WorldWideScience

Sample records for suppresses endogenous glucose

  1. Suppression of Endogenous Glucose Production by Isoleucine and Valine and Impact of Diet Composition

    Directory of Open Access Journals (Sweden)

    Isabel Arrieta-Cruz

    2016-02-01

    Full Text Available Leucine has been shown to acutely inhibit hepatic glucose production in rodents by a mechanism requiring its metabolism to acetyl-CoA in the mediobasal hypothalamus (MBH. In the early stages, all branched-chain amino acids (BCAA are metabolized by a shared set of enzymes to produce a ketoacid, which is later metabolized to acetyl-CoA. Consequently, isoleucine and valine may also modulate glucose metabolism. To examine this possibility we performed intrahypothalamic infusions of isoleucine or valine in rats and assessed whole body glucose kinetics under basal conditions and during euglycemic pancreatic clamps. Furthermore, because high fat diet (HFD consumption is known to interfere with central glucoregulation, we also asked whether the action of BCAAs was affected by HFD. We fed rats a lard-rich diet for a short interval and examined their response to central leucine. The results showed that both isoleucine and valine individually lowered blood glucose by decreasing liver glucose production. Furthermore, the action of the BCAA leucine was markedly attenuated by HFD feeding. We conclude that all three BCAAs centrally modulate glucose metabolism in the liver and that their action is disrupted by HFD-induced insulin resistance.

  2. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients

    DEFF Research Database (Denmark)

    Balas, Bogdan; Baig, Muhammad R; Watson, Catherine

    2007-01-01

    AIMS/HYPOTHESIS: Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1. Chronic vildagliptin treatment decreases postprandial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients. However......, little is known about the mechanism(s) by which vildagliptin promotes reduction in plasma glucose concentration. METHODS: Sixteen patients with type 2 diabetes (age, 48+/-3 yr; body mass index, 34.4+/-1.7 kg/m2; hemoglobin A1c, 9.0+/-0.3%) participated in a randomized, double-blind, placebo......-controlled trial. On separate days patients received 100 mg vildagliptin or placebo at 1730 h followed 30 min later by a meal tolerance test (MTT) performed with double tracer technique (3-(3)H-glucose iv and 1-(14)C-glucose orally). RESULTS: After vildagliptin, suppression of endogenous glucose production (EGP...

  3. High glucose induces suppression of insulin signalling and apoptosis via upregulation of endogenous IL-1beta and suppressor of cytokine signalling-1 in mouse pancreatic beta cells.

    Science.gov (United States)

    Venieratos, Panagiotis D; Drossopoulou, Garyfalia I; Kapodistria, Katerina D; Tsilibary, Effie C; Kitsiou, Paraskevi V

    2010-05-01

    Chronic hyperglycemia and inflammatory cytokines disrupt and/or attenuate signal transduction pathways that promote normal beta-cell survival, leading to the destruction of endocrine pancreas in type 2 diabetes. There is convincing evidence that autocrine insulin signalling exerts protective anti-apoptotic effects on beta cells. Suppressors of cytokine signalling (SOCS) were induced by several cytokines and inhibit insulin-initiated signal transduction. The aim of this study was to investigate whether high glucose can influence endogenous interleukin-1beta (IL-1beta) and SOCS expression thus affecting insulin signalling and survival in insulin-producing mouse pancreatic beta cells (betaTC-6). Results showed that prolonged exposure of betaTC-6 cells to increased glucose concentrations resulted in significant inhibition of insulin-induced tyrosine phosphorylation of the insulin receptor (IR), and insulin receptor substrate-2 (IRS-2) as well as PI3-kinase activation. These changes were accompanied by impaired activation of the anti-apoptotic signalling protein Akt and annulment of Akt-mediated suppression of the Forkhead family of transcription factors (FoxO) activation. Glucose-induced attenuation of IRS-2/Akt-mediated signalling was associated with increased IL-1beta expression. Enhanced endogenous IL-1beta specifically induced mRNA and protein expression of SOCS-1 in betaTC-6 cells. Inhibition of SOCS-1 expression by SOCS-1-specific small interfering RNA restored IRS-2/PI3K-mediated Akt phosphorylation suppressed by high glucose. The upregulation of endogenous cytokine signalling and FoxO activation were accompanied by enhanced caspase-3 activation and increased susceptibility of cells to apoptosis. These results indicated that glucose-induced endogenous IL-1beta expression increased betaTC-6 cells apoptosis by inhibiting, at least in part, IRS-2/Akt-mediated signalling through SOCS-1 upregulation. 2010 Elsevier Inc. All rights reserved.

  4. 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...... with a concomitant iv glucagon infusion (0.8 ng/kg/min from 0 to 25 min) designed to mimic portal glucagon concentrations during OGTT in the type 2 diabetic group). MAIN OUTCOME MEASURES: Glucose kinetics assessed by the double-tracer technique. RESULTS: Glucose rate of disappearance was higher during the OGTT vs...

  5. Hypocalcemia reduces endogenous glucose production in hyperketonemic sheep.

    Science.gov (United States)

    Schlumbohm, C; Harmeyer, J

    2003-06-01

    In previous experiments it has been shown that hyperketonemia lowered plasma glucose concentration in sheep and depressed endogenous glucose production by approximately 30%. This facilitates the onset of pregnancy toxemia. In the last trimester of gestation, hyperketonemia in sheep is often associated with hypocalcemia. There is an indication that hypocalcemia exerts an additional depressive effect on endogenous glucose production. The present study was undertaken to examine the effect in sheep of hypocalcemia on endogenous glucose production in the presence of normo- and hyperketonemia. The experiments were carried out with seven multiparous sheep during three different reproductive states, i.e., during pregnancy (10 +/- 8 d prepartum), during lactation (21 +/- 8 d postpartum), and 4 wk after weaning of the lambs. Concentration of glucose in plasma, turnover of glucose and the rate constant of glucose turnover were measured by isotope dilution during normo- and hypocalcemia and in the presence of normal and elevated beta-hydroxybutyrate (BHB) concentrations. Hypocalcemia was induced by i.v. infusions of Na2EDTA. Hyperketonemia was maintained by i.v. infusion of DL-beta-hydroxybutyrate. The experiments showed that induction of hypocalcemia: 1) induced a decline in plasma glucose concentration in all reproductive states during normo- and hyperketonemia and 2) significantly lowered endogenous production of glucose in nonpregnant hyperketonemic and in lactating normoketonemic ewes. Pregnant normoketonemic ewes were able to compensate for the hypoglycemic effect of hypocalcemia and to keep endogenous production at the normocalcemic level. We concluded that hypocalcemia does not promote the onset of pregnancy toxemia per se but will facilitate the development of the disease when it is present in combination with hyperketonemia.

  6. Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets.

    Directory of Open Access Journals (Sweden)

    Joseph P McKenna

    2016-10-01

    Full Text Available Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal's ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion.

  7. Indirect Regulation of Endogenous Glucose Production by Insulin: The Single Gateway Hypothesis Revisited.

    Science.gov (United States)

    Bergman, Richard N; Iyer, Malini S

    2017-07-01

    On the basis of studies that investigated the intraportal versus systemic insulin infusion and transendothelial transport of insulin, we proposed the "single gateway hypothesis," which supposes an indirect regulation of hepatic glucose production by insulin; the rate-limiting transport of insulin across the adipose tissue capillaries is responsible for the slow suppression of free fatty acids (FFAs), which in turn is responsible for delayed suppression of hepatic endogenous glucose production (EGP) during insulin infusion. Preventing the fall in plasma FFAs during insulin infusion either by administering intralipids or by inhibiting adipose tissue lipolysis led to failure in EGP suppression, thus supporting our hypothesis. More recently, mice lacking hepatic Foxo1 in addition to Akt1 and Akt2 (L-AktFoxo1TKO), all required for insulin signaling, surprisingly showed normal glycemia. Inhibiting the fall of plasma FFAs in these mice prevented the suppression of EGP during a clamp, reaffirming that the site of insulin action to control EGP is extrahepatic. Measuring whole-body turnover rates of glucose and FFAs in L-AktFoxo1TKO mice also confirmed that hepatic EGP was regulated by insulin-mediated control of FFAs. The knockout mouse model in combination with sophisticated molecular techniques confirmed our physiological findings and the single gateway hypothesis. © 2017 by the American Diabetes Association.

  8. Glucose Suppresses Biological Ferroelectricity in Aortic Elastin

    Science.gov (United States)

    Liu, Yuanming; Wang, Yunjie; Chow, Ming-Jay; Chen, Nataly Q.; Ma, Feiyue; Zhang, Yanhang; Li, Jiangyu

    2013-04-01

    Elastin is an intriguing extracellular matrix protein present in all connective tissues of vertebrates, rendering essential elasticity to connective tissues subjected to repeated physiological stresses. Using piezoresponse force microscopy, we show that the polarity of aortic elastin is switchable by an electrical field, which may be associated with the recently discovered biological ferroelectricity in the aorta. More interestingly, it is discovered that the switching in aortic elastin is largely suppressed by glucose treatment, which appears to freeze the internal asymmetric polar structures of elastin, making it much harder to switch, or suppressing the switching completely. Such loss of ferroelectricity could have important physiological and pathological implications from aging to arteriosclerosis that are closely related to glycation of elastin.

  9. Suppression of endogenous testosterone production attenuates the response to strength training

    DEFF Research Database (Denmark)

    Kvorning, Thue; Andersen, Marianne; Brixen, Kim

    2006-01-01

    We hypothesized that suppression of endogenous testosterone would inhibit the adaptations to strength training in otherwise healthy men. Twenty-two young men with minor experience with strength training participated in this randomized, placebo-controlled, double-blinded intervention study......-repetition maximum (RM) loads, 3/wk]. A strength test, blood sampling, and whole body DEXA scan were performed at weeks 4 and 12. Endogenous testosterone decreased significantly (P ... that endogenous testosterone is of paramount importance to the adaptation to strength training....

  10. Interaction between exogenous insulin, endogenous insulin, and glucose in type 2 diabetes patients

    DEFF Research Database (Denmark)

    Janukonyté, Jurgita; Parkner, Tina; Bruun, Niels Henrik

    2015-01-01

    Abstract BACKGROUND: Little is known about the influence of exogenous insulin and actual glucose levels on the release of endogenous insulin in insulin-treated type 2 diabetes mellitus (T2DM) patients. This study investigated the interaction among serum endogenous insulin (s-EI), serum exogenous......-IAsp, and s-EI were equal within visit TH and within visit CH, but variances were significantly higher during visit CH compared with visit TH. The s-IAsp reached lower levels at visit CH compared with visit TH (test for slope=1, P=0.005). The s-EI depended on p-glucose in a nonlinear fashion during the first...

  11. High glucose suppresses embryonic stem cell differentiation into cardiomyocytes : High glucose inhibits ES cell cardiogenesis.

    Science.gov (United States)

    Yang, Penghua; Chen, Xi; Kaushal, Sunjay; Reece, E Albert; Yang, Peixin

    2016-12-09

    Babies born to mothers with pregestational diabetes have a high risk for congenital heart defects (CHD). Embryonic stem cells (ESCs) are excellent in vitro models for studying the effect of high glucose on cardiac lineage specification because ESCs can be differentiated into cardiomyocytes. ESC maintenance and differentiation are currently performed under high glucose conditions, whose adverse effects have never been clarified. We investigated the effect of high glucose on cardiomyocyte differentiation from a well-characterized ESC line, E14, derived from mouse blastocysts. E14 cells maintained under high glucose (25 mM) failed to generate any beating cardiomyocytes using the hanging-drop embryonic body method. We created a glucose-responsive E14 cell line (GR-E14) through a graduated low glucose adaptation. The expression of stem cell markers was similar in the parent E14 cells and the GR-E14 cells. Glucose transporter 2 gene was increased in GR-E14 cells. When GR-E14 cells were differentiated into cardiomyocytes under low (5 mM) or high (25 mM) glucose conditions, high glucose significantly delayed the appearance and reduced the number of TNNT2 (Troponin T Type 2)-positive contracting cardiomyocytes. High glucose suppressed the expression of precardiac mesoderm markers, cardiac transcription factors, mature cardiomyocyte markers, and potassium channel proteins. High glucose impaired the functionality of ESC-derived cardiomyocytes by suppressing the frequencies of Ca 2+ wave and contraction. Our findings suggest that high glucose inhibits ESC cardiogenesis by suppressing key developmental genes essential for the cardiac program.

  12. Selenium suppresses leukemia through the action of endogenous eicosanoids.

    Science.gov (United States)

    Gandhi, Ujjawal H; Kaushal, Naveen; Hegde, Shailaja; Finch, Emily R; Kudva, Avinash K; Kennett, Mary J; Jordan, Craig T; Paulson, Robert F; Prabhu, K Sandeep

    2014-07-15

    Eradicating cancer stem-like cells (CSC) may be essential to fully eradicate cancer. Metabolic changes in CSC could hold a key to their targeting. Here, we report that the dietary micronutrient selenium can trigger apoptosis of CSC derived from chronic or acute myelogenous leukemias when administered at supraphysiologic but nontoxic doses. In leukemia CSC, selenium treatment activated ATM-p53-dependent apoptosis accompanied by increased intracellular levels of reactive oxygen species. Importantly, the same treatment did not trigger apoptosis in hematopoietic stem cells. Serial transplantation studies with BCR-ABL-expressing CSC revealed that the selenium status in mice was a key determinant of CSC survival. Selenium action relied upon the endogenous production of the cyclooxygenase-derived prostaglandins Δ(12)-PGJ2 and 15d-PGJ2. Accordingly, nonsteroidal anti-inflammatory drugs and NADPH oxidase inhibitors abrogated the ability of selenium to trigger apoptosis in leukemia CSC. Our results reveal how selenium-dependent modulation of arachidonic acid metabolism can be directed to trigger apoptosis of primary human and murine CSC in leukemia. ©2014 American Association for Cancer Research.

  13. Deficient Endogenous Glucose Production During Exercise After Total Pancreatectomy/Islet Autotransplantation.

    Science.gov (United States)

    Bogachus, Lindsey D; Oseid, Elizabeth; Bellin, Melena; Vella, Adrian; Robertson, R Paul

    2017-09-01

    Total pancreatectomy followed by intrahepatic islet autotransplantation (TP/IAT) is performed to alleviate severe, unrelenting abdominal pain caused by chronic pancreatitis, to improve quality of life, and to prevent diabetes. To determine the cause of exercise-induced hypoglycemia that is a common complaint in TP/IAT recipients. Participants completed 1 hour of steady-state exercise. Hospital research unit. We studied 14 TP/IAT recipients and 10 age- and body mass index-matched control subjects. Peak oxygen uptake (VO2) was determined via a symptom-limited maximal cycle ergometer test. Fasted subjects then returned for a primed [6,6-2H2]-glucose infusion to measure endogenous glucose production while completing 1 hour of bicycle exercise at either 40% or 70% peak VO2. Blood samples were obtained to measure glucose metabolism and counterregulatory hormones before, during, and after exercise. Although the Borg Rating of Perceived Exertion did not differ between recipients and control subjects, aerobic capacity was significantly higher in controls than in recipients (40.4 ± 2.0 vs 27.2 ± 1.4 mL/kg per minute; P < 0.001). This difference resulted in workload differences between control subjects and recipients to reach steady-state exercise at 40% peak VO2 (P = 0.003). Control subjects significantly increased their endogenous glucose production from 12.0 ± 1.0 to 15.2 ± 1.0 µmol/kg per minute during moderate exercise (P = 0.01). Recipients did not increase endogenous glucose production during moderate exercise (40% peak VO2) but succeeded during heavy exercise, from 10.1 ± 0.4 to 14.8 ± 2.0 µmol/kg per minute (70% peak VO2; P = 0.001). Failure to increase endogenous glucose production during moderate exercise may be a key contributor to the hypoglycemia TP/IAT recipients experience.

  14. Exogenous amino acids suppress glucose oxidation and potentiate hepatic glucose production in late gestation fetal sheep.

    Science.gov (United States)

    Brown, Laura D; Kohn, Jaden R; Rozance, Paul J; Hay, William W; Wesolowski, Stephanie R

    2017-05-01

    Acute amino acid (AA) infusion increases AA oxidation rates in normal late gestation fetal sheep. Because the fetal oxygen consumption rate does not change with increased AA oxidation, we hypothesized that AA infusion would suppress glucose oxidation pathways and that the additional carbon supply from AA would activate hepatic glucose production. To test this, late gestation fetal sheep were infused intravenously for 3 h with saline or exogenous AA (AA). Glucose tracer metabolic studies were performed and skeletal muscle and liver tissues samples were collected. AA infusion increased fetal arterial plasma branched chain AA, cortisol, and glucagon concentrations. Fetal glucose utilization rates were similar between basal and AA periods, yet the fraction of glucose oxidized and the glucose oxidation rate were decreased by 40% in the AA period. AA infusion increased expression of PDK4 , an inhibitor of glucose oxidation, nearly twofold in muscle and liver. In liver, AA infusion tended to increase PCK1 gluconeogenic gene and PCK1 correlated with plasma cortisol concentrations. AA infusion also increased liver mRNA expression of the lactate transporter gene ( MCT1) , protein expression of GLUT2 and LDHA, and phosphorylation of AMPK, 4EBP1, and S6 proteins. In isolated fetal hepatocytes, AA supplementation increased glucose production and PCK1 , LDHA , and MCT1 gene expression. These results demonstrate that AA infusion into fetal sheep competitively suppresses glucose oxidation and potentiates hepatic glucose production. These metabolic patterns support flexibility in fetal metabolism in response to increased nutrient substrate supply while maintaining a relatively stable rate of oxidative metabolism. Copyright © 2017 the American Physiological Society.

  15. Chromatin Dynamics in Genome Stability: Roles in Suppressing Endogenous DNA Damage and Facilitating DNA Repair

    Directory of Open Access Journals (Sweden)

    Nidhi Nair

    2017-07-01

    Full Text Available Genomic DNA is compacted into chromatin through packaging with histone and non-histone proteins. Importantly, DNA accessibility is dynamically regulated to ensure genome stability. This is exemplified in the response to DNA damage where chromatin relaxation near genomic lesions serves to promote access of relevant enzymes to specific DNA regions for signaling and repair. Furthermore, recent data highlight genome maintenance roles of chromatin through the regulation of endogenous DNA-templated processes including transcription and replication. Here, we review research that shows the importance of chromatin structure regulation in maintaining genome integrity by multiple mechanisms including facilitating DNA repair and directly suppressing endogenous DNA damage.

  16. Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

    Science.gov (United States)

    Glenn, Thomas C; Martin, Neil A; McArthur, David L; Hovda, David A; Vespa, Paul; Johnson, Matthew L; Horning, Michael A; Brooks, George A

    2015-06-01

    We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-(2)H2]glucose, i.e., D2-glucose, and [3-(13)C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2-10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain.

  17. Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

    Science.gov (United States)

    Kovacs, Flora E; Knop, Tim; Urbanski, Michal J; Freiman, Ilka; Freiman, Thomas M; Feuerstein, Thomas J; Zentner, Josef; Szabo, Bela

    2012-01-01

    Activation of CB1 receptors on axon terminals by exogenous cannabinoids (eg, Δ9-tetrahydrocannabinol) and by endogenous cannabinoids (endocannabinoids) released by postsynaptic neurons leads to presynaptic inhibition of neurotransmission. The aim of this study was to characterize the effect of cannabinoids on GABAergic synaptic transmission in the human neocortex. Brain slices were prepared from neocortical tissues surgically removed to eliminate epileptogenic foci. Spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) were recorded in putative pyramidal neurons using patch-clamp techniques. To enhance the activity of cannabinoid-sensitive presynaptic axons, muscarinic receptors were continuously stimulated by carbachol. The synthetic cannabinoid receptor agonist WIN55212-2 decreased the cumulative amplitude of sIPSCs. The CB1 antagonist rimonabant prevented this effect, verifying the involvement of CB1 receptors. WIN55212-2 decreased the frequency of miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin, but did not change their amplitude, indicating that the neurotransmission was inhibited presynaptically. Depolarization of postsynaptic pyramidal neurons induced a suppression of sIPSCs. As rimonabant prevented this suppression, it is very likely that it was due to endocannabinods acting on CB1 receptors. This is the first demonstration that an exogenous cannabinoid inhibits synaptic transmission in the human neocortex and that endocannabinoids released by postsynaptic neurons suppress synaptic transmission in the human brain. Interferences of cannabinoid agonists and antagonists with synaptic transmission in the cortex may explain the cognitive and memory deficits elicited by these drugs. PMID:22048459

  18. Jew's mellow leaves (Corchorus olitorius) suppress elevation of postprandial blood glucose levels in rats and humans.

    Science.gov (United States)

    Innami, Satoshi; Ishida, Hiroshi; Nakamura, Kahoru; Kondo, Mika; Tabata, Kimiko; Koguchi, Takashi; Shimizu, Jun; Furusho, Tadasu

    2005-01-01

    The study was performed to explore the suppressive effect of Jew's mellow leaves (JML) on postprandial blood glucose levels in rats and humans. A soluble dietary fiber (SDF) was extracted from the freeze-dried JML powder. An elevation of the postprandial blood glucose level in rats given 1% or 2% JML-SDF solution orally together with 20% glucose solution was significantly suppressed as compared with that observed in the control rats given only glucose solution. When seven healthy young male adults ingested 225 mL of JML mixed juice containing 15 g of freeze-dried powder with 75 g of glucose in the fasting state in the morning, the elevation of the postprandial blood glucose level was significantly suppressed as compared with the control subjects. The diffusion rate of glucose and the permeation rate of glucose in the cultured Caco-2 cells were both significantly reduced by the addition of appropriate amounts of JML-SDF when compared to the controls. These results indicate that the effective substance in JML for suppressing blood glucose elevation is a kind of mucilaginous SDF. The mechanism by which this suppression occurs may be largely attributable to the delayed absorption of glucose from the intestinal membrane in the upper digestive tract by viscous SDF.

  19. Endogenous angiotensin II suppresses stretch-induced ANP secretion via AT1 receptor pathway.

    Science.gov (United States)

    Oh, Young-Bin; Gao, Shan; Shah, Amin; Kim, Jong Hun; Park, Woo Hyun; Kim, Suhn Hee

    2011-02-01

    Angiotensin II (Ang II) is released by stretch of cardiac myocytes and has paracrine and autocrine effects on cardiac myocytes and fibroblasts. However, the direct effect of Ang II on the secretion of atrial natriuretic peptide (ANP) is unclear. The aim of the present study is to test whether Ang II affects stretch-induced ANP secretion. The isolated perfused beating atria were used from control and two-kidney one-clip hypertensive (2K1C) rats. The volume load was achieved by elevating the height of outflow catheter connected with isolated atria from 5cmH(2)O to 7.5cmH(2)O. Atrial stretch by volume load caused increases in atrial contractility by 60% and in ANP secretion by 100%. Ang II suppressed stretch-induced ANP secretion and tended to increase atrial contractility whereas losartan stimulated stretch-induced ANP secretion. Neither PD123319 nor A779 had direct effect on stretch-induced ANP secretion. The suppressive effect of Ang II on stretch-induced ANP secretion was blocked by the pretreatment of losartan but not by the pretreatment of PD123319 or A779. In hypertrophied atria from 2K1C rats, stretch-induced ANP concentration attenuated and atrial contractility augmented. The response of stretch-induced ANP secretion to Ang II and losartan augmented. The expression of AT1 receptor protein and mRNA increased but AT2 and Mas receptor mRNA did not change in 2K1C rat atria. Therefore, we suggest that Ang II generated endogenously by atrial stretch suppresses stretch-induced ANP secretion through the AT1 receptor and alteration of Ang II effect in 2K1C rat may be due to upregulation of AT1 receptor. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Hepatic insulin signalling is dispensable for suppression of glucose output by insulin in vivo

    National Research Council Canada - National Science Library

    Titchenell, Paul M; Chu, Qingwei; Monks, Bobby R; Birnbaum, Morris J

    2015-01-01

    .... Liver-specific deletion of Foxo1 (L-IRFoxo1DKO) rescues glucose tolerance and allows for normal suppression of HGP and gluconeogenic gene expression in response to insulin, despite lack of autonomous liver insulin signalling...

  1. Suppression of renal fibrosis by galectin-1 in high glucose-treated renal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Okano, Kazuhiro, E-mail: kaokano@kc.twmu.ac.jp; Tsuruta, Yuki; Yamashita, Tetsuri; Takano, Mari; Echida, Yoshihisa; Nitta, Kosaku

    2010-11-15

    Diabetic nephropathy is the most common cause of chronic kidney disease. We investigated the ability of intracellular galectin-1 (Gal-1), a prototype of endogenous lectin, to prevent renal fibrosis by regulating cell signaling under a high glucose (HG) condition. We demonstrated that overexpression of Gal-1 reduces type I collagen (COL1) expression and transcription in human renal epithelial cells under HG conditions and transforming growth factor-{beta}1 (TGF-{beta}1) stimulation. Matrix metalloproteinase 1 (MMP1) is stimulated by Gal-1. HG conditions and TGF-{beta}1 treatment augment expression and nuclear translocation of Gal-1. In contrast, targeted inhibition of Gal-1 expression reduces COL1 expression and increases MMP1 expression. The Smad3 signaling pathway is inhibited, whereas two mitogen-activated protein kinase (MAPK) pathways, p38 and extracellular signal-regulated kinase (ERK), are activated by Gal-1, indicating that Gal-1 regulates these signaling pathways in COL1 production. Using specific inhibitors of Smad3, ERK, and p38 MAPK, we showed that ERK MAPK activated by Gal-1 plays an inhibitory role in COL1 transcription and that activation of the p38 MAPK pathway by Gal-1 plays a negative role in MMP1 production. Taken together, two MAPK pathways are stimulated by increasing levels of Gal-1 in the HG condition, leading to suppression of COL1 expression and increase of MMP1 expression.

  2. Hydrogen sulfide suppresses high glucose-induced expression of intercellular adhesion molecule-1 in endothelial cells.

    Science.gov (United States)

    Guan, Qingbo; Wang, Xiaolei; Gao, Ling; Chen, Jicui; Liu, Yuantao; Yu, Chunxiao; Zhang, Nan; Zhang, Xu; Zhao, Jiajun

    2013-09-01

    Hydrogen sulfide (H₂S) is a newly identified endogenous gasotransmitter that has been implicated in the pathophysiology of several biologic systems. However, the role of H₂S in the pathogenesis of diabetic vascular injury remains unclear. The aims of this study were to determine the effect of H₂S on the high glucose (HG)-induced expression of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells and to explore the possible underlying mechanisms. Human umbilical vein endothelial cells were exposed either to a normal concentration of D-glucose (5.5 mmol/L) or to HG (16.7 mmol/L) in the absence or presence of NaHS for the indicated periods. The ICAM-1 protein and messenger RNA (mRNA) levels were analyzed by Western blotting and real-time reverse transcriptase-polymerase chain reaction, respectively. Exposure to HG for 48 or 72 hours significantly increased ICAM-1 expression at both the protein and mRNA levels, and these increases correlated with increases in both the production of intracellular reactive oxygen species and the activation of nuclear factor-κB. Pretreatment with NaHS inhibited HG-induced ICAM-1 expression at both the protein and mRNA levels and resulted in a reduction in the intracellular reactive oxygen species level and the suppression of nuclear factor-κB activity. NaHS also inhibited tumor necrosis factor-α-induced ICAM-1 protein expression, which was similar to the effect of antioxidant N-acetyl-L-cysteine. These findings indicate that H₂S might protect against HG-induced vascular damage by down-regulating ICAM-1 expression in endothelial cells.

  3. Moscatilin Inhibits Lung Cancer Cell Motility and Invasion via Suppression of Endogenous Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Akkarawut Kowitdamrong

    2013-01-01

    Full Text Available Lung cancer is the leading cause of death among cancer patients worldwide, and most of them have died from metastasis. Migration and invasion are prerequisite processes associated with high metastasis potential in cancers. Moscatilin, a bibenzyl derivative isolated from the Thai orchid Dendrobium pulchellum, has been shown to have anticancer effect against numerous cancer cell lines. However, little is known regarding the effect of moscatilin on cancer cell migration and invasion. The present study demonstrates that nontoxic concentrations of moscatilin were able to inhibit human nonsmall cell lung cancer H23 cell migration and invasion. The inhibitory effect of moscatilin was associated with an attenuation of endogenous reactive oxygen species (ROS, in which hydroxyl radical (OH∙ was identified as a dominant species in the suppression of filopodia formation. Western blot analysis also revealed that moscatilin downregulated activated focal adhesion kinase (phosphorylated FAK, Tyr 397 and activated ATP-dependent tyrosine kinase (phosphorylated Akt, Ser 473, whereas their parental counterparts were not detectable changed. In conclusion, our results indicate the novel molecular basis of moscalitin-inhibiting lung cancer cell motility and invasion and demonstrate a promising antimetastatic potential of such an agent for lung cancer therapy.

  4. Increased Hepatic Glucose Production in Fetal Sheep With Intrauterine Growth Restriction Is Not Suppressed by Insulin

    Science.gov (United States)

    Thorn, Stephanie R.; Brown, Laura D.; Rozance, Paul J.; Hay, William W.; Friedman, Jacob E.

    2013-01-01

    Intrauterine growth restriction (IUGR) increases the risk for metabolic disease and diabetes, although the developmental origins of this remain unclear. We measured glucose metabolism during basal and insulin clamp periods in a fetal sheep model of placental insufficiency and IUGR. Compared with control fetuses (CON), fetuses with IUGR had increased basal glucose production rates and hepatic PEPCK and glucose-6-phosphatase expression, which were not suppressed by insulin. In contrast, insulin significantly increased peripheral glucose utilization rates in CON and IUGR fetuses. Insulin robustly activated AKT, GSK3β, and forkhead box class O (FOXO)1 in CON and IUGR fetal livers. IUGR livers, however, had increased basal FOXO1 phosphorylation, nuclear FOXO1 expression, and Jun NH2-terminal kinase activation during hyperinsulinemia. Expression of peroxisome proliferator–activated receptor γ coactivator 1α and hepatocyte nuclear factor-4α were increased in IUGR livers during basal and insulin periods. Cortisol and norepinephrine concentrations were positively correlated with glucose production rates. Isolated IUGR hepatocytes maintained increased glucose production in culture. In summary, fetal sheep with IUGR have increased hepatic glucose production, which is not suppressed by insulin despite insulin sensitivity for peripheral glucose utilization. These data are consistent with a novel mechanism involving persistent transcriptional activation in the liver that seems to be unique in the fetus with IUGR. PMID:22933111

  5. Thermoregulatory effect in humans of suppressed endogenous melatonin by pre-sleep bright-light exposure in a cold environment.

    Science.gov (United States)

    Ishibashi, Keita; Arikura, Satoshi; Kozaki, Tomoaki; Higuchi, Shigekazu; Yasukouchi, Akira

    2010-06-01

    This study investigated the physiological function of suppressed melatonin through thermoregulation in a cold environment. Interactions between thermoregulation directly affected by exposure to a cold environment and indirectly affected by endogenous melatonin suppression by bright-light exposure were examined. Ten male subjects were exposed to two different illumination intensities (30 and 5000 lux) for 4.5 h, and two different ambient temperatures (15 and 27 degrees C) for 2 h before sleep under dark and thermoneutral conditions. Salivary melatonin level was suppressed by bright light (p cold ambient temperature (p cold exposure than thermoneutral conditions (cold: -0.54 +/- 0.07 degrees C/h; thermoneutral: -0.16 +/- 0.03 degrees C/h; p cold exposure masked the circadian rhythm with a precipitous decrease in T(re). A significant correlation between the T(re) nadir and melatonin level (r = -0.774, p cold exposure. These results suggest that suppressed endogenous melatonin inhibits the downregulation of the body temperature set-point during sleep.

  6. Activation of the cAMP-PKA pathway Antagonizes Metformin Suppression of Hepatic Glucose Production.

    Science.gov (United States)

    He, Ling; Chang, Evan; Peng, Jinghua; An, Hongying; McMillin, Sara M; Radovick, Sally; Stratakis, Constantine A; Wondisford, Fredric E

    2016-05-13

    Metformin is the most commonly prescribed oral anti-diabetic agent worldwide. Surprisingly, about 35% of diabetic patients either lack or have a delayed response to metformin treatment, and many patients become less responsive to metformin over time. It remains unknown how metformin resistance or insensitivity occurs. Recently, we found that therapeutic metformin concentrations suppressed glucose production in primary hepatocytes through AMPK; activation of the cAMP-PKA pathway negatively regulates AMPK activity by phosphorylating AMPKα subunit at Ser-485, which in turn reduces AMPK activity. In this study, we find that metformin failed to suppress glucose production in primary hepatocytes with constitutively activated PKA and did not improve hyperglycemia in mice with hyperglucagonemia. Expression of the AMPKα1(S485A) mutant, which is unable to be phosphorylated by PKA, increased both AMPKα activation and the suppression of glucose production in primary hepatocytes treated with metformin. Intriguingly, salicylate/aspirin prevents the phosphorylation of AMPKα at Ser-485, blocks cAMP-PKA negative regulation of AMPK, and improves metformin resistance. We propose that aspirin/salicylate may augment metformin's hepatic action to suppress glucose production. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Endogenous activation of adenosine A1 receptors promotes post-ischemic electrocortical burst suppression

    DEFF Research Database (Denmark)

    Ilie, A; Ciocan, D; Constantinescu, A O

    2009-01-01

    . Several lines of evidence suggest that BS reflects an impairment of neocortical connectivity. Here we tested in vivo whether synaptic depression by adenosine A1 receptor (A1R) activation contributes to BS patterns following GCI. Male Wistar rats were subjected to 1, 5 or 10 min of GCI using a "four......-min GCI the effect of DPCPX was only apparent on the initial fast decay of the BS ratio. These data suggest that endogenous adenosine release promotes BS patterns during reperfusion following transient cerebral ischemia. Furthermore, the endogenous A1R activation may be the primary underlying cause...

  8. Arctigenin suppresses unfolded protein response and sensitizes glucose deprivation-mediated cytotoxicity of cancer cells.

    Science.gov (United States)

    Sun, Shengrong; Wang, Xiong; Wang, Changhua; Nawaz, Ahmed; Wei, Wen; Li, Juanjuan; Wang, Lijun; Yu, De-Hua

    2011-01-01

    The involvement of unfolded protein response (UPR) activation in tumor survival and resistance to chemotherapies suggests a new anticancer strategy targeting UPR pathway. Arctigenin, a natural product, has been recently identified for its antitumor activity with selective toxicity against cancer cells under glucose starvation with unknown mechanism. Here we found that arctigenin specifically blocks the transcriptional induction of two potential anticancer targets, namely glucose-regulated protein-78 (GRP78) and its analog GRP94, under glucose deprivation, but not by tunicamycin. The activation of other UPR pathways, e.g., XBP-1 and ATF4, by glucose deprivation was also suppressed by arctigenin. A further transgene experiment showed that ectopic expression of GRP78 at least partially rescued arctigenin/glucose starvation-mediated cell growth inhibition, suggesting the causal role of UPR suppression in arctigenin-mediated cytotoxicity under glucose starvation. These observations bring a new insight into the mechanism of action of arctigenin and may lead to the design of new anticancer therapeutics. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Promotion or suppression of glucose isomerization in subcritical aqueous straight- and branched-chain alcohols.

    Science.gov (United States)

    Gao, Da-Ming; Kobayashi, Takashi; Adachi, Shuji

    2015-01-01

    The influence of water-miscible alcohols (methanol, 1-propanol, 2-propanol, and t-butyl alcohol) on the isomerization of glucose to fructose and mannose was investigated under subcritical aqueous conditions (180-200 °C). Primary and secondary alcohols promoted the conversion and isomerization of glucose to afford fructose and mannose with high and low selectivity, respectively. On the other hand, the decomposition (side-reaction) of glucose was suppressed in the presence of the primary and secondary alcohols compared with that in subcritical water. The yield of fructose increased with increasing concentration of the primary and secondary alcohols, and the species of the primary and secondary alcohols tested had little effect on the isomerization behavior of glucose. In contrast, the isomerization of glucose was suppressed in subcritical aqueous t-butyl alcohol. Both the conversion of glucose and the yield of fructose decreased with increasing concentration of t-butyl alcohol. In addition, mannose was not detected in reactions using subcritical aqueous t-butyl alcohol.

  10. Hepatic NPC1L1 overexpression ameliorates glucose metabolism in diabetic mice via suppression of gluconeogenesis.

    Science.gov (United States)

    Kurano, Makoto; Hara, Masumi; Satoh, Hiroaki; Tsukamoto, Kazuhisa

    2015-05-01

    Inhibition of intestinal NPC1L1 by ezetimibe has been demonstrated to improve glucose metabolism in rodent models; however, the role of hepatic NPC1L1 in glucose metabolism has not been elucidated. In this study, we analyzed the effects of hepatic NPC1L1 on glucose metabolism. We overexpressed NPC1L1 in the livers of lean wild type mice, diet-induced obesity mice and db/db mice with adenoviral gene transfer. We found that in all three mouse models, hepatic NPC1L1 overexpression lowered fasting blood glucose levels as well as blood glucose levels on ad libitum; in db/db mice, hepatic NPC1L1 overexpression improved blood glucose levels to almost the same as those found in lean wild type mice. A pyruvate tolerance test revealed that gluconeogenesis was suppressed by hepatic NPC1L1 overexpression. Further analyses revealed that hepatic NPC1L1 overexpression decreased the expression of FoxO1, resulting in the reduced expression of G6Pase and PEPCK, key enzymes in gluconeogenesis. These results indicate that hepatic NPC1L1 might have distinct properties of suppressing gluconeogenesis via inhibition of FoxO1 pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1α

    Directory of Open Access Journals (Sweden)

    Cheng Sun

    2014-12-01

    Full Text Available PGC-1α plays a central role in hepatic gluconeogenesis and has been implicated in the onset of type 2 diabetes. Acetylation is an important posttranslational modification for regulating the transcriptional activity of PGC-1α. Here, we show that PCAF is a pivotal acetyltransferase for acetylating PGC-1α in both fasted and diabetic states. PCAF acetylates two lysine residues K328 and K450 in PGC-1α, which subsequently triggers its proteasomal degradation and suppresses its transcriptional activity. Adenoviral-mediated expression of PCAF in the obese mouse liver greatly represses gluconeogenic enzyme activation and glucose production and improves glucose homeostasis and insulin sensitivity. Moreover, liver-specific knockdown of PCAF stimulates PGC-1α activity, resulting in an increase in blood glucose and hepatic glucose output. Our results suggest that PCAF might be a potential pharmacological target for developing agents against metabolic disorders associated with hyperglycemia, such as obesity and diabetes.

  12. Insoluble Fiber in Young Barley Leaf Suppresses the Increment of Postprandial Blood Glucose Level by Increasing the Digesta Viscosity

    Directory of Open Access Journals (Sweden)

    Akira Takano

    2013-01-01

    Full Text Available Barley (Hordeum vulgare L. is a well-known cereal plant. Young barley leaf is consumed as a popular green-colored drink, which is named “Aojiru” in Japan. We examined the effects of barley leaf powder (BLP and insoluble fibers derived from BLP on postprandial blood glucose in rats and healthy Japanese volunteers. BLP and insoluble fibers derived from BLP suppressed the increment of postprandial blood glucose levels in rats (, and increased the viscosity of their digesta. The insoluble fibers present in BLP might play a role in controlling blood glucose level by increasing digesta viscosity. In human, BLP suppressed the increment of postprandial blood glucose level only in those which exhibited higher blood glucose levels after meals (. BLP might suppress the increment of postprandial blood glucose level by increasing digesta viscosity in both of rats and humans who require blood glucose monitoring.

  13. Comparative analysis of RNA silencing suppression activities between viral suppressors and an endogenous plant RNA-dependent RNA polymerase.

