable Gain, a Simulation Study.

    Science.gov (United States)

    Dinani, Soudabeh Taghian; Zekri, Maryam; Kamali, Marzieh

    2015-01-01

    Diabetes is considered as a global affecting disease with an increasing contribution to both mortality rate and cost damage in the society. Therefore, tight control of blood glucose levels has gained significant attention over the decades. This paper proposes a method for blood glucose level regulation in type 1 diabetics. The control strategy is based on combining the fuzzy logic theory and single order sliding mode control (SOSMC) to improve the properties of sliding mode control method and to alleviate its drawbacks. The aim of the proposed controller that is called SOSMC combined with fuzzy on-line tunable gain is to tune the gain of the controller adaptively. This merit causes a less amount of control effort, which is the rate of insulin delivered to the patient body. As a result, this method can decline the risk of hypoglycemia, a lethal phenomenon in regulating blood glucose level in diabetics caused by a low blood glucose level. Moreover, it attenuates the chattering observed in SOSMC significantly. It is worth noting that in this approach, a mathematical model called minimal model is applied instead of the intravenously infused insulin-blood glucose dynamics. The simulation results demonstrate a good performance of the proposed controller in meal disturbance rejection and robustness against parameter changes. In addition, this method is compared to fuzzy high-order sliding mode control (FHOSMC) and the superiority of the new method compared to FHOSMC is shown in the results.

  2. Application of optical lens of a CD writer for detecting the blood glucose semi-invasively

    Science.gov (United States)

    Meshram, N. D.; Dahikar, P. B.

    2014-10-01

    Recent technological advancements in the photonics industry have led to a resurgence of interest in optical glucose sensing and to realistic progress toward the development of an optical glucose sensor. Such a sensor has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements more convenient. Currently over 100 small companies and universities are working to develop noninvasive or minimally invasive glucose sensing technologies, and optical methods play a large role in these efforts. It has become overwhelmingly clear that frequent monitoring and tight control of blood sugar levels are requisite for effective management of Diabetes mellitus and reduction of the complications associated with this disease. The pain and trouble associated with current "finger-stick" methods for blood glucose monitoring result in decreased patient compliance and a failure to control blood sugar levels. Thus, the development of a convenient noninvasive blood glucose monitor holds the potential to significantly reduce the morbidity and mortality associated with Diabetes. A method and apparatus for noninvasive measurement of blood glucose concentration based on transilluminated laser beam via the Index Finger has been reported in this paper. This method depends on photodiode based laser operating at 632.8 nm wavelength. During measurement, the index finger is inserted into the glucose sensing unit, the transilluminated optical signal is converted into an electrical signal, compared with the reference electrical signal, and the obtained difference signal is processed by signal processing unit which presents the results in the form of blood glucose concentration. This method would enable the monitoring blood glucose level of the diabetic patient continuously, safely and noninvasively..

  3. Application of optical lens of a CD writer for detecting the blood glucose semi-invasively

    International Nuclear Information System (INIS)

    Meshram, N. D.; Dahikar, P. B.

    2014-01-01

    Recent technological advancements in the photonics industry have led to a resurgence of interest in optical glucose sensing and to realistic progress toward the development of an optical glucose sensor. Such a sensor has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements more convenient. Currently over 100 small companies and universities are working to develop noninvasive or minimally invasive glucose sensing technologies, and optical methods play a large role in these efforts. It has become overwhelmingly clear that frequent monitoring and tight control of blood sugar levels are requisite for effective management of Diabetes mellitus and reduction of the complications associated with this disease. The pain and trouble associated with current “finger-stick” methods for blood glucose monitoring result in decreased patient compliance and a failure to control blood sugar levels. Thus, the development of a convenient noninvasive blood glucose monitor holds the potential to significantly reduce the morbidity and mortality associated with Diabetes. A method and apparatus for noninvasive measurement of blood glucose concentration based on transilluminated laser beam via the Index Finger has been reported in this paper. This method depends on photodiode based laser operating at 632.8 nm wavelength. During measurement, the index finger is inserted into the glucose sensing unit, the transilluminated optical signal is converted into an electrical signal, compared with the reference electrical signal, and the obtained difference signal is processed by signal processing unit which presents the results in the form of blood glucose concentration. This method would enable the monitoring blood glucose level of the diabetic patient continuously, safely and noninvasively.

  4. Application of optical lens of a CD writer for detecting the blood glucose semi-invasively

    Energy Technology Data Exchange (ETDEWEB)

    Meshram, N. D., E-mail: meshramnileshsd@gmail.com [Mathuradas Mohota College of Sciences, Nagpur-440009 (India); Dahikar, P. B., E-mail: pbdahikar@rediffmail.com [Kamla Nehru Mahavidyalaya, Sakkardara Square, Nagpur-440009 (India)

    2014-10-15

    Recent technological advancements in the photonics industry have led to a resurgence of interest in optical glucose sensing and to realistic progress toward the development of an optical glucose sensor. Such a sensor has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements more convenient. Currently over 100 small companies and universities are working to develop noninvasive or minimally invasive glucose sensing technologies, and optical methods play a large role in these efforts. It has become overwhelmingly clear that frequent monitoring and tight control of blood sugar levels are requisite for effective management of Diabetes mellitus and reduction of the complications associated with this disease. The pain and trouble associated with current “finger-stick” methods for blood glucose monitoring result in decreased patient compliance and a failure to control blood sugar levels. Thus, the development of a convenient noninvasive blood glucose monitor holds the potential to significantly reduce the morbidity and mortality associated with Diabetes. A method and apparatus for noninvasive measurement of blood glucose concentration based on transilluminated laser beam via the Index Finger has been reported in this paper. This method depends on photodiode based laser operating at 632.8 nm wavelength. During measurement, the index finger is inserted into the glucose sensing unit, the transilluminated optical signal is converted into an electrical signal, compared with the reference electrical signal, and the obtained difference signal is processed by signal processing unit which presents the results in the form of blood glucose concentration. This method would enable the monitoring blood glucose level of the diabetic patient continuously, safely and noninvasively.

  5. Impact of buccal glucose spray, liquid sugars and dextrose tablets on the evolution of plasma glucose concentration in healthy persons.

    Science.gov (United States)

    Chlup, Rudolf; Zapletalova, Jana; Peterson, Karolina; Poljakova, Iveta; Lenhartova, Eva; Tancred, Adam; Perera, Russel; Smital, Jan

    2009-09-01

    The purpose of this prospective controlled trial was to assess the efficacy of three commercially available glucose products, (1) buccal glucose spray, (2) liquid sugars, and (3) dextrose tablet, on the evolution of plasma glucose concentration (PG). Sixteen healthy volunteers aged 21.8 +/- 0.78 y (mean +/- SE), BMI 23.5 +/- 0.84 kg/m(2), tested their PG over the course of 3 sets of 4 sessions (S) each: S(0)-control fasting, S(1)-buccal administration of 10 glucose spray-doses (0.84 g of glucose) without swallowing; S(2-) consumption of 1 sachet (13 ml) of liquid sugar (ca. 5.2 g glucose, 5.2 g fructose, 5.2 g sucrose); S(3-) consumption of one dextrose tablet (6 g). PG was tested in finger-prick capillary blood using a personal glucometer Linus at the start, and at 5, 10, 15, 20 and 30 min. The means of 3 respective sessions for each of the 16 subjects were analyzed. The Wilcoxon signed rank test revealed no significant differences between changes in the mean PG at the start vs. 5-minute interval either in control, or any intervention sessions. Analysis of regression coefficients after 30 min compared to the control session, demonstrated an increase in PG with the sachet of liquid sugars (0.068 mmol/l/min, p = 0.001) which was greater than a single dextrose tablet (0.052 mmol/l/min, p = 0.002), but no significant PG increase was found after buccal glucose spray. Liquid sugars or dextrose tablets, but not the buccal glucose spray, are effective means to increase PG within 10 minutes after ingestion.

  6. Glucose-lowering effect of whey protein depends upon clinical characteristics of patients with type 2 diabetes

    OpenAIRE

    Almario, Rogelio U; Buchan, Wendy M; Rocke, David M; Karakas, Sidika E

    2017-01-01

    Objective Whey protein (WP) intake has been shown to reduce postprandial glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute challenge or weight loss studies. It is not known if WP supplementation can provide sustained glucose lowering. Our goal was to investigate the effects of WP on glycemia comprehensively by using continuous glucose monitoring (CGM) while avoiding the confounding effects of variable food intake through controlled feeding. Research design and methods...

  7. Effect of polysaccharide of dendrobium candidum on proliferation and apoptosis of human corneal epithelial cells in high glucose

    Science.gov (United States)

    Li, Qiangxiang; Chen, Jing; Li, Yajia; Chen, Ting; Zou, Jing; Wang, Hua

    2017-01-01

    Abstract Background: The aim of the study was to observe the effect of polysaccharide of dendrobium candidum (PDC) and high glucose on proliferation, apoptosis of human corneal epithelial cells (HCEC). Methods: The MTT method was used to screen and take the optimal high-glucose concentration, treatment time, and PDC concentration using HCEC and divide it into 4 groups: control group (C), high glucose group (HG), PDC group, and HG + PDC group. We observed and compared the effect of the 4 groups on HCEC proliferation by MTT, apoptosis by Annexin V-FITC/PI double fluorescent staining and flow cytometry (FCM), and expression of bax mRNA and bcl-2 mRNA by RT-qPCR. Results: Compared with the control group, proliferative activity of HCEC cells was reduced; the cells apoptosis ratio was increased; the expression of bax mRNA was increased, and the expression of bcl-2 mRNA was reduced in the HG group. Proliferative activity of HCEC cells in the PDC group was increased, and the expression of bcl-2 mRNA was increased but that of bax mRNA was decreased. Proliferative activity of HCEC cells in the HG + PDC group was increased, but it could not restore to the normal level; the expression of bax mRNA was significantly decreased but the expression of bcl-2 mRNA was significantly increased. Conclusions: Our results demonstrate that high glucose can inhibit proliferative activity and induce apoptosis of HCEC. PDC can improve the proliferative activity of HCEC cells under the high glucose environment and reduce the apoptosis of cells by regulating the expression of bax and bcl-2. PDC play a very important role on protecting and repairing of corneal epithelial cells damage in high glucose. PMID:28796073