    Science.gov (United States)

    Yoon, Ju-Yeon; Han, Kyoung-Sik; Park, Han-Yong; Choi, Seung-Kook

    2012-06-01

    RNA silencing is an evolutionarily conserved system that functions as an antiviral mechanism in eukaryotes, including higher plants. To counteract this, several plant viruses express silencing suppressors that inhibit RNA silencing in host plants. Here, we show that both 2b protein from peanut stunt virus (PSV) and a hairpin construct (designated hp-RDR6) that silences endogenous RNA-dependent RNA polymerase 6 (RDR6) strongly suppress RNA silencing. The Agrobacterium infiltration system was used to demonstrate that both PSV 2b and hp-RDR6 suppressed local RNA silencing as strongly as helper component (HC-Pro) from potato virus Y (PVY) and P19 from tomato bush stunt virus (TBSV). The 2b protein from PSV eliminated the small-interfering RNAs (siRNAs) associated with RNA silencing and prevented systemic silencing, similar to 2b protein from cucumber mosaic virus (CMV). On the other hand, hp-RDR6 suppressed RNA silencing by inhibiting the generation of secondary siRNAs. The small coat protein (SCP) of squash mosaic virus (SqMV) also displayed weak suppression activity of RNA silencing. Agrobacterium-mediated gene transfer was used to investigate whether viral silencing suppressors or hp-RDR6 enhanced accumulations of green fluorescence protein (GFP) and β-glucuronidase (GUS) as markers of expression in leaf tissues of Nicotina benthamiana. Expression of both GFP and GUS was significantly enhanced in the presence of PSV 2b or CMV 2b, compared to no suppression or the weak SqMV SCP suppressor. Co-expression with hp-RDR6 also significantly increased the expression of GFP and GUS to levels similar to those induced by PVY HC-Pro and TBSV P19.

  14. Endogenous activation of adenosine A(1) receptors accelerates ischemic suppression of spontaneous electrocortical activity

    DEFF Research Database (Denmark)

    Ilie, Andrei; Ciocan, Dragos; Zagrean, Ana-Maria

    2006-01-01

    Cerebral ischemia induces a rapid suppression of spontaneous brain rhythms prior to major alterations in ionic homeostasis. It was found in vitro during ischemia that the rapidly formed adenosine, resulting from the intracellular breakdown of ATP, may inhibit synaptic transmission via the A(1...

  15. Seizure-induced neuronal death is suppressed in the absence of the endogenous lectin Galectin-1.

    Science.gov (United States)

    Bischoff, Vincent; Deogracias, Rubén; Poirier, Françoise; Barde, Yves-Alain

    2012-10-31

    Pilocarpine injection induces epileptic seizures in rodents, an experimental paradigm extensively used to model temporal lobe epilepsy in humans. It includes conspicuous neuronal death in the forebrain and previous work has demonstrated an involvement of the neurotrophin receptor p75(NTR) in this process. Following the identification of Galectin-1 (Gal-1) as a downstream effector of p75(NTR), we examine here the role of this endogenous lectin in pilocarpine-induced cell death in adult mice. We found that most somatostatin-positive neurons also express Gal-1 and that in mice lacking the corresponding gene Lgals1, pilocarpine-induced neuronal death was essentially abolished in the forebrain. We also found that the related lectin Galectin-3 (Gal-3) was strongly upregulated by pilocarpine in microglial cells. This upregulation was absent in Lgals1 mutants and our results with Lgals3-null animals show that Gal-3 is not required for neuronal death in the hippocampus. These findings provide new insights into the roles and regulation of endogenous lectins in the adult CNS and a surprisingly selective proapoptotic role of Gal-1 for a subpopulation of GABAergic interneurons.

  16. Chronic Sucralose or L-Glucose Ingestion Does Not Suppress Food Intake.

    Science.gov (United States)

    Wang, Qiao-Ping; Simpson, Stephen J; Herzog, Herbert; Neely, G Gregory

    2017-08-01

    Despite widespread consumption of non-nutritive sweeteners (NNSs), the impact of manipulating the perceived sweetness of food is unclear. Previously we reported that chronic consumption of the NNSs sucralose or L-glucose led to increased calories consumed post-exposure; however, a recent study suggested this effect occurs because NNSs acutely suppress food intake, leading to a caloric debt. Here we show that acute ingestion of sucralose in the context of a low-carbohydrate diet causes a pronounced increase in calories consumed. Moreover, neither sucralose nor L-glucose had a lasting effect on food intake during chronic exposure; however, both NNSs enhance food intake post-exposure. Together these data confirm that sucralose and L-glucose promote food intake under a variety of experimental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Cloning and endogenous expression of a Eucalyptus grandis UDP-glucose dehydrogenase cDNA

    Directory of Open Access Journals (Sweden)

    Mônica T. Veneziano Labate

    2010-01-01

    Full Text Available UDP-glucose dehydrogenase (UGDH catalyzes the oxidation of UDP-glucose (UDP-Glc to UDP-glucuronate (UDP-GlcA, a key sugar nucleotide involved in the biosynthesis of plant cell wall polysaccharides. A full-length cDNA fragment coding for UGDH was cloned from the cambial region of 6-month-old E. grandis saplings by RT-PCR. The 1443-bp-ORF encodes a protein of 480 amino acids with a predicted molecular weight of 53 kDa. The recombinant protein expressed in Escherichia coli catalyzed the conversion of UDP-Glc to UDP-GlcA, confirming that the cloned cDNA encodes UGDH. The deduced amino acid sequence of the cDNA showed a high degree of identity with UGDH from several plant species. The Southern blot assay indicated that more than one copy of UGDH is present in Eucalyptus. These results were also confirmed by the proteomic analysis of the cambial region of 3- and 22-year-old E. grandis trees by 2-DE and LC-MS/MS, showing that at least two isoforms are present. The cloned gene is mainly expressed in roots, stem and bark of 6-month-old saplings, with a lower expression in leaves. High expression levels were also observed in the cambial region of 3- and 22-year-old trees. The results described in this paper provide a further view of the hemicellulose biosynthesis during wood formation in E. grandis.

  18. Fibroblast growth factor 21 is not required for glucose homeostasis, ketosis and tumour suppression associated to ketogenic diets in mice

    Science.gov (United States)

    Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M.; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J.F.; Müller, Timo D.; Pfluger, Paul T.; Seeley, Randy J.

    2016-01-01

    AIMS/HYPOTHESIS Ketogenic diets (KDs) increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. Metabolic benefits of KDs are regularly ascribed towards enhanced hepatic secretion of fibroblast growth factor (FGF) 21, and its systemic effects on fatty acid oxidation, energy expenditure and body weight. Ambiguous data from Fgf21 knockout strains and low FGF21 concentrations reported for humans in ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating therapeutic benefits of KDs on metabolism and cancer. METHODS We established a dietary model of increased vs. decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted or enriched with protein, respectively. We furthermore used wild type and Fgf21 knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumor growth after transplantation of Lewis-Lung-Carcinoma cells. RESULTS Hepatic and circulating but not adipose tissue FGF21 levels were profoundly increased by protein starvation and independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycemia upon protein and carbohydrate starvation and is dispensable for the effects of KDs on energy expenditure. Furthermore, the tumor-suppressing effects of KDs were independent from FGF21, and rather driven by concomitant protein and carbohydrate starvation. CONCLUSION/INTERPRETATION Our data indicate that multiple systemic effects of KDs exposure in mice that were previously ascribed towards increased FGF21 secretion are rather a consequence of protein malnutrition. PMID:26099854

  19. FGF21 is not required for glucose homeostasis, ketosis or tumour suppression associated with ketogenic diets in mice.

    Science.gov (United States)

    Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J F; Müller, Timo D; Pfluger, Paul T; Seeley, Randy J

    2015-10-01

    Ketogenic diets (KDs) have increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. The metabolic benefits of KDs are regularly ascribed to enhanced hepatic secretion of fibroblast growth factor 21 (FGF21) and its systemic effects on fatty-acid oxidation, energy expenditure (EE) and body weight. Ambiguous data from Fgf21-knockout animal strains and low FGF21 concentrations reported in humans with ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating the therapeutic benefits of KDs on metabolism and cancer. We established a dietary model of increased vs decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted of protein or enriched with protein. We furthermore used wild-type and Fgf21-knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumour growth after transplantation of Lewis lung carcinoma cells. Hepatic and circulating, but not adipose tissue, FGF21 levels were profoundly increased by protein starvation, independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycaemia upon protein and carbohydrate starvation and is therefore not needed for the effects of KDs on EE. Furthermore, the tumour-suppressing effects of KDs were independent of FGF21 and, rather, driven by concomitant protein and carbohydrate starvation. Our data indicate that the multiple systemic effects of KD exposure in mice, previously ascribed to increased FGF21 secretion, are rather a consequence of protein malnutrition.

  20. Glycated albumin suppresses glucose-induced insulin secretion by impairing glucose metabolism in rat pancreatic β-cells

    Directory of Open Access Journals (Sweden)

    Muto Takashi

    2011-04-01

    Full Text Available Abstract Background Glycated albumin (GA is an Amadori product used as a marker of hyperglycemia. In this study, we investigated the effect of GA on insulin secretion from pancreatic β cells. Methods Islets were collected from male Wistar rats by collagenase digestion. Insulin secretion in the presence of non-glycated human albumin (HA and GA was measured under three different glucose concentrations, 3 mM (G3, 7 mM (G7, and 15 mM (G15, with various stimulators. Insulin secretion was measured with antagonists of inducible nitric oxide synthetase (iNOS, and the expression of iNOS-mRNA was investigated by real-time PCR. Results Insulin secretion in the presence of HA and GA was 20.9 ± 3.9 and 21.6 ± 5.5 μU/3 islets/h for G3 (P = 0.920, and 154 ± 9.3 and 126.1 ± 7.3 μU/3 islets/h (P = 0.046, for G15, respectively. High extracellular potassium and 10 mM tolbutamide abrogated the inhibition of insulin secretion by GA. Glyceraldehyde, dihydroxyacetone, methylpyruvate, GLP-1, and forskolin, an activator of adenylate cyclase, did not abrogate the inhibition. Real-time PCR showed that GA did not induce iNOS-mRNA expression. Furthermore, an inhibitor of nitric oxide synthetase, aminoguanidine, and NG-nitro-L-arginine methyl ester did not abrogate the inhibition of insulin secretion. Conclusion GA suppresses glucose-induced insulin secretion from rat pancreatic β-cells through impairment of intracellular glucose metabolism.

  1. Aronia juice suppresses the elevation of postprandial blood glucose levels in adult healthy Japanese

    Directory of Open Access Journals (Sweden)

    Takuya Yamane

    2017-04-01

    Full Text Available Aronia has various functions toward human health, including the beneficial effect on hypertension, hyperglycemia and hyperlipidemia. Recently, we identified cyanidin-3,5-O-diglucoside as DPP IV inhibitor from Aronia juice. We also found its beneficial effect on hyperglycemia in KKAy mice fed aronia juice. In this study, to examine the effect of aronia juice on postprandial blood glucose levels in Japanese, we performed an oral meal tolerance test (OMTT. We found that postprandial blood glucose levels were reduced in aronia juice-administered adult healthy Japanese. We also found that there was no difference of reduction levels of postprandial blood glucose between male and female. We also found that activities of dipeptidyl peptidase IV (DPP IV, α-glucosidase and angiotensin-converting enzyme (ACE were reduced by aronia juice. These results suggest that aronia juice suppresses the elevation of postprandial blood glucose levels through inhibition of these enzyme activities and may be useful for prevention of metabolic diseases in adult healthy Japanese.

  2. Glucagon suppression during OGTT worsens while suppression during IVGTT sustains alongside development of glucose intolerance in patients with chronic pancreatitis

    DEFF Research Database (Denmark)

    Knop, F K; Vilsbøll, T; Larsen, Steen

    2010-01-01

    To examine plasma glucagon responses to oral and intravenous (iv) glucose in patients with chronic pancreatitis (CP) and either normal glucose tolerance (NGT), secondary impaired glucose tolerance (IGT) or secondary diabetes mellitus (DM)....

  3. Human monoclonal antibodies against glucagon receptor improve glucose homeostasis by suppression of hepatic glucose output in diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Wook-Dong Kim

    Full Text Available AIM: Glucagon is an essential regulator of hepatic glucose production (HGP, which provides an alternative therapeutic target for managing type 2 diabetes with glucagon antagonists. We studied the effect of a novel human monoclonal antibody against glucagon receptor (GCGR, NPB112, on glucose homeostasis in diet-induced obese (DIO mice. METHODS: The glucose-lowering efficacy and safety of NPB112 were investigated in DIO mice with human GCGR for 11 weeks, and a hyperinsulinemic-euglycemic clamp study was conducted to measure HGP. RESULTS: Single intraperitoneal injection of NPB112 with 5 mg/kg effectively decreased blood glucose levels in DIO mice for 5 days. A significant reduction in blood glucose was observed in DIO mice treated with NPB112 at a dose ≥5 mg/kg for 6 weeks, and its glucose-lowering effect was dose-dependent. Long-term administration of NPB112 also caused a mild 29% elevation in glucagon level, which was returned to the normal range after discontinuation of treatment. The clamp study showed that DIO mice injected with NPB112 at 5 mg/kg were more insulin sensitive than control mice, indicating amelioration of insulin resistance by treatment with NPB112. DIO mice treated with NPB112 showed a significant improvement in the ability of insulin to suppress HGP, showing a 33% suppression (from 8.3 mg/kg/min to 5.6 mg/kg/min compared to the 2% suppression (from 9.8 mg/kg/min to 9.6 mg/kg/min in control mice. In addition, no hypoglycemia or adverse effect was observed during the treatment. CONCLUSIONS: A novel human monoclonal GCGR antibody, NPB112, effectively lowered the glucose level in diabetic animal models with mild and reversible hyperglucagonemia. Suppression of excess HGP with NPB112 may be a promising therapeutic modality for the treatment of type 2 diabetes.

  4. Immunoneutralization of endogenous glucagon reduces hepatic glucose output and improves long-term glycemic control in diabetic ob/ob mice

    DEFF Research Database (Denmark)

    Sørensen, Heidi; Brand, Christian L; Neschen, Susanne

    2006-01-01

    In type 2 diabetes, glucagon levels are elevated in relation to the prevailing insulin and glucose levels. The relative hyperglucagonemia is linked to increased hepatic glucose output (HGO) and hyperglycemia. Antagonizing the effects of glucagon is therefore considered an attractive target...... for treatment of type 2 diabetes. In the current study, effects of eliminating glucagon signaling with a glucagon monoclonal antibody (mAb) were investigated in the diabetic ob/ob mouse. Acute effects of inhibiting glucagon action were studied by an oral glucose tolerance test (OGTT) and by measurement of HGO...... synthesis. Glucagon mAb treatment for 5 days lowered plasma glucose and triglyceride levels, whereas 14 days of glucagon mAb treatment reduced A1C. In conclusion, acute and subchronic neutralization of endogenous glucagon improves glycemic control, thus supporting the contention that glucagon antagonism may...

  5. Production of human growth hormone in transgenic rice seeds: co-introduction of RNA interference cassette for suppressing the gene expression of endogenous storage proteins.

    Science.gov (United States)

    Shigemitsu, Takanari; Ozaki, Shinji; Saito, Yuhi; Kuroda, Masaharu; Morita, Shigeto; Satoh, Shigeru; Masumura, Takehiro

    2012-03-01

    Rice seeds are potentially useful hosts for the production of pharmaceutical proteins. However, low yields of recombinant proteins have been observed in many cases because recombinant proteins compete with endogenous storage proteins. Therefore, we attempt to suppress endogenous seed storage proteins by RNA interference (RNAi) to develop rice seeds as a more efficient protein expression system. In this study, human growth hormone (hGH) was expressed in transgenic rice seeds using an endosperm-specific promoter from a 10 kDa rice prolamin gene. In addition, an RNAi cassette for reduction of endogenous storage protein expressions was inserted into the hGH expression construct. Using this system, the expression levels of 13 kDa prolamin and glutelin were effectively suppressed and hGH polypeptides accumulated to 470 μg/g dry weight at the maximum level in transgenic rice seeds. These results suggest that the suppression of endogenous protein gene expression by RNAi could be of great utility for increasing transgene products.

  6. 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...

  7. Mediation of Endogenous β-Endorphin in the Plasma Glucose-Lowering Action of Herbal Products Observed in Type 1-Like Diabetic Rats

    Directory of Open Access Journals (Sweden)

    I. M. Liu

    2011-01-01

    Full Text Available Recently, there have been advances in the development of new substances effective in managing diabetic disorders. Opioid receptors couple multiple systems to result in various biological effects, although opioids are best known for analgesia. In the present review, we used our recent data to describe the advance in plasma glucose-lowering action of herbal products, especially the mediation of β-endorphin in glucose homeostasis of insulin-deficient diabetes. In type 1-like streptozotocin-induced diabetic rats, we identified many products purified from herbs that show a dose-dependent plasma glucose-lowering action. Increase in β-endorphin secretion from the adrenal gland may activate peripheral opioid μ-receptors (MOR to enhance the expression of muscle glucose transporters and/or to reduce hepatic gluconeogenesis at the gene level, thereby leading to improved glucose utilization in peripheral tissues for amelioration of severe hyperglycemia. It has also been observed that stimulation of α1-adrenoceptors (α1-ARs in the adrenal gland by some herbal products is responsible for the increase in β-endorphin secretion via a phospholipase C-protein kinase dependent pathway. However, an increase in β-endorphin secretion from the adrenal gland by herbal products can function via another receptor. New insights into the mediation of endogenous β-endorphin activation of peripheral MOR by herbal products for regulation of glucose homeostasis without the presence of insulin have been established. Therefore, an increase in β-endorphin secretion and/or direct stimulation of peripheral MOR via an insulin-independent action might serve as the potential target for development of a therapeutic agent or promising adjuvant in intensive plasma glucose control.

  8. Endogenous glucose production increases in response to metformin treatment in the glycogen-depleted state in humans

    DEFF Research Database (Denmark)

    Christensen, Mette Marie H; Højlund, Kurt; Hother-Nielsen, Ole

    2015-01-01

    AIMS/HYPOTHESIS: Metformin is believed to reduce glucose levels primarily by inhibiting hepatic glucose production. Recent data indicate that metformin antagonises glucagon-dependent glucose output, suggesting that compensatory mechanisms protect against hypoglycaemia. Here, we examined the effect...... of metformin on glucose metabolism in humans after a glycogen-depleting fast and the role of reduced-function alleles in OCT1 (also known as SLC22A1). METHODS: In a randomised, crossover trial, healthy individuals with or without reduced-function alleles in OCT1 were fasted for 42 h twice, either...... with or without prior treatment with 1 g metformin twice daily. Participants were recruited from the Pharmacogenomics Biobank of the University of Southern Denmark. Treatment allocation was generated by the Good Clinical Practice Unit, Odense University Hospital, Denmark. Variables of whole-body glucose...

  9. Pycnogenol modulates apoptosis by suppressing oxidative stress and inflammation in high glucose-treated renal tubular cells.

    Science.gov (United States)

    Kim, You Jung; Kim, Young Ae; Yokozawa, Takako

    2011-09-01

    Compelling evidence indicates that polyphenolic antioxidants protect against diabetic nephropathy. Pycnogenol is made up of flavonoids, mainly procyanidins and phenolic compounds, and is a known powerful antioxidant. Hyperglycemia is characteristic of diabetic nephropathy and induces renal tubular cell apoptosis. Thus, in this study, we used high glucose-treated renal tubular cells to investigate the protective action of pycnogenol against high glucose-induced apoptosis and diabetic nephropathy. We also sought to further delineate the underlying mechanisms elicited by oxidative stress and inflammation and suppressed by pycnogenol. Results show that pycnogenol significantly suppressed the high glucose-induced morphological changes and the reduction in cell viability associated with cytotoxicity. Bcl2/Bax protein levels indicated pycnogenol's anti-apoptotic effect against high glucose-induced apoptotic cell death. In addition, several key markers of oxidative stress and inflammation were measured for pycnogenol's beneficial effects. Results indicate pycnogenol's anti-oxidative and anti-inflammatory efficacy in suppressing lipid peroxidation, total reactive species (RS), superoxide ((·)O(2)), nitric oxide (NO(·)), peroxynitrite (ONOO(-)), pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) nuclear translocation. Based on these results, we conclude that pycnogenol's anti-oxidative and anti-inflammatory properties underlie its anti-apoptotic effects, suggesting further investigation of pycnogenol as a promising treatment against diabetic nephropathy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Insoluble Fiber in Young Barley Leaf Suppresses the Increment of Postprandial Blood Glucose Level by Increasing the Digesta Viscosity

    OpenAIRE

    Takano, Akira; Kamiya, Tomoyasu; Tomozawa, Hiroshi; Ueno, Shiori; Tsubata, Masahito; Ikeguchi, Motoya; Takagaki, Kinya; Okushima, Ayaka; Miyata, Yu; Tamaru, Shizuka; Tanaka, Kazunari; Takahashi, Toru

    2013-01-01

    Barley (Hordeum vulgare L.) is a well-known cereal plant. Young barley leaf is consumed as a popular green-colored drink, which is named ?Aojiru? in Japan. We examined the effects of barley leaf powder (BLP) and insoluble fibers derived from BLP on postprandial blood glucose in rats and healthy Japanese volunteers. BLP and insoluble fibers derived from BLP suppressed the increment of postprandial blood glucose levels in rats (P < 0.01), and increased the viscosity of their digesta. The insolu...

  11. Enhanced glucose cycling and suppressed de novo synthesis of glucose-6-phosphate result in a net unchanged hepatic glucose output in ob/ob mice

    NARCIS (Netherlands)

    Bandsma, RHJ; Grefhorst, A; van Dijk, TH; van der Sluijs, FH; Hammer, A; Reijngoud, DJ; Kuipers, F

    2004-01-01

    Aims/hypothesis. Leptin-deficient ob/ob mice are hyperinsulinaemic and hyperglycaemic; however, the cause of hyperglycaemia remains largely unknown. Methods. Glucose metabolism in vivo in 9-h fasted ob/ob mice and lean littermates was studied by infusing [U-C-13]-glucose, [2-C-13]-glycerol,

  12. 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

  13. Pretranslational Suppression of an Insulin-Responsive Glucose Transporter in Rats with Diabetes Mellitus

    Science.gov (United States)

    Garvey, W. Timothy; Huecksteadt, Thomas P.; Birnbaum, Morris J.

    1989-07-01

    A prominent feature of diabetes mellitus is the inability of insulin to appropriately increase the transport of glucose into target tissues. The contributions of different glucose transport proteins to insulin resistance in rats with streptozotocin-induced diabetes was evaluated. A glucose transporter messenger RNA and its cognate protein that are exclusively expressed in muscle and adipose tissue were specifically depleted in diabetic animals, and these effects were reversed after insulin therapy; a different glucose transporter and its messenger RNA that exhibit a less restricted tissue distribution were not specifically modulated in this way. Depletion of the muscle- and adipose-specific glucose transporter species correlates with and may account for the major portion of cellular insulin resistance in diabetes in these animals.

  14. Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study.

    Science.gov (United States)

    Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

    2016-11-01

    Kale (Brassica oleracea var. acephala), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21-64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140-187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30-120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (Cmax; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); Pkale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe.

  15. Rosmarinic Acid suppressed high glucose-induced apoptosis in H9c2 cells by ameliorating the mitochondrial function and activating STAT3.

    Science.gov (United States)

    Diao, Jiayu; Wei, Jin; Yan, Rui; Liu, Xin; Li, Qing; Lin, Lin; Zhu, Yanhe; Li, Hong

    2016-09-02

    Mitochondrial injury characterized by intracellular reactive oxygen species (ROS) accumulation plays a critical role in hyperglycemia-induced myocardium dysfunction. Previous studies have demonstrated that Rosmarinic Acid (RA) treatment and activating Signal transducer and activator of transcription 3 (STAT3) signaling pathway have protective effects on mitochondrial dysfunction in cardiomyocyte, but there is little data regarding cardiomyocyte under condition of high-glucose. The present study was undertaken to determine the relationship between RA and STAT3 activation, as well as their effects on high glucose-induced mitochondrial injury and apoptosis in H9c2 cardiomyocyte. Our results revealed that RA pretreatment suppressed high glucose-induced apoptosis in H9c2 cells. Moreover, the effect of RA on apoptosis was related with improved mitochondrial function, which was demonstrated by that RA attenuated high glucose-induced ROS generation, inhibited mitochondrial permeability transition pore (MPTP) activation, suppressed cytochrome c release and caspase-3 activation. In addition, the phosphorylation of STAT3 in H9c2 cells was inhibited under condition of high-glucose, but RA improved STAT3 phosphorylation. Importantly, inhibition of STAT3 expression by using STAT3-siRNA partly suppressed the effect of RA on high glucose-induced apoptosis. Taken together, pretreatment with RA suppressed high glucose-induced apoptosis in cardiomyocyte by ameliorating mitochondrial function and activating STAT3. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Buddleja officinalis suppresses high glucose-induced vascular smooth muscle cell proliferation: role of mitogen-activated protein kinases, nuclear factor-kappaB and matrix metalloproteinases.

    Science.gov (United States)

    Lee, Yun Jung; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

    2010-02-01

    Diabetes mellitus is a well-established risk factor for vascular diseases caused by atherosclerosis. In the development of diabetic atherogenesis, vascular smooth muscle cell proliferation is recognized as a key event. Thus, we aimed to investigate whether an ethanol extract of Buddleja officinalis (EBO) suppresses high glucose-induced proliferation in primary cultured human aortic smooth muscle cells (HASMC). [(3)H]-thymidine incorporation revealed that incubation of HASMC with a high concentration of glucose (25 mmol/L) increased cell proliferation. The expression levels of cell cycle protein were also increased by treatment with high glucose concentration. Pretreatment of HASMC with EBO significantly attenuated the increase of high glucose-induced cell proliferation as well as p38 mitogen-activated protein kinases (MAPK) and JNK phosphorylation. EBO suppressed high glucose-induced matrix metalloproteinase (MMP)-9 activity in a dose-dependent manner. In addition, EBO suppressed nuclear factor-kappaB (NF-kappaB) nuclear translocation and transcriptional activity in high glucose conditions. Taken together, the present data suggest that EBO could suppress high glucose-induced atherosclerotic processes through inhibition of p38, JNK, NF-kappaB and MMP signal pathways in HASMC.

  17. Cholera Toxin Production Induced upon Anaerobic Respiration is Suppressed by Glucose Fermentation in Vibrio cholerae.

    Science.gov (United States)

    Oh, Young Taek; Lee, Kang-Mu; Bari, Wasimul; Kim, Hwa Young; Kim, Hye Jin; Yoon, Sang Sun

    2016-03-01

    The causative agent of pandemic cholera, Vibrio cholerae, infects the anaerobic environment of the human intestine. Production of cholera toxin (CT), a major virulence factor of V. cholerae, is highly induced during anaerobic respiration with trimethylamine N-oxide (TMAO) as an alternative electron acceptor. However, the molecular mechanism of TMAO-stimulated CT production is not fully understood. Herein, we reveal that CT production during anaerobic TMAO respiration is affected by glucose fermentation. When the seventh pandemic V. cholerae O1 strain N16961 was grown with TMAO and additional glucose, CT production was markedly reduced. Furthermore, an N16961 Δcrp mutant, devoid of cyclic AMP receptor protein (CRP), was defective in CT production during growth by anaerobic TMAO respiration, further suggesting a role of glucose metabolism in regulating TMAO-mediated CT production. TMAO reductase activity was noticeably decreased when grown together with glucose or by mutation of the crp gene. A CRP binding region was identified in the promoter region of the torD gene, which encodes a structural subunit of the TMAO reductase. Gel shift assays further confirmed the binding of purified CRP to the torD promoter sequence. Together, our results suggest that the bacterial ability to respire using TMAO is controlled by CRP, whose activity is dependent on glucose availability. Our results reveal a novel mechanism for the regulation of major virulence factor production by V. cholerae under anaerobic growth conditions.

  18. Glucose phosphorylated on carbon 6 suppresses lipopolysaccharide binding to lipopolysaccharide-binding protein and inhibits its bioactivities.

    Science.gov (United States)

    Fujita, Yuu; Yagi, Kiyohito

    2017-04-01

    Lipid A comprises the active region of lipopolysaccharide (LPS), and its phosphate group is required for LPS activities. Additionally, it is essential for effects of inhibitors of LPS-induced coagulation activity in limulus amebocyte lysate (LAL) tests. Lipid A has phosphorylated glucosamine residues, which are structurally similar to glucose 1-phosphate (G1P) and glucose 6-phosphate (G6P). This study focused on the antagonistic effects of glucose phosphates on the action of protein or non-protein inhibitors against LAL coagulation, LPS-LPS-binding protein (LBP) interaction, and LPS bioactivities. These effects of glucose phosphates were evaluated and compared with those of other charged sugars such as fructose 6-phosphate and glucuronic acid by LAL tests, ELISA-based LPS-LBP binding assay, cell-based assay, and using a mouse endotoxin shock model. G6P neutralized the interfering actions of drug substances and plasma proteins on LPS coagulation activity in LAL tests. Compared to other sugars, G6P more strongly inhibited LPS binding to LBP, leading to significant inhibition of LPS-induced cellular responses in human umbilical vein endothelial cells and in the THP-1 human leukemic line. Consistent herewith, G6P inhibited inflammatory cytokine release and decreased serum alanine aminotransferase and hepatic caspase-3/7 activities and mortality in LPS-stimulated d-galactosamine-sensitized mice. These data indicated that the structural properties of G6P, such as its glucose moiety and phosphorylation on carbon 6, are important for suppressing the interaction of proteins with LPS. Therefore, G6P is useful to improve sensitivity and accuracy of plasma and drug LPS assays, and such structural property is more suitable to antagonize LPS activities. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Jinggangmycin-suppressed reproduction in the small brown planthopper (SBPH), Laodelphax striatellus (Fallen), is mediated by glucose dehydrogenase (GDH).

    Science.gov (United States)

    Ding, Jun; Wu, You; You, Lin-Lin; Xu, Bin; Ge, Lin-Quan; Yang, Guo-Qing; Wu, Jin-Cai

    2017-06-01

    The small brown planthopper (SBPH), Laodelphax striatellus (Fallen), is a serious pest insect of rice, wheat, and maize in China. SBPH not only sucks plant sap but also transmits plant disease viruses, causing serious damage. These viruses include rice striped virus disease (RSV disease), black streaked dwarf, and maize rough disease virus. SBPH outbreaks are related to the overuse of pesticides in China. Some pesticides, such as triazophos, stimulate the reproduction of SBPH, but an antibiotic fungicide jinggangmycin (JGM) suppresses its reproduction. However, mechanisms of decreased reproduction of SBPH induced by JGM remain unclear. The present findings show that JGM suppressed reproduction of SBPH (↓approximately 35.7%) and resulted in the down-regulated expression of glucose dehydrogenase (GDH). GDH-silenced control females (control+dsGDH) show that the number of eggs laid was reduced by 48.6% compared to control females. Biochemical tests show that the total lipid and fatty acid contents in JGM-treated and control+dsGDH females decreased significantly. Thus, we propose that the suppression of reproduction in SBPH induced by JGM is mediated by GDH via metabolic pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Tetrahydrobiopterin Has a Glucose-Lowering Effect by Suppressing Hepatic Gluconeogenesis in an Endothelial Nitric Oxide Synthase–Dependent Manner in Diabetic Mice

    Science.gov (United States)

    Abudukadier, Abulizi; Fujita, Yoshihito; Obara, Akio; Ohashi, Akiko; Fukushima, Toru; Sato, Yuichi; Ogura, Masahito; Nakamura, Yasuhiko; Fujimoto, Shimpei; Hosokawa, Masaya; Hasegawa, Hiroyuki; Inagaki, Nobuya

    2013-01-01

    Endothelial nitric oxide synthase (eNOS) dysfunction induces insulin resistance and glucose intolerance. Tetrahydrobiopterin (BH4) is an essential cofactor of eNOS that regulates eNOS activity. In the diabetic state, BH4 is oxidized to 7,8-dihydrobiopterin, which leads to eNOS dysfunction owing to eNOS uncoupling. The current study investigates the effects of BH4 on glucose metabolism and insulin sensitivity in diabetic mice. Single administration of BH4 lowered fasting blood glucose levels in wild-type mice with streptozotocin (STZ)-induced diabetes and alleviated eNOS dysfunction by increasing eNOS dimerization in the liver of these mice. Liver has a critical role in glucose-lowering effects of BH4 through suppression of hepatic gluconeogenesis. BH4 activated AMP kinase (AMPK), and the suppressing effect of BH4 on gluconeogenesis was AMPK-dependent. In addition, the glucose-lowering effect and activation of AMPK by BH4 did not appear in mice with STZ-induced diabetes lacking eNOS. Consecutive administration of BH4 in ob/ob mice ameliorated glucose intolerance and insulin resistance. Taken together, BH4 suppresses hepatic gluconeogenesis in an eNOS-dependent manner, and BH4 has a glucose-lowering effect as well as an insulin-sensitizing effect in diabetic mice. BH4 has potential in the treatment of type 2 diabetes. PMID:23649519

  1. Competitive Expression of Endogenous Wheat CENH3 May Lead to Suppression of Alien ZmCENH3 in Transgenic Wheat × Maize Hybrids.

    Science.gov (United States)

    Chen, Wei; Zhu, Qilin; Wang, Haiyan; Xiao, Jin; Xing, Liping; Chen, Peidu; Jin, Weiwei; Wang, Xiu-E

    2015-11-20

    Uniparental chromosome elimination in wheat × maize hybrid embryos is widely used in double haploid production of wheat. Several explanations have been proposed for this phenomenon, one of which is that the lack of cross-species CENH3 incorporation may act as a barrier to interspecies hybridization. However, it is unknown if this mechanism applies universally. To study the role of CENH3 in maize chromosome elimination of wheat × maize hybrid embryos, maize ZmCENH3 and wheat αTaCENH3-B driven by the constitutive CaMV35S promoter were transformed into wheat variety Yangmai 158. Five transgenic lines for ZmCENH3 and six transgenic lines for αTaCENH3-B were identified. RT-PCR analysis showed that the transgene could be transcribed at a low level in all ZmCENH3 transgenic lines, whereas transcription of endogenous wheat CENH3 was significantly up-regulated. Interestingly, the expression levels of both wheat CENH3 and ZmCENH3 in the ZmCENH3 transgenic wheat × maize hybrid embryos were higher than those in the non-transformed Yangmai 158 × maize hybrid embryos. This indicates that the alien ZmCENH3 in wheat may induce competitive expression of endogenous wheat CENH3, leading to suppression of ZmCENH3 over-expression. Eliminations of maize chromosomes in hybrid embryos of ZmCENH3 transgenic wheat × maize and Yangmai 158 × maize were compared by observations on micronuclei presence, by marker analysis using maize SSRs (simple sequence repeats), and by FISH (fluorescence in situ hybridization) using 45S rDNA as a probe. The results indicate that maize chromosome elimination events in the two crosses are not significantly different. Fusion protein ZmCENH3-YFP could not be detected in ZmCENH3 transgenic wheat by either Western blotting or immnunostaining, whereas accumulation and loading of the αTaCENH3-B-GFP fusion protein was normal in αTaCENH3-B transgenic lines. As ZmCENH3-YFP did not accumulate after AM114 treatment, we speculate that low levels of Zm

  2. Metastasized lung cancer suppression by Morinda citrifolia (Noni) leaf compared to Erlotinib via anti-inflammatory, endogenous antioxidant responses and apoptotic gene activation.

    Science.gov (United States)

    Lim, Swee-Ling; Mustapha, Noordin M; Goh, Yong-Meng; Bakar, Nurul Ain Abu; Mohamed, Suhaila

    2016-05-01

    Metastasized lung and liver cancers cause over 2 million deaths annually, and are amongst the top killer cancers worldwide. Morinda citrifolia (Noni) leaves are traditionally consumed as vegetables in the tropics. The macro and micro effects of M. citrifolia (Noni) leaves on metastasized lung cancer development in vitro and in vivo were compared with the FDA-approved anti-cancer drug Erlotinib. The extract inhibited the proliferation and induced apoptosis in A549 cells (IC50 = 23.47 μg/mL) and mouse Lewis (LL2) lung carcinoma cells (IC50 = 5.50 μg/mL) in vitro, arrested cancer cell cycle at G0/G1 phases and significantly increased caspase-3/-8 without changing caspase-9 levels. The extract showed no toxicity on normal MRC5 lung cells. Non-small-cell lung cancer (NSCLC) A549-induced BALB/c mice were fed with 150 and 300 mg/kg M. citrifolia leaf extract and compared with Erlotinib (50 mg/kg body weight) for 21 days. It significantly increased the pro-apoptotic TRP53 genes, downregulated the pro-tumourigenesis genes (BIRC5, JAK2/STAT3/STAT5A) in the mice tumours, significantly increased the anti-inflammatory IL4, IL10 and NR3C1 expression in the metastasized lung and hepatic cancer tissues and enhanced the NFE2L2-dependent antioxidant responses against oxidative injuries. The extract elevated serum neutrophils and reduced the red blood cells, haemoglobin, corpuscular volume and cell haemoglobin concentration in the lung cancer-induced mammal. It suppressed inflammation and oedema, and upregulated the endogenous antioxidant responses and apoptotic genes to suppress the cancer. The 300 mg/kg extract was more effective than the 50 mg/kg Erlotinib for most of the parameters measured.

  3. Efficacy of Intra-arterial Norcantharidin in Suppressing Tumour 14C-labelled Glucose Oxidative Metabolism in rat Morris Hepatoma

    Directory of Open Access Journals (Sweden)

    Peter Mack

    1996-01-01

    Full Text Available Norcantharidin is the demethylated form of Cantharidin, which is the active ingredient of the blister beetle, Mylabris, a long used Chinese traditional medicine. Though not well publicised outside China, Norcantharidin is known to possess significant anti-hepatoma activity, and is relatively free from side effects. In the present study, glucose oxidation in tumour and liver tissue slices harvested from hepatomabearing animals was quantified by measuring the radioactivity of 14C-labelled CO released from 14C-glucose in oxygen-enriched incubation medium. Results were expressed asa tumour/liver ratio. For comparison, treatments with Norcantharidin, Adriamycin and with hepatic artery ligation were studied. The mean tumour/liver ratio was 4.2+2.2 in untreated controls, but dropped significantly to 2.3+0.5 (p<0.05 with intra-arterial Norcantharidin (0.5 mg/kg and to 2.3+0.7 (p<0.05 with intra-arterial Adriamycin (2.4 mg/kg, and to 2.2+0.7 (p<0.05 with hepatic artery ligation. However, with intravenous Adriamycin at 2.4 mg/kg, the mean tumour/liver ratio was reduced to only 3.5+2.0 and was not significantly different from untreated controls. It is concluded that intra-arterial Norcantharidin is as effective as intraarterial Adriamycin and hepatic artery ligation in suppressing tumour glucose oxidative metabolism. These results imply that Norcantharidin may have a role to play in the chemotherapy ofprimary livercancer.

  4. Notoginsenoside R1 Alleviates Oxygen-Glucose Deprivation/Reoxygenation Injury by Suppressing Endoplasmic Reticulum Calcium Release via PLC.

    Science.gov (United States)

    Wang, Yan; Tu, Liu; Li, Yingbo; Chen, Di; Liu, Zhao; Hu, Xuelian; Wang, Shali

    2017-11-24

    As documented in our previous study, notoginsenoside R1 (NGR1) can inhibit neuron apoptosis and the expression of endoplasmic reticulum (ER) stress-associated pro-apoptotic proteins in hypoxic-ischemic encephalopathy. Recent evidence indicates that the Phospholipase C (PLC)/inositol 1,4,5-trisphosphate receptor (IP3R) is important for the regulation of Ca 2+ release in the ER. Ca 2+ imbalance can stimulate ER stress, CAMKII, and cell apoptosis. The purpose of this study was to further investigate the neuroprotective effect of NGR1 and elucidate how NGR1 regulates ER stress and cell apoptosis in the oxygen-glucose deprivation/reoxygenation (OGD/R) model. Cells were exposed to NGR1 or the PLC activator m-3M3FBS. Then, IP3R- and IP3-induced Ca 2+ release (IICR) and activation of the ER stress and CaMKII signal pathway were measured. The results showed that NGR1 inhibited IICR and strengthened the binding of GRP78 with PERK and IRE1. NGR1 also alleviated the activation of the CaMKII pathway. Pretreatment with m-3M3FBS attenuated the neuroprotective effect of NGR1; IICR was activated, activation of the ER stress and CaMKII pathway was increased, and more cells were injured. These results indicate that NGR1 may suppress activation of the PLC/IP3R pathway, subsequently inhibiting ER Ca 2+ release, ER stress, and CaMKII and resulting in suppressed cell apoptosis.

  5. Metformin Ameliorates Dysfunctional Traits of Glibenclamide- and Glucose-Induced Insulin Secretion by Suppression of Imposed Overactivity of the Islet Nitric Oxide Synthase-NO System.