  8. Strategies for glucose control in a study population with diabetes, renal disease and anemia (Treat study).

    Science.gov (United States)

    Weinrauch, Larry A; D'Elia, John A; Finn, Peter; Lewis, Eldrin F; Desai, Akshay S; Claggett, Brian L; Cooper, Mark E; McGill, Janet B

    2016-03-01

    Glucose lowering medication use among patients with type 2 diabetes and advanced renal disease (eGFRrenal disease advances, most of the oral anti-diabetic agents requiring renal clearance must be reduced or discontinued. The potential for prolonged hypoglycemia, fluid/volume overload and congestive heart failure may complicate medication choices. In order to evaluate patterns of glycemia management we describe glucose lowering medication use among patients with advanced renal disease and type 2 diabetes in a large multinational outcome trial designed to focus on patients with eGFRrenal function when compared with standard populations with normal kidney function. The use of multiple oral agents, or oral agents plus insulin was quite common. While gender did not appear to play a role in medication choices, there were significant regional variations. For example, oral agents were used more in North America compared with other regions (Latin America, Australia/Western Europe, Russia/Eastern Europe). Patients enrolled at more advanced ages were less likely to be on a regimen of rapid-acting insulin alone consistent with recommendations that suggest a preference for longer-acting preparations in the geriatric population (1). Higher degrees of obesity were associated more complex treatment regimens. Despite this population being at high risk for cardiovascular events, the use of beta blockers (50%), statins (64%) and aspirin (48%) were relatively low, especially in the group that did not require medications to achieve adequate glycemic control. Current attempts to compare strategies for diabetes therapy must control for baseline demographic group differences influencing treatment choice. Future recommendations for glycemic control in patients with Grade 3 or higher chronic kidney disease require additional studies, with matched populations. We suggest that evaluation of studies similar to TREAT will assist in determining the optimal therapeutic regimens for populations

  9. Effects of Providing High-Fat versus High-Carbohydrate Meals on Daily and Postprandial Physical Activity and Glucose Patterns: a Randomised Controlled Trial

    Directory of Open Access Journals (Sweden)

    Evelyn B. Parr

    2018-04-01

    Full Text Available We determined the effects of altering meal timing and diet composition on temporal glucose homeostasis and physical activity measures. Eight sedentary, overweight/obese men (mean ± SD, age: 36 ± 4 years; BMI: 29.8 ± 1.8 kg/m2 completed two × 12-day (12-d measurement periods, including a 7-d habitual period, and then 5 d of each diet (high-fat diet [HFD]: 67:15:18% fat:carbohydrate:protein versus high-carbohydrate diet [HCD]: 67:15:18% carbohydrate:fat:protein of three meals/d at ±30 min of 0800 h, 1230 h, and 1800 h, in a randomised order with an 8-d washout. Energy intake (EI, the timing of meal consumption, blood glucose regulation (continuous glucose monitor system (CGMS, and activity patterns (accelerometer and inclinometer were assessed across each 12-d period. Meal provision did not alter the patterns of reduced physical activity, and increased sedentary behaviour following dinner, compared with following breakfast and lunch. The HCD increased peak (+1.6 mmol/L, p < 0.001, mean (+0.5 mmol/L, p = 0.001, and total area under the curve (+670 mmol/L/min, p = 0.001, as well as 3-h postprandial meal glucose concentrations (all p < 0.001 compared with the HFD. In overweight/obese males, the provision of meals did not alter physical activity patterns, but did affect glycaemic control. Greater emphasis on meal timing and composition is required in diet and/or behaviour intervention studies to ensure relevance to real-world behaviours.

  10. Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine

    DEFF Research Database (Denmark)

    Orskov, C; Jeppesen, J; Madsbad, S

    1991-01-01

    We investigated the major products of proglucagon (PG) processing in plasma in the fasting state, after intravenous arginine and after an oral glucose load in noninsulin-dependent diabetics (NIDDM) and in weight matched controls using specific radioimmunoassays and analytical gel filtration...... integrated incremental responses after intravenous arginine were identical in the two groups. After oral glucose the insulin concentrations in plasma were lower and the concentrations of all proglucagon products were higher in the NIDDM group compared to the control group. The gel filtration analysis showed....... In the fasting state the glucagonlike peptide-1 (GLP-1) immunoreactivity was significantly elevated in the NIDDM group compared with the control group. Both after intravenous arginine and after an oral glucose load a rise in the plasma concentrations of all immunoreactive moieties measured was seen. All...

  11. Thermal decomposition of specifically phosphorylated D-glucoses and their role in the control of the Maillard reaction.

    Science.gov (United States)

    Yaylayan, Varoujan A; Machiels, David; Istasse, Louis

    2003-05-21

    One of the main shortcomings of the information available on the Maillard reaction is the lack of knowledge to control the different pathways, especially when it is desired to direct the reaction away from the formation of carcinogenic and other toxic substances to more aroma and color generation. The use of specifically phosphorylated sugars may impart some elements of control over the aroma profile generated by the Maillard reaction. Thermal decomposition of 1- and 6-phosphorylated glucoses was studied in the presence and absence of ammonia and selected amino acids through pyrolysis/gas chromatography/mass spectrometry using nonpolar PLOT and medium polar DB-1 columns. The analysis of the data has indicated that glucose-1-phosphate relative to glucose undergoes more extensive phosphate-catalyzed ring opening followed by formation of sugar-derived reactive intermediates as was indicated by a 9-fold increase in the amount of trimethylpyrazine and a 5-fold increase in the amount of 2,3-dimethylpyrazine, when pyrolyzed in the presence of glycine. In addition, glucose-1-phosphate alone generated a 6-fold excess of acetol as compared to glucose. On the other hand, glucose-6-phosphate enhanced retro-aldol reactions initiated from a C-6 hydroxyl group and increased the subsequent formation of furfural and 4-cyclopentene-1,3-dione. Furthermore, it also stabilized 1- and 3-deoxyglucosone intermediates and enhanced the formation of six carbon atom-containing Maillard products derived directly from them through elimination reactions such as 1,6-dimethyl-2,4-dihydroxy-3-(2H)-furanone (acetylformoin), 2-acetylpyrrole, 5-methylfurfural, 5-hydroxymethylfurfural, and 4-hydroxy-2,5-dimethyl-3-(2H)-furanone (Furaneol), due to the enhanced leaving group ability of the phosphate moiety at the C-6 carbon. However, Maillard products generated through the nucleophilic action of the C-6 hydroxyl group such as 2-acetylfuran and 2,3-dihydro-3,5-dihydroxy-4H-pyran-4-one were retarded, due

  12. DLK1 Regulates Whole-Body Glucose Metabolism

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Ditzel, Nicholas; Laborda, Jorge

    2015-01-01

    due to impaired insulin signaling in OB and lowered Glu-OCN serum levels. Furthermore, Dlk1(-/-) mice treated with Glu-OC experienced significantly lower blood glucose levels than Glu-OCN-treated wild-type mice. The data suggest that Glu-OCN-controlled production of DLK1 by pancreatic β-cells acts...... metabolism. We show that Glu-OCN specifically stimulates Dlk1 expression by the pancreas. Conversely, Dlk1-deficient (Dlk1(-/-) ) mice exhibited increased circulating Glu-OCN levels and increased insulin sensitivity, whereas mice overexpressing Dlk1 in OB displayed reduced insulin secretion and sensitivity...

  13. Thermogenic Effect of Glucose in Hypothyroid Subjects

    Directory of Open Access Journals (Sweden)

    Agnieszka Kozacz

    2014-01-01

    Full Text Available The importance of thyroid hormone, catecholamines, and insulin in modification of the thermogenic effect of glucose (TEG was examined in 34 healthy and 32 hypothyroid subjects. We calculated the energy expenditure at rest and during oral glucose tolerance test. Blood samples for determinations of glucose, plasma insulin, adrenaline (A, and noradrenaline (NA were collected. It was found that TEG was lower in hypothyroid than in control group (19.68±3.90 versus 55.40±7.32 kJ, resp., P<0.0004. Mean values of glucose and insulin areas under the curve were higher in women with hypothyroidism than in control group (286.79±23.65 versus 188.41±15.84 mmol/L·min, P<0.003 and 7563.27±863.65 versus 4987.72±583.88 mU/L·min, P<0.03 resp.. Maximal levels of catecholamines after glucose ingestion were higher in hypothyroid patients than in control subjects (Amax—0.69±0.08 versus 0.30±0.07 nmol/L, P<0.0001, and NAmax—6.42±0.86 versus 2.54±0.30 nmol/L, P<0.0002. It can be concluded that in hypothyroidism TEG and glucose tolerance are decreased while the adrenergic response to glucose administration is enhanced. Presumably, these changes are related to decreased insulin sensitivity and responsiveness to catecholamine action.

  14. Effect of Syzygium Aromaticum (CLOVE) Extract on Blood Glucose Level in Streptozotocin induced Diabetic Rats

    International Nuclear Information System (INIS)

    Chaudhry, Z. R.; Chaudhry, S. R.; Naseer, A.; Chaudhry, F. R.

    2013-01-01

    Objective: To evaluate the glucose lowering effect of 50% ethanol extract of Syzygium aromaticum in comparison with that of standard insulin in streptozotocin induced diabetic rats. Study Design: Randomized control trial. Place and Duration of Study: National Institute of Health Islamabad. Jul 2011- Dec 2011 Material and Methods: It was carried out on 48 adult rats of Sprague dawley specie. Rats were equally divided into 6 groups (I-VI). Group - I served as control. Diabetes was induced by giving single intraperitoneal injection of STZ in Group II to VI. Group-II served as diabetic control, while groups III, IV, V and VI served as experimental groups. Group III, IV and V rats received 50% ethanol extract of Syzygium aromaticum at a dose of 250, 500 and 750 mg/kg body weight respectively for sixty days. Group VI (standard) received humulin insulin 70/30 at dose of 0.6 units<-kg body weight subcutaneously bid for sixty days. Fasting blood samples were taken at zero day, 15 day, 30 day and 60 day after giving injection STZ. Although Syzygium aromaticum with the doses of 250, 500 and 750 mg/kg body weight and insulin reduced the level of glucose in rats but on comparison Syzygium aromaticum 750 mg=kg dose reduced glucose more effectively than 250 and 500 mg/kg dose. While in group III, IV subjects, blood glucose levels remained above normal level. In group VI receiving insulin the level of this parameter remained almost closer to group IV rats. On studying the weight of the animals after receiving STZ there was initial reduction in the weight of all the experimental groups but after receiving the extract of plant improvement was seen and the weight of group V getting 750 mg=kg/body weight of Syzygium aromaticum became almost closer to the weight of control group. Conclusion: Syzygium aromaticum extract has glucose lowering effect in STZ induced diabetic rats and this effect is dose related and the dose of 750 mg/kg body weight has produced maximum effect. (author)

  15. Activity-Dependent Regulation of Surface Glucose Transporter-3

    OpenAIRE

    Ferreira, Jainne M.; Burnett, Arthur L.; Rameau, Gerald A.

    2011-01-01

    Glucose transporter 3 (GLUT3) is the main facilitative glucose transporter in neurons. Glucose provides neurons with a critical energy source for neuronal activity. However, the mechanism by which neuronal activity controls glucose influx via GLUT3 is unknown. We investigated the influence of synaptic stimulation on GLUT3 surface expression and glucose import in primary cultured cortical and hippocampal neurons. Synaptic activity increased surface expression of GLUT3 leading to an elevation o...

  16. Comparison of 3H-galactose and 3H-glucose as precursors of hepatic glycogen in control-fed rats

    International Nuclear Information System (INIS)

    Michaels, J.E.; Garfield, S.A.; Hung, J.T.; Cardell, R.R. Jr.

    1989-01-01

    Labeling of hepatic glycogen derived from 3H-galactose and 3H-glucose was compared shortly after intravenous injection in control-fed rats. The rats were allowed to accumulate 5-8% glycogen prior to receiving label. Fifteen minutes to 2 hours after labeling, liver was excised and processed for routine light (LM) and electron microscopic (EM) radioautography (RAG) or biochemical analysis. After injection of 3H-galactose, LM-RAGs revealed that the percentage of heavily labeled hepatocytes increased from 37% after 15 minutes to 68% after 1 hour but showed no further increase after 2 hours. alpha-Amylase treatment removed most glycogen and incorporated label; thus few silver grains were observed, indicating little incorporation of label except into glycogen. EM-RAGs demonstrated that most label occurred where glycogen was located. Biochemical analysis showed initially a high blood level of label that rapidly plateaued at a reduced level by 5 minutes. Concomitantly, glycogen labeling determined by liquid scintillation counting reflected the increases observed in the RAGs. After injection of 3H-glucose, LM-RAGs revealed that only 12% of the hepatocytes were heavily labeled at 1 hour and 20% at 2 hours. In tissue treated with alpha-amylase, glycogen was depleted and label was close to background level at each interval observed. EM-RAGs showed most grains associated with glycogen deposits. Biochemically, blood levels of label persisted at a high level for 30 minutes and tissue levels increased slowly over the 2-hour period. This study shows that incorporation from 3H-galactose was more rapid than incorporation of 3H-glucose; however, label derived from both carbohydrates appeared to be incorporated mainly into glycogen

  17. Astrocytes in the nucleus of the solitary tract are activated by low glucose or glucoprivation: evidence for glial involvement in glucose homeostasis.

    Science.gov (United States)

    McDougal, David H; Hermann, Gerlinda E; Rogers, Richard C

    2013-01-01

    Glucose homeostasis is maintained through interplay between central and peripheral control mechanisms which are aimed at storing excess glucose following meals and mobilizing these same stores during periods of fasting. The nucleus of the solitary tract (NST) in the dorsal medulla has long been associated with the central detection of glucose availability and the control of glucose homeostasis. Recent evidence has emerged which supports the involvement of astrocytes in glucose homeostasis. The aim of the present study was to investigate whether NST-astrocytes respond to physiologically relevant decreases in glucose availability, in vitro, as well as to the presence of the glucoprivic compound 2-deoxy-D-Glucose. This report demonstrates that some NST-astrocytes are capable of responding to low glucose or glucoprivation by increasing cytoplasmic calcium; a change that reverses with restoration of normal glucose availability. While some NST-neurons also demonstrate an increase in calcium signaling during low glucose availability, this effect is smaller and somewhat delayed compared to those observed in adjacent astrocytes. TTX did not abolish these hypoglycemia mediated responses of astrocytes, suggesting that NST-astrocytes may be directly sensing low glucose levels as opposed to responding to neuronal detection of hypoglycemia. Thus, chemodetection of low glucose by NST-astrocytes may play an important role in the autonomic regulation of glucose homeostasis.

  18. Astrocytes in the nucleus of the solitary tract are activated by low glucose or glucoprivation: evidence for glial involvement in glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    David Harry McDougal

    2013-12-01

    Full Text Available Glucose homeostasis is maintained through interplay between central and peripheral control mechanisms which are aimed at storing excess glucose following meals and mobilizing these same stores during periods of fasting. The nucleus of the solitary tract (NST in the dorsal medulla has long been associated with the central detection of glucose availability and the control of glucose homeostasis. Recent evidence has emerged which supports the involvement of astrocytes in glucose homeostasis. The aim of the present study was to investigate whether NST-astrocytes respond to physiologically relevant decreases in glucose availability, in vitro, as well as to the presence of the glucoprivic compound 2-deoxy-D-Glucose. This report demonstrates that some NST-astrocytes are capable of responding to low glucose or glucoprivation by increasing cytoplasmic calcium; a change that reverses with restoration of normal glucose availability. While some NST-neurons also demonstrate an increase in calcium signaling during low glucose availability, this effect is smaller and somewhat delayed compared to those observed in adjacent astrocytes. TTX did not abolish these hypoglycemia mediated responses of astrocytes, suggesting that NST-astrocytes may be directly sensing low glucose levels as opposed to responding to neuronal detection of hypoglycemia. Thus, chemodetection of low glucose by NST-astrocytes may play an important role in the autonomic regulation of glucose homeostasis.

  19. Dietary thylakoids suppress blood glucose and modulate appetite-regulating hormones in pigs exposed to oral glucose tolerance test

    DEFF Research Database (Denmark)

    Montelius, Caroline; Szwiec, Katarzyna; Kardas, Marek

    2014-01-01

    BACKGROUND & AIMS: Dietary chloroplast thylakoids have previously been found to reduce food intake and body weight in animal models, and to change metabolic profiles in humans in mixed-food meal studies. The aim of this study was to investigate the modulatory effects of thylakoids on glucose...... metabolism and appetite-regulating hormones during an oral glucose tolerance test in pigs fed a high fat diet. METHODS: Six pigs were fed a high fat diet (36 energy% fat) for one month before oral glucose tolerance test (1 g/kg d-glucose) was performed. The experiment was designed as a cross-over study......, either with or without addition of 0.5 g/kg body weight of thylakoid powder. RESULTS: The supplementation of thylakoids to the oral glucose tolerance test resulted in decreased blood glucose concentrations during the first hour, increased plasma cholecystokinin concentrations during the first two hours...

  20. Does overnight normalization of plasma glucose by insulin infusion affect assessment of glucose metabolism in Type 2 diabetes?

    DEFF Research Database (Denmark)

    Staehr, P; Højlund, Kurt; Hother-Nielsen, O

    2003-01-01

    AIMS: In order to perform euglycaemic clamp studies in Type 2 diabetic patients, plasma glucose must be reduced to normal levels. This can be done either (i) acutely during the clamp study using high-dose insulin infusion, or (ii) slowly overnight preceding the clamp study using a low-dose insulin...... infusion. We assessed whether the choice of either of these methods to obtain euglycaemia biases subsequent assessment of glucose metabolism and insulin action. METHODS: We studied seven obese Type 2 diabetic patients twice: once with (+ ON) and once without (- ON) prior overnight insulin infusion. Glucose...... turnover rates were quantified by adjusted primed-constant 3-3H-glucose infusions, and insulin action was assessed in 4-h euglycaemic, hyperinsulinaemic (40 mU m-2 min-1) clamp studies using labelled glucose infusates (Hot-GINF). RESULTS: Basal plasma glucose levels (mean +/- sd) were 5.5 +/- 0.5 and 10...

  1. Multiple-Input Subject-Specific Modeling of Plasma Glucose Concentration for Feedforward Control.

    Science.gov (United States)

    Kotz, Kaylee; Cinar, Ali; Mei, Yong; Roggendorf, Amy; Littlejohn, Elizabeth; Quinn, Laurie; Rollins, Derrick K

    2014-11-26

    The ability to accurately develop subject-specific, input causation models, for blood glucose concentration (BGC) for large input sets can have a significant impact on tightening control for insulin dependent diabetes. More specifically, for Type 1 diabetics (T1Ds), it can lead to an effective artificial pancreas (i.e., an automatic control system that delivers exogenous insulin) under extreme changes in critical disturbances. These disturbances include food consumption, activity variations, and physiological stress changes. Thus, this paper presents a free-living, outpatient, multiple-input, modeling method for BGC with strong causation attributes that is stable and guards against overfitting to provide an effective modeling approach for feedforward control (FFC). This approach is a Wiener block-oriented methodology, which has unique attributes for meeting critical requirements for effective, long-term, FFC.

  2. Improvement in C-reactive protein and advanced glycosylation end-products in poorly controlled diabetics is independent of glucose control.

    Science.gov (United States)

    Md Isa, S H; Najihah, I; Nazaimoon, W M Wan; Kamarudin, N A; Umar, N A; Mat, N H; Khalid, B A K

    2006-04-01

    We studied the efficacy of four different treatment regimens (sulphonylurea and metformin+/-acarbose versus glimepiride and rosiglitazone versus glimepiride and bedtime NPH insulin versus multiple actrapid and NPH insulin injections) in poorly controlled type 2 diabetes subjects on hs-CRP, VCAM-1 and AGE at 4, 8 and 12 weeks of treatment. Multiple insulin injections rapidly improved HbA(1c) by 0.6+/-0.9% (pimprovement in blood glucose. AGE improved in all groups irrespective of type of treatment, glycaemic control and CRP levels. Our data indicate rapid glycaemic control alone does not necessarily result in improvement in markers of inflammation in type 2 diabetes patients.