    Science.gov (United States)

    Lundquist, Ingmar; Mohammed Al-Amily, Israa; Meidute Abaraviciene, Sandra; Salehi, Albert

    2016-01-01

    Metformin lowers diabetic blood glucose primarily by reducing hepatic gluconeogenesis and increasing peripheral glucose uptake. However, possible effects by metformin on beta-cell function are incompletely understood. We speculated that metformin might positively influence insulin secretion through impacting the beta-cell nitric oxide synthase (NOS)-NO system, a negative modulator of glucose-stimulated insulin release. In short-time incubations with isolated murine islets either glibenclamide or high glucose augmented insulin release associated with increased NO production from both neural and inducible NOS. Metformin addition suppressed the augmented NO generation coinciding with amplified insulin release. Islet culturing with glibenclamide or high glucose revealed pronounced fluorescence of inducible NOS in the beta-cells being abolished by metformin co-culturing. These findings were reflected in medium nitrite-nitrate levels. A glucose challenge following islet culturing with glibenclamide or high glucose revealed markedly impaired insulin response. Metformin co-culturing restored this response. Culturing murine islets and human islets from controls and type 2 diabetics with high glucose or high glucose + glibenclamide induced a pronounced decrease of cell viability being remarkably restored by metformin co-culturing. We show here, that imposed overactivity of the beta-cell NOS-NO system by glibenclamide or high glucose leads to insulin secretory dysfunction and reduced cell viability and also, importantly, that these effects are relieved by metformin inhibiting beta-cell NO overproduction from both neural and inducible NOS thus ameliorating a concealed negative influence by NO induced by sulfonylurea treatment and/or high glucose levels. This double-edged effect of glibenclamide on the beta-cellsuggests sulfonylurea monotherapy in type 2 diabetes being avoided.

  6. Metformin Ameliorates Dysfunctional Traits of Glibenclamide- and Glucose-Induced Insulin Secretion by Suppression of Imposed Overactivity of the Islet Nitric Oxide Synthase-NO System.

    Directory of Open Access Journals (Sweden)

    Ingmar Lundquist

    Full Text Available Metformin lowers diabetic blood glucose primarily by reducing hepatic gluconeogenesis and increasing peripheral glucose uptake. However, possible effects by metformin on beta-cell function are incompletely understood. We speculated that metformin might positively influence insulin secretion through impacting the beta-cell nitric oxide synthase (NOS-NO system, a negative modulator of glucose-stimulated insulin release. In short-time incubations with isolated murine islets either glibenclamide or high glucose augmented insulin release associated with increased NO production from both neural and inducible NOS. Metformin addition suppressed the augmented NO generation coinciding with amplified insulin release. Islet culturing with glibenclamide or high glucose revealed pronounced fluorescence of inducible NOS in the beta-cells being abolished by metformin co-culturing. These findings were reflected in medium nitrite-nitrate levels. A glucose challenge following islet culturing with glibenclamide or high glucose revealed markedly impaired insulin response. Metformin co-culturing restored this response. Culturing murine islets and human islets from controls and type 2 diabetics with high glucose or high glucose + glibenclamide induced a pronounced decrease of cell viability being remarkably restored by metformin co-culturing. We show here, that imposed overactivity of the beta-cell NOS-NO system by glibenclamide or high glucose leads to insulin secretory dysfunction and reduced cell viability and also, importantly, that these effects are relieved by metformin inhibiting beta-cell NO overproduction from both neural and inducible NOS thus ameliorating a concealed negative influence by NO induced by sulfonylurea treatment and/or high glucose levels. This double-edged effect of glibenclamide on the beta-cellsuggests sulfonylurea monotherapy in type 2 diabetes being avoided.

  7. Suppressing glucose uptake and acetic acid production increases membrane protein overexpression in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Larsson Gen

    2011-05-01

    Full Text Available Abstract Background The production of integral membrane spanning proteins (IMP's constitutes a bottleneck in pharmaceutical development. It was long considered that the state-of-the-art was to produce the proteins as inclusion bodies using a powerful induction system. However, the quality of the protein was compromised and the production of a soluble protein that is incorporated into the membrane from which it is extracted is now considered to be a better method. Earlier research has indicated that a slower rate of protein synthesis might overcome the tendency to form inclusion bodies. We here suggest the use of a set of E. coli mutants characterized by a slower rate of growth and protein synthesis as a tool for increasing the amount of soluble protein in high- throughput protein production processes. Results A set of five IMP's was chosen which were expressed in three mutants and the corresponding WT cell (control. The mutations led to three different substrate uptake rates, two of which were considerably slower than that of the wild type. Using the mutants, we were able to express three out of the five membrane proteins. Most successful was the mutant growing at 50% of the wild type growth rate. A further effect of a low growth rate is a low acetic acid formation, and we believe that this is a possible reason for the better production. This hypothesis was further supported by expression from the BL21(DE3 strain, using the same plasmid. This strain grows at a high growth rate but nevertheless yields only small amounts of acetic acid. This strain was also able to express three out of the five IMP's, although at lower quantities. Conclusions The use of mutants that reduce the specific substrate uptake rate seems to be a versatile tool for overcoming some of the difficulties in the production of integral membrane spanning proteins. A set of strains with mutations in the glucose uptake system and with a lower acetic acid formation were able to

  8. Dynamin-related protein inhibitor downregulates reactive oxygen species levels to indirectly suppress high glucose-induced hyperproliferation of vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Maimaitijiang, Alimujiang; Zhuang, Xinyu; Jiang, Xiaofei; Li, Yong, E-mail: 11211220031@fudan.edu.cn

    2016-03-18

    Hyperproliferation of vascular smooth muscle cells is a pathogenic mechanism common in diabetic vascular complications and is a putatively important therapeutic target. This study investigated multiple levels of biology, including cellular and organellar changes, as well as perturbations in protein synthesis and morphology. Quantitative and qualitative analysis was utilized to assess the effect of mitochondrial dynamic changes and reactive oxygen species(ROS) levels on high-glucose-induced hyperproliferation of vascular smooth muscle cells. The data demonstrated that the mitochondrial fission inhibitor Mdivi-1 and downregulation of ROS levels both effectively inhibited the high-glucose-induced hyperproliferation of vascular smooth muscle cells. Downregulation of ROS levels played a more direct role and ROS levels were also regulated by mitochondrial dynamics. Increased ROS levels induced excessive mitochondrial fission through dynamin-related protein (Drp 1), while Mdivi-1 suppressed the sensitivity of Drp1 to ROS levels, thus inhibiting excessive mitochondrial fission under high-glucose conditions. This study is the first to propose that mitochondrial dynamic changes and ROS levels interact with each other and regulate high-glucose-induced hyperproliferation of vascular smooth muscle cells. This finding provides novel ideas in understanding the pathogenesis of diabetic vascular remodeling and intervention. - Highlights: • Mdivi-1 inhibits VSMC proliferation by lowering ROS level in high-glucose condition. • ROS may be able to induce mitochondrial fission through Drp1 regulation. • Mdivi-1 can suppress the sensitivity of Drp1 to ROS.

  9. Engineering of an endogenous hexose transporter into a specific D-xylose transporter facilitates glucose-xylose co-consumption in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Nijland, Jeroen G.; Shin, Hyun Yong; de Jong, Rene M.; De Waal, Paul P.; Klaassen, Paul; Driessen, Arnold J. M.

    2014-01-01

    Background: Engineering of Saccharomyces cerevisiae for the simultaneous utilization of hexose and pentose sugars is vital for cost-efficient cellulosic bioethanol production. This yeast lacks specific pentose transporters and depends on endogenous hexose transporters for low affinity pentose

  10. Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose.

    Science.gov (United States)

    Burmeister, Melissa A; Ayala, Jennifer; Drucker, Daniel J; Ayala, Julio E

    2013-04-01

    Glucagon-like peptide-1 (GLP-1) suppresses food intake via activation of a central (i.e., brain) GLP-1 receptor (GLP-1R). Central AMP-activated protein kinase (AMPK) is a nutrient-sensitive regulator of food intake that is inhibited by anorectic signals. The anorectic effect elicited by hindbrain GLP-1R activation is attenuated by the AMPK stimulator AICAR. This suggests that central GLP-1R activation suppresses food intake via inhibition of central AMPK. The present studies examined the mechanism(s) by which central GLP-1R activation inhibits AMPK. Supporting previous findings, AICAR attenuated the anorectic effect elicited by intracerebroventricular (icv) administration of the GLP-1R agonist exendin-4 (Ex-4). We demonstrate that Ex-4 stimulates glycolysis and suppresses AMPK phosphorylation in a glucose-dependent manner in hypothalamic GT1-7 cells. This suggests that inhibition of AMPK and food intake by Ex-4 requires central glucose metabolism. Supporting this, the glycolytic inhibitor 2-deoxyglucose (2-DG) attenuated the anorectic effect of Ex-4. However, icv glucose did not enhance the suppression of food intake by Ex-4. AICAR had no effect on Ex-4-mediated reduction in locomotor activity. We also tested whether other carbohydrates affect the anorectic response to Ex-4. Intracerebroventricular pretreatment with the sucrose metabolite fructose, an AMPK activator, attenuated the anorectic effect of Ex-4. This potentially explains the increased food intake observed in sucrose-fed mice. In summary, we propose a model whereby activation of the central GLP-1R reduces food intake via glucose metabolism-dependent inhibition of central AMPK. We also suggest that fructose stimulates food intake by impairing central GLP-1R action. This has significant implications given the correlation between sugar consumption and obesity.

  11. Saponarin activates AMPK in a calcium-dependent manner and suppresses gluconeogenesis and increases glucose uptake via phosphorylation of CRTC2 and HDAC5.

    Science.gov (United States)

    Seo, Woo-Duck; Lee, Ji Hae; Jia, Yaoyao; Wu, Chunyan; Lee, Sung-Joon

    2015-11-15

    This study investigated the molecular mechanism of saponarin, a flavone glucoside, in the regulation of insulin sensitivity. Saponarin suppressed the rate of gluconeogenesis and increased cellular glucose uptake in HepG2 and TE671 cells by regulating AMPK. Using an in vitro kinase assay, we showed that saponarin did not directly interact with the AMPK protein. Instead, saponarin increased intracellular calcium levels and induced AMPK phosphorylation, which was diminished by co-stimulation with STO-609, an inhibitor of CAMKKβ. Transcription of hepatic gluconeogenesis genes was upregulated by nuclear translocation of CRTC2 and HDAC5, coactivators of CREB and FoxO1 transcription factors, respectively. This nuclear translocation was inhibited by increased phosphorylation of CRTC2 and HDAC5 by saponarin-induced AMPK in HepG2 cells and suppression of CREB and FoxO1 transactivation activities in cells stimulated by saponarin. The results from a chromatin immunoprecipitation assay confirmed the reduced binding of CRTC2 on the PEPCK and G6Pase promoters. In TE671 cells, AMPK phosphorylated HDAC5, which suppressed nuclear penetration and upregulated GLUT4 transcription, leading to enhanced glucose uptake. Collectively, these results suggest that saponarin activates AMPK in a calcium-dependent manner, thus regulating gluconeogenesis and glucose uptake. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Combination Therapy with a Sodium-Glucose Cotransporter 2 Inhibitor and a Dipeptidyl Peptidase-4 Inhibitor Additively Suppresses Macrophage Foam Cell Formation and Atherosclerosis in Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Michishige Terasaki

    2017-01-01

    Full Text Available Dipeptidyl peptidase-4 inhibitors (DPP-4is, in addition to their antihyperglycemic roles, have antiatherosclerotic effects. We reported that sodium-glucose cotransporter 2 inhibitors (SGLT2is suppress atherosclerosis in a glucose-dependent manner in diabetic mice. Here, we investigated the effects of combination therapy with SGLT2i and DPP-4i on atherosclerosis in diabetic mice. SGLT2i (ipragliflozin, 1.0 mg/kg/day and DPP-4i (alogliptin, 8.0 mg/kg/day, either alone or in combination, were administered to db/db mice or streptozotocin-induced diabetic apolipoprotein E-null (Apoe−/− mice. Ipragliflozin and alogliptin monotherapies improved glucose intolerance; however, combination therapy did not show further improvement. The foam cell formation of peritoneal macrophages was suppressed by both the ipragliflozin and alogliptin monotherapies and was further enhanced by combination therapy. Although foam cell formation was closely associated with HbA1c levels in all groups, DPP-4i alone or the combination group showed further suppression of foam cell formation compared with the control or SGLT2i group at corresponding HbA1c levels. Both ipragliflozin and alogliptin monotherapies decreased scavenger receptors and increased cholesterol efflux regulatory genes in peritoneal macrophages, and combination therapy showed additive changes. In diabetic Apoe−/− mice, combination therapy showed the greatest suppression of plaque volume in the aortic root. In conclusion, combination therapy with SGLT2i and DPP4i synergistically suppresses macrophage foam cell formation and atherosclerosis in diabetic mice.

  13. [Endogenous hypertriglyceridemia].

    Science.gov (United States)

    Tsukamoto, Kazuhisa

    2013-09-01

    Endogenous hypertriglyceridemia, which includes familial hypertriglyceridemia and idiopathic hypertriglyceridemia, is characterized by the increased level of VLDL-triglycerides in the blood. Increased production of VLDL from the liver and the decreased catabolism of VLDL-TG in the vessel, which are also the main metabolic features of insulin resistance, have been proposed to be the causes of endogenous hypertriglyceridemia. Genetic factors responsible for endogenous hypertriglyceridemia have been elucidated in several studies, however, these factors have so far not been clearly identified yet; thus the causes of endogenous hypertriglyceridemia would be polygenic. Recent advances in the genetic analytical methods like genome-wide association study would hopefully unveil the whole pictures of endogenous hypertriglyceridemia.

  14. Ginkgolide B Suppresses TLR4-Mediated Inflammatory Response by Inhibiting the Phosphorylation of JAK2/STAT3 and p38 MAPK in High Glucose-Treated HUVECs

    Directory of Open Access Journals (Sweden)

    Kun Chen

    2017-01-01

    Full Text Available Aim. Ginkgolide B is a Ginkgo biloba leaf extract that has been identified as a natural platelet-activating factor receptor (PAFR antagonist. We investigated the effect of ginkgolide B on high glucose-induced TLR4 activation in human umbilical vein endothelial cells (HUVECs. Methods. Protein expression was analyzed by immunoblotting. Small-interfering RNA (siRNA was used to knock down PAFR and TLR4 expression. Results. Ginkgolide B suppressed the expression of TLR4 and MyD88 that was induced by high glucose. Ginkgolide B also reduced the levels of platelet endothelial cell adhesion molecule-1, interleukin-6, and monocyte chemotactic protein 1. Further, we examined the association between PAFR and TLR4 by coimmunoprecipitation. The result showed that high glucose treatment caused the binding of PAFR and TLR4, whereas ginkgolide B abolished this binding. The functional analysis indicated that PAFR siRNA treatment reduced TLR4 expression, and TLR4 siRNA treatment decreased PAFR expression in high glucose-treated HUVECs, further supporting the coimmunoprecipitation data. Ginkgolide B inhibited the phosphorylation of Janus kinase 2 (JAK2/signal transducer and activator of transcription 3 (STAT3 and p38 mitogen-activated protein kinase (MAPK. Conclusion. Ginkgolide B exerted protective effects by inhibiting the TLR4-mediated inflammatory response in high glucose-treated endothelial cells. The mechanism of action of ginkgolide B might be associated with inhibition of the JAK2/STAT3 and p38 MAPK phosphorylation.

  15. Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet.

    Science.gov (United States)

    Wada, Tsutomu; Kenmochi, Hiroki; Miyashita, Yusuke; Sasaki, Motohiro; Ojima, Minoru; Sasahara, Masakiyo; Koya, Daisuke; Tsuneki, Hiroshi; Sasaoka, Toshiyasu

    2010-05-01

    Recent evidence suggests that treatment with mineralocorticoid receptor antagonist suppressed local inflammation in vascular tissues or cardiomyocytes; therefore, we examined the effect of spironolactone on glucose and lipid metabolism in a mouse model with diet-induced diabetes and nonalcoholic fatty liver disease. C57BL/6 mice were fed either the control diet, 60% fat diet with 30% fructose water (HFFD), or HFFD with spironolactone for 8 wk. HFFD mice demonstrated apparent phenotypes of metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, and fatty liver. Although treatment with spironolactone did not affect the increased calorie intake and body weight by HFFD, the increments of epididymal fat weight, blood pressure, serum triglyceride, free fatty acids, leptin, and total cholesterol levels were significantly suppressed. Elevation of blood glucose during glucose and insulin tolerance tests in HFFD mice was significantly lowered by spironolactone. Notably, increased glucose levels during pyruvate tolerance test in HFFD mice were almost completely ameliorated to control levels by the treatment. Staining with hematoxylin-eosin (HE) and Oil-red-O demonstrated marked accumulation of triglycerides in the centrilobular part of the hepatic lobule in HFFD mice, and these accumulations were effectively improved by spironolactone. Concomitantly HFFD feeding markedly up-regulated hepatic mRNA expression of proinflammatory cytokines (TNFalpha, IL-6, and monocyte chemoattractant protein-1), gluconeogenic gene phosphoenolpyruvate carboxykinase, transcription factor carbohydrate response element binding protein, and its downstream lipogenic enzymes, all of which were significantly suppressed by spironolactone. These results indicate that inhibition of mineralocorticoid receptor might be a beneficial therapeutic approach for diet-induced phenotypes of metabolic syndrome and fatty liver.

  16. Suppression of EAE by oral tolerance is independent of endogenous IFN-beta whereas treatment with recombinant IFN-beta ameliorates EAE

    DEFF Research Database (Denmark)

    Liu, Yawei; Teige, Ingrid; Ericsson, Ida

    2010-01-01

    (IFN-beta(+/+)). The non-self-antigen ovalbumin induced oral tolerance in both groups. These data indicate that endogenous IFN-beta is not required for induction of oral tolerance, whereas delivery of recombinant IFN-beta results in significant reduction in clinical score of EAE. Oral tolerance...

  17. Endogenous GLP-1 acts on paraventricular nucleus to suppress feeding: projection from nucleus tractus solitarius and activation of corticotropin-releasing hormone, nesfatin-1 and oxytocin neurons.

    Science.gov (United States)

    Katsurada, Kenichi; Maejima, Yuko; Nakata, Masanori; Kodaira, Misato; Suyama, Shigetomo; Iwasaki, Yusaku; Kario, Kazuomi; Yada, Toshihiko

    2014-08-22

    Glucagon-like peptide-1 (GLP-1) receptor agonists have been used to treat type 2 diabetic patients and shown to reduce food intake and body weight. The anorexigenic effects of GLP-1 and GLP-1 receptor agonists are thought to be mediated primarily via the hypothalamic paraventricular nucleus (PVN). GLP-1, an intestinal hormone, is also localized in the nucleus tractus solitarius (NTS) of the brain stem. However, the role of endogenous GLP-1, particularly that in the NTS neurons, in feeding regulation remains to be established. The present study examined whether the NTS GLP-1 neurons project to PVN and whether the endogenous GLP-1 acts on PVN to restrict feeding. Intra-PVN injection of GLP-1 receptor antagonist exendin (9-39) increased food intake. Injection of retrograde tracer into PVN combined with immunohistochemistry for GLP-1 in NTS revealed direct projection of NTS GLP-1 neurons to PVN. Moreover, GLP-1 evoked Ca(2+) signaling in single neurons isolated from PVN. The majority of GLP-1-responsive neurons were immunoreactive predominantly to corticotropin-releasing hormone (CRH) and nesfatin-1, and less frequently to oxytocin. These results indicate that endogenous GLP-1 targets PVN to restrict feeding behavior, in which the projection from NTS GLP-1 neurons and activation of CRH and nesfatin-1 neurons might be implicated. This study reveals a neuronal basis for the anorexigenic effect of endogenous GLP-1 in the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Two days of a very low calorie diet reduces endogenous glucose production in obese type 2 diabetic patients despite the withdrawal of blood glucose-lowering therapies including insulin

    NARCIS (Netherlands)

    Jazet, Ingrid M.; Pijl, Hanno; Frölich, Marijke; Romijn, Johannes A.; Meinders, A. Edo

    2005-01-01

    The mechanism of the blood glucose-lowering effect of a 2-day very low calorie diet (VLCD; 1890 kJ/d) in combination with the cessation of all blood glucose-lowering agents was studied in 12 (7 women, 5 men) obese (body mass index, 36.3 +/- 1.0 kg/m 2 [mean +/- SEM]) type 2 diabetic patients (age,

  19. Wheat alkylresorcinols suppress high-fat, high-sucrose diet-induced obesity and glucose intolerance by increasing insulin sensitivity and cholesterol excretion in male mice.

    Science.gov (United States)

    Oishi, Katsutaka; Yamamoto, Saori; Itoh, Nanako; Nakao, Reiko; Yasumoto, Yuki; Tanaka, Keiko; Kikuchi, Yosuke; Fukudome, Shin-ichi; Okita, Kimiko; Takano-Ishikawa, Yuko

    2015-02-01

    Epidemiologic studies have shown that the consumption of whole grains can reduce the risk of type 2 diabetes mellitus, cardiovascular disease, and all-cause mortality. However, the underlying mechanisms remain a matter of debate. We aimed to determine the effects of wheat bran-derived alkylresorcinols on diet-induced metabolic disorders in mice. We fed C57BL/6J mice a normal refined diet or a high-fat, high-sucrose diet [29.1% fat, 20.7% protein, 34.0% carbohydrates containing 20.0% sucrose (w/w)] alone (FS) or containing 0.4% (wt:wt) alkylresorcinols (FS-AR) for 10 wk. The alkylresorcinols suppressed FS-induced increases in body weight by 31.0% as well as FS-induced hepatic triglyceride accumulation (means ± SEMs: 29.6 ± 3.18 and 19.8 ± 2.42 mg/g tissue in the FS and FS-AR groups, respectively), without affecting energy intake. We measured circadian changes in blood metabolic hormones and found that FS-induced hyperinsulinemia (5.1 and 2.1 μg/L at night in the FS and FS-AR groups, respectively) and hyperleptinemia (21.6 and 10.8 μg/L at night in the FS and FS-AR groups, respectively) were suppressed by alkylresorcinols. Glucose and insulin tolerance tests showed that alkylresorcinols significantly reduced fasting blood glucose concentrations (190 ± 3.62 and 160 ± 8.98 mg/dL in the FS and FS-AR groups, respectively) and suppressed glucose intolerance as well as insulin resistance induced by the FS diet. Furthermore, alkylresorcinols significantly increased insulin-stimulated hepatic serine/threonine protein kinase B phosphorylation compared to the FS diet (+81.3% and +57.4% for Ser473 and Thr308, respectively). On the other hand, pyruvate and starch tolerance tests suggested that alkylresorcinols did not affect gluconeogenesis and carbohydrate digestion, respectively. Alkylresorcinols significantly increased fecal cholesterol excretion by 39.6% and reduced blood cholesterol concentrations by 30.4%, while upregulating the expression of hepatic cholesterol

  20. Estimation of Insulin Resistance in Mexican Adults by the [13C]Glucose Breath Test Corrected for Endogenous Total CO2 Production

    Directory of Open Access Journals (Sweden)

    Erika Ibarra-Pastrana

    2012-01-01

    Full Text Available Objective. To evaluate the efficacy of the [13C]glucose breath test for measuring insulin resistance in Mexican adults with different glycemic states. Research Design and Methods. Fifty-eight adults underwent a [13C]glucose breath test with simultaneous measurement of total CO2 production by indirect calorimetry, at baseline and 90 minutes after the ingestion of 15 g of dextrose and 25 mg of [13C]glucose. HOMA was used as a marker of insulin resistance. Results. We found an inverse correlation between HOMA and the breath test δ13CO2 (‰, r=-0.41 (P=0.001. After adjusting for total CO2 production, correlations between HOMA and fasting glucose were less strong but remained significant. An ROC curve was constructed using δ13CO2 (‰ and HOMA values; the cut-off point was 9.99‰ δ13CO2, corresponding to a sensitivity of 80.0 (95% CI: 51.9, 95.7 and a specificity of 67.4 (95% CI: 51.5, 80.9. Conclusions. The [13C]glucose breath test is a simple noninvasive procedure but was not sufficiently robust for an accurate diagnosis of insulin resistance. Our findings suggest that the test might be helpful in identifying individuals who are not IR, which in turn may contribute to improved diabetes prevention.

  1. Estimation of Insulin Resistance in Mexican Adults by the [13C]Glucose Breath Test Corrected for Endogenous Total CO2 Production

    Science.gov (United States)

    Ibarra-Pastrana, Erika; Candia Plata, Maria del Carmen; Alvarez, Gerardo; Valencia, Mauro E.

    2012-01-01

    Objective. To evaluate the efficacy of the [13C]glucose breath test for measuring insulin resistance in Mexican adults with different glycemic states. Research Design and Methods. Fifty-eight adults underwent a [13C]glucose breath test with simultaneous measurement of total CO2 production by indirect calorimetry, at baseline and 90 minutes after the ingestion of 15 g of dextrose and 25 mg of [13C]glucose. HOMA was used as a marker of insulin resistance. Results. We found an inverse correlation between HOMA and the breath test δ 13CO2 (‰), r = −0.41 (P = 0.001). After adjusting for total CO2 production, correlations between HOMA and fasting glucose were less strong but remained significant. An ROC curve was constructed using δ 13CO2 (‰) and HOMA values; the cut-off point was 9.99‰ δ 13CO2, corresponding to a sensitivity of 80.0 (95% CI: 51.9, 95.7) and a specificity of 67.4 (95% CI: 51.5, 80.9). Conclusions. The [13C]glucose breath test is a simple noninvasive procedure but was not sufficiently robust for an accurate diagnosis of insulin resistance. Our findings suggest that the test might be helpful in identifying individuals who are not IR, which in turn may contribute to improved diabetes prevention. PMID:22848216

  2. Determination of the transient period of the EIS complex and investigation of the suppression of blood glucose levels by L-arabinose in healthy adults.

    Science.gov (United States)

    Shibanuma, Kiyoshi; Degawa, Yoko; Houda, Koichi

    2011-09-01

    L-Arabinose uncompetitively inhibits intestinal sucrase by forming an enzyme-inhibitor-substrate (EIS) complex. The transient period of the EIS complex affects the time span of inhibition. We determined the apparent transient period of the EIS complex of sucrase, L-arabinose, and sucrose both in vitro and in humans. Intestinal acetone powder (a source of sucrase), L-arabinose, and sucrose were mixed and injected into a dialysis membrane that was placed in a sucrose solution. The production rate of D-glucose and the release rate of L-arabinose from sucrase were determined. We also investigated the suppression of blood glucose levels by L-arabinose in 21 healthy volunteers. Sucrose (40 g) was ingested with or without L-arabinose (2 g), then blood glucose values were measured, which returned to steady-state conditions within 2 h. Volunteers were then given 90 g of commercial adzuki bean jelly containing 40 g sucrose as the sucrose load, and blood glucose values were measured again. Addition of L-arabinose reduced the production rate of D -glucose compared to the rates measured in the absence of L-arabinose for several hours in vitro. L-Arabinose was released at a lower rate in the presence of sucrose than in its absence. Blood glucose values measured 2 h after sucrose was given with L -arabinose were significantly lower than those measured when L-arabinose was not given (Δ change in maximum value: with L-arabinose, 53.8 ± 19.7 mg/dL; without L-arabinose, 65.0 ± 17.7 mg/dL). The EIS complex of sucrase-L -arabinose-sucrose was maintained for several hours both in vitro and in humans.

  3. Cerebral ischemia-induced elevation of hepatic inflammatory factors accompanied by glucose intolerance suppresses hypothalamic orexin-A-mediated vagus nerve activation.

    Science.gov (United States)

    Harada, Shinichi; Nozaki, Yudai; Matsuura, Wataru; Yamazaki, Yui; Tokuyama, Shogo

    2017-04-15

    Activation of vagus nerve exerts orexin-A (OXA)-mediated suppression of post-ischemic glucose intolerance and cerebral ischemic neuronal damage. Cerebral ischemia induces hepatic inflammatory factors and contributes to the development of hepatic insulin resistance by activating sympathetic nerves. However, it is not enough to understand whether OXA regulates these phenomena through activation of vagus nerve. In this study, we demonstrated that the involvement of OXA-induced activation of vagus nerve in the induction of hepatic inflammatory factors by cerebral ischemia. Focal cerebral ischemic model construction was performed by 2h of middle cerebral artery occlusion (MCAO) in ddY male mice. OXA-positive neurons were visualized using the retrograde tracer Fluoro-Gold™. Intrahypothalamic OXA (5pmol/mouse) administration significantly suppressed the MCAO-induced post-ischemic glucose intolerance and neuronal damage. The MCAO-induced decrease in hepatic insulin receptors and increase in hepatic gluconeogenic enzymes were suppressed by OXA administration. These effects were canceled by N-butylscopolamine (a muscarinic receptor antagonist). MCAO-induced increases in hepatic F4/80, tumor necrosis factor-α, and interleukin-1β on day 1 after MCAO were reversed by OXA administration. These effects were abolished by N-butylscopolamine or hepatic vagotomy. These results suggest that OXA-induced activation of vagus nerve regulates the post-ischemic elevation of hepatic inflammatory factors, and which may be contributed to part of OXA-mediated regulation of post-ischemic glucose intolerance. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects

    DEFF Research Database (Denmark)

    Nielsen, Michael F; Caumo, Andrea; Chandramouli, Visvanathan

    2004-01-01

    Excess cortisol has been demonstrated to impair hepatic and extrahepatic insulin action. To determine whether glucose effectiveness and, in terms of endogenous glucose release (EGR), gluconeogenesis, also are altered by hypercortisolemia, eight healthy subjects were studied after overnight infusion...... contribution of gluconeogenesis to EGR (P = 0.33) did not differ on the two study days. During the prandial glucose infusion, the integrated glycemic response above baseline was higher in the presence of hydrocortisone than during saline infusion (P .... In conclusion, short-term hypercortisolemia in healthy individuals with normal beta-cell function decreases insulin action but does not alter rates of EGR and gluconeogenesis. In addition, cortisol impairs the ability of glucose to suppress its own production, which due to accumulation of glucose in the glucose...

  5. D-sorbose inhibits disaccharidase activity and demonstrates suppressive action on postprandial blood levels of glucose and insulin in the rat.

    Science.gov (United States)

    Oku, Tsuneyuki; Murata-Takenoshita, Yoko; Yamazaki, Yuko; Shimura, Fumio; Nakamura, Sadako

    2014-11-01

    In an attempt to develop D-sorbose as a new sweetener that could help in preventing lifestyle-related diseases, we investigated the inhibitory effect of D-sorbose on disaccharidase activity, using the brush border membrane vesicles of rat small intestines. The inhibitory effect was compared with that of L-sorbose and other rare sugars, and the small intestinal disaccharidases in rats was compared with that of humans as well. In humans and the small intestines of rats, d-sorbose strongly inhibited sucrase activity and weakly inhibited maltase activity. Inhibition by D-sorbose of sucrase activity was similar to that of L-arabinose, and the K(i) of D-sorbose was 7.5 mM. Inhibition by D-sorbose was very strong in comparison with that of L-sorbose (K(i), 60.8 mM), whereas inhibition of d-tagatose was between that of D-sorbose and L-sorbose. The inhibitory mode of D-sorbose for sucrose and maltase was uncompetitive, and that of L-sorbose was competitive. To determine a suppressive effect on postprandial blood levels of glucose and insulin via inhibition of sucrase activity, sucrose solution with or without D-sorbose was administered to rats. Increments in the blood levels of glucose and insulin were suppressed significantly after administration of sucrose solution with D-sorbose to rats, in comparison to administration of sucrose solution without D-sorbose. In contrast, the suppressive effect of L-sorbose on postprandial blood levels of glucose and insulin was very weak. These results suggest that D-sorbose may have an inhibitory effect on disaccharidase activity and could be used as a sweetener to suppress the postprandial elevation of blood levels of glucose and insulin. The use of D-sorbose as a sweetener may contribute to the prevention of lifestyle-related diseases, such as type 2 diabetes mellitus. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Involvement of KLF11 in hepatic glucose metabolism in mice via suppressing of PEPCK-C expression.

    Directory of Open Access Journals (Sweden)

    Huabing Zhang

    Full Text Available Abnormal hepatic gluconeogenesis is related to hyperglycemia in mammals with insulin resistance. Despite the strong evidences linking Krüppel-like factor 11 (KLF11 gene mutations to development of Type 2 diabetes, the precise physiological functions of KLF11 in vivo remain largely unknown.In current investigation, we showed that KLF11 is involved in modulating hepatic glucose metabolism in mice. Overexpression of KLF11 in primary mouse hepatocytes could inhibit the expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase (cytosolic isoform, PEPCK-C and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α, subsequently decreasing the cellular glucose output. Diabetic mice with overexpression of KLF11 gene in livers significantly ameliorated hyperglycemia and glucose intolerance; in contrast, the knockdown of KLF11 expression in db/m and C57BL/6J mice livers impaired glucose tolerance.Our data strongly indicated the involvement of KLF11 in hepatic glucose homeostasis via modulating the expression of PEPCK-C.

  7. Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia

    Directory of Open Access Journals (Sweden)

    Protim Sarker

    2014-07-01

    Full Text Available Antibiotics exert several effects on host cells including regulation of immune components. Antimicrobial peptides (AMPs, e.g., cathelicidins and defensins display multiple functions in innate immunity. In colonic mucosa, cathelicidins are induced by butyrate, a bacterial fermentation product. Here, we investigated the effect of antibiotics on butyrate-induced expression of cathelicidins and beta-defensins in colon epithelial cells. Real-time PCR analysis revealed that ciprofloxacin and clindamycin reduce butyrate-induced transcription of the human cathelicidin LL-37 in the colonic epithelial cell line HT-29. Suppression of LL-37 peptide/protein by ciprofloxacin was confirmed by Western blot analysis. Immunohistochemical analysis demonstrated that ciprofloxacin suppresses the rabbit cathelicidin CAP-18 in rectal epithelia of healthy and butyrate-treated Shigella-infected rabbits. Ciprofloxacin also down-regulated butyrate-induced transcription of the human beta-defensin-3 in HT-29 cells. Microarray analysis of HT-29 cells revealed upregulation by butyrate with subsequent down-regulation by ciprofloxacin of additional genes encoding immune factors. Dephosphorylation of histone H3, an epigenetic event provided a possible mechanism of the suppressive effect of ciprofloxacin. Furthermore, LL-37 peptide inhibited Clostridium difficile growth in vitro. In conclusion, ciprofloxacin and clindamycin exert immunomodulatory function by down-regulating AMPs and other immune components in colonic epithelial cells. Suppression of AMPs may contribute to the overgrowth of C. difficile, causing antibiotic-associated diarrhea.

  8. Continued glucose output after re-feeding contributes to glucose intolerance in hyperthyroidism.

    OpenAIRE

    Holness, M J; Sugden, M C

    1987-01-01

    The effects of hyperthyroidism to elicit glucose intolerance after glucose administration were decreased under conditions where hepatic glucose output was suppressed. It is concluded that continued hepatic glucose output contributes to abnormal glucose tolerance in hyperthyroidism.

  9. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Peng [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); School of Public Health, China Medical University, Shenyang 110001 (China); Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Sun, Guifan [School of Public Health, China Medical University, Shenyang 110001 (China); Andersen, Melvin E. [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

    2011-04-08

    Highlights: {yields} In 3T3-L1 adipocytes iAs{sup 3+} decreases insulin-stimulated glucose uptake. {yields} iAs{sup 3+} attenuates insulin-induced phosphorylation of AKT S473. {yields} iAs{sup 3+} activates the cellular adaptive oxidative stress response. {yields} iAs{sup 3+} impairs insulin-stimulated ROS signaling. {yields} iAs{sup 3+} decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 {mu}M) inorganic arsenite (iAs{sup 3+}) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs{sup 3+} exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs{sup 3+} exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4

  10. Estriol blunts postprandial blood glucose rise in male rats through regulating intestinal glucose transporters.

    Science.gov (United States)

    Yamabe, Noriko; Kang, Ki Sung; Lee, Woojung; Kim, Su-Nam; Zhu, Bao Ting

    2015-03-01

    Despite increased total food intake in healthy, late-stage pregnant women, their peak postprandial blood sugar levels are normally much lower than the levels seen in healthy nonpregnant women. In this study, we sought to determine whether estriol (E3), an endogenous estrogen predominantly produced during human pregnancy, contributes to the regulation of the postprandial blood glucose level in healthy normal rats. In vivo studies using rats showed that E3 blunted the speed and magnitude of the blood glucose rise following oral glucose administration, but it did not appear to affect the total amount of glucose absorbed. E3 also did not affect insulin secretion, but it significantly reduced the rate of intestinal glucose transport compared with vehicle-treated animals. Consistent with this finding, expression of the sodium-dependent glucose transporter 1 and 2 was significantly downregulated by E3 treatment in the brush-border membrane and basolateral membrane, respectively, of enterocytes. Most of the observed in vivo effects were noticeably stronger with E3 than with 17β-estradiol. Using differentiated human Caco-2 enterocyte monolayer culture as an in vitro model, we confirmed that E3 at physiologically relevant concentrations could directly inhibit glucose uptake via suppression of glucose transporter 2 expression, whereas 17β-estradiol did not have a similar effect. Collectively, these data showed that E3 can blunt the postprandial glycemic surge in rats through modulating the level of intestinal glucose transporters. Copyright © 2015 the American Physiological Society.

  11. Suppression of glucose-6-phosphate-isomerase induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of glucose-6-phosphate-isomerase.

    Science.gov (United States)

    Hirota, Tomoya; Tsuboi, Hiroto; Iizuka-Koga, Mana; Takahashi, Hiroyuki; Asashima, Hiromitsu; Yokosawa, Masahiro; Kondo, Yuya; Ohta, Masaru; Wakasa, Yuhya; Matsumoto, Isao; Takaiwa, Fumio; Sumida, Takayuki

    2017-05-01

    To investigate the effects of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (hGPI 325-339 ) in mice model of GPI-induced arthritis (GIA). We generated transgenic rice expressing T-cell epitope of hGPI 325-339 and APL12 contained in the seed endosperm. The transgenic rice seeds were orally administered prophylactically before the induction of GIA. The severity of arthritis and titers of serum anti-GPI antibodies were evaluated. We examined for IL-17 production in splenocytes and inguinal lymph node (iLN) cells, and analyzed the expression levels of functional molecules in splenocytes. Prophylactic treatment of GIA mice with APL12 transgenic (APL12-TG) rice seeds significantly reduced the severity of arthritis and titers of serum anti-GPI antibodies compared with non-transgenic (Non-TG) rice-treated mice. APL12-TG and hGPI 325-339 transgenic (hGPI 325-339 -TG) rice seeds improved the histopathological arthritis scores and decreased IL-17 production compared with non-TG rice-treated mice. APL12-TG rice-treated GIA mice showed upregulation of Foxp3 and GITR protein in CD4  +  CD25  +  Foxp3 +  cells in the spleen compared with non-TG rice- and hGPI 325-339 -TG rice-treated mice. APL12-TG rice seeds improved the severity of GIA through a decrease in production of IL-17 and anti-GPI antibodies via upregulation of Foxp3 and GITR expression on Treg cells in spleen.

  12. Inosine, an Endogenous Purine Nucleoside, Suppresses Immune Responses and Protects Mice from Experimental Autoimmune Encephalomyelitis: a Role for A2A Adenosine Receptor.

    Science.gov (United States)

    Junqueira, Stella Célio; Dos Santos Coelho, Igor; Lieberknecht, Vicente; Cunha, Mauricio Peña; Calixto, João B; Rodrigues, Ana Lúcia S; Santos, Adair Roberto Soares; Dutra, Rafael Cypriano

    2017-07-01

    Multiple sclerosis (MS) is a T cell autoimmune, inflammatory, and demyelinating disease of the central nervous system (CNS). Currently available therapies have partially effective actions and numerous side reactions. Inosine, an endogenous purine nucleoside, has immunomodulatory, neuroprotective, and analgesic properties. Herein, we evaluated the effect of inosine on the development and progression of experimental autoimmune encephalomyelitis (EAE), an experimental model of MS. Inosine (1 or 10 mg/kg, i.p.) was administrated twice a day for 40 days. Immunological and inflammatory responses were evaluated by behavioral, histological, immunohistochemical, ELISA, RT-PCR, and Western blotting analysis. The administration of inosine exerted neuroprotective effects against EAE by diminishing clinical signs, including thermal and mechanical hyperalgesia, as well as weight loss typical of the disease. These beneficial effects of inosine seem to be associated with the blockade of inflammatory cell entry into the CNS, especially lymphocytes, thus delaying the demyelinating process and astrocytes activation. In particular, up-regulation of IL-17 levels in the secondary lymphoid tissues, a result of EAE, was prevented by inosine treatment in EAE mice. Additionally, inosine consistently prevented A2AR up-regulation in the spinal cord, likely, through an ERK1-independent pathway. Altogether, these results allow us to propose that this endogenous purine might be a putative novel and helpful tool for the prevention of autoimmune and neurodegenerative diseases, such as MS. Thus, inosine could have considerable implications for future therapies of MS, and this study may represent the starting point for further investigation into the role of inosine and adenosinergic receptors in neuroinflammation processes. Graphical Abstract Preventive treatment with inosine inhibits the development and progression of EAE in C57Bl/6 mice. Furthermore, neuroinflammation and demyelinating processes

  13. RNAi-mediated suppression of endogenous storage proteins leads to a change in localization of overexpressed cholera toxin B-subunit and the allergen protein RAG2 in rice seeds.