  3. Metabolic fate of glucose in rats with traumatic brain injury and pyruvate or glucose treatments: A NMR spectroscopy study.

    Science.gov (United States)

    Shijo, Katsunori; Sutton, Richard L; Ghavim, Sima S; Harris, Neil G; Bartnik-Olson, Brenda L

    2017-01-01

    Administration of sodium pyruvate (SP; 9.08 μmol/kg, i.p.), ethyl pyruvate (EP; 0.34 μmol/kg, i.p.) or glucose (GLC; 11.1 μmol/kg, i.p.) to rats after unilateral controlled cortical impact (CCI) injury has been reported to reduce neuronal loss and improve cerebral metabolism. In the present study these doses of each fuel or 8% saline (SAL; 5.47 nmoles/kg) were administered immediately and at 1, 3, 6 and 23 h post-CCI. At 24 h all CCI groups and non-treated Sham injury controls were infused with [1,2 13 C] glucose for 68 min 13 C nuclear magnetic resonance (NMR) spectra were obtained from cortex + hippocampus tissues from left (injured) and right (contralateral) hemispheres. All three fuels increased lactate labeling to a similar degree in the injured hemisphere. The amount of lactate labeled via the pentose phosphate and pyruvate recycling (PPP + PR) pathway increased in CCI-SAL and was not improved by SP, EP, and GLC treatments. Oxidative metabolism, as assessed by glutamate labeling, was reduced in CCI-SAL animals. The greatest improvement in oxidative metabolism was observed in animals treated with SP and fewer improvements after EP or GLC treatments. Compared to SAL, all three fuels restored glutamate and glutamine labeling via pyruvate carboxylase (PC), suggesting improved astrocyte metabolism following fuel treatment. Only SP treatments restored the amount of [4 13 C] glutamate labeled by the PPP + PR pathway to sham levels. Milder injury effects in the contralateral hemisphere appear normalized by either SP or EP treatments, as increases in the total pool of 13 C lactate and labeling of lactate in glycolysis, or decreases in the ratio of PC/PDH labeling of glutamine, were found only for CCI-SAL and CCI-GLC groups compared to Sham. The doses of SP, EP and GLC examined in this study all enhanced lactate labeling and restored astrocyte-specific PC activity but differentially affected neuronal metabolism after CCI injury. The restoration of

  4. Glucose tolerance in two unacculturated Indian tribes of Brazil.

    Science.gov (United States)

    Spielman, R S; Fajans, S S; Neel, J V; Pek, S; Floyd, J C; Oliver, W J

    1982-08-01

    Plasma levels of glucose, insulin, growth hormone, and pancreatic polypeptide in response to a standard oral glucose load were studied in the Yanomama and the Marubo, two relatively unacculturated Amerindian tribes of the Brazilian Amazon. The findings in the two tribes differed significantly from each other and in the degree of deviation from control subjects. The average responses in both tribes differed significantly from those of age- and sex-matched Caucasoid control subjects studied in Ann Arbor, Michigan; however, of the two tribes, the Marubo, the more acculturated group, resembled the controls more closely. Plasma concentrations of glucose and the hormones at three time points (fasting, 1 h, 2 h) were compared by means of a multivariate analysis. When the Marubo were compared with the control subjects, the only highly significant difference was in the plasma glucose concentrations (all three points were higher in the Marubo); however, the Yanomama differed significantly from the control subjects with respect to all four plasma indicators (p less than 0.05). Unlike the Marubo, the Yanomama showed no significant rise in plasma glucose at 1 h and no decrease at 2 h. Neither tribe exhibited the bimodality of the 2 h glucose value characteristic of acculturated Amerindians, such as the Pima, but the samples studied were small.

  5. Effect of nitroimidazoles on glucose utilization and lactate accumulation in mouse brain

    International Nuclear Information System (INIS)

    Chao, C.F.; Subjeck, J.R.; Brody, H.; Shen, J.; Johnson, R.J.R.

    1984-01-01

    The radiation sensitizers misonidazole (MISO) and desmethylmisonidazole (DMM) can produce central and peripheral neuropathy in patients and laboratory animals. Nitroimidazoles can also interfere with glycolysis in vitro under aerobic and anaerobic conditions. In the present work, the authors studied the effect of MISO or DMM on lactate production and glucose utilization in mouse brain. It is observed that these compounds result in a 25% inhibition of lactate production in brain slices relative to the control at a 10 mM level. Additionally, MISO (1.0 mg/g/day) or DMM (1.4 mg/g/day) were administered daily (oral) for 1, 4, 7, or 14 days to examine the effect of these two drugs on the regional glucose utilization in C3Hf mouse brain. Five microcuries of 2-deoxy[ 14 C]glucose was given following the last drug dose and autoradiographs of serial brain sections were made and analyzed by a densitometer. Following a single dose of either MISO or DMM, no significant differences in glucose uptake were observed when compared with controls. However, following 4, 7, and 14 doses the rate of glucose utilization was significantly reduced in the intoxicated animals. Larger reductions were measured in specific regions including the posterior colliculus, cochlear nuclei, vestibular nuclei, and pons with increasing effects observed at later stages. These results share a degree of correspondence with the regional brain pathology produced by these nitroimidazoles

  6. Herpes simplex virus vectors overexpressing the glucose transporter gene protect against seizure-induced neuron loss.

    OpenAIRE

    Lawrence, M S; Ho, D Y; Dash, R; Sapolsky, R M

    1995-01-01

    We have generated herpes simplex virus (HSV) vectors vIE1GT and v alpha 4GT bearing the GLUT-1 isoform of the rat brain glucose transporter (GT) under the control of the human cytomegalovirus ie1 and HSV alpha 4 promoters, respectively. We previously reported that such vectors enhance glucose uptake in hippocampal cultures and the hippocampus. In this study we demonstrate that such vectors can maintain neuronal metabolism and reduce the extent of neuron loss in cultures after a period of hypo...

  7. Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control.

    Science.gov (United States)

    Ramírez, Sara; Gómez-Valadés, Alicia G; Schneeberger, Marc; Varela, Luis; Haddad-Tóvolli, Roberta; Altirriba, Jordi; Noguera, Eduard; Drougard, Anne; Flores-Martínez, Álvaro; Imbernón, Mónica; Chivite, Iñigo; Pozo, Macarena; Vidal-Itriago, Andrés; Garcia, Ainhoa; Cervantes, Sara; Gasa, Rosa; Nogueiras, Ruben; Gama-Pérez, Pau; Garcia-Roves, Pablo M; Cano, David A; Knauf, Claude; Servitja, Joan-Marc; Horvath, Tamas L; Gomis, Ramon; Zorzano, Antonio; Claret, Marc

    2017-06-06

    Proopiomelanocortin (POMC) neurons are critical sensors of nutrient availability implicated in energy balance and glucose metabolism control. However, the precise mechanisms underlying nutrient sensing in POMC neurons remain incompletely understood. We show that mitochondrial dynamics mediated by Mitofusin 1 (MFN1) in POMC neurons couple nutrient sensing with systemic glucose metabolism. Mice lacking MFN1 in POMC neurons exhibited defective mitochondrial architecture remodeling and attenuated hypothalamic gene expression programs during the fast-to-fed transition. This loss of mitochondrial flexibility in POMC neurons bidirectionally altered glucose sensing, causing abnormal glucose homeostasis due to defective insulin secretion by pancreatic β cells. Fed mice lacking MFN1 in POMC neurons displayed enhanced hypothalamic mitochondrial oxygen flux and reactive oxygen species generation. Central delivery of antioxidants was able to normalize the phenotype. Collectively, our data posit MFN1-mediated mitochondrial dynamics in POMC neurons as an intrinsic nutrient-sensing mechanism and unveil an unrecognized link between this subset of neurons and insulin release. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Long-term feeding of red algae (Gelidium amansii) ameliorates glucose and lipid metabolism in a high fructose diet-impaired glucose tolerance rat model.

    Science.gov (United States)

    Liu, Hshuan-Chen; Chang, Chun-Ju; Yang, Tsung-Han; Chiang, Meng-Tsan

    2017-07-01

    This study was designed to investigate the effect of Gelidium amansii (GA) on carbohydrate and lipid metabolism in rats with high fructose (HF) diet (57.1% w/w). Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1) control diet group (Con); (2) HF diet group (HF); and (3) HF with GA diet group (HF + 5% GA). The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation of GA caused a decrease in plasma glucose, insulin, tumor necrosis factor-α, and leptin. HF diet increased hepatic lipid content. However, intake of GA reduced the accumulation of hepatic lipids including total cholesterol (TC) and triglyceride contents. GA elevated the excretion of fecal lipids and bile acid in HF diet-fed rats. Furthermore, GA significantly decreased plasma TC, triglyceride, low density lipoprotein plus very low density lipoprotein cholesterol, and TC/high density lipoprotein cholesterol ratio in HF diet-fed rats. HF diet induced an in plasma glucose and an impaired glucose tolerance, but GA supplementation decreased homeostasis model assessment equation-insulin resistance and improved impairment of glucose tolerance. Taken together, these results indicate that supplementation of GA can improve the impairment of glucose and lipid metabolism in an HF diet-fed rat model. Copyright © 2016. Published by Elsevier B.V.

  9. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition.

    Science.gov (United States)

    Vallon, Volker; Thomson, Scott C

    2017-02-01

    Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule. In the absence or with inhibition of SGLT2, the renal reabsorptive capacity for glucose declines to ∼80 g/day (the residual capacity of SGLT1), i.e. the safety valve opens at a lower threshold, which makes it relevant to glucose homeostasis from day-to-day. Several SGLT2 inhibitors are now approved glucose lowering agents for individuals with type 2 diabetes and preserved kidney function. By inducing glucosuria, these drugs improve glycaemic control in all stages of type 2 diabetes, while their risk of causing hypoglycaemia is low because they naturally stop working when the filtered glucose load falls below ∼80 g/day and they do not otherwise interfere with metabolic counterregulation. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. Because SGLT2 reabsorbs sodium along with glucose, SGLT2 blockers are natriuretic and antihypertensive. Also, because they work in the proximal tubule, SGLT2 inhibitors increase delivery of fluid and electrolytes to the macula densa, thereby activating tubuloglomerular feedback and increasing tubular back pressure. This mitigates glomerular hyperfiltration, reduces the kidney's demand for oxygen and lessens albuminuria. For reasons that are less well understood, SGLT2 inhibitors are

  10. Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons

    Directory of Open Access Journals (Sweden)

    Annamaria Morelli

    2013-01-01

    Full Text Available Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose effects in the human GnRH-secreting FNC-B4 cells. Gene expression profiling by qRT-PCR, confirmed that FNC-B4 cells express GnRH and several genes relevant for GnRH neuron function (KISS1R, KISS1, sex steroid and leptin receptors, FGFR1, neuropilin 2, and semaphorins, along with glucose transporters (GLUT1, GLUT3, and GLUT4. High glucose exposure (22 mM; 40 mM significantly reduced gene and protein expression of GnRH, KISS1R, KISS1, and leptin receptor, as compared to normal glucose (5 mM. Consistent with previous studies, leptin treatment significantly induced GnRH mRNA expression at 5 mM glucose, but not in the presence of high glucose concentrations. In conclusion, our findings demonstrate a deleterious direct contribution of high glucose on human GnRH neurons, thus providing new insights into pathogenic mechanisms linking metabolic disorders to reproductive dysfunctions.

  11. Validation of 123I-6-deoxy-6-iodo-D-glucose (6-DIC) as tracer for the in-vivo glucose transport

    International Nuclear Information System (INIS)

    Perret, P.; Ghezzi, C.; Mathieu, J.P.; Morin, C.; Vidal, M.; Comet, M.; Fagret, D.

    1997-01-01

    The evaluation of the glucose transport is very important clinically because alterations of this transport were described in numerous pathologies, in neurology, oncology and endocrinology. A new analog of the 123 I-labelled has been synthesized: 123 I-6-deoxy-6-iodo-D-glucose (6-DIG). Its in-vitro biological behaviour is similar to that of 3-O-methyl-D-glucose (3-OMG), the reference tracer of glucose transport. The aim of the study was to determine if it is possible to make evident by 6-DIG a variations of in-vivo glucose transport. The studies were effected on a model of homozygote mice (db/db), genetically diabetic (NIDDM), presenting a severe insulin-resistance, characterized by deficient glucose transport in response to insulin. The studies of 6-DIG biodistribution (5 nmol/mouse) with (1.5 UI/Kg) or without exogenous insulin, were conducted in diabetic mice (db/db) and in non-diabetic (db/+) control mice. The results show that the capture of 6-DIG, as well as that of glucose, increases (by 30%) in response to insulin in most of insulin-sensitive tissues in control mice. In the insulin-resistant and hyperglycemic db/db mouse, the capture of 6-DIG is not modified, no matter whether the exogenous insulin is present. In conclusion, the 6-DIG is able to make evident a lack of glucose transport in heart, diaphragm and skeletal muscle in diabetic mouse and a physiological variation of this transport in response to insulin, in the control mouse. This result should be stressed because for the first time it is possible to evidence in-vivo variations into glucose transport with a iodated molecule

  12. Plasma Volume Expansion Resulting from Intravenous Glucose Tolerance Test

    Directory of Open Access Journals (Sweden)

    Robert G. Hahn

    2011-01-01

    Full Text Available Objective. To quantify the degree of plasma volume expansion that occurs during an intravenous glucose tolerance test (IVGTT. Methods. Twenty healthy volunteers (mean age, 28 years underwent IVGTTs in which 0.3 g/kg of glucose 30% was injected as a bolus over 1 min. Twelve blood samples were collected over 75 min. The plasma glucose and blood hemoglobin concentrations were used to calculate the volume distribution (Vd and the clearance (CL of both the exogenous glucose and the injected fluid volume. Results. The IVGTT caused a virtually instant plasma volume expansion of 10%. The half-life of the glucose averaged 15 min and the plasma volume expansion 16 min. Correction of the fluid kinetic model for osmotic effects after injection reduced CL for the infused volume by 85%, which illustrates the strength of osmosis in allocating fluid back to the intracellular fluid space. Simulations indicated that plasma volume expansion can be reduced to 60% by increasing the injection time from 1 to 5 min and reducing the glucose load from 0.3 to 0.2 g/kg. Conclusion. A regular IVGTT induced an acute plasma volume expansion that peaked at 10% despite the fact that only 50–80 mL of fluid were administered.

  13. Effects of indigestible dextrin on glucose tolerance in rats.

    Science.gov (United States)

    Wakabayashi, S; Kishimoto, Y; Matsuoka, A

    1995-03-01

    A recently developed indigestible dextrin (IDex) was studied for its effects on glucose tolerance in male Sprague-Dawley rats. IDex is a low viscosity, water-soluble dietary fibre obtained by heating and enzyme treatment of potato starch. It has an average molecular weight of 1600. An oral glucose tolerance test was conducted with 8-week-old rats to evaluate the effects of IDex on the increase in plasma glucose and insulin levels after a single administration of various sugars (1.5 g/kg body weight). The increase in both plasma glucose and insulin levels following sucrose, maltose and maltodextrin loading was significantly reduced by IDex (0.15 g/kg body weight). This effect was not noted following glucose, high fructose syrup and lactose loading. To evaluate the effects of continual IDex ingestion on glucose tolerance, 5-week-old rats were kept for 8 weeks on a stock diet, a high sucrose diet or an IDex-supplemented high sucrose diet. An oral glucose (1.5 g/kg body weight) tolerance test was conducted in week 8. Increases in both plasma glucose and insulin levels following glucose loading were higher in the rats given a high sucrose diet than in the rats fed a stock diet. However, when IDex was included in the high sucrose diet, the impairment of glucose tolerance was alleviated. Moreover, IDex feeding also significantly reduced accumulation of body fat, regardless of changes in body weight. These findings suggest that IDex not only improves glucose tolerance following sucrose, maltose and maltodextrin loading but also stops progressive decrease in glucose tolerance by preventing a high sucrose diet from causing obesity.

  14. IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated Using Continuous Glucose Monitoring and a Standardized Meal Test.

    Science.gov (United States)

    Holst, Jens J; Buse, John B; Rodbard, Helena W; Linjawi, Sultan; Woo, Vincent C; Boesgaard, Trine Welløv; Kvist, Kajsa; Gough, Stephen C

    2015-10-06

    IDegLira is a novel, fixed-ratio combination of the long-acting basal insulin, insulin degludec, and the long-acting glucagon-like peptide-1 analog liraglutide. We studied the effect of IDegLira versus its components on postprandial glucose (PPG) in type 2 diabetes. In this substudy, 260 (15.6%) of the original 1663 patients with inadequate glycemic control participating in a 26-week, open-label trial (DUAL I) were randomized 2:1:1 to once-daily IDegLira, insulin degludec or liraglutide. Continuous glucose monitoring (CGM) for 72 hours and a meal test were performed. At week 26, IDegLira produced a significantly greater decrease from baseline in mean PPG increment (normalized iAUC0-4h) than insulin degludec (estimated treatment difference [ETD] -12.79 mg/dl [95% CI: -21.08; -4.68], P = .0023) and a similar magnitude of decrease as liraglutide (ETD -1.62 mg/dl [95% CI: -10.09; 6.67], P = .70). CGM indicated a greater reduction in change from baseline in PPG increment (iAUC0-4h) for IDegLira versus insulin degludec over all 3 main meals (ETD -6.13 mg/dl [95% CI: -10.27, -1.98], P = .0047) and similar reductions versus liraglutide (ETD -1.80 mg/dl [95% CI: -2.52, 5.95], P = .4122). Insulin secretion ratio and static index were greater for IDegLira versus insulin degludec (P = .048 and P = .006, respectively) and similar to liraglutide (P = .45 and P = .895, respectively). Once-daily IDegLira provides significantly better PPG control following a mixed meal test than insulin degludec. The improvement is at least partially explained by higher endogenous insulin secretion and improved beta cell function with IDegLira. The benefits of liraglutide on PPG control are maintained across all main meals in the combination. © 2015 Diabetes Technology Society.

  15. Facilitated transport of glucose from blood to brain in man and the effect of moderate hypoglycaemia on cerebral glucose utilization

    International Nuclear Information System (INIS)

    Blomqvist, G.; Widen, L.; Hellstrand, E.; Gutniak, M.; Grill, V.

    1991-01-01

    The effect of steady-state moderate hypoglycaemia on human brain homeostasis has been studied with positron emission tomography using D-glucose 11 C(ul) as tracer. To rule out any effects of insulin, the plasma insulin concentration was maintained at the same level under normo- and hypoglycaemic conditions. Reduction of blood glucose by 55% increased the glucose clearance through the blood-brain barrier by 50% and reduced brain glucose consumption by 40%. Blood flow was not affected. The results are consistent with facilitated transport of glucose from blood to brain in humans. The maximal transport rate of glucose from blood to brain was found to be 62±19 (mean±SEM) μmol hg -1 min -1 , and the half-saturation constant was found to be 4.1±3.2 mM. (orig.)