    Science.gov (United States)

    Kurokawa, Shiho; Kuroda, Masaharu; Mejima, Mio; Nakamura, Rika; Takahashi, Yuko; Sagara, Hiroshi; Takeyama, Natsumi; Satoh, Shigeru; Kiyono, Hiroshi; Teshima, Reiko; Masumura, Takehiro; Yuki, Yoshikazu

    2014-01-01

    RNAi-mediated suppression of the endogenous storage proteins in MucoRice-CTB-RNAi seeds affects not only the levels of overexpressed CTB and RAG2 allergen, but also the localization of CTB and RAG2. A purification-free rice-based oral cholera vaccine (MucoRice-CTB) was previously developed by our laboratories using a cholera toxin B-subunit (CTB) overexpression system. Recently, an advanced version of MucoRice-CTB was developed (MucoRice-CTB-RNAi) through the use of RNAi to suppress the production of the endogenous storage proteins 13-kDa prolamin and glutelin, so as to increase CTB expression. The level of the α-amylase/trypsin inhibitor-like protein RAG2 (a major rice allergen) was reduced in MucoRice-CTB-RNAi seeds in comparison with wild-type (WT) rice. To investigate whether RNAi-mediated suppression of storage proteins affects the localization of overexpressed CTB and major rice allergens, we generated an RNAi line without CTB (MucoRice-RNAi) and investigated gene expression, and protein production and localization of two storage proteins, CTB, and five major allergens in MucoRice-CTB, MucoRice-CTB-RNAi, MucoRice-RNAi, and WT rice. In all lines, glyoxalase I was detected in the cytoplasm, and 52- and 63-kDa globulin-like proteins were found in the aleurone particles. In WT, RAG2 and 19-kDa globulin were localized mainly in protein bodies II (PB-II) of the endosperm cells. Knockdown of glutelin A led to a partial destruction of PB-II and was accompanied by RAG2 relocation to the plasma membrane/cell wall and cytoplasm. In MucoRice-CTB, CTB was localized in the cytoplasm and PB-II. In MucoRice-CTB-RNAi, CTB was produced at a level six times that in MucoRice-CTB and was localized, similar to RAG2, in the plasma membrane/cell wall and cytoplasm. Our findings indicate that the relocation of CTB in MucoRice-CTB-RNAi may contribute to down-regulation of RAG2.

  14. Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM

    Energy Technology Data Exchange (ETDEWEB)

    Mitrakou, A.; Kelley, D.; Veneman, T.; Jenssen, T.; Pangburn, T.; Reilly, J.; Gerich, J. (Univ. of Pittsburgh School of Medicine, PA (USA))

    1990-11-01

    To assess the role of muscle and liver in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), we administered an oral glucose load enriched with (14C)glucose to 10 NIDDM subjects and 10 age- and weight-matched nondiabetic volunteers and compared muscle glucose disposal by measuring forearm balance of glucose, lactate, alanine, O2, and CO2. In addition, we used the dual-lable isotope method to compare overall rates of glucose appearance (Ra) and disappearance (Rd), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1-1.5 h after glucose ingestion, plasma glucose increased by approximately 8 mM in NIDDM vs. approximately 3 mM in nondiabetic subjects (P less than 0.01); overall glucose Ra was nearly 11 g greater in NIDDM than nondiabetic subjects, but glucose Rd was not significantly different in NIDDM and nondiabetic subjects. The greater overall glucose Ra of NIDDM subjects was due to 6.8 g greater endogenous glucose output (13.7 +/- 1.1 vs. 6.8 +/- 1.0 g, P less than 0.01) and 3.8 g less oral glucose splanchnic sequestration of the oral load (31.4 +/- 1.5 vs. 27.5 +/- 0.9 g, P less than 0.05). Although glucose taken up by muscle was not significantly different in NIDDM and nondiabetic subjects (39.3 +/- 3.5 vs. 41.0 +/- 2.5 g/5 h), a greater amount of the glucose taken up by muscle in NIDDM was released as lactate and alanine (11.7 +/- 1.0 vs. 5.2 +/- 0.3 g in nondiabetic subjects, P less than 0.01), and less was stored (11.7 +/- 1.3 vs. 16.9 +/- 1.5 g, P less than 0.05). We conclude that increased systemic glucose delivery, due primarily to reduced suppression of endogenous hepatic glucose output and, to a lesser extent, reduced splanchnic glucose sequestration, is the predominant factor responsible for postprandial hyperglycemia in NIDDM.

  15. High glucose suppresses human islet insulin biosynthesis by inducing miR-133a leading to decreased polypyrimidine tract binding protein-expression

    DEFF Research Database (Denmark)

    Fred, Rikard G; Bang-Berthelsen, Claus H; Mandrup-Poulsen, Thomas

    2010-01-01

    BACKGROUND: Prolonged periods of high glucose exposure results in human islet dysfunction in vitro. The underlying mechanisms behind this effect of high glucose are, however, unknown. The polypyrimidine tract binding protein (PTB) is required for stabilization of insulin mRNA and the PTB mRNA 3....../PRINCIPAL FINDINGS: Human islets were cultured for 24 hours in the presence of low (5.6 mM) or high glucose (20 mM). Islets were also exposed to sodium palmitate or the proinflammatory cytokines IL-1beta and IFN-gamma, since saturated free fatty acids and cytokines also cause islet dysfunction. RNA was then isolated...... protein levels and insulin biosynthesis rates were decreased in response to high glucose. The miR-133a inhibitor prevented the high glucose-induced decrease in PTB and insulin biosynthesis, and the miR-133a precursor decreased PTB levels and insulin biosynthesis similarly to high glucose. CONCLUSION...

  16. Induction of the Pho Regulon Suppresses the Growth Defect of an Escherichia coli sgrS Mutant, Connecting Phosphate Metabolism to the Glucose-Phosphate Stress Response

    OpenAIRE

    Richards, Gregory R.; Vanderpool, Carin K.

    2012-01-01

    Some bacteria experience stress when glucose-6-phosphate or analogues like α-methyl glucoside-6-phosphate (αMG6P) accumulate in the cell. In Escherichia coli, the small SgrS RNA is vital to recovery from glucose-phosphate stress; the growth of sgrS mutants is strongly inhibited by αMG. SgrS helps to restore growth in part through inhibiting translation of the ptsG mRNA, which encodes the major glucose transporter EIICBGlc. While the regulatory mechanism of SgrS has been characterized, little ...

  17. Induction and suppression of the key enzymes of glycolysis and gluconeogenesis in isolated perfused rat liver in response to glucose, fructose and lactate

    Science.gov (United States)

    Wimhurst, Janet M.; Manchester, K. L.

    1973-01-01

    1. Measurements were made of the activities of the four key enzymes involved in gluconeogenesis, pyruvate carboxylase (EC 6.4.1.1), phosphoenolpyruvate carboxylase (EC 4.1.1.32), fructose 1,6-diphosphatase (EC 3.1.3.11) and glucose 6-phosphatase (EC 3.1.3.9), of serine dehydratase (EC 4.2.1.13) and of the four enzymes unique to glycolysis, glucokinase (EC 2.7.1.2), hexokinase (EC 2.7.1.1), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40), in livers from starved rats perfused with glucose, fructose or lactate. Changes in perfusate concentrations of glucose, fructose, lactate, pyruvate, urea and amino acid were monitored for each perfusion. 2. Addition of 15mm-glucose at the start of perfusion decreased the activity of pyruvate carboxylase. Constant infusion of glucose to maintain the concentration also decreased the activities of phosphoenolpyruvate carboxylase, fructose 1,6-diphosphatase and serine dehydratase. Addition of 2.2mm-glucose initially to give a perfusate sugar concentration similar to the blood sugar concentration of starved animals had no effect on the activities of the enzymes compared with zero-time controls. 3. Addition of 15mm-fructose initially decreased glucokinase activity. Constant infusion of fructose decreased activities of glucokinase, phosphofructokinase, pyruvate carboxylase, phosphoenolpyruvate carboxylase, glucose 6-phosphatase and serine dehydratase. 4. Addition of 7mm-lactate initially elevated the activity of pyruvate carboxylase, as also did constant infusion; maintenance of a perfusate lactate concentration of 18mm induced both pyruvate carboxylase and phosphoenolpyruvate carboxylase activities. 5. Addition of cycloheximide had no effect on the activities of the enzymes after 4h of perfusion at either low or high concentrations of glucose or at high lactate concentration. Cycloheximide also prevented the loss or induction of pyruvate carboxylase and phosphoenolpyruvate carboxylase activities with high substrate

  18. Ketoisocaproic acid, a metabolite of leucine, suppresses insulin-stimulated glucose transport in skeletal muscle cells in a BCAT2-dependent manner.

    Science.gov (United States)

    Moghei, Mahshid; Tavajohi-Fini, Pegah; Beatty, Brendan; Adegoke, Olasunkanmi A J

    2016-09-01

    Although leucine has many positive effects on metabolism in multiple tissues, elevated levels of this amino acid and the other branched-chain amino acids (BCAAs) and their metabolites are implicated in obesity and insulin resistance. While some controversies exist about the direct effect of leucine on insulin action in skeletal muscle, little is known about the direct effect of BCAA metabolites. Here, we first showed that the inhibitory effect of leucine on insulin-stimulated glucose transport in L6 myotubes was dampened when other amino acids were present, due in part to a 140% stimulation of basal glucose transport (P glucose transport (-34%, P glucose transport was abrogated in cells depleted of branched-chain aminotransferase 2 (BCAT2), the enzyme that catalyzes the reversible transamination of KIC to leucine. We conclude that although KIC can modulate muscle glucose metabolism, this effect is likely a result of its transamination back to leucine. Therefore, limiting the availability of leucine, rather than those of its metabolites, to skeletal muscle may be more critical in the management of insulin resistance and its sequelae. Copyright © 2016 the American Physiological Society.

  19. Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics

    NARCIS (Netherlands)

    Coelho, M.; Nunes, P.; Mendes, V.M.; Manadas, B.; Heerschap, A.; Jones, J.G.

    2015-01-01

    Mice deficient in adipose triglyceride lipase (ATGL(-/-)) present elevated ectopic lipid levels but are paradoxically glucose-tolerant. Measurement of endogenous glucose production (EGP) and Cori cycle activity provide insights into the maintenance of glycemic control in these animals. These

  20. Comparison of the physiological relevance of systemic vs. portal insulin delivery to evaluate whole body glucose flux during an insulin clamp.

    Science.gov (United States)

    Farmer, Tiffany D; Jenkins, Erin C; O'Brien, Tracy P; McCoy, Gregory A; Havlik, Allison E; Nass, Erik R; Nicholson, Wendell E; Printz, Richard L; Shiota, Masakazu

    2015-02-01

    To understand the underlying pathology of metabolic diseases, such as diabetes, an accurate determination of whole body glucose flux needs to be made by a method that maintains key physiological features. One such feature is a positive differential in insulin concentration between the portal venous and systemic arterial circulation (P/S-IG). P/S-IG during the determination of the relative contribution of liver and extra-liver tissues/organs to whole body glucose flux during an insulin clamp with either systemic (SID) or portal (PID) insulin delivery was examined with insulin infusion rates of 1, 2, and 5 mU·kg(-1)·min(-1) under either euglycemic or hyperglycemic conditions in 6-h-fasted conscious normal rats. A P/S-IG was initially determined with endogenous insulin secretion to exist with a value of 2.07. During an insulin clamp, while inhibiting endogenous insulin secretion by somatostatin, P/S-IG remained at 2.2 with PID, whereas, P/S-IG disappeared completely with SID, which exhibited higher arterial and lower portal insulin levels compared with PID. Consequently, glucose disappearance rates and muscle glycogen synthetic rates were higher, but suppression of endogenous glucose production and liver glycogen synthetic rates were lower with SID compared with PID. When the insulin clamp was performed with SID at 2 and 5 mU·kg(-1)·min(-1) without managing endogenous insulin secretion under euglycemic but not hyperglycemic conditions, endogenous insulin secretion was completely suppressed with SID, and the P/S-IG disappeared. Thus, compared with PID, an insulin clamp with SID underestimates the contribution of liver in response to insulin to whole body glucose flux. Copyright © 2015 the American Physiological Society.

  1. p16(INK4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Li

    2011-02-01

    Full Text Available Although caloric restriction (CR has been shown to increase lifespan in various animal models, the mechanisms underlying this phenomenon have not yet been revealed. We developed an in vitro system to mimic CR by reducing glucose concentration in cell growth medium which excludes metabolic factors and allows assessment of the effects of CR at the cellular and molecular level. We monitored cellular proliferation of normal WI-38, IMR-90 and MRC-5 human lung fibroblasts and found that glucose restriction (GR can inhibit cellular senescence and significantly extend cellular lifespan compared with cells receiving normal glucose (NG in the culture medium. Moreover, GR decreased expression of p16(INK4a (p16, a well-known senescence-related gene, in all of the tested cell lines. Over-expressed p16 resulted in early replicative senescence in glucose-restricted cells suggesting a crucial role of p16 regulation in GR-induced cellular lifespan extension. The decreased expression of p16 was partly due to GR-induced chromatin remodeling through effects on histone acetylation and methylation of the p16 promoter. GR resulted in an increased expression of SIRT1, a NAD-dependent histone deacetylase, which has positive correlation with CR-induced longevity. The elevated SIRT1 was accompanied by enhanced activation of the Akt/p70S6K1 signaling pathway in response to GR. Furthermore, knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling. Collectively, these results provide new insights into interactions between epigenetic and genetic mechanisms on CR-induced longevity that may contribute to anti-aging approaches and also provide a general molecular model for studying CR in vitro in mammalian systems.

  2. [Role of orexin-A-mediated communication system between brain and peripheral tissues on the development of post-ischemic glucose intolerance-induced neuronal damage].

    Science.gov (United States)

    Harada, Shinichi

    2014-01-01

    I recently found that cerebral ischemic stress per se causes hyperglycemia (i.e., post-ischemic glucose intolerance) and suppression of post-ischemic glucose intolerance might be important to improve prognosis. Here, I analyzed the efficacy of suppression of post-ischemic glucose intolerance using orexin-A (OXA) endogenous neuropeptide as a novel therapeutic strategy against cerebral ischemic neuronal damage. OXA in hypothalamus plays a role in many physiological functions including regulation of glucose metabolism. I previously found that the development of post-ischemic glucose intolerance is suppressed by OXA. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic OXA-mediated suppression of post-ischemic glucose intolerance and neuronal damage. Intrahypothalamic administration of OXA significantly suppressed the development of post-ischemic glucose intolerance on day 1 and of neuronal damage on day 3 after middle cerebral artery occlusion (MCAO). In the liver, MCAO-induced decrease in insulin receptors and increase in gluconeogenic enzymes on day 1 was recovered to control levels by OXA; these effects were reversed by hepatic vagotomy. In the medulla oblongata, OXA induced co-localization of the cholinergic neuronal marker choline acetyltransferase with orexin-1 receptor and c-Fos. These results suggest that the vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates neuroprotection by hypothalamic OXA.

  3. Differential impact of selective GH deficiency and endogenous GH excess on insulin-mediated actions in muscle and liver of male mice.

    Science.gov (United States)

    Cordoba-Chacon, Jose; Gahete, Manuel D; McGuinness, Owen P; Kineman, Rhonda D

    2014-11-15

    A reciprocal relationship between insulin sensitivity and glucose tolerance has been reported in some mouse models and humans with isolated changes in growth hormone (GH) production and signaling. To determine if this could be explained in part by tissue-specific changes in insulin sensitivity, hyperinsulinemic-euglycemic clamps were performed in mice with adult-onset, isolated GH deficiency and in mice with elevated endogenous GH levels due to somatotrope-specific loss of IGF-I and insulin receptors. Our results demonstrate that circulating GH levels are negatively correlated with insulin-mediated glucose uptake in muscle but positively correlated with insulin-mediated suppression of hepatic glucose production. A positive relationship was also observed between GH levels and endpoints of hepatic lipid metabolism known to be regulated by insulin. These results suggest hepatic insulin resistance could represent an early metabolic defect in GH deficiency.

  4. Structure, function and protein engineering in starch debranching enzyme systems. Barley limit dextrinase and its endogenous inhibitor

    DEFF Research Database (Denmark)

    Møller, Marie Sofie

    Starch is the most abundant storage carbohydrate in cereal grains. It is composed primarily of amylopectin, a polymer of glucose in which α-1,4-linked glucan chains are branched with α-1,6-bonds. Enzymatic degradation of starch in germinating barley seeds involves an initial solubilisation, mainly...... seed, it has a key role in malting and brewing. But an endogenous inhibitor, limit dextrinase inhibitor (LDI), is present in barley seeds. It specifically inhibits LD, and thereby suppresses the degradation of branched limit dextrins to fermentable sugars. The knowledge about this enzyme:inhibitor pair....... Here I present crystal structures of LD, and LD in complex with 62-α-maltotriosyl-maltotriose, i.e. a limit dextrin, or two maltotriose molecules. The branched ligand is in contact with LD via interactions between all six glucose units and amino acid residues of LD. The active site cleft of LD can...

  5. Estimates of insulin sensitivity from the intravenous-glucose-modified-clamp test depend on suppression of lipolysis in type 2 diabetes: a randomised controlled trial.

    Science.gov (United States)

    Kahl, Sabine; Nowotny, Bettina; Piepel, Simon; Nowotny, Peter J; Strassburger, Klaus; Herder, Christian; Pacini, Giovanni; Roden, Michael

    2014-10-01

    The combined IVGTT-hyperinsulinaemic-euglycaemic clamp (Botnia clamp) allows the assessment of insulin secretion and sensitivity in one experiment. It remains unclear whether this clamp yields results comparable with those of the standard hyperinsulinaemic-euglycaemic clamp (SHEC) in diabetes patients. We hypothesised that the IVGTT induces responses affecting insulin sensitivity assessment. Of 22 randomised diet- or metformin-treated patients with well-controlled type 2 diabetes, 19 randomly underwent a Botnia clamp and an SHEC, spaced by 2 weeks, in one clinical research centre in a crossover study. The main outcomes were whole-body and hepatic insulin sensitivity as measured by the clamp and [6,6-(2)H2]glucose. Substrate utilisation was assessed from indirect calorimetry and beta cell function from insulin dynamics during IVGTT. The values of whole-body insulin sensitivity obtained from Botnia clamp and SHEC were correlated (r = 0.87, p clamp, but differed after IVGTT. The contribution of glucose oxidation to glucose disposal increased by 2.2 ± 0.3 and 1.2 ± 0.4 mg kg fat-free mass (FFM)(-1) min(-1) (Botnia and SHEC, p clamps correlated with individual variations of insulin sensitivity. The Botnia clamp provides similar estimates of insulin sensitivity as SHEC in patients with type 2 diabetes, but changes in NEFA during IVGTT may affect insulin sensitivity and thereby the discrimination between insulin-sensitive and insulin-resistant individuals. ClinicalTrials.gov NCT01397279 FUNDING: The study was funded by the Ministry of Science and Research of the State of North Rhine-Westphalia and the German Federal Ministry of Health, and supported in part by grants from the Federal Ministry for Research to the Centers for Diabetes Research, Helmholtz Alliance Imaging and Curing Environmental Metabolic Diseases and the Schmutzler-Stiftung.

  6. Protocatechuic Acid, a Phenolic from Sansevieria roxburghiana Leaves, Suppresses Diabetic Cardiomyopathy via Stimulating Glucose Metabolism, Ameliorating Oxidative Stress, and Inhibiting Inflammation

    Directory of Open Access Journals (Sweden)

    Niloy Bhattacharjee

    2017-05-01

    Full Text Available Persistent hyperglycemia, impairment of redox status and establishment of inflammatory pathophysiology integrally play important role in the pathogenesis of diabetic cardiomyopathy (DC. Present study examined the therapeutic potential of protocatechuic acid isolated from the Sansevieria roxburghiana rhizomes against DC employing rodent model of type 2 diabetes (T2D. T2D was induced by high fat diet + a low-single dose of streptozotocin (35 mg/kg, i.p.. T2D rats exhibited significantly (p < 0.01 high fasting blood glucose level. Alteration in serum lipid profile (p < 0.01 and increased levels of lactate dehydrogenase (p < 0.01 and creatine kinase (p < 0.01 in the sera of T2D rats revealed the occurrence of hyperlipidemia and diabetic pathophysiology. A significantly (p < 0.01 high levels of serum C-reactive protein and pro-inflammatory mediators revealed the establishment of inflammatory occurrence in T2D rats. Besides, significantly high levels of troponins in the sera revealed the establishment of cardiac dysfunctions in T2D rats. However, protocatechuic acid (50 and 100 mg/kg, p.o. treatment could significantly reverse the changes in serum biochemical parameters related to cardiac dysfunctions. Molecular mechanism studies demonstrated impairment of signaling cascade, IRS1/PI3K/Akt/AMPK/p 38/GLUT4, in glucose metabolism in the skeletal muscle of T2D rats. Significant (p < 0.01 activation of polyol pathway, enhanced production of AGEs, oxidative stress and up-regulation of inflammatory signaling cascades (PKC/NF-κB/PARP were observed in the myocardial tissue of T2D rats. However, protocatechuic acid (50 and 100 mg/kg, p.o. treatment could significantly (p < 0.05–0.01 stimulate glucose metabolism in skeletal muscle, regulated glycemic and lipid status, reduced the secretion of pro-inflammatory cytokines, and restored the myocardial physiology in T2D rats near to normalcy. Histological assessments were also in agreement with the above findings

  7. Endogenous price leadership

    OpenAIRE

    van Damme, E.E.C.; Hurkens, S.

    2004-01-01

    We consider a linear price setting duopoly game with differentiated products and determine endogenously which of the players will lead and which will follow. While the follower role is most attractive for each firm, we show that waiting is more risky for the low cost firm so that, consequently, risk dominance considerations, as in Harsanyi and Selten (1988), allow the conclusion that only the high cost firm will choose to wait. Hence, the low cost firm will emerge as the endogenous price leader.

  8. Dietary Fatty Acids Differentially Associate with Fasting Versus 2-Hour Glucose Homeostasis: Implications for The Management of Subtypes of Prediabetes.

    Directory of Open Access Journals (Sweden)

    Nicola Guess

    Full Text Available Over-nutrition has fuelled the global epidemic of type 2 diabetes, but the role of individual macronutrients to the diabetogenic process is not well delineated. We aimed to examine the impact of dietary fatty acid intake on fasting and 2-hour plasma glucose concentrations, as well as tissue-specific insulin action governing each. Normoglycemic controls (n = 15, athletes (n = 14, and obese (n = 23, as well as people with prediabetes (n = 10 and type 2 diabetes (n = 11, were queried about their habitual diet using a Food Frequency Questionnaire. All subjects were screened by an oral glucose tolerance test (OGTT and studied using the hyperinsulinemic/euglycemic clamp with infusion of 6,62H2-glucose. Multiple regression was performed to examine relationships between dietary fat intake and 1 fasting plasma glucose, 2 % suppression of endogenous glucose production, 3 2-hour post-OGTT plasma glucose, and 4 skeletal muscle insulin sensitivity (glucose rate of disappearance (Rd and non-oxidative glucose disposal (NOGD. The %kcal from saturated fat (SFA was positively associated with fasting (β = 0.303, P = 0.018 and 2-hour plasma glucose (β = 0.415, P<0.001, and negatively related to % suppression of hepatic glucose production (β = -0.245, P = 0.049, clamp Rd (β = -0.256, P = 0.001 and NOGD (β = -0.257, P = 0.001. The %kcal from trans fat was also negatively related to clamp Rd (β = -0.209, P = 0.008 and NOGD (β = -0.210, P = 0.008. In contrast, the %kcal from polyunsaturated fat (PUFA was negatively associated with 2-hour glucose levels (β = -0.383, P = 0.001, and positively related to Rd (β = 0.253, P = 0.007 and NOGD (β = 0.246, P = 0.008. Dietary advice to prevent diabetes should consider the underlying pathophysiology of the prediabetic state.

  9. Omeprazole and PGC-formulated heparin binding epidermal growth factor normalizes fasting blood glucose and suppresses insulitis in multiple low dose streptozotocin diabetes model

    Science.gov (United States)

    Castillo, Gerardo M.; Nishimoto-Ashfield, Akiko; Banerjee, Aryamitra A.; Landolfi, Jennifer A.; Lyubimov, Alexander V.; Bolotin, Elijah M.

    2013-01-01

    Purpose Our objective was to develop novel nanocarriers (protected graft copolymer, PGC) that improve the stability of heparin binding EGF (HBEGF) and gastrin and then to use PGC-formulated HBEGF (PGC-HBEGF) and Omeprazole (+/− PGC-gastrin) for normalizing fasting blood glucose (FBG) and improving islet function in diabetic mice. Method HBEGF, PGC-HBEGF, Omeprazole, Omeprazole+PGC-HBEGF, Omeprazole+PGC-gastrin+PGC-HBEGF and epidermal growth factor (EGF)+gastrin were tested in multiple low dose streptozotocin diabetic mice. Results Omeprazole+PGC-HBEGF normalized FBG and is better than EGF+gastrin at improving islet function and decreasing insulitis. Groups treated with Omeprazole, Omeprazole+PGC-HBEGF, or EGF+gastrin have significantly improved islet function versus saline control. All animals that received PGC-HBEGF had significantly reduced islet insulitis versus saline control. Non-FBG was lower for Omeprazole+PGC-gastrin+PGC-HBEGF but Omeprazole+PGC-HBEGF alone showed better FBG and glucose tolerance. Conclusions Omeprazole+PGC-HBEGF provides a sustained exposure to both EGFRA and gastrin, improves islet function, and decreases insulitis in multiple low dose streptozotocin diabetic mice. Although HBEGF or EGF elevates non-FBG, it facilitates a reduction of insulitis and, in the presence of Omeprazole, provides normalization of FBG at the end of treatment. The study demonstrates Omeprazole and PGC-HBEGF is a viable treatment for diabetes. PMID:23793991

  10. Hyperglucagonemia precedes a decline in insulin secretion and causes hyperglycemia in chronically glucose-infused rats

    Science.gov (United States)

    Jamison, Rachel A.; Stark, Romana; Dong, Jianying; Yonemitsu, Shin; Zhang, Dongyan; Shulman, Gerald I.

    2011-01-01

    Islet damage from glucose toxicity is implicated in the pathogenesis of type 2 diabetes, but the sequence of events leading to islet cell dysfunction and hyperglycemia remains unclear. To examine the early stages of islet pathology resulting from increased basal glucose loads, normal awake rats were infused with glucose continuously for 10 days. Plasma glucose and markers of islet and liver function were monitored throughout the infusion. After initial hyperglycemia, rats adapted to the infusion and maintained euglycemia for approximately 4 days. Continued infusion led to worsening hyperglycemia in just 5% of rats after 6 days, but 69% after 8 days and 89% after 10 days, despite unchanged basal and stimulated plasma insulin and C-peptide concentrations. In contrast, plasma glucagon concentrations increased fivefold. Endogenous glucose production (EGP) was appropriately suppressed after 4 days (2.8 ± 0.7 vs. 6.1 ± 0.4 mg·kg−1·min−1 on day 0, P insulin secretion. Such hyperglucagonemia could lead to excessive glucose production overwhelming the capacity of the β-cell to maintain glucose homeostasis. PMID:21862723

  11. Enhanced apoptotic reaction correlates with suppressed tumor glucose utilization after cytotoxic chemotherapy: use of 99mTc-Annexin V, 18F-FDG, and histologic evaluation.

    Science.gov (United States)

    Takei, Toshiki; Kuge, Yuji; Zhao, Songji; Sato, Masayuki; Strauss, H William; Blankenberg, Francis G; Tait, Jonathan F; Tamaki, Nagara

    2005-05-01

    Cancer chemotherapy enhances the apoptosis, whereas apoptosis is a suicidal mechanism requiring energy. We determined the relationship between apoptosis and glucose utilization during cancer chemotherapy using (99m)Tc-annexin V ((99m)Tc-annexin A5) and (18)F-FDG and compared their uptake with histologic findings in a rat tumor model. Allogenic hepatoma cells (KDH-8) were inoculated into the left calf muscle of male Wistar rats (WKA). Eleven days after the inoculation, the rats were randomly divided into 3 groups: The first group (n = 7) received a single dose of gemcitabine (90 mg/kg, intravenously), the second group (n = 8) received cyclophosphamide (150 mg/kg, intraperitoneally), and the third group (n = 7) was untreated and served as the control group. We injected (99m)Tc-annexin V 48 h after the chemotherapy and then injected (18)F-FDG to all rats 1 h before sacrifice. Six hours after (99m)Tc-annexin V injection, the rats were sacrificed and the organs, including the tumor, were removed and radioactivity was counted. The radioactivities of (18)F and (99m)Tc in the organs were determined using normalization by tissue weight. Histologic evaluation by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method and the immunostaining of glucose transporter-1 (GLUT-1) were also performed to obtain the indices of apoptosis and glucose utilization, respectively. The rate of positively stained cells was calculated and analyzed statistically. After chemotherapy using gemcitabine and cyclophosphamide, the (99m)Tc-annexin V uptake (percentage injected dose per gram x kg [(%ID/g) x kg]; mean +/- SD) in tumor increased significantly (0.062 +/- 0.012 (%ID/g) x kg in the gemcitabine-treated group and 0.050 +/- 0.012 (%ID/g) x kg in the cyclophosphamide group vs. 0.031 +/- 0.005 (%ID/g) x kg in the control group; P chemotherapy as determined using radiotracers and histologic evaluation. The increase in (99m)Tc-annexin V and the

  12. Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions

    Directory of Open Access Journals (Sweden)

    Huang Po-Hsun

    2012-08-01

    Full Text Available Abstract Background Far infra-red (IFR therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC and EPC-related vasculogenesis remain unclear. We hypothesized that IFR radiation can restore blood flow recovery in ischemic hindlimb in diabetic mice by enhancement of EPCs functions and homing process. Materials and methods Starting at 4 weeks after the onset of diabetes, unilateral hindlimb ischemia was induced in streptozotocine (STZ-induced diabetic mice, which were divided into control and IFR therapy groups (n = 6 per group. The latter mice were placed in an IFR dry sauna at 34°C for 30 min once per day for 5 weeks. Results Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group. Flow cytometry analysis showed impaired EPCs (Sca-1+/Flk-1+ mobilization after ischemia surgery in diabetic mice with or without IFR therapy (n = 6 per group. However, as compared to those in the control group, bone marrow-derived EPCs differentiated into endothelial cells defined as GFP+/CD31+ double-positive cells were significantly increased in ischemic tissue around the vessels in diabetic mice that received IFR radiation. In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H2O2 production. Nude mice received human EPCs treated with IFR in high glucose medium showed a significant improvement in blood flow recovery in ischemic limb compared to those without IFR therapy. IFR therapy promoted blood flow recovery and new vessel formation in STZ-induced diabetic mice. Conclusions Administration of IFR therapy promoted collateral flow recovery and new vessel formation in STZ

  13. Disturbance of endogenous hydrogen sulfide generation and endoplasmic reticulum stress in hippocampus are involved in homocysteine-induced defect in learning and memory of rats.

    Science.gov (United States)

    Li, Man-Hong; Tang, Ji-Ping; Zhang, Ping; Li, Xiang; Wang, Chun-Yan; Wei, Hai-Jun; Yang, Xue-Feng; Zou, Wei; Tang, Xiao-Qing

    2014-04-01

    Homocysteine (Hcy) is a risk factor for Alzheimer's disease (AD). Hydrogen sulfide (H2S) acts as an endogenous neuromodulator and neuroprotectant. It has been shown that endoplasmic reticulum (ER) stress is involved in the pathological mechanisms of the learning and memory dysfunctions and that H2S exerts its neuroprotective role via suppressing ER stress. In the present work, we explored the effects of intracerebroventricular injection of Hcy on the formation of learning and memory, the generation of endogenous H2S, and the expression of ER stress in the hippocampus of rats. We found that intracerebroventricular injection of Hcy in rats leads to learning and memory dysfunctions in the Morris water maze and novel of object recognition test and decreases in the expression of cystathionine-β-synthase, the major enzyme responsible for endogenous H2S generation, and the generation of endogenous H2S in the hippocampus of rats. We also showed that exposure of Hcy could up-regulate the expressions of glucose-regulated protein 78 (GRP78), CHOP, and cleaved caspase-12, which are the major mark proteins of ER stress, in the hippocampus of rats. Taken together, these results suggest that the disturbance of hippocampal endogenous H2S generation and the increase in ER stress in the hippocampus are related to Hcy-induced defect in learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion.

    Science.gov (United States)

    Li, Tingting; Xu, Jie; Qin, Xinghua; Hou, Zuoxu; Guo, Yongzheng; Liu, Zhenhua; Wu, Jianjiang; Zheng, Hong; Zhang, Xing; Gao, Feng

    2017-11-01

    Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia-reperfusion (I/R) injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. We found that glucose uptake was remarkably diminished in the myocardium following reperfusion in Sprague-Dawley rats as detected by 18 F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by threefold and GLUT4 translocation remained unchanged compared with those of sham-treated rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated I/R injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, whereas its knockdown increased glucose uptake, suggesting that PDK4 has a role in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial I/R. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in the myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial I/R injury. Copyright © 2017 the American Physiological Society.

  15. Evolution of endogenous analgesia

    NARCIS (Netherlands)

    Niesters, Marieke

    2014-01-01

    Endogenous pain modulation is a complex phenomenon involved in the perception of pain. It consists of top-down inhibitory and facilitatory pathways that originate at higher sites within the central nervous system and converge at dorsal horn neurons in the spinal cord, to modulate incoming afferent

  16. Unemployment and endogenous growth

    NARCIS (Netherlands)

    van Schaik, A.B.T.M.; de Groot, H.L.F.

    1995-01-01

    In this paper we develop a two-sector endogenous growth model with a dual labour market, based on efficiency wages. Growth is driven by intentional R&D performed in the high-tech and high-wage sector. It is examined how a change in rivalry among firms affects simultaneously growth and unemployment.

  17. The Endogenous Feedback Network

    DEFF Research Database (Denmark)

    Augustenborg, Claudia Carrara

    2010-01-01

    proposals, it will first be considered the extents of their reciprocal compatibility, tentatively shaping an integrated, theoretical profile of consciousness. A new theory, the Endogenous Feedback Network (EFN) will consequently be introduced which, beside being able to accommodate the main tenets...

  18. Endogenous leadership in teams

    OpenAIRE

    Huck, S; Rey Biel, P.

    2004-01-01

    In this paper we study the mechanics of ``leading by example'' in teams. Leadership is beneficial for the entire team when agents are conformists, i.e., dislike effort differentials. We also show how leadership can arise endogenously and discuss what type of leader benefits a team most.

  19. Overexpression of miR-130a-3p/301a-3p attenuates high glucose-induced MPC5 podocyte dysfunction through suppression of TNF-α signaling.

    Science.gov (United States)

    Jiang, Yan; Wang, Wei; Liu, Zong-Yang; Xie, Yi; Qian, Yuan; Cai, Xue-Ni

    2018-01-01

    Tumor necrosis factor (TNF)-α has been reported to be important in glomerulonephritis, which is closely associated with podocyte dysfunction and apoptosis. However, the precise mechanisms by which TNF-α expression are regulated remain unclear. The purpose of the present study was to investigate the role of microRNA (miR)-130a-3p/301a-3p in the post-transcriptional control of TNF-α expression and high glucose (HG)-induced podocyte dysfunction. Mice MPC5 podocytes were incubated with HG and transfected with miR-130a-3p/301a-3p mimics or inhibitors, reactive oxygen species (ROS) levels were measured by flow cytometry assay, and the mRNA and protein levels were assayed by using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The targeted genes were predicted by a bioinformatics algorithm and verified using a dual luciferase reporter assay. It was observed that miR-130a-3p/301a-3p was a novel regulator of TNF-α in mouse podocytes. miR-130a-3p/301a-3p mimics inhibited TNF-α 3'-untranslated region luciferase reporter activity, in addition to endogenous TNF-α protein expression. Furthermore, forced expression of miR-130a-3p or miR-301a-3p resulted in the downregulation of ROS and malondialdehyde (MDA) and the upregulation of superoxide dismutase (SOD) 1 in the presence of HG. Inhibition of TNF-α level prevented a remarkable reduction in SOD activity and a marked increase in ROS and MDA levels in HG-treated podocytes. Furthermore, TNF-α loss-of-function significantly reversed HG-induced podocyte apoptosis. These data demonstrated a novel up-stream role for miR-130a-3p/301a-3p in TNF-α-mediated podocyte dysfunction and apoptosis in the presence of HG.

  20. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  1. Endogenous growth and the environment

    NARCIS (Netherlands)

    Withagen, C.A.A.M.; Vellinga, N.

    2001-01-01

    This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

  2. Glucose Sensing

    CERN Document Server

    Geddes, Chris D

    2006-01-01

    Topics in Fluorescence Spectroscopy, Glucose Sensing is the eleventh volume in the popular series Topics in Fluorescence Spectroscopy, edited by Drs. Chris D. Geddes and Joseph R. Lakowicz. This volume incorporates authoritative analytical fluorescence-based glucose sensing reviews specialized enough to be attractive to professional researchers, yet also appealing to the wider audience of scientists in related disciplines of fluorescence. Glucose Sensing is an essential reference for any lab working in the analytical fluorescence glucose sensing field. All academics, bench scientists, and industry professionals wishing to take advantage of the latest and greatest in the continuously emerging field of glucose sensing, and diabetes care & management, will find this volume an invaluable resource. Topics in Fluorescence Spectroscopy Volume 11, Glucose Sensing Chapters include: Implantable Sensors for Interstitial Fluid Smart Tattoo Glucose Sensors Optical Enzyme-based Glucose Biosensors Plasmonic Glucose Sens...

  3. Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals

    DEFF Research Database (Denmark)

    Jacobsen, Siv H; Bojsen-Møller, Kirstine N; Dirksen, Carsten

    2013-01-01

    after RYGB is rapid entry of glucose into the systemic circulation due to modified gastrointestinal anatomy, causing hypersecretion of insulin and other hormones influencing glucose disappearance and endogenous glucose production. METHODS: We determined glucose absorption and metabolism and the rate....... These changes were brought about by changes in glucose kinetics: (1) a more rapid appearance of ingested glucose in the systemic circulation, and a concomitant increase in insulin and glucagon-like peptide-1 secretion; (2) postprandial glucose disappearance was maintained at a high rate for a longer time after...... RYGB. Endogenous glucose production was similar before and after surgery. Postoperative glucagon secretion increased and showed a biphasic response after RYGB. Adipose tissue basal rate of lipolysis was higher after RYGB. CONCLUSIONS/INTERPRETATION: A rapid rate of absorption of ingested glucose...

  4. Effects of taurine on plasma glucose concentration and active glucose transport in the small intestine.

    Science.gov (United States)

    Tsuchiya, Yo; Kawamata, Koichi

    2017-11-01

    Taurine lowers blood glucose levels and improves hyperglycemia. However, its effects on glucose transport in the small intestine have not been investigated. Here, we elucidated the effect of taurine on glucose absorption in the small intestine. In the oral glucose tolerance test, addition of 10 mmol/L taurine suppressed the increase in hepatic portal glucose concentrations. To investigate whether the suppressive effect of taurine occurs via down-regulation of active glucose transport in the small intestine, we performed an assay using the everted sac of the rat jejunum. Addition of taurine to the mucosal side of the jejunum suppressed active glucose transport via sodium-glucose cotransporter 1 (SGLT1). After elimination of chloride ions from the mucosal solution, taurine did not show suppressive effects on active glucose transport. These results suggest that taurine suppressed the increase in hepatic portal glucose concentrations via suppression of SGLT1 activity in the rat jejunum, depending on chloride ions. © 2017 Japanese Society of Animal Science.