  16. Glucose metabolism in diabetic blood vessels

    International Nuclear Information System (INIS)

    Brown, B.J.; Crass, M.F. III

    1986-01-01

    Since glycolysis appears to be coupled to active ion transport in vascular smooth muscle, alterations in glucose metabolism may contribute to cellular dysfunction and angiopathy in diabetes. Uptake and utilization of glucose were studied in perfused blood vessels in which pulsatile flow and perfusion pressure were similar to those measured directly in vivo. Thoracic aortae isolated from 8-wk alloxan diabetic (D) and nondiabetic control rabbits were cannulated, tethered, and perfused with oxygenated buffer containing 7 or 25 mM glucose and tracer amounts of glucose-U -14 C. Norepinephrine (NE) (10 -6 M) and/or insulin (I) (150 μU/ml) and albumin (0.2%) were added. NE-induced tension development increased glucose uptake 39% and 14 CO 2 and lactate production 2.3-fold. With 7 mM glucose, marked decreases in glucose uptake (74%), 14 CO 2 (68%), lactate (30%), total tissue glycogen (75%), and tissue phospholipids (70%) were observed in D. Addition of I or elevation of exogenous glucose to 25 mM normalized glucose uptake, but had differential effects on the pattern of substrate utilization. Thus, in D, there was a marked depression of vascular glucose metabolism that was partially reversed by addition of low concentrations of insulin or D levels of glucose

  17. Retrospective study on the efficacy of a low-carbohydrate diet for impaired glucose tolerance

    Directory of Open Access Journals (Sweden)

    Maekawa S

    2014-06-01

    Full Text Available Satoshi Maekawa,1 Tetsuya Kawahara,2 Ryosuke Nomura,1 Takayuki Murase,1 Yasuyoshi Ann,1 Masayuki Oeholm,1 Masaru Harada31Department of Gastroenterology and Hepatology, 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Japan Labor Health and Welfare Organization, Niigata Rosai Hospital, Joetsu, Niigata, Japan; 3Third Department of Internal Medicine, University of Occupational and Environmental Health, Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, JapanBackground: In recent years, the number of people with impaired glucose tolerance (IGT has increased steadily worldwide. It is clear that the prevention of diabetes is important from the perspective of public health, medical care, and economics. It was recently reported that a low-carbohydrate diet (LCD is useful for achieving weight loss and glycemic control, but there is no information about the effects of the LCD on IGT. We designed a 7-day in-hospital educational program focused on the LCD for IGT.Methods: The subjects were 72 patients with IGT (36 in the LCD group and 36 in the control group who were enrolled from April 2007–March 2012 and followed for 12 months. We retrospectively compared the LCD group with the control group.Results: In 69.4% of the LCD group, blood glucose was normalized at 12 months and the 2-hour plasma glucose level in the oral glucose tolerance test (OGTT was reduced by 33 mg/dL. In addition, the incidence of diabetes was significantly lower in the LCD group than in the control group at 12 months (0% versus 13.9%, P=0.02. The LCD group showed a significant decrease in fasting plasma glucose, hemoglobin A1c, the homeostasis model of assessment of insulin resistance value, body weight and serum triglycerides (TGs at 12 months, while there was a significant increase of the serum high-density lipoprotein (HDL cholesterol level.Conclusion: The LCD is effective for normalizing blood glucose and preventing progression to type 2 diabetes in

  18. Glucose-stimulated insulin response in pregnant sheep following acute suppression of plasma non-esterified fatty acid concentrations

    Directory of Open Access Journals (Sweden)

    Sriskandarajah Nadarajah

    2004-09-01

    Full Text Available Abstract Background Elevated non-esterified fatty acids (NEFA concentrations in non-pregnant animals have been reported to decrease pancreatic responsiveness. As ovine gestation advances, maternal insulin concentrations fall and NEFA concentrations increase. Experiments were designed to examine if the pregnancy-associated rise in NEFA concentration is associated with a reduced pancreatic sensitivity to glucose in vivo. We investigated the possible relationship of NEFA concentrations in regulating maternal insulin concentrations during ovine pregnancy at three physiological states, non-pregnant, non-lactating (NPNL, 105 and 135 days gestational age (dGA, term 147+/- 3 days. Methods The plasma concentrations of insulin, growth hormone (GH and ovine placental lactogen (oPL were determined by double antibody radioimmunoassay. Insulin responsiveness to glucose was measured using bolus injection and hyperglycaemic clamp techniques in 15 non-pregnant, non-lactating ewes and in nine pregnant ewes at 105 dGA and near term at 135 dGA. Plasma samples were also collected for hormone determination. In addition to bolus injection glucose and insulin Area Under Curve calculations, the Mean Plasma Glucose Increment, Glucose Infusion Rate and Mean Plasma Insulin Increment and Area Under Curve were determined for the hyperglycaemic clamp procedures. Statistical analysis of data was conducted with Students t-tests, repeated measures ANOVA and 2-way ANOVA. Results Maternal growth hormone, placental lactogen and NEFA concentrations increased, while basal glucose and insulin concentrations declined with advancing gestation. At 135 dGA following bolus glucose injections, peak insulin concentrations and insulin area under curve (AUC profiles were significantly reduced in pregnant ewes compared with NPNL control ewes (p Conclusions Results suggest that despite an acute suppression of circulating NEFA concentrations during pregnancy, the associated steroids and hormones

  19. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kover, Karen, E-mail: kkover@cmh.edu [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Tasch, James; Hager, Melissa [Kansas City University Medical Biosciences, Kansas City, MO (United States); Clements, Mark; Moore, Wayne V. [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States)

    2015-06-19

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose

  20. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    International Nuclear Information System (INIS)

    Kover, Karen; Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu; Tasch, James; Hager, Melissa; Clements, Mark; Moore, Wayne V.

    2015-01-01

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H 2 O 2 assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H 2 O 2 levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose-induced TXNIP

  1. The Relation between Anxiety, Depression and Sexual Dysfunction and the Level of Blood Glucose Control in Patients with Type 2 Diabetes Attending Endocrine Clinic of Taleghani Hospital

    Directory of Open Access Journals (Sweden)

    Afarin Ahmadian

    2018-02-01

    Full Text Available Diabetes, as a common disease, is one of the major health problems in countries all over the world. There has been evidence of an increase in the prevalence rate of psychological disorders such as anxiety and depression and sexual dysfunction in people with diabetes compared to other people. The study aimed to investigate the relation between blood glucose control and anxiety, depression and sexual dysfunction. For this purpose, 141 patients with type 2 diabetes attending to Endocrine clinic of Taleghani Hospital in Tehran were randomly selected. In order to assess the prevalence rate of anxiety and depression, the HADS questionnaire was applied, and ARIZONA questionnaire was used to assess prevalence rate of sexual dysfunction. The status of blood glucose control was assessed based on the HbA1c scale as well. According to the results of the present research, 93.9% of the subjects in the uncontrolled blood glucose group suffered from either anxiety or depression, or both of them, and 6.1% in the control blood glucose group. 77.2% of patients in uncontrolled blood glucose group had severe sexual disorder; while, 22.8% of patients in controlled blood glucose group had this problem. Based on the obtained results of data analysis, there is a significant relationship between the status of blood glucose control based on the HbA1c scale and the prevalence rate of anxiety, depression and sexual dysfunction.

  2. The glucose oxidase-peroxidase assay for glucose

    Science.gov (United States)

    The glucose oxidase-peroxidase assay for glucose has served as a very specific, sensitive, and repeatable assay for detection of glucose in biological samples. It has been used successfully for analysis of glucose in samples from blood and urine, to analysis of glucose released from starch or glycog...

  3. Salivary glucose concentration and excretion in normal and diabetic subjects.

    Science.gov (United States)

    Jurysta, Cedric; Bulur, Nurdan; Oguzhan, Berrin; Satman, Ilhan; Yilmaz, Temel M; Malaisse, Willy J; Sener, Abdullah

    2009-01-01

    The present report aims mainly at a reevaluation of salivary glucose concentration and excretion in unstimulated and mechanically stimulated saliva in both normal and diabetic subjects. In normal subjects, a decrease in saliva glucose concentration, an increase in salivary flow, but an unchanged glucose excretion rate were recorded when comparing stimulated saliva to unstimulated saliva. In diabetic patients, an increase in salivary flow with unchanged salivary glucose concentration and glucose excretion rate were observed under the same experimental conditions. Salivary glucose concentration and excretion were much higher in diabetic patients than in control subjects, whether in unstimulated or stimulated saliva. No significant correlation between glycemia and either glucose concentration or glucose excretion rate was found in the diabetic patients, whether in unstimulated or stimulated saliva. In the latter patients, as compared to control subjects, the relative magnitude of the increase in saliva glucose concentration was comparable, however, to that of blood glucose concentration. The relationship between these two variables was also documented in normal subjects and diabetic patients undergoing an oral glucose tolerance test.

  4. Hemodynamic and renal implications of sodium-glucose cotransporter- 2 inhibitors in type 2 diabetes mellitus.

    Science.gov (United States)

    Tejedor Jorge, Alberto

    2016-11-01

    In DM2, there is increased expression of the proximal glucose transporter SGLT2. The increased glucose reabsorption from the urine to the proximal tubule and subsequently to the bloodstream, has three direct effects on the prognosis of patients with DM2: a) it increases the daily glucose load by raising the renal threshold for glucose, thus augmenting requirements for oral antidiabetics and insulin. This progressive increase occurs throughout the course of the disease and in parallel with the increase in renal mass (renal hypertrophy); b) because of the greater glucose reabsorption, glycosuria is lower than the level corresponding to glycaemia, decreasing the stimulus on the tubuloglomerular feedback system of the distal nephron. As a result, the glomerular vasodilation caused by hyperglycaemia is not arrested, maintaining glomerular hyperfiltration, and c) the excess glucose transported to the proximal tubular cells modifies their redox status, increasing local production of glycosylating products and activating local production of proinflammatory and profibrotic proliferative mediators. These mediators are responsible for the direct free radical damage to proximal tubular cells, for increased SGLT2 expression, increased production of collagen IV and extracellular matrix, and activation of monocyte/macrophages able to cause endothelial injury. The use of SGLT2 inhibitors not only reduces the reabsorption of glucose from the glomerular filtrate back into the circulationthus improving metabolic control in diabetesbut also restores tubuloglomerular feedback by increasing glycosuria and distal urinary flow. However, the most notable effect is due to inhibition of glucose entry to the proximal tubular cells. Glycosuria is toxic to the kidney: it harms glucosetransporting cells, that is, the proximal cells, which contain SGLT2. In animal models, SGLT2 inhibition reduces local production of oxygen-free radicals, the formation of mesangial matrix and collagen IV

  5. Long-term inhibition of dipeptidyl peptidase IV improves glucose tolerance and preserves islet function in mice

    DEFF Research Database (Denmark)

    Reimer, M Kvist; Holst, Jens Juul; Ahrén, B

    2002-01-01

    DPPIV activity to 0.01+/-0.03 mU/ml vs 3.26+/-0.19 mU/ml in controls (PGlucose tolerance after gastric glucose gavage, as judged by the area under the curve for plasma glucose levels over the 120 min study period, was increased after 8 weeks by NVP DPP728 in mice fed normal diet (P=0.......029) and in mice fed a high-fat diet (P=0.036). This was accompanied by increased plasma levels of insulin and intact GLP-1. Glucose-stimulated insulin secretion from islets isolated from NVP DPP728-treated animals after 8 weeks of treatment was increased as compared with islets from control animals at 5.6, 8...... and such mice rendered glucose-intolerant and insulin-resistant by feeding a high-fat diet. DESIGN: In mice fed a standard diet (11% fat) or a high-fat diet (58% fat), NVP DPP728 (0.12 micromol/g body weight) was administered in the drinking water for an 8 week period. RESULTS: DPPIV inhibition reduced plasma...