  5. The immediate effects of a single bout of aerobic exercise on oral glucose tolerance across the glucose tolerance continuum

    DEFF Research Database (Denmark)

    Knudsen, Sine H; Karstoft, Kristian; Pedersen, Bente K

    2014-01-01

    , plasma glucose concentrations and kinetics, insulin, C-peptide, and glucagon were measured. Rates (mg kg(-1) min(-1)) of glucose appearance from endogenous (RaEndo) and exogenous (oral glucose; Ra OGTT) sources, and glucose disappearance (Rd) were determined. We found that exercise increased RaEndo, Ra......We investigated glucose tolerance and postprandial glucose fluxes immediately after a single bout of aerobic exercise in subjects representing the entire glucose tolerance continuum. Twenty-four men with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D; age......: 56 ± 1 years; body mass index: 27.8 ± 0.7 kg/m(2), P > 0.05) underwent a 180-min oral glucose tolerance test (OGTT) combined with constant intravenous infusion of [6,6-(2)H2]glucose and ingestion of [U-(13)C]glucose, following 1 h of exercise (50% of peak aerobic power) or rest. In both trials...

  6. Involvement of progranulin in hypothalamic glucose sensing and feeding regulation.

    Science.gov (United States)

    Kim, Hyun-Kyong; Shin, Mi-Seon; Youn, Byung-Soo; Namkoong, Churl; Gil, So Young; Kang, Gil Myoung; Yu, Ji Hee; Kim, Min-Seon

    2011-12-01

    Progranulin (PGRN) is a secreted glycoprotein with multiple biological functions, including modulation of wound healing and inflammation. Hypothalamic PGRN has been implicated in the development of sexual dimorphism. In the present study, a potential role for PGRN in the hypothalamic regulation of appetite and body weight was investigated. In adult rodents, PGRN was highly expressed in periventricular tanycytes and in hypothalamic neurons, which are known to contain glucose-sensing machinery. Hypothalamic PGRN expression levels were decreased under low-energy conditions (starvation and 2-deoxy-D-glucose administration) but increased under high-energy condition (postprandially). Intracerebrovetricular administration of PGRN significantly suppressed nocturnal feeding as well as hyperphagia induced by 2-deoxyglucose, neuropeptide Y, and Agouti-related peptide. Moreover, the inhibition of hypothalamic PGRN expression or action increased food intake and promoted weight gain, suggesting that endogenous PGRN functions as an appetite suppressor in the hypothalamus. Investigation of the mechanism of action revealed that PGRN diminished orexigenic neuropeptide Y and Agouti-related peptide production but stimulated anorexigenic proopiomelanocortin production, at least in part through the regulation of hypothalamic AMP-activated protein kinase. Notably, PGRN was also expressed in hypothalamic microglia. In diet-induced obese mice, microglial PGRN expression was increased, and the anorectic response to PGRN was blunted. These findings highlight a physiological role for PGRN in hypothalamic glucose-sensing and appetite regulation. Alterations in hypothalamic PGRN production or action may be linked to appetite dysregulation in obesity.

  7. Endogenous cannabinoids and appetite.

    Science.gov (United States)

    Kirkham, T C; Williams, C M

    2001-06-01

    Since pre-history, Cannabis sativa has been exploited for its potent and manifold pharmacological actions. Amongst the most renowned of these actions is a tendency to provoke ravenous eating. The characterization of the psychoactive principals in cannabis (exogenous cannabinoids) and, more recently, the discovery of specific brain cannabinoid receptors and their endogenous ligands (endocannabinoids) has stimulated research into the physiological roles of endocannabinoid systems. In this review, we critically discuss evidence from the literature that describe studies on animals and human subjects to support endocannabinoid involvement in the control of appetite. We describe the hyperphagic actions of the exogenous cannabinoid, Delta9-tetrahydrocannabinol, and the endogenous CB1 ligands, anandamide and 2-arachidonylglycerol, and present evidence to support a specific role of endocannabinoid systems in appetitive processes related to the incentive and reward properties of food. A case is made for more comprehensive and systematic analyses of cannabinoid actions on eating, in the anticipation of improved therapies for disorders of appetite and body weight, and a better understanding of the biopsychological processes underlying hunger.

  8. Sweet taste receptor serves to activate glucose- and leptin-responsive neurons in the hypothalamic arcuate nucleus and participates in glucose responsiveness.

    Directory of Open Access Journals (Sweden)

    Daisuke Kohno

    2016-11-01

    Full Text Available The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC: glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanism underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2 and taste type 1 receptor 3 (T1R3 and senses sweet tastes. T1R2 and T1R3 receptors are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca2+ concentration ([Ca2+]i in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10-5 M-10-2 M dose dependently increased [Ca2+]i in 12-16% of ARC neurons. The sucralose-induced [Ca2+]i increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca2+]i increase was inhibited under an extracellular Ca2+-free condition and in the presence of an L-type Ca2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentage of proopiomelanocortin (POMC neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular

  9. Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness

    Science.gov (United States)

    Kohno, Daisuke; Koike, Miho; Ninomiya, Yuzo; Kojima, Itaru; Kitamura, Tadahiro; Yada, Toshihiko

    2016-01-01

    The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC): glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanisms underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2) and taste type 1 receptor 3 (T1R3) and senses sweet tastes. T1R2 and T1R3 are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca2+ concentration ([Ca2+]i) in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10−5–10−2 M dose dependently increased [Ca2+]i in 12–16% of ARC neurons. The sucralose-induced [Ca2+]i increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca2+]i increase was inhibited under an extracellular Ca2+-free condition and in the presence of an L-type Ca2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentages of proopiomelanocortin (POMC) neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular activation mainly

  10. Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness.

    Science.gov (United States)

    Kohno, Daisuke; Koike, Miho; Ninomiya, Yuzo; Kojima, Itaru; Kitamura, Tadahiro; Yada, Toshihiko

    2016-01-01

    The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC): glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanisms underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2) and taste type 1 receptor 3 (T1R3) and senses sweet tastes. T1R2 and T1R3 are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca2+ concentration ([Ca2+]i) in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10-5-10-2 M dose dependently increased [Ca2+]i in 12-16% of ARC neurons. The sucralose-induced [Ca2+]i increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca2+]i increase was inhibited under an extracellular Ca2+-free condition and in the presence of an L-type Ca2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentages of proopiomelanocortin (POMC) neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular activation mainly occurs on

  11. Progesterone impairs cell respiration and suppresses a compensatory increase in glucose transport in isolated rat skeletal muscle: a non-genomic mechanism contributing to metabolic adaptation to late pregnancy?

    Science.gov (United States)

    Gras, F; Brunmair, B; Quarré, L; Szöcs, Z; Waldhäusl, W; Fürnsinn, C

    2007-12-01

    The aim of the study was to gain better insight into the mechanisms responsible for impaired glucose metabolism during late pregnancy. We explored the direct effects of progesterone on glucose metabolism of skeletal muscle. Specimens of skeletal muscle from untreated rats were incubated with progesterone and rates of substrate fluxes through the various pathways of glucose metabolism were analysed. Progesterone dose-dependently reduced the rates of glucose and pyruvate oxidation (insulin-stimulated rates after 5 h of exposure to 1 and 10 mumol/l progesterone: glucose oxidation, -6 +/- 4%, NS, and -39 +/- 4%, p glucose transport, but this response was blunted in the case of progesterone (change of glucose transport in response to 10 mumol/l progesterone vs 60 nmol/l rotenone, both causing a reduction in glucose oxidation by -39%: progesterone, +14 +/- 8% vs rotenone, +84 +/- 23%, p glucose oxidation after 30 min: -29 +/- 7%, p glucose transport, causing cellular carbohydrate deficiency in isolated rat skeletal muscle. This effect is mediated by a direct, rapid and non-genomic mechanism and could contribute to pregnancy-associated changes in glucose homeostasis.

  12. Glucose-dependent insulinotropic polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel Bring

    2016-01-01

    The hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted by enteroendocrine cells in the intestinal mucosa in response to nutrient ingestion. They are called incretin hormones because of their ability to enhance insulin secretion. However, i...... glucose to prevent hypoglycaemia. In conclusion, the studies position GIP as a bifunctional blood glucose stabilising hormone that glucose-dependently regulates insulin and glucagon responses in humans.......The hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted by enteroendocrine cells in the intestinal mucosa in response to nutrient ingestion. They are called incretin hormones because of their ability to enhance insulin secretion. However...... 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...

  13. Endogenous Lunar Volatiles

    Science.gov (United States)

    McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Boyce, J. W.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Magna, T.; Ni, P.; Tartese, R.; hide

    2017-01-01

    The chapter will begin with an introduction that defines magmatic volatiles (e.g., H, F, Cl, S) versus geochemical volatiles (e.g., K, Rb, Zn). We will discuss our approach of understanding both types of volatiles in lunar samples and lay the ground work for how we will determine the overall volatile budget of the Moon. We will then discuss the importance of endogenous volatiles in shaping the "Newer Views of the Moon", specifically how endogenous volatiles feed forward into processes such as the origin of the Moon, magmatic differentiation, volcanism, and secondary processes during surface and crustal interactions. After the introduction, we will include a re-view/synthesis on the current state of 1) apatite compositions (volatile abundances and isotopic compositions); 2) nominally anhydrous mineral phases (moderately to highly volatile); 3) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar pyroclastic glass beads; 4) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar basalts; 5) volatile (moderately to highly volatile) abundances in and isotopic compositions of melt inclusions; and finally 6) experimental constraints on mineral-melt partitioning of moderately to highly volatile elements under lunar conditions. We anticipate that each section will summarize results since 2007 and focus on new results published since the 2015 Am Min review paper on lunar volatiles [9]. The next section will discuss how to use sample abundances of volatiles to understand the source region and potential caveats in estimating source abundances of volatiles. The following section will include our best estimates of volatile abundances and isotopic compositions (where permitted by available data) for each volatile element of interest in a number of important lunar reservoirs, including the crust, mantle, KREEP, and bulk Moon. The final section of the chapter will focus upon future work, outstanding questions

  14. Plasma adiponectin and endogenous glucose production in humans

    DEFF Research Database (Denmark)

    Stefan, Norbert; Stumvoll, Michael; Vozarova, Barbora

    2003-01-01

    High plasma adiponectin is associated with reduced risk of type 2 diabetes, probably a consequence of its insulin-sensitizing properties. In vivo data in rodents suggest that the insulin-sensitization responsible for improvement of glycemia occurs in muscle and liver. Whereas associations of plas...

  15. Endogenous Fertility and Development Traps with Endogenous Lifetime

    Directory of Open Access Journals (Sweden)

    Luciano Fanti

    2011-01-01

    Full Text Available We extend the literature on endogenous lifetime and economic growth by Chakraborty (2004 and Bunzel and Qiao (2005 to endogenous fertility. We show that development traps due to underinvestments in health cannot appear when fertility is an economic decision variable and the costs of children are represented by a constant fraction of the parents' income used for their upbringing.

  16. Origin of endogenous DNA abasic sites in Saccharomyces cerevisiae.

    Science.gov (United States)

    Guillet, Marie; Boiteux, Serge

    2003-11-01

    Abasic (AP) sites are among the most frequent endogenous lesions in DNA and present a strong block to replication. In Saccharomyces cerevisiae, an apn1 apn2 rad1 triple mutant is inviable because of its incapacity to repair AP sites and related 3'-blocked single-strand breaks (M. Guillet and S. Boiteux, EMBO J. 21:2833, 2002). Here, we investigated the origin of endogenous AP sites in yeast. Our results show that the deletion of the UNG1 gene encoding the uracil DNA glycosylase suppresses the lethality of the apn1 apn2 rad1 mutant. In contrast, inactivation of the MAG1, OGG1, or NTG1 and NTG2 genes encoding DNA glycosylases involved in the repair of alkylation or oxidation damages does not suppress lethality. Although viable, the apn1 apn2 rad1 ung1 mutant presents growth delay due to a G(2)/M checkpoint. These results point to uracil as a critical source of the formation of endogenous AP sites in DNA. Uracil can arise in DNA by cytosine deamination or by the incorporation of dUMP during replication. Here, we show that the overexpression of the DUT1 gene encoding the dUTP pyrophosphatase (Dut1) suppresses the lethality of the apn1 apn2 rad1 mutant. Therefore, this result points to the dUTP pool as an important source of the formation of endogenous AP sites in eukaryotes.

  17. Possible modulatory effect of endogenous islet catecholamines on insulin secretion

    Directory of Open Access Journals (Sweden)

    Gagliardino Juan J

    2001-10-01

    Full Text Available Abstract Background The possible participation of endogenous islet catecholamines (CAs in the control of insulin secretion was tested. Methods Glucose-induced insulin secretion was measured in the presence of 3-Iodo-L-Tyrosine (MIT, a specific inhibitor of tyrosine-hydroxylase activity, in fresh and precultured islets isolated from normal rats. Incubated islets were also used to measure CAs release in the presence of low and high glucose, and the effect of α2-(yohimbine [Y] and idazoxan [I] and α1-adrenergic antagonists (prazosin [P] and terazosin [T] upon insulin secretion elicited by high glucose. Results Fresh islets incubated with 16.7 mM glucose released significantly more insulin in the presence of 1 μM MIT (6.66 ± 0.39 vs 5.01 ± 0.43 ng/islet/h, p Conclusion Our results suggest that islet-originated CAs directly modulate insulin release in a paracrine manner.

  18. Glucose allostasis

    DEFF Research Database (Denmark)

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert

    2003-01-01

    In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy...... individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose...... concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus...

  19. Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

    NARCIS (Netherlands)

    Coomans, C.P.; Biermasz, N.R.; Geerling, J.J.; Guigas, B.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

    2011-01-01

    OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated

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

    Energy Technology Data Exchange (ETDEWEB)

    Wajngot, A.; Khan, A.; Giacca, A.; Vranic, M.; Efendic, S. (Karolinska Hospital, Stockholm (Sweden))

    1990-11-01

    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.

  1. Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

    Directory of Open Access Journals (Sweden)

    Sarah Everman

    Full Text Available Plasma branched-chain amino acids (BCAA are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity.To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans.Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5 to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5. In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U in association with the above BCAA infusion (N = 4 or under the same conditions without BCAA infusion (N = 3. Plasma glucose turnover was measured prior to and during insulin infusion.Insulin infusion completely suppressed the endogenous glucose production (EGP across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05. Insulin infusion stimulated whole-body glucose disposal rate (GDR across all groups. However, the increase (% in GDR was not different [median (1st quartile - 3rd quartile] between Control and BCAA in either the 40U ([199 (167-278 vs. 186 (94-308] or 80 U ([491 (414-548 vs. 478 (409-857] experiments (P > 0.05. Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P 0.05.Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

  2. Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

    Science.gov (United States)

    Everman, Sarah; Mandarino, Lawrence J; Carroll, Chad C; Katsanos, Christos S

    2015-01-01

    Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity. To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans. Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U) during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5) to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5). In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U) in association with the above BCAA infusion (N = 4) or under the same conditions without BCAA infusion (N = 3). Plasma glucose turnover was measured prior to and during insulin infusion. Insulin infusion completely suppressed the endogenous glucose production (EGP) across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05). Insulin infusion stimulated whole-body glucose disposal rate (GDR) across all groups. However, the increase (%) in GDR was not different [median (1st quartile - 3rd quartile)] between Control and BCAA in either the 40U ([199 (167-278) vs. 186 (94-308)] or 80 U ([491 (414-548) vs. 478 (409-857)] experiments (P > 0.05). Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P BCAA in either of the experiments (P > 0.05). Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

  3. Endogenous, Imperfectly Competitive Business Cycles

    DEFF Research Database (Denmark)

    Whitta-Jacobsen, Hans Jørgen

    We investigate how imperfect competition affects the occurrence and the properties of endogenous, rational expectations business cycles in an overlapping generations model with constant returns to scale in production. The model has explicit product and labor markets all characterized...

  4. Suppressed Belief

    Directory of Open Access Journals (Sweden)

    Komarine Romdenh-Romluc

    2009-12-01

    Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

  5. Blood Test: Glucose

    Science.gov (United States)

    ... Videos for Educators Search English Español Blood Test: Glucose KidsHealth / For Parents / Blood Test: Glucose What's in ... liver or kidneys) is working. What Is a Glucose Test? A glucose test measures how much glucose ...

  6. Blood Glucose Monitoring Devices

    Science.gov (United States)

    ... In Vitro Diagnostics Blood Glucose Monitoring Devices Blood Glucose Monitoring Devices Share Tweet Linkedin Pin it More ... care settings to measure the amount of sugar (glucose) in your blood. What is glucose? Glucose is ...

  7. Thought suppression.

    Science.gov (United States)

    Wenzlaff, R M; Wegner, D M

    2000-01-01

    Although thought suppression is a popular form of mental control, research has indicated that it can be counterproductive, helping assure the very state of mind one had hoped to avoid. This chapter reviews the research on suppression, which spans a wide range of domains, including emotions, memory, interpersonal processes, psychophysiological reactions, and psychopathology. The chapter considers the relevant methodological and theoretical issues and suggests directions for future research.

  8. Comparison of 5% versus 15% sucrose intakes as part of a eucaloric diet in overweight and obese subjects: effects on insulin sensitivity, glucose metabolism, vascular compliance, body composition and lipid profile. A randomised controlled trial.

    Science.gov (United States)

    Lewis, Anthony S; McCourt, Hannah J; Ennis, Cieran N; Bell, Patrick M; Courtney, C Hamish; McKinley, Michelle C; Young, Ian S; Hunter, Steven J

    2013-05-01

    The effect of dietary sucrose on insulin resistance and the pathogenesis of diabetes and vascular disease is unclear. We assessed the effect of 5% versus 15% sucrose intakes as part of a weight maintaining, eucaloric diet in overweight/obese subjects. Thirteen subjects took part in a randomised controlled crossover study (M:F 9:4, median age 46 years, range 37-56 years, BMI 31.7±0.9 kg/m(2)). Subjects completed two 6 week dietary periods separated by 4 week washout. Diets were designed to have identical macronutrient profile. Insulin action was assessed using a two-step hyperinsulinaemic euglycaemic clamp; glucose tolerance, vascular compliance, body composition and lipid profiles were also assessed. There was no change in weight or body composition between diets. There was no difference in peripheral glucose utilization or suppression of endogenous glucose production. Fasting glucose was significantly lower after the 5% diet. There was no demonstrated effect on lipid profiles, blood pressure or vascular compliance. A low-sucrose diet had no beneficial effect on insulin resistance as measured by the euglycaemic glucose clamp. However, reductions in fasting glucose, one hour insulin and insulin area under the curve with the low sucrose diet on glucose tolerance testing may indicate a beneficial effect and further work is required to determine if this is the case. Clinical Trial Registration number ISRCTN50808730. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. The uniqueness of social attention revisited: working memory load interferes with endogenous but not social orienting.

    Science.gov (United States)

    Hayward, Dana A; Ristic, Jelena

    2013-12-01

    It is well known that perceived eye gaze direction influences attentional orienting. However, it still remains unclear whether social orienting involves exogenous or endogenous attentional control. To address this issue, we examined if social orienting and endogenous orienting were differentially modulated by working memory load, which is known to interfere with endogenous but not exogenous attention. To do so, we manipulated eye direction as either spatially counterpredictive in Experiment 1 or spatially predictive in Experiment 2 while participants performed a cueing task either in isolation or under working memory load. We found that when social attention and endogenous attention diverged spatially in Experiment 1, social orienting elicited by gaze direction remained intact while endogenous orienting elicited by the cue's predictive meaning was suppressed under working memory load, suggesting independence between social orienting and endogenous orienting. Indeed, a comparison between the sum of isolated social orienting and endogenous orienting magnitudes from Experiment 1 relative to their combined measure from Experiment 2 confirmed that social attention and endogenous attention operated in parallel. Together, our data show that social orienting is independent from endogenous orienting and further suggest that paying attention to social information might involve either exogenous or unique attentional mechanisms.

  10. Glucose-responsive hydrogel electrode for biocompatible glucose transistor.

    Science.gov (United States)

    Kajisa, Taira; Sakata, Toshiya

    2017-01-01

    In this paper, we propose a highly sensitive and biocompatible glucose sensor using a semiconductor-based field effect transistor (FET) with a functionalized hydrogel. The principle of the FET device contributes to the easy detection of ionic charges with high sensitivity, and the hydrogel coated on the electrode enables the specific detection of glucose with biocompatibility. The copolymerized hydrogel on the Au gate electrode of the FET device is optimized by controlling the mixture ratio of biocompatible 2-hydroxyethylmethacrylate (HEMA) as the main monomer and vinylphenylboronic acid (VPBA) as a glucose-responsive monomer. The gate surface potential of the hydrogel FETs shifts in the negative direction with increasing glucose concentration from 10 μM to 40 mM, which results from the increase in the negative charges on the basis of the diol-binding of PBA derivatives with glucose molecules in the hydrogel. Moreover, the hydrogel coated on the gate suppresses the signal noise caused by the nonspecific adsorption of proteins such as albumin. The hydrogel FET can serve as a highly sensitive and biocompatible glucose sensor in in vivo or ex vivo applications such as eye contact lenses and sheets adhering to the skin.

  11. Coping with an exogenous glucose overload: glucose kinetics of rainbow trout during graded swimming

    Science.gov (United States)

    Choi, Kevin

    2015-01-01

    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. PMID:26719305

  12. A note on endogenous transfers

    NARCIS (Netherlands)

    S. Brakman (Steven); J.G.M. van Marrewijk (Charles)

    1991-01-01

    textabstractIn a competitive and Walrasian stable world with two goods transfer paradoxes are very robust to endogenization (relating the size of the transfer to either the donor's or the recipient's GNP). Donor enrichment and/or recipient impoverishment occur in very general formulations of

  13. Monopoly Insurance and Endogenous Information

    DEFF Research Database (Denmark)

    Lagerlöf, Johan N. M.; Schottmüller, Christoph

    2017-01-01

    We study a monopoly insurance model with endogenous information acquisi- tion. Through a continuous effort choice, consumers can determine the precision of a privately observed signal that is informative about their accident risk. The equilibrium effort is, depending on parameter values, either...

  14. 24-hour glucose profiles during continuous or oscillatory insulin infusion. Demonstration of the functional significance of ultradian insulin oscillations.

    Science.gov (United States)

    Sturis, J; Scheen, A J; Leproult, R; Polonsky, K S; van Cauter, E

    1995-01-01

    Under basal and stimulated conditions, normal insulin secretion oscillates with periods in the ultradian 100-150-min range. To test the hypothesis that oscillatory insulin delivery is more efficient in reducing blood glucose levels than continuous administration, nine normal young men were each studied on two occasions during a 28-h period including a period of polygraphically recorded sleep. Endogenous insulin secretion was suppressed by somatostatin, a constant intravenous glucose infusion was administered, and exogenous insulin was infused either at a constant rate or in a sinusoidal pattern with a period of 120 min. The mean glucose level over the 28-h period was 0.72 +/- 0.31 mmol/liter lower when insulin was infused in an oscillatory pattern than when the rate of infusion was constant (P < 0.05). The greater hypoglycemic effect of oscillatory versus constant infusion was particularly marked during the daytime, with the difference averaging 1.04 +/- 0.38 mmol/liter (P < 0.03). Serum insulin levels tended to be lower during oscillatory than constant infusion, although the same amount of exogenous insulin was administered under both conditions. Ultradian insulin oscillations appear to promote more efficient glucose utilization. PMID:7706450

  15. Interocular suppression

    Science.gov (United States)

    Tuna, Ana Rita; Almeida Neves Carrega, Filipa; Nunes, Amélia Fernandes

    2017-08-01

    The objective of this work is to quantify the suppressive imbalance, based on the manipulation of ocular luminance, between a group of subjects with normal binocular vision and a group of subjects with amblyopia. The result reveals that there are statistically significant differences in interocular dominance between two groups, evidencing a greater suppressive imbalance in amblyopic subjects. The technique used, proved to be a simple, easy to apply and economic method, for quantified ocular dominance. It is presented as a technique with the potential to accompany subjects with a marked dominance in one of the eyes that makes fusion difficult.

  16. Osteopontin upregulates the expression of glucose transporters in osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    I-Shan Hsieh

    Full Text Available Osteosarcoma is the most common primary malignancy of bone. Even after the traditional standard surgical therapy, metastasis still occurs in a high percentage of patients. Glucose is an important source of metabolic energy for tumor proliferation and survival. Tumors usually overexpress glucose transporters, especially hypoxia-responsive glucose transporter 1 and glucose transporter 3. Osteopontin, hypoxia-responsive glucose transporter 1, and glucose transporter 3 are overexpressed in many types of tumors and have been linked to tumorigenesis and metastasis. In this study, we investigated the regulation of glucose transporters by osteopontin in osteosarcoma. We observed that both glucose transporters and osteopontin were upregulated in hypoxic human osteosarcoma cells. Endogenously released osteopontin regulated the expression of glucose transporter 1 and glucose transporter 3 in osteosarcoma and enhanced glucose uptake into cells via the αvβ3 integrin. Knockdown of osteopontin induced cell death in 20% of osteosarcoma cells. Phloretin, a glucose transporter inhibitor, also caused cell death by treatment alone. The phloretin-induced cell death was significantly enhanced in osteopontin knockdown osteosarcoma cells. Combination of a low dose of phloretin and chemotherapeutic drugs, such as daunomycin, 5-Fu, etoposide, and methotrexate, exhibited synergistic cytotoxic effects in three osteosarcoma cell lines. Inhibition of glucose transporters markedly potentiated the apoptotic sensitivity of chemotherapeutic drugs in osteosarcoma. These results indicate that the combination of a low dose of a glucose transporter inhibitor with cytotoxic drugs may be beneficial for treating osteosarcoma patients.

  17. Suppression of Very Early Stage Of Adipogenesis by Baicalein, a Plant-Derived Flavonoid through Reduced Akt-C/EBPα-GLUT4 Signaling-Mediated Glucose Uptake in 3T3-L1 Adipocytes.

    Directory of Open Access Journals (Sweden)

    Yukari Nakao

    Full Text Available Baicalein has been used as a Chinese medicine, and is an abundant plant flavonoid present in fruits and vegetables. Here, we examined the effects of baicalein in adipogenesis and investigated its molecular mechanism in adipocytes. Baicalein lowered the intracellular lipid accumulation and decreased the transcription levels of the adipocyte-specific genes in mouse 3T3-L1 adipocytes. Glucose uptake mediated by glucose transporter 4 (GLUT4 was reduced, causing down-regulation of the intracellular lipid accumulation. These reductions were also observed even when baicalein was added in only early stage of adipogenesis (0-2 days of 6-day-adipogenesis. Chromatin immunoprecipitation assay showed that baicalein decreased the binding level of C/EBPα protein to the promoter region of the GLUT4 gene. Phosphorylation of Akt at 1 h after the initiation of adipogenesis was inhibited by the treatment with baicalein. Inhibition during only the first 1.5 h after the initiation of adipogenesis by baicalein or an Akt inhibitor was enough to decrease the lipid contents in the cells undergoing adipocyte differentiation for 6 days. These results indicate that baicalein decreased the intracellular lipid accumulation by down-regulation of glucose uptake via repression of Akt-C/EBPα-GLUT4 signaling in the very early stage of adipogenesis of 3T3-L1 adipocytes.

  18. Neuroscience of glucose homeostasis

    NARCIS (Netherlands)

    La Fleur, S E; Fliers, E; Kalsbeek, A

    2014-01-01

    Plasma glucose concentrations are homeostatically regulated and maintained within strict boundaries. Several mechanisms are in place to increase glucose output when glucose levels in the circulation drop as a result of glucose utilization, or to decrease glucose output and increase tissue glucose

  19. Defects in beta cell Ca2+ signalling, glucose metabolism and insulin secretion in a murine model of KATP channel-induced neonatal diabetes mellitus

    Science.gov (United States)

    Benninger, R. K. P.; Remedi, M. S.; Head, W. S.; Ustione, A.; Piston, D. W.; Nichols, C. G.

    2011-01-01

    Aims/hypothesis Mutations that render ATP-sensitive potassium (KATP) channels insensitive to ATP inhibition cause neonatal diabetes mellitus. In mice, these mutations cause insulin secretion to be lost initially and, as the disease progresses, beta cell mass and insulin content also disappear. We investigated whether defects in calcium signalling alone are sufficient to explain short-term and long-term islet dysfunction. Methods We examined the metabolic, electrical and insulin secretion response in islets from mice that become diabetic after induction of ATP-insensitive Kir6.2 expression. To separate direct effects of KATP overactivity on beta cell function from indirect effects of prolonged hyperglycaemia, normal glycaemia was maintained by protective exogenous islet transplantation. Results In endogenous islets from protected animals, glucose-dependent elevations of intracellular free-calcium activity ([Ca2+]i) were severely blunted. Insulin content of these islets was normal, and sulfonylureas and KCl stimulated increased [Ca2+]i. In the absence of transplant protection, [Ca2+]i responses were similar, but glucose metabolism and redox state were dramatically altered; sulfonylurea- and KCl-stimulated insulin secretion was also lost, because of systemic effects induced by long-term hyperglycaemia and/or hypoinsulinaemia. In both cases, [Ca2+]i dynamics were synchronous across the islet. After reduction of gap-junction coupling, glucose-dependent [Ca2+]i and insulin secretion was partially restored, indicating that excitability of weakly expressing cells is suppressed by cells expressing mutants, via gap-junctions. Conclusions/interpretation The primary defect in KATP-induced neonatal diabetes mellitus is failure of glucose metabolism to elevate [Ca2+]i, which suppresses insulin secretion and mildly alters islet glucose metabolism. Loss of insulin content and mitochondrial dysfunction are secondary to the long-term hyperglycaemia and/or hypoinsulinaemia that

  20. Defects in beta cell Ca²+ signalling, glucose metabolism and insulin secretion in a murine model of K(ATP) channel-induced neonatal diabetes mellitus.

    Science.gov (United States)

    Benninger, R K P; Remedi, M S; Head, W S; Ustione, A; Piston, D W; Nichols, C G

    2011-05-01

    Mutations that render ATP-sensitive potassium (K(ATP)) channels insensitive to ATP inhibition cause neonatal diabetes mellitus. In mice, these mutations cause insulin secretion to be lost initially and, as the disease progresses, beta cell mass and insulin content also disappear. We investigated whether defects in calcium signalling alone are sufficient to explain short-term and long-term islet dysfunction. We examined the metabolic, electrical and insulin secretion response in islets from mice that become diabetic after induction of ATP-insensitive Kir6.2 expression. To separate direct effects of K(ATP) overactivity on beta cell function from indirect effects of prolonged hyperglycaemia, normal glycaemia was maintained by protective exogenous islet transplantation. In endogenous islets from protected animals, glucose-dependent elevations of intracellular free-calcium activity ([Ca(2+)](i)) were severely blunted. Insulin content of these islets was normal, and sulfonylureas and KCl stimulated increased [Ca(2+)](i). In the absence of transplant protection, [Ca(2+)](i) responses were similar, but glucose metabolism and redox state were dramatically altered; sulfonylurea- and KCl-stimulated insulin secretion was also lost, because of systemic effects induced by long-term hyperglycaemia and/or hypoinsulinaemia. In both cases, [Ca(2+)](i) dynamics were synchronous across the islet. After reduction of gap-junction coupling, glucose-dependent [Ca(2+)](i) and insulin secretion was partially restored, indicating that excitability of weakly expressing cells is suppressed by cells expressing mutants, via gap-junctions. The primary defect in K(ATP)-induced neonatal diabetes mellitus is failure of glucose metabolism to elevate [Ca(2+)](i), which suppresses insulin secretion and mildly alters islet glucose metabolism. Loss of insulin content and mitochondrial dysfunction are secondary to the long-term hyperglycaemia and/or hypoinsulinaemia that result from the absence of glucose

  1. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2017-01-01

    We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely and is i......We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely...... and is indistinguishable from that of a generalized version of the classical Vickrey bottleneck model, based on exogenous trip-timing preferences, but optimal policies differ: the Vickrey model will misstate the benefits of a capacity increase, it will underpredict the benefits of congestion pricing, and pricing may make...

  2. TXNIP Regulates Peripheral Glucose Metabolism in Humans

    Science.gov (United States)

    Parikh, Hemang; Carlsson, Emma; Chutkow, William A; Johansson, Lovisa E; Storgaard, Heidi; Poulsen, Pernille; Saxena, Richa; Ladd, Christine; Schulze, P. Christian; Mazzini, Michael J; Jensen, Christine Bjørn; Krook, Anna; Björnholm, Marie; Tornqvist, Hans; Zierath, Juleen R; Ridderstråle, Martin; Altshuler, David; Lee, Richard T; Vaag, Allan; Groop, Leif C; Mootha, Vamsi K

    2007-01-01

    Background Type 2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and action. Impaired glucose uptake in skeletal muscle is believed to be one of the earliest features in the natural history of T2DM, although underlying mechanisms remain obscure. Methods and Findings We combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated to total body measures of glucose uptake. Forced expression of TXNIP in cultured adipocytes significantly reduced glucose uptake, while silencing with RNA interference in adipocytes and in skeletal muscle enhanced glucose uptake, confirming that the gene product is also a regulator of glucose uptake. TXNIP expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM. Conclusions TXNIP regulates both insulin-dependent and insulin-independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic β-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM. PMID:17472435

  3. TXNIP regulates peripheral glucose metabolism in humans.

    Directory of Open Access Journals (Sweden)

    Hemang Parikh

    2007-05-01

    Full Text Available Type 2 diabetes mellitus (T2DM is characterized by defects in insulin secretion and action. Impaired glucose uptake in skeletal muscle is believed to be one of the earliest features in the natural history of T2DM, although underlying mechanisms remain obscure.We combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated to total body measures of glucose uptake. Forced expression of TXNIP in cultured adipocytes significantly reduced glucose uptake, while silencing with RNA interference in adipocytes and in skeletal muscle enhanced glucose uptake, confirming that the gene product is also a regulator of glucose uptake. TXNIP expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM.TXNIP regulates both insulin-dependent and insulin-independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic beta-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM.

  4. Exogenous and endogenous cannabimimetic metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Di Marzo, V.; Bisogno, T.; Melck, D. [CNR, Arco Felice, Naples (Italy). Ist. per la Chimica di Molecole di Interesse Biologico; De Petrocellis, L. [CNR, Arco Felice, Naples (Italy). Ist. di Cibernetica

    1998-04-01

    Only a few discoveries in the fields of pharmacology and physiology have benefited from the work of organic and synthetic chemists like the identification of the existence and possible physiological function of the `endogenous cannabinoid system`. The review emphasizes the key role played by chemists in this area of pharmacological research, and highlights the possible industrial implications of the discovery of cannabimimetic metabolites and of their mechanism of action.

  5. Resolving the sources of plasma glucose excursions following a glucose tolerance test in the rat with deuterated water and [U-13C]glucose.

    Directory of Open Access Journals (Sweden)

    Teresa C Delgado

    Full Text Available Sources of plasma glucose excursions (PGE following a glucose tolerance test enriched with [U-(13C]glucose and deuterated water were directly resolved by (13C and (2H Nuclear Magnetic Resonance spectroscopy analysis of plasma glucose and water enrichments in rat. Plasma water (2H-enrichment attained isotopic steady-state within 2-4 minutes following the load. The fraction of PGE derived from endogenous sources was determined from the ratio of plasma glucose position 2 and plasma water (2H-enrichments. The fractional gluconeogenic contributions to PGE were obtained from plasma glucose positions 2 and 5 (2H-positional enrichment ratios and load contributions were estimated from plasma [U-(13C]glucose enrichments. At 15 minutes, the load contributed 26±5% of PGE while 14±2% originated from gluconeogenesis in healthy control rats. Between 15 and 120 minutes, the load contribution fell whereas the gluconeogenic contribution remained constant. High-fat fed animals had significant higher 120-minute blood glucose (173±6 mg/dL vs. 139±10 mg/dL, p<0.05 and gluconeogenic contributions to PGE (59±5 mg/dL vs. 38±3 mg/dL, p<0.01 relative to standard chow-fed controls. In summary, the endogenous and load components of PGE can be resolved during a glucose tolerance test and these measurements revealed that plasma glucose synthesis via gluconeogenesis remained active during the period immediately following a glucose load. In rats that were placed on high-fat diet, the development of glucose intolerance was associated with a significantly higher gluconeogenic contribution to plasma glucose levels after the load.

  6. Endogenous retroviral promoter exaptation in human cancer

    Directory of Open Access Journals (Sweden)

    Artem Babaian

    2016-12-01

    Full Text Available Abstract Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the “dark side” of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.

  7. Glucose production, oxidation and disposal correlate with plasma lactate levels in HIV-infected patients on HAART

    DEFF Research Database (Denmark)

    Haugaard, S.B.; Andersen, Ove; Madsbad, Sten

    2007-01-01

    .g. glucose turnover may contribute to hyperlactatemia. METHODS: HIV-infected patients receiving HAART who had lipodystrophy (LIPO, n=18) or were without lipodystrophy (NONLIPO, n=18) were investigated. Insulin sensitivity (M-value), glucose oxidation rate (GOX) and fasting endogenous glucose production (EGP...

  8. On the origins of endogenous thoughts.

    Science.gov (United States)

    Tillas, Alexandros

    2017-05-01

    Endogenous thoughts are thoughts that we activate in a top-down manner or in the absence of the appropriate stimuli. We use endogenous thoughts to plan or recall past events. In this sense, endogenous thinking is one of the hallmarks of our cognitive lives. In this paper, I investigate how it is that we come to possess endogenous control over our thoughts. Starting from the close relation between language and thinking, I look into speech production-a process motorically controlled by the inferior frontal gyrus (IFG). Interestingly, IFG is also closely related to silent talking, as well as volition. The connection between IFG and volition is important given that endogenous thoughts are or at least greatly resemble voluntary actions. Against this background, I argue that IFG is key to understanding the origins of conscious endogenous thoughts. Furthermore, I look into goal-directed thinking and show that IFG plays a key role also in unconscious endogenous thinking.

  9. Acute modulation of cytokine gene expression in bovine peripheral blood mononuclear cells (PBMCs) by endogenous cortisol

    Science.gov (United States)

    Cortisol suppresses many aspects of immune function. However, recent publications suggest acute cortisol exposure may actually enhance immune function (Dhabhar. 2009. Neuroimmunomod. 16:300). The objective of this study was to determine the influence of acute increases in endogenous cortisol on expr...

  10. Endogenous Cortisol: Acute Modulation of Cytokine Gene Expression in Bovine PBMCs

    Science.gov (United States)

    Cortisol suppresses many aspects of immune function. However, recent publications suggest acute cortisol exposure may actually enhance immune function (Dhabhar, Neuroimmunomod 2009;16:300). The objective of this study was to determine the influence of acute increases in endogenous cortisol on expres...

  11. Acute modulation of cytokine gene expression in bovine PBMCs by endogenous cortisol

    Science.gov (United States)

    Cortisol suppresses many aspects of immune function. However, recent publications suggest acute cortisol exposure may actually enhance immune function (Dhabhar, Neuroimmunomod 2009;16:300). The objective of this study was to determine the influence of acute increases in endogenous cortisol on expres...

  12. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg

    2007-01-01

    Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

  13. Endogeneity in prison risk classification.

    Science.gov (United States)

    Shermer, Lauren O'Neill; Bierie, David M; Stock, Amber

    2013-10-01

    Security designation tools are a key feature of all prisons in the United States, intended as objective measures of risk that funnel inmates into security levels-to prison environments varying in degree of intrusiveness, restriction, dangerousness, and cost. These tools are mostly (if not all) validated by measuring inmates on a set of characteristics, using scores from summations of that information to assign inmates to prisons of varying security level, and then observing whether inmates assumed more risky did in fact offend more. That approach leaves open the possibility of endogeneity--that the harsher prisons are themselves bringing about higher misconduct and thus biasing coefficients assessing individual risk. The current study assesses this potential bias by following an entry cohort of inmates to more than 100 facilities in the Federal Bureau of Prisons (BOP) and exploiting the substantial variation in classification scores within a given prison that derive from systematic overrides of security-level designations for reasons not associated with risk of misconduct. By estimating pooled models of misconduct along with prison-fixed effects specifications, the data show that a portion of the predictive accuracy thought associated with the risk-designation tool used in BOP was a function of facility-level contamination (endogeneity).

  14. Endogenous Retroviruses in Domestic Animals

    Science.gov (United States)

    Garcia-Etxebarria, Koldo; Sistiaga-Poveda, Maialen; Jugo, Begoña Marina

    2014-01-01

    Endogenous retroviruses (ERVs) are genomic elements that are present in a wide range of vertebrates. Although the study of ERVs has been carried out mainly in humans and model organisms, recently, domestic animals have become important, and some species have begun to be analyzed to gain further insight into ERVs. Due to the availability of complete genomes and the development of new computer tools, ERVs can now be analyzed from a genome-wide viewpoint. In addition, more experimental work is being carried out to analyze the distribution, expression and interplay of ERVs within a host genome. Cats, cattle, chicken, dogs, horses, pigs and sheep have been scrutinized in this manner, all of which are interesting species in health and economic terms. Furthermore, several studies have noted differences in the number of endogenous retroviruses and in the variability of these elements among different breeds, as well as their expression in different tissues and the effects of their locations, which, in some cases, are near genes. These findings suggest a complex, intriguing relationship between ERVs and host genomes. In this review, we summarize the most important in silico and experimental findings, discuss their implications and attempt to predict future directions for the study of these genomic elements. PMID:25132796

  15. Low Blood Glucose (Hypoglycemia)

    Science.gov (United States)

    ... Dental Problems Diabetes & Sexual & Urologic Problems Low Blood Glucose (Hypoglycemia) What is hypoglycemia? Hypoglycemia, also called low ... actions can also help prevent hypoglycemia: Check blood glucose levels Knowing your blood glucose level can help ...

  16. Glucose and cardiovascular risk

    NARCIS (Netherlands)

    Fuchs, M.; Hoekstra, J. B. L.; Mudde, A. H.

    2002-01-01

    The American Diabetes Association and the World Health Organisation have recently redefined the spectrum of abnormal glucose tolerance. The criteria for diabetes mellitus were sharpened and impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were classified as intermediate stages

  17. The Deacetylase HDAC6 Mediates Endogenous Neuritic Tau Pathology

    Directory of Open Access Journals (Sweden)

    Jui-Heng Tseng

    2017-08-01

    Full Text Available The initiating events that promote tau mislocalization and pathology in Alzheimer’s disease (AD are not well defined, partly because of the lack of endogenous models that recapitulate tau dysfunction. We exposed wild-type neurons to a neuroinflammatory trigger and examined the effect on endogenous tau. We found that tau re-localized and accumulated within pathological neuritic foci, or beads, comprised of mostly hypo-phosphorylated, acetylated, and oligomeric tau. These structures were detected in aged wild-type mice and were enhanced in response to neuroinflammation in vivo, highlighting a previously undescribed endogenous age-related tau pathology. Strikingly, deletion or inhibition of the cytoplasmic shuttling factor HDAC6 suppressed neuritic tau bead formation in neurons and mice. Using mass spectrometry-based profiling, we identified a single neuroinflammatory factor, the metalloproteinase MMP-9, as a mediator of neuritic tau beading. Thus, our study uncovers a link between neuroinflammation and neuritic tau beading as a potential early-stage pathogenic mechanism in AD.

  18. Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans.

    Directory of Open Access Journals (Sweden)

    Mikael Lehtihet

    Full Text Available Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia.We used a sensitive and specific dual-monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b with GH deficiency before and after 12 months substitution treatment, (c with hyperthyroidism before and after normalization, and (d with hyperprolactinemia before and after six months of treatment with a dopamine agonist.In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01. Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels.In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency.

  19. Initial evidence that GLP-1 receptor blockade fails to suppress postprandial satiety or promote food intake in humans.

    Science.gov (United States)

    Melhorn, Susan J; Tyagi, Vidhi; Smeraglio, Anne; Roth, Christian L; Schur, Ellen A

    2014-11-01

    Glucagon-like peptide 1 (GLP-1) has incretin effects that are well-documented, but the independent role of GLP-1 action in human satiety perception is debated. We hypothesized that blockade of GLP-1 receptors would suppress postprandial satiety and increase voluntary food intake. After an overnight fast, eight normal weight participants (seven men, BMI 19-24.7 kg/m(2), age 19-29 year) were enrolled in a double-blind, placebo-controlled, randomized crossover study of the GLP-1 antagonist Exendin-[9-39] (Ex-9) to determine if the satiating effects of a meal are dependent on GLP-1 signaling in humans. Following a fasting blood draw, iv infusion of Ex-9 (600-750 pmol/kg/min) or saline began. Thirty minutes later, subjects consumed a standardized breakfast followed 90 min later (at the predicted time of maximal endogenous circulating GLP-1) by an ad libitum buffet meal to objectively measure satiety. Infusions ended once the buffet meal was complete. Visual analog scale ratings of hunger and fullness and serial assessments of plasma glucose, insulin, and GLP-1 concentrations were done throughout the experiment. Contrary to the hypothesis, during Ex-9 infusion subjects reported a greater decrease in hunger due to consumption of the breakfast (Ex-9 -62 ± 5; placebo -41 ± 9; P=0.01) than during placebo. There were no differences in ad libitum caloric intake between Ex-9 and placebo. Ex-9 increased glucose, insulin, and endogenous GLP-1, which may have counteracted any effects of Ex-9 infusion to block satiety signaling. Blockade of GLP-1 receptors failed to suppress subjective satiety following a standardized meal or increase voluntary food intake in healthy, normal-weight subjects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Endogenous Protease Nexin-1 Protects against Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Jonathan Thevenet

    2013-08-01

    Full Text Available The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC, leading to tolerance to cerebral ischemia. Here we studied the role of thrombin’s endogenous potent inhibitor, protease nexin-1 (PN-1, in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI exposed to oxygen and glucose deprivation (OGD. We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1−/− mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection.

  1. Synthetic Oligodeoxynucleotides Containing Multiple Telemeric TTAGGG Motifs Suppress Inflammasome Activity in Macrophages Subjected to Oxygen and Glucose Deprivation and Reduce Ischemic Brain Injury in Stroke-Prone Spontaneously Hypertensive Rats.

    Directory of Open Access Journals (Sweden)

    Jing Zhao

    Full Text Available The immune system plays a fundamental role in both the development and pathobiology of stroke. Inflammasomes are multiprotein complexes that have come to be recognized as critical players in the inflammation that ultimately contributes to stroke severity. Inflammasomes recognize microbial and host-derived danger signals and activate caspase-1, which in turn controls the production of the pro-inflammatory cytokine IL-1β. We have shown that A151, a synthetic oligodeoxynucleotide containing multiple telemeric TTAGGG motifs, reduces IL-1β production by activated bone marrow derived macrophages that have been subjected to oxygen-glucose deprivation and LPS stimulation. Further, we demonstrate that A151 reduces the maturation of caspase-1 and IL-1β, the levels of both the iNOS and NLRP3 proteins, and the depolarization of mitochondrial membrane potential within such cells. In addition, we have demonstrated that A151 reduces ischemic brain damage and NLRP3 mRNA levels in SHR-SP rats that have undergone permanent middle cerebral artery occlusion. These findings clearly suggest that the modulation of inflammasome activity via A151 may contribute to a reduction in pro-inflammatory cytokine production by macrophages subjected to conditions that model brain ischemia and modulate ischemic brain damage in an animal model of stroke. Therefore, modulation of ischemic pathobiology by A151 may have a role in the development of novel stroke prevention and therapeutic strategies.

  2. The RUNX2 Transcription Factor Negatively Regulates SIRT6 Expression to Alter Glucose Metabolism in Breast Cancer Cells.

    Science.gov (United States)

    Choe, Moran; Brusgard, Jessica L; Chumsri, Saranya; Bhandary, Lekhana; Zhao, Xianfeng Frank; Lu, Song; Goloubeva, Olga G; Polster, Brian M; Fiskum, Gary M; Girnun, Geoffrey D; Kim, Myoung Sook; Passaniti, Antonino

    2015-10-01

    Activation of genes promoting aerobic glycolysis and suppression of mitochondrial oxidative phosphorylation is one of the hallmarks of cancer. The RUNX2 transcription factor mediates breast cancer (BC) metastasis to bone and is regulated by glucose availability. But, the mechanisms by which it regulates glucose metabolism and promotes an oncogenic phenotype are not known. RUNX2 expression in luminal BC cells correlated with lower estrogen receptor-α (ERα) levels, anchorage-independent growth, expression of glycolytic genes, increased glucose uptake, and sensitivity to glucose starvation, but not to inhibitors of oxidative phosphorylation. Conversely, RUNX2 knockdown in triple-negative BC cells inhibited mammosphere formation and glucose dependence. RUNX2 knockdown resulted in lower LDHA, HK2, and GLUT1 glycolytic gene expression, but upregulation of pyruvate dehydrogenase-A1 (PDHA1) mRNA and enzymatic activity, which was consistent with lower glycolytic potential. The NAD-dependent histone deacetylase, SIRT6, a known tumor suppressor, was a critical regulator of these RUNX2-mediated metabolic changes. RUNX2 expression resulted in elevated pAkt, HK2, and PDHK1 glycolytic protein levels that were reduced by ectopic expression of SIRT6. RUNX2 also repressed mitochondrial oxygen consumption rates (OCR), a measure of oxidative phosphorylation (respiration). Overexpression of SIRT6 increased respiration in RUNX2-positive cells, but knockdown of SIRT6 in cells expressing low RUNX2 decreased respiration. RUNX2 repressed SIRT6 expression at both the transcriptional and post-translational levels and endogenous SIRT6 expression was lower in malignant BC tissues or cell lines that expressed high levels of RUNX2. These results support a hypothesis whereby RUNX2-mediated repression of the SIRT6 tumor suppressor regulates metabolic pathways that promote BC progression. © 2015 Wiley Periodicals, Inc.

  3. Estriol blunts postprandial blood glucose rise in male rats through regulating intestinal glucose transporters

    OpenAIRE

    Yamabe, Noriko; Kang, Ki Sung; Lee, Woojung; Kim, Su-Nam; Zhu, Bao Ting

    2014-01-01

    Despite increased total food intake in healthy, late-stage pregnant women, their peak postprandial blood sugar levels are normally much lower than the levels seen in healthy nonpregnant women. In this study, we sought to determine whether estriol (E3), an endogenous estrogen predominantly produced during human pregnancy, contributes to the regulation of the postprandial blood glucose level in healthy normal rats. In vivo studies using rats showed that E3 blunted the speed and magnitude of the...

  4. CSF glucose test

    Science.gov (United States)

    Glucose test - CSF; Cerebrospinal fluid glucose test ... The glucose level in the CSF should be 50 to 80 mg/100 mL (or greater than 2/3 ... Abnormal results include higher and lower glucose levels. Abnormal ... or fungus) Inflammation of the central nervous system Tumor

  5. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know ... Checking Your Blood Glucose A1C and eAG Hypoglycemia (Low blood glucose) Hyperglycemia (High blood glucose) Dawn Phenomenon Checking for Ketones Tight ...

  6. Loss of 50% of excess weight using a very low energy diet improves insulin-stimulated glucose disposal and skeletal muscle insulin signalling in obese insulin-treated type 2 diabetic patients

    NARCIS (Netherlands)

    Jazet, I. M.; Schaart, G.; Gastaldelli, A.; Ferrannini, E.; Hesselink, M. K.; Schrauwen, P.; Romijn, J. A.; Maassen, J. A.; Pijl, H.; Ouwens, D. M.; Meinders, A. E.

    2008-01-01

    Both energy restriction (ER) per se and weight loss improve glucose metabolism in obese insulin-treated type 2 diabetic patients. Short-term ER decreases basal endogenous glucose production (EGP) but not glucose disposal. In contrast the blood glucose-lowering mechanism of long-term ER with

  7. Endogenous Peer Effects: Fact or Fiction?

    Science.gov (United States)

    Yeung, Ryan; Nguyen-Hoang, Phuong

    2016-01-01

    The authors examine endogenous peer effects, which occur when a student's behavior or outcome is a function of the behavior or outcome of his or her peer group. Endogenous peer effects have important implications for educational policies such as busing, school choice and tracking. In this study, the authors quantitatively review the literature on…

  8. New mechanism of lipotoxicity in diabetic cardiomyopathy: Deficiency of Endogenous H2S Production and ER stress.

    Science.gov (United States)

    Guo, Runmin; Wu, Zijun; Jiang, Jiamei; Liu, Chang; Wu, Bin; Li, Xingyue; Li, Teng; Mo, Hailiang; He, Songjian; Li, Shanghai; Yan, Hai; Huang, Ruina; You, Qiong; Wu, Keng

    2017-03-01

    To investigate the roles and mechanisms of endogenous hydrogen sulfide (H2S) and endoplasmic reticulum (ER) stress in the development of diabetic cardiomyopathy (DCM). Blood of DCM patients included in the study were collected. The model of DCM rats was established using streptozotocin (STZ) injection. Cardiac lipotoxicity in vitro models were established using 500μM palmitic acid (PA) treatment for 24h in AC16 cardiomyocytes. Endogenous H2S production in plasma, culture supernatant and heart was measured by sulphur ion-selective electrode assay. Cell viability was tested by using the cell counting kit-8 (CCK-8) kit. Glucose regulated protein (GRP78), CCAAT/enhancer binding protein homologous transcription factor (C/EBP) homologous protein (CHOP), caspase-3 and caspase-12 expressions were measured using western blot analysis. Lipid droplet was evaluated by Oil Red O staining. Apoptosis in hearts of DCM rats was analyzed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. H2S levels in serum of DCM patients and DCM rats were significant lower, H2S contents and cystathionine-γ-lyase (CSE) expression in heart tissues of DCM rats were also markedly lower. H2S levels in supernatants of PA-treated AC16 cardiac cells were decreased. Cardiac lipotoxicity demonstrated by increase in TUNEL positive cells and lipid deposit in vivo and in vitro accompanied by a decrease of H2S levels. Pretreatment AC16 cells with 100μmol/L of NaHS (a donor of H2S) could suppress the PA-induced myocardial injury similar to the effects of 4-phenylbutyric acid (4-PBA, an endoplasmic reticulum (ER) stress inhibitor), leading to an increase in cell viability and preventing lipid deposit. Meanwhile, administration diabetic rats with NaHS or 4-PBA alleviated cardiac lipotoxicity, as evidenced by decrease in TUNEL positive cells, cleaved caspase-3 expression and lipid accumulation. Deficiency of endogenous H2S was involved in lipotoxicity-induced myocardial injury

  9. Glucose Transporters in Brain: In Health and in Alzheimer's Disease.

    Science.gov (United States)

    Szablewski, Leszek

    2017-01-01

    Neurons need a continuous supply of glucose, the major source of energy for mammalian brain metabolism. The central nervous system is protected by three main physiological cell barriers. Cell membranes are impermeable for glucose, therefore glucose is transferred across the cell membranes by specific transport proteins: sodium-independent glucose transporters (GLUTs), encoded by SLC2 genes, and sodium-dependent glucose transporters (for example SGLTs), encoded by SLC5 genes. Human brain expresses 10 GLUT proteins and 10 proteins encoded by SLC5 genes. In patients with brain diseases, particularly Alzheimer's (AD) and Huntington's diseases, abnormalities in neuronal glucose metabolism have been showed. The levels of GLUT1 and GLUT3, the major brain glucose transporters, are decreased, especially in the cerebral cortex. Therefore, in AD, hypometabolism of glucose and deficits in energy are observed. Production of ATP from glucose metabolism in sporadic AD declines to 50% and the tendency to decline continues throughout the progression of the disease. This decrease is correlated with O-GlcAcetylation and tau hyperphosphorylation, as the compensatory mechanisms in AD are the utilization of endogenous brain substances and drastic increase in GLUT2 levels. The present review focuses on the changes in the expression of glucose transporters due to AD.

  10. Effect of macronutrients, age, and obesity on 6- and 24-h postprandial glucose metabolism in cats

    OpenAIRE

    Hoenig, Margarethe; Jordan, Erin T.; Glushka, John; Kley, Saskia; Patil, Avinash; Waldron, Mark; Prestegard, James H.; Ferguson, Duncan C.; Wu, Shaoxiong; Olson, Darin E

    2011-01-01

    Obesity and age are risk factors for feline diabetes. This study aimed to test the hypothesis that age, long-term obesity, and dietary composition would lead to peripheral and hepatorenal insulin resistance, indicated by higher endogenous glucose production (EGP) in the fasted and postprandial state, higher blood glucose and insulin, and higher leptin, free thyroxine, and lower adiponectin concentrations. Using triple tracer—2H2O, [U-13C3] propionate, and [3,4-13C2] glucose infusion, and indi...

  11. Approaches towards endogenous pancreatic regeneration.

    Science.gov (United States)

    Banerjee, Meenal; Kanitkar, Meghana; Bhonde, Ramesh R

    2005-01-01

    The phenomenon of pancreatic regeneration in mammals has been well documented. It has been shown that pancreatic tissue is able to regenerate in several species of mammal after surgical insult. This tissue is also known to have the potential to maintain or increase its beta-cell mass in response to metabolic demands during pregnancy and obesity. Since deficiency in beta-cell mass is the hallmark of most forms of diabetes, it is worthwhile understanding pancreatic regeneration in the context of this disease. With this view in mind, this article aims to discuss the potential use in clinical strategies of knowledge that we obtained from studies carried out in animal models of diabetes. Approaches to achieve this goal involve the use of biomolecules, adult stem cells and gene therapy. Various molecules, such as glucagon-like peptide-1, beta-cellulin, nicotinamide, gastrin, epidermal growth factor-1 and thyroid hormone, play major roles in the initiation of endogenous islet regeneration in diabetes. The most accepted hypothesis is that these molecules stimulate islet precursor cells to undergo neogenesis or to induce replication of existing beta-cells, emphasizing the importance of pancreas-resident stem/progenitor cells in islet regeneration. Moreover, the potential of adult stem cell population from bone marrow, umbilical cord blood, liver, spleen, or amniotic membrane, is also discussed with regard to their potential to induce pancreatic regeneration.

  12. Comparison of the effects of slowly and rapidly absorbed carbohydrates on postprandial glucose metabolism in type 2 diabetes mellitus patients: a randomized trial.

    Science.gov (United States)

    Ang, Meidjie; Linn, Thomas

    2014-10-01

    Isomaltulose attenuates postprandial glucose and insulin concentrations compared with sucrose in patients with type 2 diabetes mellitus (T2DM). However, the mechanism by which isomaltulose limits postprandial hyperglycemia has not been clarified. The objective was therefore to assess the effects of bolus administration of isomaltulose on glucose metabolism compared with sucrose in T2DM. In a randomized, double-blind, crossover design, 11 participants with T2DM initially underwent a 3-h euglycemic-hyperinsulinemic (0.8 mU · kg(-1) · min(-1)) clamp that was subsequently combined with 1 g/kg body wt of an oral (13)C-enriched isomaltulose or sucrose load. Hormonal responses and glucose kinetics were analyzed during a 4-h postprandial period. Compared with sucrose, absorption of isomaltulose was prolonged by ∼50 min (P = 0.004). Mean plasma concentrations of insulin, C-peptide, glucagon, and glucose-dependent insulinotropic peptide were ∼10-23% lower (P insulin-to-glucagon ratio (P Insulin action was enhanced after isomaltulose compared with sucrose (P = 0.013). Ingestion of slowly absorbed isomaltulose attenuates postprandial hyperglycemia by reducing oral glucose appearance, inhibiting endogenous glucose production (EGP), and increasing SGU compared with ingestion of rapidly absorbed sucrose in patients with T2DM. In addition, GLP-1 secretion contributes to a beneficial shift in the insulin-to-glucagon ratio, suppression of EGP, and enhancement of SGU after isomaltulose consumption. This trial was registered at clinicaltrials.gov as NCT01070238. © 2014 American Society for Nutrition.

  13. Immunoneutralization of endogenous glucagon-like peptide-2 reduces adaptive intestinal growth in diabetic rats

    DEFF Research Database (Denmark)

    Hartmann, Bolette; Thulesen, Jesper; Hare, Kristine Juul

    2002-01-01

    in the proximal part of the small intestine (10.84+/-0.44 mm(2)). Antibody treatment had no effect on body weight, blood glucose concentrations and food intake. Thus, blocking of endogenous GLP-2 in a model of adaptive intestinal growth reduces the growth response, providing strong evidence for a physiological......Supraphysiological doses of glucagon-like peptide-2 (GLP-2) have been shown to induce intestinal growth by increasing villus height and crypt depth and by decreasing apoptosis, but a physiological effect of GLP-2 has not yet been demonstrated. Earlier, we found elevated levels of endogenous GLP-2...... in untreated streptozotocin diabetic rats associated with marked intestinal growth. In the present study, we investigated the role of endogenous GLP-2 for this adaptive response. We included four groups of six rats: (1) diabetic rats treated with saline, (2) diabetic rats treated with non-specific antibodies...

  14. Glucose utilization rates regulate intake levels of artificial sweeteners

    Science.gov (United States)

    Tellez, Luis A; Ren, Xueying; Han, Wenfei; Medina, Sara; Ferreira, Jozélia G; Yeckel, Catherine W; de Araujo, Ivan E

    2013-01-01

    It is well established that animals including humans attribute greater reinforcing value to glucose-containing sugars compared to their non-caloric counterparts, generally termed ‘artificial sweeteners’. However, much remains to be determined regarding the physiological signals and brain systems mediating the attribution of greater reinforcing value to sweet solutions that contain glucose. Here we show that disruption of glucose utilization in mice produces an enduring inhibitory effect on artificial sweetener intake, an effect that did not depend on sweetness perception or aversion. Indeed, such an effect was not observed in mice presented with a less palatable, yet caloric, glucose solution. Consistently, hungry mice shifted their preferences away from artificial sweeteners and in favour of glucose after experiencing glucose in a hungry state. Glucose intake was found to produce significantly greater levels of dopamine efflux compared to artificial sweetener in dorsal striatum, whereas disrupting glucose oxidation suppressed dorsal striatum dopamine efflux. Conversely, inhibiting striatal dopamine receptor signalling during glucose intake in sweet-naïve animals resulted in reduced, artificial sweetener-like intake of glucose during subsequent gluco-deprivation. Our results demonstrate that glucose oxidation controls intake levels of sweet tastants by modulating extracellular dopamine levels in dorsal striatum, and suggest that glucose utilization is one critical physiological signal involved in the control of goal-directed sweetener intake. PMID:24060992

  15. Involvement of endogenous glucagon-like peptide-1 in regulation of gastric motility and pancreatic endocrine secretion

    DEFF Research Database (Denmark)

    Witte, Anne-Barbara; Grybäck, Per; Jacobsson, Hans

    2011-01-01

    Objective. To study the role of endogenous glucagon-like peptide-1 (GLP-1) on gastric emptying rates of a solid meal as well as postprandial hormone secretion and glucose disposal. Material and methods. In nine healthy subjects, gastric emptying of a 310-kcal radio-labelled solid meal and plasma ...

  16. Hyperosmolarity in the small intestine contributes to postprandial ghrelin suppression.

    Science.gov (United States)

    Overduin, Joost; Tylee, Tracy S; Frayo, R Scott; Cummings, David E

    2014-06-15

    Plasma levels of the orexigenic hormone ghrelin are suppressed by meals with an efficacy dependent on their macronutrient composition. We hypothesized that heterogeneity in osmolarity among macronutrient classes contributes to these differences. In three studies, the impact of small intestinal hyperosmolarity was examined in Sprague-Dawley rats. In study 1, isotonic, 2.5×, and 5× hypertonic solutions of several agents with diverse absorption and metabolism properties were infused duodenally at a physiological rate (3 ml/10 min). Jugular vein blood was sampled before and at 30, 60, 90, 120, 180, 240, and 300 min after infusion. Plasma ghrelin was suppressed dose dependently and most strongly by glucose. Hyperosmolar infusions of lactulose, which transits the small intestine unabsorbed, and 3-O-methylglucose (3-O-MG), which is absorbed like glucose but remains unmetabolized, also suppressed ghrelin. Glucose, but not lactulose or 3-O-MG, infusions increased plasma insulin. In study 2, intestinal infusions of hyperosmolar NaCl suppressed ghrelin, a response that was not attenuated by coinfusion with the neural blocker lidocaine. In study 3, we reconfirmed that the low-osmolar lipid emulsion Intralipid suppresses ghrelin more weakly than isocaloric (but hypertonic) glucose. Importantly, raising Intralipid's osmolarity to that of the glucose solution by nonabsorbable lactulose supplementation enhanced ghrelin suppression to that seen after glucose. Hyperosmolar ghrelin occurred particularly during the initial 3 postinfusion hours. We conclude that small intestinal hyperosmolarity 1) is sufficient to suppress ghrelin, 2) may combine with other postprandial mechanisms to suppress ghrelin, 3) might contribute to altered ghrelin regulation after gastric bypass surgery, and 4) may inform dietary modifications for metabolic health.

  17. Control of blood glucose in the absence of hepatic glucose production during prolonged fasting in mice: induction of renal and intestinal gluconeogenesis by glucagon.

    Science.gov (United States)

    Mutel, Elodie; Gautier-Stein, Amandine; Abdul-Wahed, Aya; Amigó-Correig, Marta; Zitoun, Carine; Stefanutti, Anne; Houberdon, Isabelle; Tourette, Jean-André; Mithieux, Gilles; Rajas, Fabienne

    2011-12-01

    Since the pioneering work of Claude Bernard, the scientific community has considered the liver to be the major source of endogenous glucose production in all postabsorptive situations. Nevertheless, the kidneys and intestine can also produce glucose in blood, particularly during fasting and under protein feeding. The aim of this study was to better define the importance of the three gluconeogenic organs in glucose homeostasis. We investigated blood glucose regulation during fasting in a mouse model of inducible liver-specific deletion of the glucose-6-phosphatase gene (L-G6pc(-/-) mice), encoding a mandatory enzyme for glucose production. Furthermore, we characterized molecular mechanisms underlying expression changes of gluconeogenic genes (G6pc, Pck1, and glutaminase) in both the kidneys and intestine. We show that the absence of hepatic glucose release had no major effect on the control of fasting plasma glucose concentration. Instead, compensatory induction of gluconeogenesis occurred in the kidneys and intestine, driven by glucagon, glucocorticoids, and acidosis. Moreover, the extrahepatic action of glucagon took place in wild-type mice. Our study provides a definitive quantitative estimate of the capacity of extrahepatic gluconeogenesis to sustain fasting endogenous glucose production under the control of glucagon, regardless of the contribution of the liver. Thus, the current dogma relating to the respective role of the liver and of extrahepatic gluconeogenic organs in glucose homeostasis requires re-examination.

  18. Four grams of glucose

    OpenAIRE

    Wasserman, David H.

    2008-01-01

    Four grams of glucose circulates in the blood of a person weighing 70 kg. This glucose is critical for normal function in many cell types. In accordance with the importance of these 4 g of glucose, a sophisticated control system is in place to maintain blood glucose constant. Our focus has been on the mechanisms by which the flux of glucose from liver to blood and from blood to skeletal muscle is regulated. The body has a remarkable capacity to satisfy the nutritional need for glucose, while ...

  19. Salidroside inhibits endogenous hydrogen peroxide induced cytotoxicity of endothelial cells.

    Science.gov (United States)

    Zhao, Xingyu; Jin, Lianhai; Shen, Nan; Xu, Bin; Zhang, Wei; Zhu, Hongli; Luo, Zhengli

    2013-01-01

    Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L., shows potent antioxidant property. Herein, we investigated the protective effects of salidroside against hydrogen peroxide (H2O2)-induced oxidative damage in human endothelial cells (EVC-304). EVC-304 cells were incubated in the presence or absence of low steady states of H2O2 (3-4 µM) generated by glucose oxidase (GOX) with or without salidroside. 3(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) assays were performed, together with Hoechst 33258 staining and flow cytometric analysis using Annexin-V and propidium iodide (PI) label. The results indicated that salidroside pretreatment attenuated endogenous H2O2 induced apoptotic cell death in EVC-304 cells in a dose-dependent pattern. Furthermore, Western blot data revealed that salidroside inhibited activation of caspase-3, 9 and cleavage of poly(ADP-ribose) polymerase (PARP) induced by endogenous H2O2. It also decreased the expression of Bax and rescued the balance of pro- and anti-apoptotic proteins. All these results demonstrated that salidroside may present a potential therapy for oxidative stress in cardiovascular and cerebrovascular diseases.

  20. Determination of nitrite, nitrate, and glucose-6-phosphate in muscle tissues and cured meat by IC/MS.

    Science.gov (United States)

    Saccani, Giovanna; Tanzi, Enrica; Cavalli, Silvano; Rohrer, Jeff

    2006-01-01

    The endogenous nitrate concentration in fresh meat and the residual nitrate and nitrite contents after curing are related to food quality and safety. Most ion chromatography (IC) methods suffer from interferences, especially in fresh meat samples, in which the endogenous nitrate content is low, and in cured meat products, in which other nitrogenous compounds can interfere with the separation of inorganic anions. One of the major classes of interfering compounds in fresh meat are sugar phosphates, which originate from glycolysis during the conversion of muscle glycogen to lactic acid. Nitrate can be separated from interfering compounds with a high-capacity anion-exchange column that was manufactured for use with hydroxide eluents (i.e., hydroxide-selective). This column has a different selectivity than traditional IC columns that use carbonate eluents and facilitates the determination of nitrate in both fresh and cured meats. Nitrate was detected by both suppressed conductivity measurement and mass spectrometry (MS). The identifications of nitrate and glucose-6-phosphate were confirmed by MS detection. The described IC/MS method is robust, sensitive to nitrate concentrations as low as 0.10 mg/kg, and can determine sugar phosphates that are useful for monitoring meat freshness. We successfully used this method to determine nitrate in nearly 100 muscle tissues and cured meat samples.

  1. Ocimum basilicum extract exhibits antidiabetic effects via inhibition of hepatic glucose mobilization and carbohydrate metabolizing enzymes.

    Science.gov (United States)

    Ezeani, Chinelo; Ezenyi, Ifeoma; Okoye, Theophine; Okoli, Charles

    2017-01-01

    Ocimum basilicum L (Lamiaceae) is used as a traditional remedy for different ailments, including diabetes mellitus. This study investigated the antidiabetic effects of an extract of aerial parts of O. basilicum. Antihyperglycemic effect of the extract was determined by its effects on α-amylase and α-glucosidase in vitro, while antidiabetic properties were studied in alloxan induced diabetic rats treated for 28 days with extract and compared to those treated with oral metformin (150 mg/kg). The study and analysis was conducted between 2014 and 2015. The treatment with 100 and 200 mg/kg extract significantly (P < 0.05) reduced fasting blood glucose concentration and slightly increased mean body weight in treated groups. Oral glucose tolerance was also significantly (P < 0.05, 0.001) improved in 100 and 400 mg/kg extract-treated groups. The extract caused a dose-dependent increase in liver glycogen content, while it decreased alanine transferase (18.9-30.56%) and aspartate transferase (6.48-34.3%) levels in a non-dose-dependent manner. A dose of 100 mg/kg also reduced serum cholesterol and triglycerides by 19.3 and 39.54%, compared to a 2.6% reduction of cholesterol seen in the metformin-treated group. The extract was observed to produce significant (P < 0.001) concentration-dependent inhibition of α-glucosidase (35.71-100%) and also α-amylase (23.55-81.52%), with estimated inhibitory concentration values of 1.62 and 3.86 mg/mL, respectively. The antidiabetic properties of the extract may be due to its ability to suppress endogenous glucose release, inhibit glycogenolysis and/or stimulate glycogenesis.

  2. Chemometric endogenous fluorescence for tissue diagnosis

    Science.gov (United States)

    Li, Run; Vasquez, Kevin; Xu, M.

    2017-02-01

    Endogenous fluorescence is a powerful technique for probing both structure and function of tissue. We show that enabling wide-field fluorescence microscopy with chemometrics can significantly enhance the performance of tissue diagnosis with endogenous fluorescence. The spatial distribution and absolute concentration of fluorophores is uncovered with non-negative factorization aided by the spatial diversity from microscopic autofluorescence color images. Fluorescence quantification in terms of its absolute concentration map avoids issues dependent on specific measurement approach or systems and yields biologically meaningful data. The standardization of endogenous fluorescence in terms of absolute concentration will facilitate its translation to the clinics and simplifies the assessment of competing methods relating to tissue fluorescence.

  3. Glucose, memory, and aging.

    Science.gov (United States)

    Korol, D L; Gold, P E

    1998-04-01

    Circulating glucose concentrations regulate many brain functions, including learning and memory. Much of the evidence for this view comes from experiments assessing stress-related release of epinephrine with subsequent increases in blood glucose concentrations. One application of this work has been to investigate whether age-related memory impairments result from dysfunctions in the neuroendocrine regulation of the brain processes responsible for memory. Like humans, aged rodents exhibit some memory impairments that can be reversed by administration of epinephrine or glucose. In elderly humans, ingestion of glucose enhances some cognitive functions, with effects best documented thus far on tests of verbal contextual and noncontextual information. Glucose also effectively enhances cognition in persons with Alzheimer disease or Down syndrome. Although earlier evidence suggested that glucose does not enhance cognitive function in healthy young adults, more recent findings suggest that glucose is effective in this population, provided the tests are sufficiently difficult. In college students, glucose consumption significantly enhanced memory of material in a paragraph. Glucose also appeared to enhance attentional processes in these students. Neither face and word recognition nor working memory was influenced by treatment with glucose. The neurobiological mechanisms by which glucose acts are under current investigation. Initial evidence suggests that glucose or a metabolite may activate release of the neurotransmitter acetylcholine in rats when they are engaged in learning. Consequently, the issue of nutrition and cognition becomes increasingly important in light of evidence that circulating glucose concentrations have substantial effects on brain and cognitive functions.

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

    Energy Technology Data Exchange (ETDEWEB)

    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-/sup 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/sup -1/ during continuous infusion and varied between 95 and 501 pg x ml/sup -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.

  5. Glucose test (image)

    Science.gov (United States)

    ... person with diabetes constantly manages their blood's sugar (glucose) levels. After a blood sample is taken and tested, it is determined whether the glucose levels are low or high. Following your health ...

  6. Glucose-6-phosphate dehydrogenase

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003671.htm Glucose-6-phosphate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) is a protein that ...

  7. Your Glucose Meter

    Science.gov (United States)

    ... by Audience For Women Women's Health Topics Your Glucose Meter Share Tweet Linkedin Pin it More sharing ... Your Blood Sugar and Caring for Your Meter Glucose meters test and record how much sugar (called ...

  8. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... high blood glucose (blood sugar). High blood glucose happens when the body has too little insulin or ... give 5% back to the Association. » « Connect With Us Register for diabetes news, research and food & fitness ...

  9. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women ... Living With Diabetes > Treatment and Care > Blood Glucose Testing Share: Print Page Text Size: A A A ...

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... your doctor about how to handle this condition. Medical IDs Many people with diabetes, particularly those who ... In this section Living With Diabetes Treatment and Care Blood Glucose Testing Checking Your Blood Glucose A1C ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high blood glucose (blood sugar). High ... called ketones are produced. Your body cannot tolerate large amounts of ketones and will try to get ...

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... you to lower your blood glucose level. Cutting down on the amount of food you eat might ... use glucose for fuel, so your body breaks down fats to use for energy. When your body ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose ... Complications Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose ...

  15. [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.

  16. Luminal leptin induces rapid inhibition of active intestinal absorption of glucose mediated by sodium-glucose cotransporter 1.

    Science.gov (United States)

    Ducroc, Robert; Guilmeau, Sandra; Akasbi, Khalil; Devaud, Hélène; Buyse, Marion; Bado, André

    2005-02-01

    The effect of leptin on glucose transport was studied in rat jejunal mucosa in Ussing chambers. Leptin was added in the luminal or the serosal compartment before the tissues were challenged with 1, 10, or 50 mmol/l glucose. In response to 10 mmol/l glucose, the increase in short-circuit current (DeltaIsc) reached 26.8 +/- 2.1 microA/cm(2). Luminal addition of leptin dramatically decreased glucose-induced Isc (90.5% for 10 nmol/l leptin). Inhibition was maximal after 5 min and dose dependent (IC(50) = 0.13 nM). Western blot analysis showed that rapid inhibition of glucose-induced Isc by leptin was associated with a parallel decrease in the abundance of sodium-glucose transporter-1 in brush border membranes. Inhibition by luminal leptin of DeltaIsc was prevented by inhibitor of conventional protein kinase C isoforms. Serosal addition of leptin did not decrease glucose-induced Isc within 5 min and reached maximum after 10 min. The effect of leptin from serosal side was blocked by cholecystokinin (CCK) receptor-2 receptor antagonist YM022. Altogether, these data demonstrate that luminal leptin induces rapid inhibition of glucose entry into enterocyte. The slower action of leptin on the serosal side of mucosa seems indirect and is likely mediated by endogenous CCK. They demonstrate that gut leptin is a major regulator of rapid intestinal glucose transport.

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... by Mail Close www.diabetes.org > Living With Diabetes > Treatment and Care > Blood Glucose Testing Share: Print Page Text Size: ... and-how-tos, . In this section Living With Diabetes Treatment and Care Blood Glucose Testing Checking Your Blood Glucose A1C ...

  18. Discovery and Characterization of an Endogenous CXCR4 Antagonist

    Directory of Open Access Journals (Sweden)

    Onofrio Zirafi

    2015-05-01

    Full Text Available CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.

  19. Suppression in simultaneous masking.

    Science.gov (United States)

    Fastl, H; Bechly, M

    1983-09-01

    Suppression, i.e., the decrease of masked threshold caused by the addition of a second masker M2 to a first masker M1, is measured for the case of simultaneous masking. The magnitude of suppression decreases with increasing test tone duration; pulsed maskers elicit somewhat more suppression than continuous maskers. In comparison to suppression effects obtained in nonsimultaneous masking (post-masking, pulsation threshold) suppression in simultaneous masking is considerably smaller and was found only at the lower slopes of the two maskers. Suppression in simultaneous masking would not be predicted by those models of suppression which require nonsimultaneous presentation of maskers and test sound.

  20. Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis

    Science.gov (United States)

    Nakano, Haruko; Minami, Itsunari; Braas, Daniel; Pappoe, Herman; Wu, Xiuju; Sagadevan, Addelynn; Vergnes, Laurent; Fu, Kai; Morselli, Marco; Dunham, Christopher; Ding, Xueqin; Stieg, Adam Z; Gimzewski, James K; Pellegrini, Matteo; Clark, Peter M; Reue, Karen; Lusis, Aldons J; Ribalet, Bernard; Kurdistani, Siavash K; Christofk, Heather; Nakatsuji, Norio

    2017-01-01

    The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway. Blood glucose level in embryos is stable in utero during normal pregnancy, but glucose uptake by fetal cardiac tissue is drastically reduced in late gestational stages. In a murine model of diabetic pregnancy, fetal hearts showed cardiomyopathy with increased mitotic activity and decreased maturity. These data suggest that high glucose suppresses cardiac maturation, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy. PMID:29231167

  1. Glucose screening tests during pregnancy

    Science.gov (United States)

    Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... During the first step, you will have a glucose screening test: You DO NOT need to prepare ...

  2. Glucose tolerance and lipid profile in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomised controlled trial

    NARCIS (Netherlands)

    Heemstra, K. A.; Smit, J. W. A.; Eustatia-Rutten, C. F. A.; Heijboer, A. C.; Frölich, M.; Romijn, J. A.; Corssmit, E. P. M.

    2006-01-01

    The impact of prolonged subclinical hyperthyroidism on glucose and lipid metabolism is unclear. Therefore, we evaluated glucose and lipid metabolism in patients with differentiated thyroid carcinoma (DTC) on TSH suppressive thyroxine therapy as a model for subclinical hyperthyroidism and

  3. The Role of Endogenous Neurogenesis in Functional Recovery and Motor Map Reorganization Induced by Rehabilitative Therapy after Stroke in Rats.