  6. Effects of dietary carbohydrates on glucose and lipid metabolism in golden Syrian hamsters.

    Science.gov (United States)

    Kasim-Karakas, S E; Vriend, H; Almario, R; Chow, L C; Goodman, M N

    1996-08-01

    Frequent coexistence of insulin resistance, central obesity, and hypertriglyceridemia in the same individual suggests an underlying common pathogenesis. Insulin resistance and hypertriglyceridemia can be induced by carbohydrate feeding in rats. Golden Syrian hamsters are believed to be resistant to the metabolic effects of dietary carbohydrates. We investigated the effects of diets containing 60% fructose or sucrose on glucose and lipid metabolism in hamsters, both in the fasting state and during an intravenous glucose tolerance test. Fructose caused obesity (weight after treatment: 131 +/- 7 gm in the control group, 155 +/- 5 gm in the fructose group, 136 +/- 7 gm in sucrose group, p < 0.04). Fructose also reduced glucose disappearance rate (KG: 2.69% +/- 0.39% in the control group, 1.45% +/- 0.18% in the fructose group, p < 0.02). Sucrose caused a marginal decrease in glucose disappearance (KG: 1.93% +/- 0.21%, p = 0.08 vs the control group). Only fructose feeding increased fasting plasma nonesterified fatty acids (0.645 +/- 0.087 mEq/L in the control group, 1.035 +/- 0.083 mEq/L in the fructose group, 0.606 +/- 0.061 mEq/L in the sucrose group, p < 0.002), plasma triglycerides (84 +/- 6 mg/dl in the control group, 270 +/- 65 mg/dl in the fructose group, 94 +/- 16 mg/dl in the sucrose group, p < 0.0002), and liver triglycerides (1.88 +/- 0.38 mg/gm liver weight in the control group, 2.35 =/- 0.24 mg/gm in the fructose group, 1.41 +/- 0.13 mg/gm in the sucrose group, p < 0.04). Previous studies in the rat have suggested that dietary carbohydrates induce insulin resistance by increasing plasma nonesterified fatty acids and triglycerides, which are preferentially used by the muscles. The present report shows that sucrose also can cause some decrease in glucose disappearance in the hamster without causing hypertriglyceridemia or increasing plasma nonesterified fatty acids. Thus other mechanisms may also contribute to the insulin resistance in the hamster. These

  7. Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

    Science.gov (United States)

    Murovets, Vladimir O; Bachmanov, Alexander A; Zolotarev, Vasiliy A

    2015-01-01

    The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+) inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-). Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain.

  8. Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

    Directory of Open Access Journals (Sweden)

    Vladimir O Murovets

    Full Text Available The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+ inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-. Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain.

  9. The effects of glucose ingestion and glucose regulation on memory performance in older adults with mild cognitive impairment.

    Science.gov (United States)

    Riby, L M; Marriott, A; Bullock, R; Hancock, J; Smallwood, J; McLaughlin, J

    2009-04-01

    Previous research investigating the impact of glucose ingestion and/or improvements in glucose regulation has found selective cognitive facilitation on episodic memory tasks in successful ageing and dementia. The present study aimed to extend this research to mild cognitive impairment (MCI). In a repeated-measures design, 24 older adults with and 24 older adults without MCI performed a battery of memory and attention tasks after 25 g of glucose or a sweetness matched placebo. In addition, to assess the impact of individual differences in glucose regulation, blood glucose measurements were taken throughout the testing session. Consistent with previous research, cognitive facilitation was observed for episodic memory tasks only in both successful ageing and MCI. Older adults with MCI had a similar glucose regulatory response as controls but their fasting levels were elevated. Notably, higher levels of blood glucose were associated with impaired memory performance in both the glucose and placebo conditions. Importantly, both blood glucose and memory performance indices were significant predictors of MCI status. The utility of glucose supplementation and the use of glucose regulation as a biological marker are discussed in relation to these data.

  10. Glucose administration attenuates spatial memory deficits induced by chronic low-power-density microwave exposure.

    Science.gov (United States)

    Lu, Yonghui; Xu, Shangcheng; He, Mindi; Chen, Chunhai; Zhang, Lei; Liu, Chuan; Chu, Fang; Yu, Zhengping; Zhou, Zhou; Zhong, Min

    2012-07-16

    Extensive evidence indicates that glucose administration attenuates memory deficits in rodents and humans, and cognitive impairment has been associated with reduced glucose metabolism and uptake in certain brain regions including the hippocampus. In the present study, we investigated whether glucose treatment attenuated memory deficits caused by chronic low-power-density microwave (MW) exposure, and the effect of MW exposure on hippocampal glucose uptake. We exposed Wistar rats to 2.45 GHz pulsed MW irradiation at a power density of 1 mW/cm(2) for 3 h/day, for up to 30 days. MW exposure induced spatial learning and memory impairments in rats. Hippocampal glucose uptake was also reduced by MW exposure in the absence or presence of insulin, but the levels of blood glucose and insulin were not affected. However, these spatial memory deficits were reversed by systemic glucose treatment. Our results indicate that glucose administration attenuates the spatial memory deficits induced by chronic low-power-density MW exposure, and reduced hippocampal glucose uptake may be associated with cognitive impairment caused by MW exposure. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Sensing of glucose in the brain.

    Science.gov (United States)

    Thorens, Bernard

    2012-01-01

    The brain, and in particular the hypothalamus and brainstem, have been recognized for decades as important centers for the homeostatic control of feeding, energy expenditure, and glucose homeostasis. These structures contain neurons and neuronal circuits that may be directly or indirectly activated or inhibited by glucose, lipids, or amino acids. The detection by neurons of these nutrient cues may become deregulated, and possibly cause metabolic diseases such as obesity and diabetes. Thus, there is a major interest in identifying these neurons, how they respond to nutrients, the neuronal circuits they form, and the physiological function they control. Here I will review some aspects of glucose sensing by the brain. The brain is responsive to both hyperglycemia and hypoglycemia, and the glucose sensing cells involved are distributed in several anatomical sites that are connected to each other. These eventually control the activity of the sympathetic or parasympathetic nervous system, which regulates the function of peripheral organs such as liver, white and brown fat, muscle, and pancreatic islets alpha and beta cells. There is now evidence for an extreme diversity in the sensing mechanisms used, and these will be reviewed.

  12. Review of human studies investigating the post-prandial blood-glucose lowering ability of oat and barley food products.

    Science.gov (United States)

    Tosh, S M

    2013-04-01

    Oat and barley foods have been shown to reduce human glycaemic response, compared to similar wheat foods or a glucose control. The strength of the evidence supporting the hypothesis that the soluble fibre, mixed linkage β-glucan, reduces glycaemic response was evaluated. A search of the literature was conducted to find clinical trials with acute glycaemic response as an end point using oat or barley products. Of the 76 human studies identified, 34 met the inclusion and exclusion criteria. Dose response and ratio of β-glucan to available carbohydrate as predictors of glycaemic response were assessed. Meals provided 0.3-12.1 g oat or barley β-glucan, and reduced glycaemic response by an average of 48 ± 33 mmol · min/l compared to a suitable control. Regression analysis on 119 treatments indicated that change in glycaemic response (expressed as incremental area under the post-prandial blood-glucose curve) was greater for intact grains than for processed foods. For processed foods, glycaemic response was more strongly related to the β-glucan dose alone (r(2)=0.48, Pfoods containing 4 g of β-glucan, the linear model predicted a decrease in glycaemic response of 27 ± 3 mmol · min/l, and 76% of treatments significantly reduced glycaemic response. Thus, intact grains as well as a variety of processed oat and barley foods containing at least 4 g of β-glucan and 30-80 g available carbohydrate can significantly reduce post-prandial blood glucose.

  13. The dietary flavonoids naringenin and quercetin acutely impair glucose metabolism in rodents possibly via inhibition of hypothalamic insulin signalling.

    Science.gov (United States)

    Koch, Christiane E; Ganjam, Goutham K; Steger, Juliane; Legler, Karen; Stöhr, Sigrid; Schumacher, Daniela; Hoggard, Nigel; Heldmaier, Gerhard; Tups, Alexander

    2013-03-28

    Secondary metabolites of herbs and spices are widely used as an alternative strategy in the therapy of various diseases. The polyphenols naringenin, quercetin and curcumin have been characterised as anti-diabetic agents. Conversely, in vitro, naringenin and quercetin are described to inhibit phosphoinositide-3-kinase (PI3K), an enzyme that is essential for the neuronal control of whole body glucose homoeostasis. Using both in vitro and in vivo experiments, we tested whether the inhibitory effect on PI3K occurs in neurons and if it might affect whole body glucose homoeostasis. Quercetin was found to inhibit basal and insulin-induced phosphorylation of Akt (Ser473), a downstream target of PI3K, in HT-22 cells, whereas naringenin and curcumin had no effect. In Djungarian hamsters (Phodopus sungorus) naringenin and quercetin (10 mg/kg administered orally) diminished insulin-induced phosphorylation of Akt (Ser473) in the arcuate nucleus, indicating a reduction in hypothalamic PI3K activity. In agreement with this finding, glucose tolerance in naringenin-treated hamsters (oral) and mice (oral and intracerebroventricular) was reduced compared with controls. Dietary quercetin also impaired glucose tolerance, whereas curcumin was ineffective. Circulating levels of insulin and insulin-like growth factor-binding protein were not affected by the polyphenols. Oral quercetin reduced the respiratory quotient, suggesting that glucose utilisation was impaired after treatment. These data demonstrate that low doses of naringenin and quercetin acutely and potently impair glucose homoeostasis. This effect may be mediated by inhibition of hypothalamic PI3K signalling. Whether chronic impairments in glucose homoeostasis occur after long-term application remains to be identified.