    Science.gov (United States)

    Shiromoto, Takashi; Okabe, Naohiko; Lu, Feng; Maruyama-Nakamura, Emi; Himi, Naoyuki; Narita, Kazuhiko; Yagita, Yoshiki; Kimura, Kazumi; Miyamoto, Osamu

    2017-02-01

    Endogenous neurogenesis is associated with functional recovery after stroke, but the roles it plays in such recovery processes are unknown. This study aims to clarify the roles of endogenous neurogenesis in functional recovery and motor map reorganization induced by rehabilitative therapy after stroke by using a rat model of cerebral ischemia (CI). Ischemia was induced via photothrombosis in the caudal forelimb area of the rat cortex. First, we examined the effect of rehabilitative therapy on functional recovery and motor map reorganization, using the skilled forelimb reaching test and intracortical microstimulation. Next, using the same approaches, we examined how motor map reorganization changed when endogenous neurogenesis after stroke was inhibited by cytosine-β-d-arabinofuranoside (Ara-C). Rehabilitative therapy for 4 weeks after the induction of stroke significantly improved functional recovery and expanded the rostral forelimb area (RFA). Intraventricular Ara-C administration for 4-10 days after stroke significantly suppressed endogenous neurogenesis compared to vehicle, but did not appear to influence non-neural cells (e.g., microglia, astrocytes, and vascular endothelial cells). Suppressing endogenous neurogenesis via Ara-C administration significantly inhibited (~50% less than vehicle) functional recovery and RFA expansion (~33% of vehicle) induced by rehabilitative therapy after CI. After CI, inhibition of endogenous neurogenesis suppressed both the functional and anatomical markers of rehabilitative therapy. These results suggest that endogenous neurogenesis contributes to functional recovery after CI related to rehabilitative therapy, possibly through its promotion of motor map reorganization, although other additional roles cannot be ruled out. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  4. Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients

    DEFF Research Database (Denmark)

    Muscelli, Elza; Mari, Andrea; Casolaro, Arturo

    2008-01-01

    OBJECTIVE: To quantitate the separate impact of obesity and hyperglycemia on the incretin effect (i.e., the gain in beta-cell function after oral glucose versus intravenous glucose). RESEARCH DESIGN AND METHODS: Isoglycemic oral (75 g) and intravenous glucose administration was performed in 51...... subjects (24 with normal glucose tolerance [NGT], 17 with impaired glucose tolerance [IGT], and 10 with type 2 diabetes) with a wide range of BMI (20-61 kg/m(2)). C-peptide deconvolution was used to reconstruct insulin secretion rates, and beta-cell glucose sensitivity (slope of the insulin secretion.......01). Glucagon suppression during the oral glucose tolerance test was blunted in diabetic patients. CONCLUSIONS: Potentiation of insulin secretion, glucose sensing, glucagon-like peptide-1 release, and glucagon suppression are physiological manifestations of the incretin effect. Glucose tolerance and obesity...

  5. Effects of hyperglycemia on glucose production and utilization in humans. Measurement with (3H)-2-, (3H)-3-, and (14C)-6-glucose

    Energy Technology Data Exchange (ETDEWEB)

    Bell, P.M.; Firth, R.G.; Rizza, R.A.

    1986-06-01

    Studies with tritiated isotopes of glucose have demonstrated that hyperglycemia per se stimulates glucose utilization and suppresses glucose production in humans. These conclusions rely on the assumption that tritiated glucose provides an accurate measure of glucose turnover. However, if in the presence of hyperglycemia the isotope either loses its label during futile cycling or retains its label during cycling through glycogen, then this assumption is not valid. To examine this question, glucose utilization and glucose production rates were measured in nine normal subjects with a simultaneous infusion of (/sup 3/H)-2-glucose, an isotope that may undergo futile cycling but does not cycle through glycogen; (/sup 14/C)-6-glucose, an isotope that may cycle through glycogen but does not futile cycle; and (/sup 3/H)-3-glucose, an isotope that can both undergo futile cycling and cycle through glycogen. In the postabsorptive state at plasma glucose concentration of 95 mg X dl-1, glucose turnover determined with (/sup 14/C)-6-glucose (2.3 +/- 0.1 mg X kg-1 X min-1) was greater than that determined with (3/sup 3/H)glucose (2.1 +/- 0.1 mg X kg-1 X min-1, P = 0.002) and slightly less than that determined with (/sup 3/H)-2-glucose (2.7 +/- 0.2 mg X kg-1 X min-1, P = 0.08). Plasma glucose was then raised from 95 to 135 to 175 mg X dl-1 while insulin secretion was inhibited, and circulating insulin, glucagon, and growth hormone concentrations were maintained constant by infusion of these hormones and somatostatin. Glucose production and utilization rates determined with (/sup 14/C)-6-glucose continued to be less than those determined with (/sup 3/H)-2-glucose and greater than those seen with (/sup 3/H)-3-glucose.

  6. Evolution and phylogeny of insect endogenous retroviruses.

    Science.gov (United States)

    Terzian, C; Pélisson, A; Bucheton, A

    2001-01-01

    The genome of invertebrates is rich in retroelements which are structurally reminiscent of the retroviruses of vertebrates. Those containing three open reading frames (ORFs), including an env-like gene, may well be considered as endogenous retroviruses. Further support to this similarity has been provided by the ability of the env-like gene of DmeGypV (the Gypsy endogenous retrovirus of Drosophila melanogaster) to promote infection of Drosophila cells by a pseudotyped vertebrate retrovirus vector. To gain insights into their evolutionary story, a sample of thirteen insect endogenous retroviruses, which represents the largest sample analysed until now, was studied by computer-assisted comparison of the translated products of their gag, pol and env genes, as well as their LTR structural features. We found that the three phylogenetic trees based respectively on Gag, Pol and Env common motifs are congruent, which suggest a monophyletic origin for these elements. We showed that most of the insect endogenous retroviruses belong to a major clade group which can be further divided into two main subgroups which also differ by the sequence of their primer binding sites (PBS). We propose to name IERV-K and IERV-S these two major subgroups of Insect Endogenous Retro Viruses (or Insect ERrantiVirus, according to the ICTV nomenclature) which respectively use Lys and Ser tRNAs to prime reverse transcription.

  7. Mediation of glucose-induced anorexia by central nervous system interleukin 1 signaling.

    Science.gov (United States)

    Mizuno, Tooru M; Lew, Pei San; Spirkina, Alexandra; Xu, Yang

    2013-11-01

    Hypothalamic glucose sensing plays a critical role in the regulation of food intake and metabolism. Glucose injection, either centrally or peripherally suppresses food intake. However, the mechanism of glucose-induced feeding suppression is not fully understood. It has been demonstrated that hypothalamic interleukin 1 beta (IL-1β) mRNA levels are altered by metabolic states and IL-1 signaling participates in the regulation of food intake. Therefore, we hypothesized that hypothalamic IL-1 gene expression is regulated by glucose and glucose-induced feeding suppression is mediated via hypothalamic IL-1 signaling. To address this hypothesis, we examined the effect of glucose on IL-1α and IL-1β mRNA expression in the hypothalamus. We also examined the effect of intraperitoneal injection of glucose on food intake in wild-type and type I IL-1 receptor (IL-1RI)-deficient mice. Levels of IL-1α and IL-1β mRNA in the hypothalamus were increased in response to feeding and intraperitoneal injection of glucose, and were positively correlated with blood glucose levels in mice. Exposure of hypothalamic explants to high glucose (10 mM) media increased IL-1α and IL-1β mRNA levels compared to low glucose (1 mM) media. Intraperitoneal glucose administration reduced food intake in wild-type mice, while the feeding-suppressing effect of glucose was attenuated in IL-1RI-deficient mice. These findings support the role for hypothalamic IL-1 signaling in the mediation of the anorectic effect of glucose. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Maintenance, endogeneous, respiration, lysis, decay and predation

    DEFF Research Database (Denmark)

    loosdrecht, Marc C. M. Van; Henze, Mogens

    1999-01-01

    mechanism is microbiologically correct. The lysis/decay model mechanism is a strongly simplified representation of reality. This paper tries to review the processes grouped under endogenous respiration in activated sludge models. Mechanisms and processes such as maintenance, lysis, internal and external...... and maintenance processes. This conversion will in general be denoted as endogenous respiration. Based on the literature review the phenomena are discussed and organised, in order to create a working platform for discussing more detailed activated sludge models, one of which is being sketched. (C) 1999 IAWQ......In activated sludge processes an increased sludge age is associated with a decreased sludge production. This phenomenon is generally interpreted as a result of endogenous respiration processes. In the activated sludge models cell lysis (or decay) is incorporated. The lysis is modelled...

  9. Endogeneity in Strategy-Performance Analysis

    DEFF Research Database (Denmark)

    Rocha, Vera; Van Praag, Mirjam; B. Folta, Timothy

    2018-01-01

    Managers engage in a variety of strategies, not randomly, but having in mind their performance implications. Therefore, strategic choices are endogenous in performance equations. Despite increasing efforts by various scholars in solving endogeneity bias, prior attempts have almost exclusively......, such as employees, strategic partners, customers, or investors, whose choices and preferences also affect the final decision. We discuss how endogeneity can plague the measurement of the performance effects of these two-sided strategic decisions—which are more complex, but more realistic, than prior representations...... of organizational decision making. We provide an empirical demonstration of possible methods to deal with three different sources of bias, by analyzing the performance effects of two human capital choices made by founders at startup: the size and average quality of the initial workforce....

  10. Dexamethasone suppression test

    Science.gov (United States)

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

  11. Growth hormone suppression test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  12. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

    OpenAIRE

    Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram

    2004-01-01

    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide...

  13. Endogenous network of firms and systemic risk

    Science.gov (United States)

    Ma, Qianting; He, Jianmin; Li, Shouwei

    2018-02-01

    We construct an endogenous network characterized by commercial credit relationships connecting the upstream and downstream firms. Simulation results indicate that the endogenous network model displays a scale-free property which exists in real-world firm systems. In terms of the network structure, with the expansion of the scale of network nodes, the systemic risk increases significantly, while the heterogeneities of network nodes have no effect on systemic risk. As for firm micro-behaviors, including the selection range of trading partners, actual output, labor requirement, price of intermediate products and employee salaries, increase of all these parameters will lead to higher systemic risk.

  14. An endogenous model of the credit network

    Science.gov (United States)

    He, Jianmin; Sui, Xin; Li, Shouwei

    2016-01-01

    In this paper, an endogenous credit network model of firm-bank agents is constructed. The model describes the endogenous formation of firm-firm, firm-bank and bank-bank credit relationships. By means of simulations, the model is capable of showing some obvious similarities with empirical evidence found by other scholars: the upper-tail of firm size distribution can be well fitted with a power-law; the bank size distribution can be lognormally distributed with a power-law tail; the bank in-degrees of the interbank credit network as well as the firm-bank credit network fall into two-power-law distributions.

  15. Biostable glucose permeable polymer

    DEFF Research Database (Denmark)

    2017-01-01

    A new biostable glucose permeable polymer has been developed which is useful, for example, in implantable glucose sensors. This biostable glucose permeable polymer has a number of advantageous characteristics and, for example, does not undergo hydrolytic cleavage and degradation, thereby providing...... a composition that facilitates long term sensor stability in vivo. The versatile characteristics of this polymer allow it to be used in a variety of contexts, for example to form the body of an implantable glucose sensor. The invention includes the polymer composition, sensor systems formed from this polymer...

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  17. Blood Glucose Levels

    Directory of Open Access Journals (Sweden)

    Carlos Estela

    2011-01-01

    Full Text Available The purpose of this study was to establish a mathematical model which can be used to estimate glucose levels in the blood over time. The equations governing this process were manipulated with the use of techniques such as separation of variables and integration of first order differential equations, which resulted in a function that described the glucose concentration in terms of time. This function was then plotted, which allowed us to find when glucose concentration was at its highest. The model was then used to analyze two cases where the maximum glucose level could not exceed a certain level while the amount of carbohydrates and glycemic index were varied, independently.

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy ...

  19. Effect of adrenaline on glucose kinetics during exercise in adrenalectomised humans

    DEFF Research Database (Denmark)

    Howlett, K; Galbo, H; Lorentsen, J

    1999-01-01

    trials. Adrenaline infusion suppressed growth hormone and elevated plasma free fatty acids, glycerol and lactate. Alanine and beta-hydroxybutyrate levels were similar between trials. 5. The results demonstrate that glucose homeostasis was maintained during exercise in adrenalectomised subjects...

  20. Place branding, embeddedness and endogenous rural development

    NARCIS (Netherlands)

    Donner, Mechthild; Horlings, Lummina; Fort, Fatiha; Vellema, Sietze

    2017-01-01

    This article deals with place branding on the regional scale, in the rural context of food and tourism networks in Europe. Place branding is linked to the concepts of endogenous rural development, territory and embeddedness, by analysing how the valorisation of specific rural assets takes shape.

  1. Leveraging Endogenous Research and Innovation for Sustainable ...

    African Journals Online (AJOL)

    In this treatise, a quick look is taken at the spectrum (range) of research from pure basic, strategic basic, applied, experimental development or research and development (R&D) to endogenous research and innovation (ER&I). It also defines development, innovation, food security, poverty; and discusses some contemporary ...

  2. Exogenous and endogenous corticosterone alter feather quality.

    Science.gov (United States)

    DesRochers, David W; Reed, J Michael; Awerman, Jessica; Kluge, Jonathan A; Wilkinson, Julia; van Griethuijsen, Linnea I; Aman, Joseph; Romero, L Michael

    2009-01-01

    We investigated how exogenous and endogenous glucocorticoids affect feather replacement in European starlings (Sturnus vulgaris) after approximately 56% of flight feathers were removed. We hypothesized that corticosterone would retard feather regrowth and decrease feather quality. After feather regrowth began, birds were treated with exogenous corticosterone or sham implants, or endogenous corticosterone by applying psychological or physical (food restriction) stressors. Exogenous corticosterone had no impact on feather length and vane area, but rectrices were lighter than controls. Exogenous corticosterone also decreased inter-barb distance for all feathers and increased barbule number for secondaries and rectrices. Although exogenous corticosterone had no affect on rachis tensile strength and stiffness, barbicel hooking strength was reduced. Finally, exogenous corticosterone did not alter the ability of Bacillus licheniformis to degrade feathers or affect the number of feathers that failed to regrow. In contrast, endogenous corticosterone via food restriction resulted in greater inter-barb distances in primaries and secondaries, and acute and chronic stress resulted in greater inter-barb distances in rectrices. Food-restricted birds had significantly fewer barbules in primaries than chronic stress birds and weaker feathers compared to controls. We conclude that, although exogenous and endogenous corticosterone had slightly different effects, some flight feathers grown in the presence of high circulating corticosterone are lighter, potentially weaker, and with altered feather micro-structure.

  3. Optimized Formation of Benzyl Isothiocyanate by Endogenous ...

    African Journals Online (AJOL)

    Purpose: To use endogenous myrosinase in Carica papaya seed to convert benzyl glucosinolate (BG) to benzyl isothiocyanate (BITC) and then extract it for further studies. Methods: Process variables including seed powder particle size, sample-to-solvent ratio, pH of buffer solution, enzymolysis temperature, enzymolysis ...

  4. endogenous retrovirus sequences expressed in male mammalian

    African Journals Online (AJOL)

    2002-01-02

    Jan 2, 2002 ... demonstrated in New Zealand Black mice, where the reproductive tract of males were shown to contain C-type retrovirus(35). Also endogenous mouse mammary tumour virus (MMTV) proteins (p28 and gp47) have been identified in the epididymis and seminal vesicles of adult Swiss. Albino mice devoid of ...

  5. Managing spillovers: an endogenous sunk cost approach

    Czech Academy of Sciences Publication Activity Database

    Senyuta, Olena; Žigić, Krešimir

    2016-01-01

    Roč. 35, June (2016), s. 45-64 ISSN 0167-6245 R&D Projects: GA ČR(CZ) GAP402/12/0961 Institutional support: PRVOUK-P23 Keywords : endogenous sunk costs * innovations * knowledge spillovers Subject RIV: AH - Economics Impact factor: 0.739, year: 2016

  6. Baboon endogenous virus evolution and ecology

    NARCIS (Netherlands)

    van der Kuyl, A. C.; Dekker, J. T.; Goudsmit, J.

    1996-01-01

    Cross-species transmission of retroviruses among primates has recently been recognized as the source of the current epidemics of HIV-1, HIV-2 and human T cell leukemia virus type 1 (HTLV-1). The distribution of baboon endogenous virus among non-human primates resembles that of exogenous viruses and

  7. Immigration, Endogenous Technology Adoption and Wages

    NARCIS (Netherlands)

    Ray Chaudhuri, A.; Pandey, Manish

    2015-01-01

    We document that immigration to U.S. states has increased the mass of workers at the lower range of the skill distribution. We use this change in skill distribution of workers to analyze the effect of immigration on wages. Our model allows firms to endogenously respond to the immigration-induced

  8. An endogenous policy model of hierarchical government

    NARCIS (Netherlands)

    Mazza, I.; van Winden, F.

    2008-01-01

    Endogenous policy models usually neglect that government policies are frequently the result of decisions taken at different tiers by different agents, each enjoying some degree of autonomy. In this paper, policies are the outcome of the choices made by two agents within a hierarchy. A legislator

  9. Endogenizing technological progress: The MESEMET model

    NARCIS (Netherlands)

    P.A.G. van Bergeijk (Peter); G.H.A. van Hagen; R.A. de Mooij (Ruud); J. van Sinderen (Jarig)

    1997-01-01

    textabstractThis paper endogenizes technology and human capital formation in the MESEM model that was developed by van Sinderen (Economic Modelling, 1993, 13, 285-300). Tax allowances for private R&D expenditures and public expenditures on both education and R& D are effective instruments to

  10. Endogenous retrovirus sequences expressed in male mammalian ...

    African Journals Online (AJOL)

    In humans, one ERV family, human endogenous retrovirus- K (HERV-K) is abundantly expressed, and is associated with germ cell tumours, while ERV3 env is expressed in normal human testis. Conclusion: The expression of ERVs in male reproductive tissues suggests a possible role in normal and disease conditions ...

  11. ENDOGENOUS ENERGY. A CAUSE OF BIASET/ TRUE ...

    African Journals Online (AJOL)

    sufficient feed. In the TME procedure, as publishecl by. Sibbald ( 1976), endogenous energy excretion is deter- mined with fasted animals, a situation which can be re- garded as being physiologically undesirable since birds would be in an energy-deficient state and to an extent also in a protein deficient state. When in a ...

  12. Applying Endogenous Knowledge in the African Context ...

    African Journals Online (AJOL)

    This requires not only an understanding of what endogenous knowledge is, but also an alignment of personal values, innovative strategies and an attitude of activism. An integral part of an extensive skills set to implement ... competence of dispute resolution practitioners in Africa. AFRICA INSIGHT Vol 42 (1) – June 2012 ...

  13. Ethnobotany and endogenous conservation of Irvingia gabonensis ...

    African Journals Online (AJOL)

    ... systematically gathered for consumption and marketing. Few studies have been done on the ethnobotany and endogenous practices determining its conservation of the species in Benin. This study aims to produce a database on those aspects in Benin. Two hundred and sixty-three people from the six major socio-cultural ...

  14. Endogenous thrombin potential in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Aziz, Mubeena; Sidelmann, Johannes J; Wissing, Marie Louise Muff

    2015-01-01

    OBJECTIVES: The objective of this study is to investigate plasma endogenous thrombin generation in four different phenotypes of polycystic ovary syndrome (PCOS) defined by Body Mass Index (BMI) and insulin resistance (IR). PCOS is diagnosed according to the Rotterdam criteria. DESIGN: Multicenter...

  15. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... when ketones are present may make your blood glucose level go even higher. You'll need to work with your doctor to find the safest way for you to lower your blood glucose level. Cutting down on the amount of food you eat might also help. Work with your dietitian to make changes in your ...

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... by Mail Close www.diabetes.org > Living With Diabetes > Treatment and Care > Blood Glucose Testing Share: Print Page ... and-how-tos, In this section Living With Diabetes Treatment and Care Blood Glucose Testing Checking Your Blood ...

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Your Carbs Count Glycemic Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type 1 Diabetes Get Started Safely Get And Stay Fit Types ... the following: High blood glucose High levels of sugar in the ... Part of managing your diabetes is checking your blood glucose often. Ask your ...

  18. Blood Glucose Determination

    DEFF Research Database (Denmark)

    Lippi, Giuseppe; Nybo, Mads; Cadamuro, Janne

    2018-01-01

    The measurement of fasting plasma glucose may be biased by a time-dependent decrease of glucose in blood tubes, mainly attributable to blood cell metabolism when glycolysis is not rapidly inhibited or blood cells cannot be rapidly separated from plasma. Although glycolysis inhibitors such as sodium...

  19. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... June 7, 2013 Last Edited: September 16, 2014 Articles from Diabetes Forecast® magazine: bg-and-a1c-hyperglycemia,tips-and-how-tos, . In this section Living With Diabetes Treatment and Care Blood Glucose Testing Checking Your Blood Glucose A1C ...

  20. 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...

  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. Natriuretic Hormones, Endogenous Ouabain, and Related Sodium Transport Inhibitors

    Directory of Open Access Journals (Sweden)

    John eHamlyn

    2014-12-01

    Full Text Available The work of deWardener and colleagues stimulated longstanding interest in natriuretic hormones (NH. In addition to the atrial peptides (APs, the circulation contains unidentified physiologically-relevant NHs. One NH is controlled by the central nervous system (CNS and likely secreted by the pituitary. Its circulating activity is modulated by salt intake and the prevailing sodium concentration of the blood and intracerebroventricular fluid, and contributes to postprandial and dehydration natriuresis. The other NH, mobilized by atrial stretch, promotes natriuresis by increasing the production of intrarenal dopamine and/or nitric oxide. Both NHs have short (<35 minutes circulating half lives, depress renotubular sodium transport, and neither requires the renal nerves. The search for NHs led to endogenous cardiotonic steroids (CTS including ouabain-, digoxin-, and bufadienolide-like materials. These CTS, given acutely in high nanomole to micromole amounts into the general or renal circulations, inhibit sodium pumps and are natriuretic. Among these CTS, only bufalin is cleared sufficiently rapidly to qualify for an NH-like role. Ouabain-like CTS are cleared slowly, and when given chronically in low daily nanomole amounts, promote sodium retention, augment arterial myogenic tone, reduce renal blood flow and glomerular filtration, suppress nitric oxide in the renal vasa recta, and increase sympathetic nerve activity and blood pressure. Moreover, lowering total body sodium raises circulating endogenous ouabain. Thus, ouabain-like CTS have physiological actions that, like aldosterone, support renal sodium retention and blood pressure. In conclusion, the mammalian circulation contains two non-AP NHs. Identification of the CNS NH should be a priority.

  3. Hyperglucagonemia mitigates the effect of metformin on glucose production in prediabetes

    OpenAIRE

    Konopka, Adam R.; Esponda, Raul Ruiz; Robinson, Matthew M.; Johnson, Matthew L.; Carter, Rickey E.; Schiavon, Michele; Cobelli, Claudio; Wondisford, Fredric E.; Lanza, Ian R.; Nair, K. Sreekumaran

    2016-01-01

    The therapeutic mechanism of metformin action remains incompletely understood. Whether metformin inhibits glucagon-stimulated endogenous glucose production (EGP), as in preclinical studies, is unclear in humans. To test this hypothesis, we studied 9 prediabetic individuals using a randomized, placebo-controlled, double-blinded, crossover study design. Metformin increased glucose tolerance, insulin sensitivity and plasma glucagon. Metformin did not alter average basal EGP, although individual ...

  4. Resolving futile glucose cycling and glycogenolytic contributions to plasma glucose levels following a glucose load

    NARCIS (Netherlands)

    Nunes, P.M.; Jarak, I.; Heerschap, A.; Jones, J.G.

    2014-01-01

    PURPOSE: After a glucose load, futile glucose/glucose-6-phosphate (G6P) cycling (FGC) generates [2-(2) H]glucose from (2) H2 O thereby mimicking a paradoxical glycogenolytic contribution to plasma glucose levels. Contributions of load and G6P derived from gluconeogenesis, FGC, and glycogenolysis to

  5. Model for Simulating Fasting Glucose in Type 2 Diabetes and the Effect of Adherence to Treatment

    DEFF Research Database (Denmark)

    Aradóttir, Tinna Björk; Boiroux, Dimitri; Bengtsson, Henrik

    2017-01-01

    The primary goal of this paper is to predict fasting glucose levels in type 2 diabetes (T2D) in long-acting insulin treatment. The paper presents a model for simulating insulin-glucose dynamics in T2D patients. The model combines a physiological model of type 1 diabetes (T1D) and an endogenous...... levels during titration in a clinical trial. Adherence to insulin injections plays an important role considering variance in fasting glucose. For adherence levels 100%, 70% and 50%, the coefficient of variation of simulated fasting glucose levels were similar to observed variances in insulin treatment...... insulin production model in T2D. We include a review of sources of variance in fasting glucose values in long-acting insulin treatment, with respect to dose guidance algorithms. We use the model to simulate fasting glucose levels in T2D long-acting insulin treatment and compare the results with clinical...

  6. Corticotropin releasing hormone can selectively stimulate glucose uptake in corticotropinoma via glucose transporter 1.

    Science.gov (United States)

    Lu, Jie; Montgomery, Blake K; Chatain, Grégoire P; Bugarini, Alejandro; Zhang, Qi; Wang, Xiang; Edwards, Nancy A; Ray-Chaudhury, Abhik; Merrill, Marsha J; Lonser, Russell R; Chittiboina, Prashant

    2017-10-03

    Pre-operative detection of corticotropin (ACTH) secreting microadenomas causing Cushing's disease (CD) improves surgical outcomes. Current best magnetic resonance imaging fails to detect up to 40% of these microadenomas. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) is specific, but not sensitive in detecting corticotropinomas. Theoretically, secretagogue stimulation with corticotropin releasing hormone (CRH) could improve detection of adenomas with 18 F-FDG PET. Previous attempts with simultaneous CRH stimulation have failed to demonstrate increased 18 F-FDG uptake in corticotropinomas. We hypothesized that CRH stimulation leads to a delayed elevation in glucose uptake in corticotropinomas. Clinical data was analyzed for efficacy of CRH in improving 18 FDG-PET detection of corticotropinomas in CD. Glucose transporter 1 (GLUT1) immunoreactivity was performed on surgical specimens. Ex-vivo, viable cells from these tumors were tested for secretagogue effects (colorimetric glucose uptake), and for fate of intracellular glucose (glycolysis stress analysis). Validation of ex-vivo findings was performed with AtT-20 cells. CRH increased glucose uptake in human-derived corticotroph tumor cells and AtT-20, but not in normal murine or human corticotrophs (p fasentin suppressed baseline (p < 0.0001) and CRH-mediated glucose uptake. Expectedly, intra-operatively collected corticotropinomas demonstrated GLUT1 overexpression. Lastly, human derived corticotroph tumor cells demonstrated increased glycolysis and low glucose oxidation. Increased and delayed CRH-mediated glucose uptake differentially occurs in adenomatous corticotrophs. Delayed secretagogue-stimulated 18 F-FDG PET could improve microadenoma detection. Copyright © 2017. Published by Elsevier B.V.

  7. Endogenous retroviral promoter exaptation in human cancer

    National Research Council Canada - National Science Library

    Babaian, Artem; Mager, Dixie L

    2016-01-01

      Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes...

  8. Endogenous androgens and carotid intimal-medial thickness in women.

    Science.gov (United States)

    Bernini, G P; Sgro', M; Moretti, A; Argenio, G F; Barlascini, C O; Cristofani, R; Salvetti, A

    1999-06-01

    The influence of endogenous androgens on atherosclerotic disease in women is unknown. In this study involving 101 pre- and post-menopausal females, we evaluated the relationship between serum androgen levels and both carotid artery intimal-medial thickness (IMT) and major cardiovascular risk factors. In addition to evaluation of blood pressure, body mass index, and waist-to-hip ratio, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), total testosterone (TTS), free testosterone (FTS), insulin, cholesterol (total and high density lipoproteins), triglycerides, and glucose were measured. All women underwent carotid ultrasonography. Spearman correlation coefficients showed that serum DHEA-S and A levels were negatively related (P body mass index (P < 0.02). Stepwise multiple regression analysis indicated that A and FTS showed an inverse association with IMT measures (P < 0.05-0.001). In conclusion, our data indicate that in women serum DHEA-S and androgens decline with age and that normal hormonal levels are not associated with major cardiovascular risk factors. They also show that higher DHEA-S and androgen concentrations are related to lower carotid wall thickness; for A this association is independent of cardiovascular risk factors. Our results suggest that, in the physiological range, DHEA-S and androgens in women are correlated with lower risk of carotid artery atherosclerosis.

  9. Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea

    Directory of Open Access Journals (Sweden)

    Chang-Yun Woo

    2015-04-01

    Full Text Available BackgroundEndogenous hyperinsulinemic hypoglycemia (EHH is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS are relatively rare.MethodsTo evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital.ResultsAmong the 84 EHH patients, 74 patients (88%, five (6%, and five (6% were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months for insulinoma, 1.0 months (range, 6 days to 7 months for nesidioblastosis, and 2.0 months (range, 1 to 12 months for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL, which suggests that these patients might have had IAS, rather than nesidioblastosis.ConclusionThe results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.

  10. Deconstructing continuous flash suppression.

    Science.gov (United States)

    Yang, Eunice; Blake, Randolph

    2012-03-08

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

  11. A turn-on fluorescent probe for endogenous formaldehyde in the endoplasmic reticulum of living cells

    Science.gov (United States)

    Tang, Yonghe; Ma, Yanyan; Xu, An; Xu, Gaoping; Lin, Weiying

    2017-06-01

    As the simplest aldehyde compounds, formaldehyde (FA) is implicated in nervous system diseases and cancer. Endoplasmic reticulum is an organelle that plays important functions in living cells. Accordingly, the development of efficient methods for FA detection in the endoplasmic reticulum (ER) is of great biomedical importance. In this work, we developed the first ER-targeted fluorescent FA probe Na-FA-ER. The detection is based on the condensation reaction of the hydrazine group and FA to suppress the photo-induced electron transfer (PET) pathway, resulting in a fluorescence increase. The novel Na-FA-ER showed high sensitivity to FA. In addition, the Na-FA-ER enabled the bio-imaging of exogenous and endogenous FA in living HeLa cells. Most significantly, the new Na-FA-ER was employed to visualize the endogenous FA in the ER in living cells for the first time.

  12. Endogenous Market Structures and Labor Market Dynamics

    OpenAIRE

    Colciago, Andrea; Rossi, Lorenza

    2011-01-01

    We propose a model characterized by strategic interactions among an endogenous number of producers and search and matching frictions in the labor market. In line with U.S. data: (i) new firms account for a relatively small share of overall employment, but they create a relevant fraction of new jobs; (ii) firms’ entry is procyclical; (iii) price mark ups are countercyclical, while aggregate profits are procyclical. In response to a technology shock the labor share decreases on impact and overs...

  13. Unfunded pensions and endogenous labor supply

    DEFF Research Database (Denmark)

    Andersen, Torben M.; Bhattacharya, Joydeep

    A classic result in dynamic public economics, dating back to Aaron (1966) and Samuelson (1975), states that there is no welfare rationale for PAYG pensions in a dynamically-efficient neoclassical economy with exogenous labor supply. This paper argues that this result, under the fairly......-mild restriction that the old be no less risk-averse than the young, extends to a neoclassical economy with endogenous labor supply....

  14. Public Procurement of Innovation as Endogenous

    DEFF Research Database (Denmark)

    Rolfstam, Max

    Public procurement used as an innovation policy instrument has attracted attention the last decade. It has been argued that public procurement can be used to stimulate innovation from the demand-side. This paper problematizes ‘demand’ understood as a problem defined by a public procurer given...... underlying mechanisms critical for success. Instead the paper views public procurement of innovation as an instrument of endogenous- exogenous knowledge conversion....

  15. Unionised labour market, environment and endogenous growth

    OpenAIRE

    Bhattacharyya, Chandril; Gupta, Manash Ranjan

    2014-01-01

    In this paper, a model of endogenous economic growth is developed with special focus on the interaction between unionized labour market and environmental pollution. We introduce a trade union; and use both ‘Efficient Bargaining’ model and ‘Right to Manage’ model to solve the negotiation problem. Environmental pollution is the result of production; and the labour union bargains not only for wage and employment but also for the protection of environment. We derive properties of optimum income t...

  16. Neoclassical vs. Endogenous Growth Analysis: An Overview

    OpenAIRE

    Bennett T. McCallum

    1996-01-01

    This paper begins with an exposition of neoclassical growth theory, including several analytical results such as the distinction between golden-rule and optimal steady states. Next it emphasizes that the neoclassical approach fails to provide any explanation of steady-state growth in per capita values of output and consumption, and also cannot plausibly explain actual growth differences by reference to transitional episodes. Three types of endogenous growth models, which attempt to provide ex...

  17. Buyer Search Costs and Endogenous Product Design

    OpenAIRE

    Dmitri Kuksov

    2004-01-01

    Buyer search costs for price are changing in many markets. Through a model of buyer and seller behavior, I consider the effects of changing search costs on prices both when product differentiation is fixed and when it is endogenously determined in equilibrium. If firms cannot change product design, lower buyer search costs for price lead to increased price competition. However, if product design is a decision variable, lower search costs for price may also lead to higher product differentiati...

  18. Prices vs. Quantities with Endogenous Cost Structure

    OpenAIRE

    Storrøsten, Halvor Briseid

    2014-01-01

    Authorities often lack information for efficient regulation of the commons. This paper derives a criterion comparing prices versus tradable quantities in terms of expected welfare, given uncertainty, optimal policy and endogenous cost structure. I show that one cannot determine which regulatory instrument that induces the highest expected welfare based on the relative curvatures of the cost and benefit functions alone. Furthermore, optimal policy involves different production (or price) targe...

  19. Asset Bubbles, Endogenous Growth, and Financial Frictions

    OpenAIRE

    Hirano, Tomohiro; Yanagawa, Noriyuki

    2016-01-01

    This paper analyzes the effects of bubbles in an infinitely-lived agent model of endogenous growth with financial frictions and heterogeneous agents. We provide a complete characterization on the relationship between financial frictions and the existence of bubbles. Our model predicts that if the degree of pledgeability is sufficiently high or sufficiently low, bubbles can not exist. They can only arise at an intermediate degree. This suggests that improving the financial market condition mig...

  20. Endogenous endophthalmitis after severe burn: A case report

    Directory of Open Access Journals (Sweden)

    Seyedeh Maryam Hosseini

    2017-01-01

    Conclusion: Burn patients treated with broad-spectrum antibiotics are at risk of candidemia and its complications, including endogenous endophthalmitis. Early diagnosis of endogenous endophthalmitis in high risk patients could prevent visual loss.

  1. Proteolysis controls endogenous substance P levels.

    Directory of Open Access Journals (Sweden)

    Andrew J Mitchell

    Full Text Available Substance P (SP is a prototypical neuropeptide with roles in pain and inflammation. Numerous mechanisms regulate endogenous SP levels, including the differential expression of SP mRNA and the controlled secretion of SP from neurons. Proteolysis has long been suspected to regulate extracellular SP concentrations but data in support of this hypothesis is scarce. Here, we provide evidence that proteolysis controls SP levels in the spinal cord. Using peptidomics to detect and quantify endogenous SP fragments, we identify the primary SP cleavage site as the C-terminal side of the ninth residue of SP. If blocking this pathway increases SP levels, then proteolysis controls SP concentration. We performed a targeted chemical screen using spinal cord lysates as a proxy for the endogenous metabolic environment and identified GM6001 (galardin, ilomastat as a potent inhibitor of the SP(1-9-producing activity present in the tissue. Administration of GM6001 to mice results in a greater-than-three-fold increase in the spinal cord levels of SP, which validates the hypothesis that proteolysis controls physiological SP levels.

  2. Endogenous Generalized Weights under DEA Control

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    Non-parametric efficiency analysis, such as Data Envelopment Analysis (DEA) relies so far on endogenous local or exogenous general weights, based on revealed preferences or market prices. However, as DEA is gaining popularity in regulation and normative budgeting, the strategic interest of the ev......-priced out- puts is relevant. The results show that sector wide weighting schemes favor input/output combinations that are less variable than would individual units......Non-parametric efficiency analysis, such as Data Envelopment Analysis (DEA) relies so far on endogenous local or exogenous general weights, based on revealed preferences or market prices. However, as DEA is gaining popularity in regulation and normative budgeting, the strategic interest...... of the evaluated industry calls for attention. We offer endogenous general prices based on a reformulation of DEA where the units collectively propose the set of weights that maximize their efficiency. Thus, the sector-wide efficiency is then a result of compromising the scores of more specialized smaller units...

  3. Fanconi anemia proteins and endogenous stresses

    Energy Technology Data Exchange (ETDEWEB)

    Pang Qishen [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States); Andreassen, Paul R., E-mail: Paul.Andreassen@cchmc.org [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States)

    2009-07-31

    Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.

  4. Endogenous viral elements in animal genomes.

    Directory of Open Access Journals (Sweden)

    Aris Katzourakis

    2010-11-01

    Full Text Available Integration into the nuclear genome of germ line cells can lead to vertical inheritance of retroviral genes as host alleles. For other viruses, germ line integration has only rarely been documented. Nonetheless, we identified endogenous viral elements (EVEs derived from ten non-retroviral families by systematic in silico screening of animal genomes, including the first endogenous representatives of double-stranded RNA, reverse-transcribing DNA, and segmented RNA viruses, and the first endogenous DNA viruses in mammalian genomes. Phylogenetic and genomic analysis of EVEs across multiple host species revealed novel information about the origin and evolution of diverse virus groups. Furthermore, several of the elements identified here encode intact open reading frames or are expressed as mRNA. For one element in the primate lineage, we provide statistically robust evidence for exaptation. Our findings establish that genetic material derived from all known viral genome types and replication strategies can enter the animal germ line, greatly broadening the scope of paleovirological studies and indicating a more significant evolutionary role for gene flow from virus to animal genomes than has previously been recognized.

  5. Endogenous growth theory and regional development policy

    Directory of Open Access Journals (Sweden)

    Cvetanović Slobodan

    2015-01-01

    Full Text Available The numerous versions of endogenous explanations of economic growth emphasize the importance of technological change driving forces, as well as the existence of appropriate institutional arrangements. Endogenous growth theory contributes to a better understanding of various experiences with long-term growth of countries and regions. It changes the key assumptions of the Neoclassical growth theory and participates in the modern regional development physiology explanation. Based on these conclusions, the paper: a explicates the most important theoretical postulates of the theory, b explains the most important factors of economic growth in the regions in light of the Endogenous growth theory messages and c emphasizes the key determinants of regional competitiveness which in our view is conceptually between the phenomena of micro- and macro-competitiveness and represents their necessary and unique connection. First of all, micro-competitiveness is transformed into a regional competitiveness; then regional competitiveness is transformed into a macro-competitiveness. In turn, macro - influences the microeconomic competitiveness, and the circle is closed. After that, the process starts over again.

  6. Effect of Sleep and Salivary Glucose on Gingivitis in Children.

    Science.gov (United States)

    Alqaderi, H; Tavares, M; Hartman, M; Goodson, J M

    2016-11-01

    It has been shown that inadequate sleep has deleterious effects on health by suppressing immunity and promoting inflammation. The aim of this study was to investigate the effect of sleep and salivary glucose levels on the development of gingivitis in a prospective longitudinal study of Kuwaiti children. Data were collected from 10-y-old children ( N = 6,316) in 2012 and again in 2014. Children were approximately equally distributed from 138 elementary schools representing the 6 governorates of Kuwait. Calibrated examiners conducted oral examination, self-reported sleep evaluation interviews, anthropomorphic measurements, and unstimulated whole saliva sample collection. Salivary glucose levels were measured by a florescent glucose oxidase method; values of salivary glucose ≥1.13 mg/dL were defined as high glucose levels. A multilevel random intercept and slope analysis was conducted to determine the relationship between sleep duration and gingivitis on 3 levels: within schools, among children, and over time. The outcome was the progression of the extent of gingival inflammation in children over time. The main independent variables were the number of daily sleep hours and salivary glucose levels. Other explanatory variables and confounders assessed were governorate, dental caries and restorations, and obesity by waist circumference (adjusted for snacking and sex). Gingivitis increased over time in children who had shorter sleep duration ( P glucose levels >1.13 mg/dL predicted gingivitis ( P glucose levels were both associated with increased gingival inflammation.

  7. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose ... Diabetes causes more deaths a year than breast cancer and AIDS combined. Your gift today will help ...

  8. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips ...

  9. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips ... that smells fruity Nausea and vomiting Very dry mouth Talk to your doctor about how to handle ...

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for ... Diabetes Meal Plans Create Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook with Heart- ...

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... little insulin or when the body can't use insulin properly. What Causes Hyperglycemia? A number of ... enough insulin. Without insulin, your body can't use glucose for fuel, so your body breaks down ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... breast cancer and AIDS combined. Your gift today will help us get closer to curing diabetes and ... blood and then treating high blood glucose early will help you avoid problems associated with hyperglycemia. How ...