  14. Cerebral glucose metabolism change in patients with complex regional pain syndrome. A PET study

    International Nuclear Information System (INIS)

    Shiraishi, Satoe; Kobayashi, Hidetoshi; Nihashi, Takashi

    2006-01-01

    The aim of this study was to examine abnormalities of the central nervous system in patients with chronic pain who were diagnosed with complex regional pain syndrome (CRPS). Brain activity was assessed using 18 F-fluorodeoxyglucose positron emission tomography. The data collected from 18 patients were compared with data obtained from 13 normal age-matched controls. Our results showed that glucose metabolism was bilaterally increased in the secondary somatosensory cortex, mid-anterior cingulated cortex (ACC) or posterior cingulated cortex (PCC) (or both), parietal cortex, posterior parietal cortex (PPC), and cerebellum as well as in the right posterior insula and right thalamus in our patients. In contrast, glucose metabolism was reduced contralaterally in the dorsal prefrontal cortex and primary motor cortex. Glucose metabolism was bilaterally elevated in the mid-ACC/PCC and the PPC, which correlated with pain duration. These data suggested that glucose metabolism in the brains of patients with CRPS changes dramatically at each location. In particular, glucose metabolism was increased in the areas concerned with somatosensory perception, possibly due to continuous painful stimulation. (author)

  15. Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke (MAAS): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Osei, Elizabeth; Fonville, Susanne; Zandbergen, Adrienne A M; Brouwers, Paul J A M; Mulder, Laus J M M; Lingsma, Hester F; Dippel, Diederik W J; Koudstaal, Peter J; den Hertog, Heleen M

    2015-08-05

    Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients. The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (TIA, amaurosis fugax or minor ischemic stroke (modified Rankin scale ≤ 3) and impaired glucose tolerance, defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated standard oral glucose tolerance test, will be included. Patients with renal or liver impairment, heart failure, chronic hypoxic lung disease stage III-IV, history of lactate acidosis or diabetic ketoacidosis, pregnancy or breastfeeding, pancreatitis and use of digoxin will be excluded. The patients will be randomly assigned in a 1:1:2 ratio to metformin, sitagliptin or "no treatment." Patients allocated to metformin will start with 500 mg twice daily, which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg. Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg. The study has been registered as NTR 3196 in The Netherlands Trial Register. Primary outcomes include percentage still on treatment, percentage of (serious) adverse events, and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months. This study will give more

  16. Use of a real time continuous glucose monitoring system as an educational tool for patients with gestational diabetes.

    Science.gov (United States)

    Alfadhli, Eman; Osman, Eman; Basri, Taghreed

    2016-01-01

    Women with gestational diabetes mellitus (GDM) are required to control their blood glucose shortly after GDM diagnosis to minimize adverse pregnancy outcomes. A real time-continuous glucose monitoring system (RT-CGMS) provides the patient with continuous information about the alterations in levels of the blood glucose. This visibility may empower the patient to modify her lifestyle and engage in therapeutic management. The aim of this study was to determine whether a single application of RT-CGMS to pregnant women shortly after GDM diagnosis is useful as an educational and motivational tool. This study was a prospective open label randomized controlled study conducted at Maternity and Children Hospital, Medina, Saudi Arabia. A total of 130 pregnant women with GDM were randomised to either blood glucose self-monitor alone (SMBG group) (n = 62) or in addition to SMBG, patients wore a Guardian(®) REAL-Time Continuous Glucose Monitoring System (Medtronic MiniMed) once for 3-7 days, within 2 weeks of GDM diagnosis (RT-CGMS group) (n = 68). The primary outcomes were maternal glycemic control and pregnancy outcomes. Secondary outcomes were the changes in parameters of glucose variability, which includes mean sensor readings, standard deviation (SD) of blood glucose, and area under the curve for hyper and hypoglycaemia at the end of the RT-CGMS application. HbA1c, mean fasting and postprandial glucose levels were similar in both groups at the end of the pregnancy. Pregnancy outcomes were comparable. However, there was significant improvement in the parameters of glucose variability on the last day of sensor application; both mean glucose and the SD of mean glycaemia were reduced significantly; P = 0.016 and P = 0.034, respectively. The area under the curve for hyper and hypoglycaemia were improved, however, the results were not statistically significant. Although a single application of RT-CGMS shortly after GDM diagnosis is helpful as an educational tool, it

  17. Green tea extract with polyethylene glycol-3350 reduces body weight and improves glucose tolerance in db/db and high-fat diet mice.

    Science.gov (United States)

    Park, Jae-Hyung; Choi, Yoon Jung; Kim, Yong Woon; Kim, Sang Pyo; Cho, Ho-Chan; Ahn, Shinbyoung; Bae, Ki-Cheor; Im, Seung-Soon; Bae, Jae-Hoon; Song, Dae-Kyu

    2013-08-01

    Green tea extract (GTE) is regarded to be effective against obesity and type 2 diabetes, but definitive evidences have not been proven. Based on the assumption that the gallated catechins (GCs) in GTE attenuate intestinal glucose and lipid absorption, while enhancing insulin resistance when GCs are present in the circulation through inhibiting cellular glucose uptake in various tissues, this study attempted to block the intestinal absorption of GCs and prolong their residence time in the lumen. We then observed whether GTE containing the nonabsorbable GCs could ameliorate body weight (BW) gain and glucose intolerance in db/db and high-fat diet mice. Inhibition of the intestinal absorption of GCs was accomplished by co-administering the nontoxic polymer polyethylene glycol-3350 (PEG). C57BLKS/J db/db and high-fat diet C57BL/6 mice were treated for 4 weeks with drugs as follows: GTE, PEG, GTE+PEG, voglibose, or pioglitazone. GTE mixed with meals did not have any ameliorating effects on BW gain and glucose intolerance. However, the administration of GTE plus PEG significantly reduced BW gain, insulin resistance, and glucose intolerance, without affecting food intake and appetite. The effect was comparable to the effects of an α-glucosidase inhibitor and a peroxisome proliferator-activated receptor-γ/α agonist. These results indicate that prolonging the action of GCs of GTE in the intestinal lumen and blocking their entry into the circulation may allow GTE to be used as a prevention and treatment for both obesity and obesity-induced type 2 diabetes.

  18. Pancreatic beta-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Asmar, Meena; Højberg, Patricia V; Deacon, Carolyn F

    2010-01-01

    glucose (BG) using insulin (mean diurnal BG: 6.4+/-0.3 mmol/l; HbA(1)c: 6.6+/-0.3%). Nine matched healthy subjects acted as controls. In controls, area-under-curve (AUC) for amylin, C-peptide and proinsulin were higher with GLP-1 than saline (PAUC amylin/C-peptide ratio was similar on both......This study investigated the effects of strict glycaemic control on beta-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA(1)c: 8.0+/-0.4%) and after four weeks of near-normalization of blood...... amylin/C-peptide ratios rose to control levels. Near-normoglycaemia tended to reduce AUC proinsulin/C-peptide ratio, which was significant (P=0.04) with GLP-1, but still higher than with saline (P=0.004). In conclusion, amylin, C-peptide and proinsulin responses to glucose were unaffected by four weeks...

  19. Pancreatic ß-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Asmar, Meena; Højberg, Patricia; Deacon, Carolyn F.

    2010-01-01

    glucose (BG) using insulin (mean diurnal BG: 6.4+/-0.3 mmol/l; HbA(1)c: 6.6+/-0.3%). Nine matched healthy subjects acted as controls. In controls, area-under-curve (AUC) for amylin, C-peptide and proinsulin were higher with GLP-1 than saline (PAUC amylin/C-peptide ratio was similar on both......This study investigated the effects of strict glycaemic control on beta-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA(1)c: 8.0+/-0.4%) and after four weeks of near-normalization of blood...... amylin/C-peptide ratios rose to control levels. Near-normoglycaemia tended to reduce AUC proinsulin/C-peptide ratio, which was significant (P=0.04) with GLP-1, but still higher than with saline (P=0.004). In conclusion, amylin, C-peptide and proinsulin responses to glucose were unaffected by four weeks...

  20. Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

    Directory of Open Access Journals (Sweden)

    Reed JW

    2016-10-01

    Full Text Available James W Reed Morehouse School of Medicine, Atlanta, GA, USA Abstract: SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM. These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin on BP in patients with T2DM. Boolean searches were conducted that included terms related to BP or hypertension with terms for SGLT2 inhibitors, canagliflozin, dapagliflozin, or empagliflozin using PubMed, Google, and Google Scholar. Data from numerous randomized controlled trials of SGLT2 inhibitors in patients with T2DM demonstrated clinically relevant reductions in both systolic and diastolic BP, assessed via seated office measurements and 24-hour ambulatory BP monitoring. Observed BP lowering was not associated with compensatory increases in heart rate. Circadian BP rhythm was also maintained. The mechanism of SGLT2 inhibitor-associated BP reduction is not fully understood, but is assumed to be related to osmotic diuresis and natriuresis. Other factors that may also contribute to BP reduction include SGLT2 inhibitor-associated decreases in body weight and reduced arterial stiffness. Local inhibition of the renin–angiotensin–aldosterone system secondary to increased delivery of sodium to the juxtaglomerular apparatus during SGLT2 inhibition has also been postulated. Although SGLT2 inhibitors are not indicated as BP-lowering agents, the modest decreases in systolic and diastolic BP observed with SGLT2 inhibitors may provide an extra clinical advantage for the majority of patients with T2DM, in addition to improving blood glucose