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To ... Started Safely Get And Stay Fit Types of Activity Weight Loss Assess Your Lifestyle Getting Started Food ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... fail to treat hyperglycemia, a condition called ketoacidosis (diabetic coma) could occur. Ketoacidosis develops when your body ... glucose) Dawn Phenomenon Checking for Ketones Tight Diabetes Control donate en -- Match – Donate Now - match-donate-now. ...

  15. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day Diabetes Basics Home Symptoms Diagnosis America's ...

  16. All about Blood Glucose

    Science.gov (United States)

    ... medicines • infection or other illness • changes in hormone levels,such as during menstrual periods • stress What can make blood glucose fall? • missing a meal or snack,or having a meal or snack with less ...

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Care Blood Glucose Testing Medication Doctors, Nurses & More Oral ... someone new is diagnosed. Diabetes causes more deaths a year than breast cancer and AIDS combined. Your gift today will help ...

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... of Diabetes Research & Practice Home We Are Research Leaders World's Largest Diabetes Meeting Recent Advances Type 1 ... the urine Frequent urination Increased thirst Part of managing your diabetes is checking your blood glucose often. ...

  19. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day Diabetes Basics Home Symptoms Diagnosis America's Diabetes Challenge Type ...

  20. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... such as family conflicts or school or dating problems. You may have experienced the dawn phenomenon (a ... high blood glucose early will help you avoid problems associated with hyperglycemia. How Do I Treat Hyperglycemia? ...

  1. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ... us get closer to curing diabetes and better treatments for those living with diabetes. Other Ways to ...

  2. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... the urine Frequent urination Increased thirst Part of managing your diabetes is checking your blood glucose often. ... also help. Work with your dietitian to make changes in your meal plan. If exercise and changes ...

  3. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... your blood and then treating high blood glucose early will help you avoid problems associated with hyperglycemia. ... to detect hyperglycemia so you can treat it early — before it gets worse. If you're new ...

  4. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... for you to lower your blood glucose level. Cutting down on the amount of food you eat ... Risk Test Alert Day Prediabetes My Health Advisor Tools to Know Your Risk Diabetes Basics Symptoms Type ...

  5. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for Caregivers ... updated, this is the "take-you-by-the-hand" guide that will become a trusted friend and ...

  6. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... and Type 2 Diabetes Know Your Rights Employment Discrimination Health Care Professionals Law Enforcement Driver's License For ... symptoms include the following: High blood glucose High levels of sugar in the urine Frequent urination Increased ...

  7. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & ... cannot release all the ketones and they build up in your blood, which can lead to ketoacidosis. ...

  8. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for Caregivers Health Insurance Health ... glucose happens when the body has too little insulin or when the body can't use insulin ...

  9. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy ... 1 Type 2 Gestational Myths Statistics Common Terms Genetics Living With Diabetes Recently Diagnosed Treatment & Care Complications ...

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral ... 2 Diabetes Know Your Rights Employment Discrimination Health Care Professionals Law Enforcement Driver's License For Lawyers Food & ...

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... If you have ketones, do not exercise. Exercising when ketones are present may make your blood glucose level go even higher. You'll need to work with your doctor to find the safest way ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Superfoods Non-starchy Vegetables Grains and Starchy Vegetables Fats Alcohol What Can I Drink? Fruit Dairy Food ... glucose for fuel, so your body breaks down fats to use for energy. When your body breaks ...

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose ... About Us Who We Are Careers Contact Us Policies Corporate Support Newsroom Press Releases For Professionals En ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... for Association Events Messaging Tools Recruiting Advocates Local Market Planning Training Webinars News & Events Advocacy News Call ... Living With Diabetes > Treatment and Care > Blood Glucose Testing Share: Print Page Text Size: A A A ...

  15. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Us in the Fight for a Cure Your tax-deductible gift today can fund critical diabetes research ... glucose for fuel, so your body breaks down fats to use for energy. When your body breaks ...

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Type 2 About Us Online Community Meal Planning Sign In Search: Search More Sites Search ≡ Are You ... m.). What are the Symptoms of Hyperglycemia? The signs and symptoms include the following: High blood glucose ...

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ... glucose) Dawn Phenomenon Checking for Ketones Tight Diabetes Control donate en -- Match – Donate Now - match-donate-now. ...

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy ... planned or exercised less than planned. You have stress from an illness, such as a cold or ...

  19. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... glucose) Dawn Phenomenon Checking for Ketones Tight Diabetes Control donate en ... free program will help you live well. sticky en -- Chef Ronaldo's Sabores de Cuba - 2016- ...

  20. 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 Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C ...

  1. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health ...

  2. Biomarkers of exposure to endogenous oxidative and aldehyde stress.

    Science.gov (United States)

    Bruce, W Robert; Lee, Owen; Liu, Zhen; Marcon, Norman; Minkin, Salomon; O'Brien, Peter J

    2011-08-01

    We observed an unexpectedly strong association of three different endogenous aldehydes and noted that the association could be explained by multiple reactions in which oxidative stress increased the formation of endogenous aldehydes and endogenous aldehydes increased oxidative stress. These interactions make it reasonable to assess multiple exposures to endogenous oxidative and aldehyde stress with less specific measures such as advanced glycation end-products or protein carbonyls.

  3. Selection-endogenous ordered probit and dynamic ordered probit models

    OpenAIRE

    Alfonso Miranda; Massimiliano Bratti

    2009-01-01

    In this presentation we define two qualitatitive response models: 1) Selection Endogenous Dummy Ordered Probit model (SED-OP); 2) a Selection Endogenous Dummy Dynamic Selection Ordered Probit model (SED- DOP). The SED-OP model is a three-equation model constituted of an endogenous dummy equation, a selection equation, and a main equation which has an ordinal response form. The main feature of the model is that the endogenous dummy enters both the selection equation and the main equation. The ...

  4. Physiological functions of glucose-inhibited neurones.

    Science.gov (United States)

    Burdakov, D; González, J A

    2009-01-01

    Glucose-inhibited neurones are an integral part of neurocircuits regulating cognitive arousal, body weight and vital adaptive behaviours. Their firing is directly suppressed by extracellular glucose through poorly understood signalling cascades culminating in opening of post-synaptic K(+) or possibly Cl(-) channels. In mammalian brains, two groups of glucose-inhibited neurones are best understood at present: neurones of the hypothalamic arcuate nucleus (ARC) that express peptide transmitters NPY and agouti-related peptide (AgRP) and neurones of the lateral hypothalamus (LH) that express peptide transmitters orexins/hypocretins. The activity of ARC NPY/AgRP neurones promotes food intake and suppresses energy expenditure, and their destruction causes a severe reduction in food intake and body weight. The physiological actions of ARC NPY/AgRP cells are mediated by projections to numerous hypothalamic areas, as well as extrahypothalamic sites such as the thalamus and ventral tegmental area. Orexin/hypocretin neurones of the LH are critical for normal wakefulness, energy expenditure and reward-seeking, and their destruction causes narcolepsy. Orexin actions are mediated by highly widespread central projections to virtually all brain areas except the cerebellum, including monosynaptic innervation of the cerebral cortex and autonomic pre-ganglionic neurones. There, orexins act on two specific G-protein-coupled receptors generally linked to neuronal excitation. In addition to sensing physiological changes in sugar levels, the firing of both NPY/AgRP and orexin neurones is inhibited by the 'satiety' hormone leptin and stimulated by the 'hunger' hormone ghrelin. Glucose-inhibited neurones are thus well placed to coordinate diverse brain states and behaviours based on energy levels.

  5. Endogenous RNA interference is driven by copy number

    Science.gov (United States)

    Cruz, Cristina; Houseley, Jonathan

    2014-01-01

    A plethora of non-protein coding RNAs are produced throughout eukaryotic genomes, many of which are transcribed antisense to protein-coding genes and could potentially instigate RNA interference (RNAi) responses. Here we have used a synthetic RNAi system to show that gene copy number is a key factor controlling RNAi for transcripts from endogenous loci, since transcripts from multi-copy loci form double stranded RNA more efficiently than transcripts from equivalently expressed single-copy loci. Selectivity towards transcripts from high-copy DNA is therefore an emergent property of a minimal RNAi system. The ability of RNAi to selectively degrade transcripts from high-copy loci would allow suppression of newly emerging transposable elements, but such a surveillance system requires transcription. We show that low-level genome-wide pervasive transcription is sufficient to instigate RNAi, and propose that pervasive transcription is part of a defense mechanism capable of directing a sequence-independent RNAi response against transposable elements amplifying within the genome. DOI: http://dx.doi.org/10.7554/eLife.01581.001 PMID:24520161

  6. Chronic insulin infusion induces reversible glucose intolerance in lean rats yet ameliorates glucose intolerance in obese rats.

    Science.gov (United States)

    Hamza, Shereen M; Sung, Miranda M; Gao, Fei; Soltys, Carrie-Lynn M; Smith, Nancy P; MacDonald, Patrick E; Light, Peter E; Dyck, Jason R B

    2017-02-01

    Although insulin resistance (IR) is a key factor in the pathogenesis of type 2 diabetes (T2D), the precise role of insulin in the development of IR remains unclear. Therefore, we investigated whether chronic basal insulin infusion is causative in the development of glucose intolerance. Normoglycemic lean rats surgically instrumented with i.v. catheters were infused with insulin (3mU/kg/min) or physiological saline for 6weeks. At infusion-end, plasma insulin levels along with glucose tolerance were assessed. Six weeks of insulin infusion induced glucose intolerance and impaired insulin response in healthy rats. Interestingly, the effects of chronic insulin infusion were completely normalized following 24h withdrawal of exogenous insulin and plasma insulin response to glucose challenge was enhanced, suggesting improved insulin secretory capacity. As a result of this finding, we assessed whether the effects of insulin therapy followed by a washout could ameliorate established glucose intolerance in obese rats. Obese rats were similarly instrumented and infused with insulin or physiological saline for 7days followed by 24h washout. Seven day-insulin therapy in obese rats significantly improved glucose tolerance, which was attributed to improved insulin secretory capacity and improved insulin signaling in liver and skeletal muscle. Moderate infusion of insulin alone is sufficient to cause glucose intolerance and impair endogenous insulin secretory capacity, whereas short-term, intensive insulin therapy followed by insulin removal effectively improves glucose tolerance, insulin response and peripheral insulin sensitivity in obese rats. New insight into the link between insulin and glucose intolerance may optimize T2D management. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Synthetic LXR Agonist Suppresses Endogenous Cholesterol Biosynthesis and Efficiently Lowers Plasma Cholesterol

    OpenAIRE

    Pfeifer, Thomas; Buchebner, Marlene; Chandak, Prakash G.; Patankar, Jay; Kratzer, Adelheid; Obrowsky, Sascha; Rechberger, Gerald N.; Kadam, Rajendra S.; Kompella, Uday B.; Kostner, Gerhard M.; Kratky, Dagmar; Levak-Frank, Sanja

    2011-01-01

    The liver X receptors (LXRs) are key regulators of genes involved in cholesterol homeostasis. Natural ligands and activators of LXRs are oxysterols. Numerous steroidal and non-steroidal synthetic LXR ligands are under development as potential drugs for individuals suffering from lipid disorders. N,N-dimethyl-3ß-hydroxycholenamide (DMHCA) is a steroidal ligand of LXRs that exerts anti-atherogenic effects in apolipoprotein E-deficient mice without causing negative side effects such as liver ste...

  8. GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid.

    Science.gov (United States)

    Smith, S S; Gong, Q H; Hsu, F C; Markowitz, R S; ffrench-Mullen, J M; Li, X

    1998-04-30

    The hormone progesterone is readily converted to 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP) in the brains of males and females. In the brain, 3alpha,5alpha-THP acts like a sedative, decreasing anxiety and reducing seizure activity, by enhancing the function of GABA (gamma-aminobutyric acid), the brain's major inhibitory neurotransmitter. Symptoms of premenstrual syndrome (PMS), such as anxiety and seizure susceptibility, are associated with sharp declines in circulating levels of progesterone and, consequently, of levels of 3alpha,5alpha-THP in the brain. Abrupt discontinuation of use of sedatives such as benzodiazepines and ethanol can also produce PMS-like withdrawal symptoms. Here we report a progesterone-withdrawal paradigm, designed to mimic PMS and post-partum syndrome in a rat model. In this model, withdrawal of progesterone leads to increased seizure susceptibility and insensitivity to benzodiazepine sedatives through an effect on gene transcription. Specifically, this effect was due to reduced levels of 3alpha,5alpha-THP which enhance transcription of the gene encoding the alpha4 subunit of the GABA(A) receptor. We also find that increased susceptibility to seizure after progesferone withdrawal is due to a sixfold decrease in the decay time for GABA currents and consequent decreased inhibitory function. Blockade of the alpha4 gene transcript prevents these withdrawal properties. PMS symptoms may therefore be attributable, in part, to alterations in expression of GABA(A) receptor subunits as a result of progesterone withdrawal.

  9. Endogenous Cannabinoids Trigger the Depolarization-Induced Suppression of Excitation in the Lateral Amygdala

    Science.gov (United States)

    Kodirov, Sodikdjon A.; Jasiewicz, Julia; Amirmahani, Parisa; Psyrakis, Dimitrios; Bonni, Kathrin; Wehrmeister, Michael; Lutz, Beat

    2010-01-01

    The amygdala is a key area of the brain where the emotional memories are stored throughout the lifespan. It is well established that synapses in the lateral nucleus of amygdala (LA) can undergo long-term potentiation, a putative cellular correlate of learning and memory. However, a type of short-term synaptic plasticity, known as…

  10. Endogenous, photoperiodic and hormonal control of the body weight rhythm in the female European hamster, Cricetus cricetus.

    Science.gov (United States)

    Canguilhem, B; Masson-Pévet, M; Pévet, P; Bentz, I

    1992-03-01

    1. Body weight and hibernation rhythms were followed on normal and castrated female European hamsters raised in different conditions of photoperiod and ambient temperature. 2. In the normal females, the photoperiod was more effective than the ambient temperature regarding the control of the body weight rhythm. 3. In the castrated females, testosterone was more effective than oestradiol in suppressing both body weight and hibernation rhythms. 4. In short photoperiod conditions, the existence of endogenous rhythmicity depends upon prior photoperiodic exposure of the animals.

  11. Non-enzymatic glucose sensing by enhanced Raman spectroscopy on flexible 'as-grown' CVD graphene.

    Science.gov (United States)

    Chattopadhyay, Surojit; Li, Mau-Shiun; Kumar Roy, Pradip; Wu, C T

    2015-06-21

    Unmodified, as-grown few layered graphene on copper substrates have been used for glucose sensing using Raman spectroscopy. Graphene with a stronger 2D band is a better Raman enhancer with significant fluorescence suppression and finer line widths of the Raman signals. The origin of the graphene enhanced Raman spectroscopy (GERS) signal of glucose is attributed to a fractional charge transfer (calculated to be 0.006 using electrochemical parameters) between glucose and graphene aided by a possible π-π interaction. Physiological concentrations of glucose (10-500 mg dl(-1)) in PBS have been used for the study. For each glucose concentration, the spectral reproducibility is within 5-25% as calculated by the relative standard deviation of several measurements. The intensity ratio of the 1122 cm(-1) peak of glucose and the 2D peak of graphene varied linearly with the glucose concentration and can be used as a calibration curve for unknown sample measurements.

  12. Endogenous vs. exogenous regulations in the commons

    DEFF Research Database (Denmark)

    Abatayo, Anna Lou; Lynham, John

    2016-01-01

    It is widely believed that there is strong experimental evidence to support the idea that exogenously imposed regulations crowd out the intrinsic motivations of common pool resource (CPR) users to refrain from over-harvesting. We introduce a novel experimental design that attempts to disentangle...... levels among CPR users in a laboratory experiment. We also observe no differences between weak external regulations and no regulations, after controlling for a potential confound. However, when we add communication to our endogenous treatment, we observe significant behavioral differences between...

  13. Endogenous pancreatic polypeptide in different vascular beds

    DEFF Research Database (Denmark)

    Henriksen, J H; Schwartz, Tania; Bülow, J B

    1986-01-01

    The plasma concentration of pancreatic polypeptide (PP-like immunoreactivity) was measured in different vascular beds in order to determine regional kinetics of endogenous PP in fasting, supine subjects with normal or moderately decreased kidney function. Patients with kidney disease (n = 10) had...... concentration (r = 0.70, P less than 0.01). Hepatic venous PP was significantly higher than systemic PP in both controls and patients with kidney disease (P less than 0.001, n = 15). The values were positively correlated (r = 0.98, P less than 0.001; slope = 1.37 +/- 0.05, P less than 0.001), indicating...

  14. Psychological rehabilitation of patients with endogenous disease

    Directory of Open Access Journals (Sweden)

    Tamara Kryvonis

    2013-07-01

    Full Text Available The rationale for early psychotherapeutic intervention in combination with psychopharmatherapy in patients with endogenous disorders is provided. The mechanisms of psychological defenses to deal with traumatic experience, used by personalities functioning on a psychotic level, are also described here. Characteristic behavior patterns of extended family members in terms of emotional codependence are provided. Individual pathopsychology is considered as a symptom of abnormal functioning of the family. Emphasis is placed on the importance of inclusion of family members in psychotherapeutic interaction in order to correct interpersonal relations.

  15. ENDOGENOUS INTOxICATION AND SEPSIS

    Directory of Open Access Journals (Sweden)

    I. V. Aleksandrova

    2014-01-01

    Full Text Available RELEVANCE. Sepsis is always accompanied by endogenous intoxication (EI. It is very important to study EI in the patients with severe sepsis and septic shock.MATERIAL AND METHODS. Twenty seven patients with severe sepsis and thirteen with septic shock in the postoperative period were enrolled into the study. EI was assessed using the measurements of total and effective albumin concentrations (EAC, middle-molecular-weight proteins (MMWP and EI index (Kei=MMWP/ EACx1000.RESULTS. The use of the EI index in patients with severe sepsis and septic shock leads to improvement of diagnostic and therapy monitoring.

  16. Environmental policy, pollution, unemployment and endogenous growth

    DEFF Research Database (Denmark)

    Pedersen, Lars Haagen; Nielsen, Søren Bo; Sørensen, Peter Birch

    1995-01-01

    The paper develops a model of endogenous economic growth with pollution externalities and a labor market distorted by union monopoly power and by taxes and transfers. We study the optimal second-best pollution tax and abatement policy and find that a shift toward greener preferences will tend...... to reduce unemployment, although it will hamper growth. We also find that greater labor-market distortions call for higher pollution tax rates. Finally, we show that a switch from quantity control of pollution combined with grandfathering of pollution rights to regulation via emission charges has...

  17. Glucose Plus Fructose Ingestion for Post-Exercise Recovery-Greater than the Sum of Its Parts?

    Science.gov (United States)

    Gonzalez, Javier T; Fuchs, Cas J; Betts, James A; van Loon, Luc J C

    2017-03-30

    Carbohydrate availability in the form of muscle and liver glycogen is an important determinant of performance during prolonged bouts of moderate- to high-intensity exercise. Therefore, when effective endurance performance is an objective on multiple occasions within a 24-h period, the restoration of endogenous glycogen stores is the principal factor determining recovery. This review considers the role of glucose-fructose co-ingestion on liver and muscle glycogen repletion following prolonged exercise. Glucose and fructose are primarily absorbed by different intestinal transport proteins; by combining the ingestion of glucose with fructose, both transport pathways are utilised, which increases the total capacity for carbohydrate absorption. Moreover, the addition of glucose to fructose ingestion facilitates intestinal fructose absorption via a currently unidentified mechanism. The co-ingestion of glucose and fructose therefore provides faster rates of carbohydrate absorption than the sum of glucose and fructose absorption rates alone. Similar metabolic effects can be achieved via the ingestion of sucrose (a disaccharide of glucose and fructose) because intestinal absorption is unlikely to be limited by sucrose hydrolysis. Carbohydrate ingestion at a rate of ≥1.2 g carbohydrate per kg body mass per hour appears to maximise post-exercise muscle glycogen repletion rates. Providing these carbohydrates in the form of glucose-fructose (sucrose) mixtures does not further enhance muscle glycogen repletion rates over glucose (polymer) ingestion alone. In contrast, liver glycogen repletion rates are approximately doubled with ingestion of glucose-fructose (sucrose) mixtures over isocaloric ingestion of glucose (polymers) alone. Furthermore, glucose plus fructose (sucrose) ingestion alleviates gastrointestinal distress when the ingestion rate approaches or exceeds the capacity for intestinal glucose absorption (~1.2 g/min). Accordingly, when rapid recovery of endogenous

  18. suPAR associates to glucose metabolic aberration during glucose stimulation in HIV-infected patients on HAART

    DEFF Research Database (Denmark)

    Andersen, Ove; Eugen-Olsen, Jesper; Kofoed, Kristian

    2008-01-01

    extend these findings by investigating the association of suPAR to glucose metabolic insufficiency during an oral glucose challenge (OGTT). METHODS: In 16 HIV-infected patients with lipodystrophy and 15 HIV-infected patients without lipodystrophy, glucose tolerance, insulin sensitivity (ISI......(composite)), prehepatic insulin secretion, proinsulin level and suppression of free fatty acids (FFA) were determined during an OGTT. Stability of suPAR was tested in 6 HIV-infected patients during a 3h OGTT. RESULTS: Lipodystrophy was associated with a 70% increase in plasma suPAR (P...PAR correlated inversely with ISI(composite) and positively with 2h plasma glucose, fasting insulin secretion, fasting intact proinsulin and FFA level during the OGTT (all P

  19. Involvement of endogenous opiates in regulation of gastric emptying of fat test meals in mice

    Energy Technology Data Exchange (ETDEWEB)

    Fioramonti, J.; Fargeas, M.J.; Bueno, L.

    1988-08-01

    The role of endogenous opioids and cholecystokinin (CCK) in gastric emptying was investigated in mice killed 30 min after gavage with /sup 51/Cr-radiolabeled liquid meals. The meals consisted of 0.5 ml of milk or one of five synthetic meals containing arabic gum, glucose and/or arachis oil and/or casein. Naloxone (0.1 mg/kg sc) significantly (P less than 0.01) accelerated gastric emptying of milk and meals containing fat but did not modify gastric emptying of nonfat meals. The CCK antagonist asperlicin (0.1 mg/kg ip) increased by 25% gastric emptying of milk. The gastric emptying of meals containing glucose and casein but not fat was reduced after administration of the COOH-terminal octapeptide of cholecystokinin (CCK-8, 4 micrograms/kg ip). This decrease was antagonized by both asperlicin (10 mg/kg ip) and naloxone (0.1 mg/kg sc). Intracerebroventricular (icv) administration of an opiate antagonist that poorly crosses the blood-brain barrier, methyl levallorphan (10 micrograms/kg), did not modify gastric emptying of milk but accelerated it when peripherally administered (0.1 mg/kg sc). Similarly, asperlicin (icv) administered at a dose of 1 mg/kg did not affect milk emptying. These results indicate that endogenous opiates are involved at peripheral levels in the regulation of gastric emptying of fat meals only and that such regulation involves release of CCK.

  20. 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.

  1. The effect of vagal nerve blockade using electrical impulses on glucose metabolism in nondiabetic subjects

    Directory of Open Access Journals (Sweden)

    Sathananthan M

    2014-07-01

    Full Text Available Matheni Sathananthan,1 Sayeed Ikramuddin,2 James M Swain,3,6 Meera Shah,1 Francesca Piccinini,4 Chiara Dalla Man,4 Claudio Cobelli,4 Robert A Rizza,1 Michael Camilleri,5 Adrian Vella1 1Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA; 2Division of General Surgery, University of Minnesota, Minneapolis, MN, USA; 3Division of General Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA; 4Department of Information Engineering, University of Padua, Padua, Italy; 5Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA; 6Scottsdale Healthcare Bariatric Center, Scottsdale, AZ, USA Purpose: Vagal interruption causes weight loss in humans and decreases endogenous glucose production in animals. However, it is unknown if this is due to a direct effect on glucose metabolism. We sought to determine if vagal blockade using electrical impulses alters glucose metabolism in humans. Patients and methods: We utilized a randomized, cross-over study design where participants were studied after 2 weeks of activation or inactivation of vagal nerve blockade (VNB. Seven obese subjects with impaired fasting glucose previously enrolled in a long-term study to examine the effect of VNB on weight took part. We used a standardized triple-tracer mixed meal to enable measurement of the rate of meal appearance, endogenous glucose production, and glucose disappearance. The 550 kcal meal was also labeled with 111In-diethylene triamine pentaacetic acid (DTPA to measure gastrointestinal transit. Insulin action and ß-cell responsivity indices were estimated using the minimal model. Results: Integrated glucose, insulin, and glucagon concentrations did not differ between study days. This was also reflected in a lack of effect on β-cell responsivity and insulin action. Furthermore, fasting and postprandial endogenous glucose production, integrated meal appearance, and glucose

  2. Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance

    DEFF Research Database (Denmark)

    Vollmer, Kirsten; Holst, Jens Juul; Baller, Birgit

    2008-01-01

    participated in an oral glucose tolerance test (75 g) and a mixed meal challenge (820 kcal), both carried out over 240 min on separate occasions. Plasma levels of glucose, insulin, C-peptide, glucagon, triglycerides, free fatty acids (FFAs), gastric inhibitory polypeptide (GIP), and GLP-1 were determined......OBJECTIVE: Defects in glucagon-like peptide 1 (GLP-1) secretion have been reported in some patients with type 2 diabetes after meal ingestion. We addressed the following questions: 1) Is the quantitative impairment in GLP-1 levels different after mixed meal or isolated glucose ingestion? 2) Which...... endogenous factors are associated with the concentrations of GLP-1? In particular, do elevated fasting glucose or glucagon levels diminish GLP-1 responses? RESEARCH DESIGN AND METHODS: Seventeen patients with mild type 2 diabetes, 17 subjects with impaired glucose tolerance, and 14 matched control subjects...

  3. Nocturnal continuous glucose monitoring

    DEFF Research Database (Denmark)

    Bay, Christiane; Kristensen, Peter Lommer; Pedersen-Bjergaard, Ulrik

    2013-01-01

    Abstract Background: A reliable method to detect biochemical nocturnal hypoglycemia is highly needed, especially in patients with recurrent severe hypoglycemia. We evaluated reliability of nocturnal continuous glucose monitoring (CGM) in patients with type 1 diabetes at high risk of severe...... from 23:00 to 07:00 h for plasma glucose (PG) measurements (gold standard). Results: Valid data were obtained in 217 nights. The sensitivity of CGM was 65% (95% confidence interval, 53-77%) below 4 mmol/L, 40% (24-56%) below 3 mmol/L, and 17% (0-47%) below 2.2 mmol/L. PG and CGM readings correlated...

  4. Menstrual suppression for adolescents.

    Science.gov (United States)

    Altshuler, Anna Lea; Hillard, Paula J Adams

    2014-10-01

    The purpose of this review is to highlight the recent literature and emerging data describing clinical situations in which menstrual suppression may improve symptoms and quality of life for adolescents. A variety of conditions occurring frequently in adolescents and young adults, including heavy menstrual bleeding, and dysmenorrhea as well as gynecologic conditions such as endometriosis and pelvic pain, can safely be improved or alleviated with appropriate menstrual management. Recent publications have highlighted the efficacy and benefit of extended cycle or continuous combined oral contraceptives, the levonorgestrel intrauterine device, and progestin therapies for a variety of medical conditions. This review places menstrual suppression in an historical context, summarizes methods of hormonal therapy that can suppress menses, and reviews clinical conditions for which menstrual suppression may be helpful.

  5. Harnessing Endogenous Systems for Cancer Therapy

    DEFF Research Database (Denmark)

    Klauber, Thomas Christopher Bogh

    In the recent decade, two strategies in particular have attracted attention due to the prospect of significantly improving cancer treatment: Gene silencing therapy and immunotherapy. Both strategies work by manipulating endogenous mechanisms and theoretically promise very strong effect on the dis......In the recent decade, two strategies in particular have attracted attention due to the prospect of significantly improving cancer treatment: Gene silencing therapy and immunotherapy. Both strategies work by manipulating endogenous mechanisms and theoretically promise very strong effect...... immunotherapy (Project II). Transfer into the clinic of therapies based on gene silencing by siRNA delivered by synthetic vectors has yet to happen. A major reason is the lack of efficiency in the delivery process, partly due to insufficient understanding of cellular uptake and processing of the si...... to the conventional PEIs. However, lipid conjugation did not sufficiently reduce the inherent toxicity associated with high molecular weight PEI, and lipid conjugation of bPEI did also not change the ability of bPEI to affect lysosomal pH as a function of time. In contrast to gene silencing therapy, cancer...

  6. 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 development of isolated impaired fasting glucose, glucose intolerance, and acute insulin release. METHODS: At 0 years, 19 RELs and 18 matched control subjects had glucose effectiveness (GE), insulin sensitivity, acute insulin release (AIR)IVGTT, and disposition index measured during an iv glucose tolerance...... test (IVGTT), using the minimal model analysis. At 0 and 10 years, oral glucose tolerance (OGTT) and AIROGTT were determined. RESULTS: At 0 years, fasting glucose (FG) and GE were raised in RELs, but insulin sensitivity and AIROGTT were reduced (P ≤ .05) compared with controls. At 10 years, RELs...

  7. Biological Redundancy of Endogenous GPCR Ligands in the Gut and the Potential for Endogenous Functional Selectivity

    Directory of Open Access Journals (Sweden)

    Georgina eThompson

    2014-11-01

    Full Text Available This review focuses on the existence and function of multiple endogenous agonists of the somatostatin and opioid receptors with an emphasis on their expression in the gastrointestinal tract (GIT. These agonists generally arise from the proteolytic cleavage of prepropeptides during peptide maturation or from degradation of peptides by extracellular or intracellular endopeptidases. In other examples, endogenous peptide agonists for the same G protein-coupled receptors can be products of distinct genes but contain high sequence homology. This apparent biological redundancy has recently been challenged by the realization that different ligands may engender distinct receptor conformations linked to different intracellular signaling profiles and, as such the existence of distinct ligands may underlie mechanisms to finely tune physiological responses. We propose that further characterization of signaling pathways activated by these endogenous ligands will provide invaluable insight into the mechanisms governing biased agonism. Moreover, these ligands may prove useful in the design of novel therapeutic tools to target distinct signaling pathways, thereby favoring desirable effects and limiting detrimental on-target effects. Finally we will discuss the limitations of this area of research and we will highlight the difficulties that need to be addressed when examining endogenous bias in tissues and in animals.

  8. On Taxation in a Two-Sector Endogenous Growth Model with Endogenous Labor Supply

    NARCIS (Netherlands)

    P.A. de Hek (Paul)

    2003-01-01

    textabstractThis paper examines the effects of taxation on long-run growth in a two-sector endogenous growth model with (i) physical capital as an input in the education sector and (ii) leisure as an additional argument in the utility function. The analysis of the effects of taxation - including

  9. Live imaging of endogenous PSD-95 using ENABLED: a conditional strategy to fluorescently label endogenous proteins.

    Science.gov (United States)

    Fortin, Dale A; Tillo, Shane E; Yang, Guang; Rah, Jong-Cheol; Melander, Joshua B; Bai, Suxia; Soler-Cedeño, Omar; Qin, Maozhen; Zemelman, Boris V; Guo, Caiying; Mao, Tianyi; Zhong, Haining

    2014-12-10

    Stoichiometric labeling of endogenous synaptic proteins for high-contrast live-cell imaging in brain tissue remains challenging. Here, we describe a conditional mouse genetic strategy termed endogenous labeling via exon duplication (ENABLED), which can be used to fluorescently label endogenous proteins with near ideal properties in all neurons, a sparse subset of neurons, or specific neuronal subtypes. We used this method to label the postsynaptic density protein PSD-95 with mVenus without overexpression side effects. We demonstrated that mVenus-tagged PSD-95 is functionally equivalent to wild-type PSD-95 and that PSD-95 is present in nearly all dendritic spines in CA1 neurons. Within spines, while PSD-95 exhibited low mobility under basal conditions, its levels could be regulated by chronic changes in neuronal activity. Notably, labeled PSD-95 also allowed us to visualize and unambiguously examine otherwise-unidentifiable excitatory shaft synapses in aspiny neurons, such as parvalbumin-positive interneurons and dopaminergic neurons. Our results demonstrate that the ENABLED strategy provides a valuable new approach to study the dynamics of endogenous synaptic proteins in vivo. Copyright © 2014 the authors 0270-6474/14/3416698-15$15.00/0.

  10. Influence of endogenous androgens on carotid wall in postmenopausal women.

    Science.gov (United States)

    Bernini, G P; Moretti, A; Sgró, M; Argenio, G F; Barlascini, C O; Cristofani, R; Salvetti, A

    2001-01-01

    There is increasing evidence of a direct association between normal androgen levels and reduced cardiovascular morbidity and mortality in women. After menopause the influence of estrogens declines, whereas that of androgens increases. Therefore, we investigated the effects of androgens on atherosclerosis in postmenopausal women, by using carotid artery intimal-medial thickness as a marker of vascular damage. Blood pressure, body mass index, waist-to-hip ratio, serum dehydroepiandrosterone sulfate, androstenedione, total and free testosterone, estrone, insulin, lipid profile, and glucose were evaluated in 44 women in stable physiological menopause. All subjects underwent carotid ultrasound (Biosound 2000 II s.a. high-resolution unit). Spearman correlation coefficients indicated that serum androstenedione and free testosterone were negatively associated with several carotid intimal-medial thickness measures with correlation coefficients (r) ranging from 0.477 to 0.397 (p < 0.01-0.04). Moreover, age-adjusted androstenedione and free testosterone highest tertiles showed intimal-medial thickness values significantly (p < 0.03-0.05) lower than the other tertiles. There was a favorable association between hormones and the most important cardiovascular risk factors. This association, however, did not reach statistical significance. Stepwise multiple regression analysis showed that the inverse relationships between the hormones (androstenedione and free testosterone) and several intimal-medial thickness measures were maintained (F: 4.15-6.07, p < 0.05-0.02) after adjustment for major cardiovascular risk factors. Our data demonstrate that in postmenopausal women endogenous steroid precursors and androgens are inversely related to carotid intimal-medial thickness, an established marker of atherosclerosis. In addition, these hormones show favorable associations with cardiovascular risk factors. Therefore, our study suggests that, after menopause, normal androgen levels may

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term ... body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: If ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To ... to make changes in your meal plan. If exercise and changes in your diet don't work, your doctor may change the ...

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... to 5:00 a.m.). What are the Symptoms of Hyperglycemia? The signs and symptoms include the following: High blood glucose High levels ... Ketoacidosis is life-threatening and needs immediate treatment. Symptoms include: Shortness of breath Breath that smells fruity ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... In Memory In Honor Become a Member En Español Type 1 Type 2 About Us Online Community ... Page Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical ...

  15. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... the body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: If you have type 1, you may ... treating high blood glucose early will help you avoid problems associated with hyperglycemia. How Do I Treat ...

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know ... Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook with Heart-Healthy Foods Holiday Meal Planning ... Can I Drink? Fruit Dairy Food ...

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... may make your blood glucose level go even higher. You'll need to work with your doctor ... Online Chat Closed engagement en -- Free Type 2 Education Series - 2017-06-free-type-2-education-series. ...

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... Medicare Medicaid & CHIP For Parents & Kids Safe at School Everyday ... Care Professionals Law Enforcement Driver's License For Lawyers ...

  19. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... My Community Advocacy Research & Practice Ways to Give Close Are You at Risk? Home Prevention Diagnosing Diabetes and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor ...

  20. Reduced insulin sensitivity is related to less endogenous dopamine at D2/3 receptors in the ventral striatum of healthy nonobese humans.

    Science.gov (United States)

    Caravaggio, Fernando; Borlido, Carol; Hahn, Margaret; Feng, Zhe; Fervaha, Gagan; Gerretsen, Philip; Nakajima, Shinichiro; Plitman, Eric; Chung, Jun Ku; Iwata, Yusuke; Wilson, Alan; Remington, Gary; Graff-Guerrero, Ariel

    2015-02-25

    Food addiction is a debated topic in neuroscience. Evidence suggests diabetes is related to reduced basal dopamine levels in the nucleus accumbens, similar to persons with drug addiction. It is unknown whether insulin sensitivity is related to endogenous dopamine levels in the ventral striatum of humans. We examined this using the agonist dopamine D2/3 receptor radiotracer [(11)C]-(+)-PHNO and an acute dopamine depletion challenge. In a separate sample of healthy persons, we examined whether dopamine depletion could alter insulin sensitivity. Insulin sensitivity was estimated for each subject from fasting plasma glucose and insulin using the Homeostasis Model Assessment II. Eleven healthy nonobese and nondiabetic persons (3 female) provided a baseline [(11)C]-(+)-PHNO scan, 9 of which provided a scan under dopamine depletion, allowing estimates of endogenous dopamine at dopamine D2/3 receptor. Dopamine depletion was achieved via alpha-methyl-para-tyrosine (64mg/kg, P.O.). In 25 healthy persons (9 female), fasting plasma and glucose was acquired before and after dopamine depletion. Endogenous dopamine at ventral striatum dopamine D2/3 receptor was positively correlated with insulin sensitivity (r(7)=.84, P=.005) and negatively correlated with insulin levels (r(7)=-.85, P=.004). Glucose levels were not correlated with endogenous dopamine at ventral striatum dopamine D2/3 receptor (r(7)=-.49, P=.18). Consistently, acute dopamine depletion in healthy persons significantly decreased insulin sensitivity (t(24)=2.82, P=.01), increased insulin levels (t(24)=-2.62, P=.01), and did not change glucose levels (t(24)=-0.93, P=.36). In healthy individuals, diminished insulin sensitivity is related to less endogenous dopamine at dopamine D2/3 receptor in the ventral striatum. Moreover, acute dopamine depletion reduces insulin sensitivity. These findings may have important implications for neuropsychiatric populations with metabolic abnormalities. © The Author 2015. Published by

  1. The possible involvement of endogenous opioid peptides and catecholestrogens in provoking menstrual irregularities in women athletes.

    Science.gov (United States)

    De Crée, C

    1990-10-01

    It is well known that women athletes engaged in strenuous physical exercise and endurance training may develop "athletic menstrual irregularities" (AMI). Although many studies have appeared dealing with the immediate endocrinological and physiological changes in these women, the underlying mechanisms have remained unknown to date. A number of hypotheses have been put forward, the most well-known among them, for example, defending the existence of a critical percent of body fat necessary to trigger or maintain normal menstruation. All these theories have, however, their own, sometimes numerous, methodological inaccuracies and a teleological way of investigation. Spectacular, and perhaps promising new developments concern the possible involvement of endogenous opioid peptides and catecholestrogens in these processes. In basal circumstances beta-endorphin, the most well-known endogenous substance with opiate-like activity, may decrease LH levels by suppressing hypothalamic GnRH. This phenomenon is, however, only observed during the estrogen-dominant late-follicular and mid-luteal phases. As for catecholestrogens, it appears essential to differentiate between, for example, the 2- and 4-hydroxy derivatives of both estrone and estradiol. While some of these catecholestrogens obviously seem to suppress LH levels, others seem to potentiate and induce the LH surge. In any case, similar to beta-endorphin, these activities of catecholestrogens appear to depend upon the essential presence of a sufficiently estrogenic environment. In addition, both endogenous opioid peptides and some of the catecholestrogens appear to be able to suppress prolactin release, probably by interfering with its inhibiting factor dopamine. Other effects of catecholestrogens may include the control of the luteolysis-potent prostaglandin F2 alpha. Although a number of studies have investigated the behaviour of beta-endorphin during and post-exercise, similar studies investigating catecholestrogens as to

  2. Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral glucose in first-degree relatives of patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Nauck, Michael A; El-Ouaghlidi, Andrea; Gabrys, Bartholomäus

    2004-01-01

    ) and an "isoglycaemic" intravenous glucose infusion. Blood was drawn over 240 min for plasma glucose (glucose oxidase), insulin, C-peptide, GIP and glucagon-like peptide 1 (GLP-1; specific immunoassays). RESULTS: The pattern of glucose concentrations could precisely be copied by the intravenous glucose infusion (p=0...... and intravenous glucose to a similar degree. Nevertheless, endogenous secretion of GIP and GLP-1 is a major determinant of insulin secretion after oral glucose.......AIMS/HYPOTHESIS: Since insulin secretion in response to exogenous gastric inhibitory polypeptide (GIP) is diminished not only in patients with type 2 diabetes, but also in their normal glucose-tolerant first-degree relatives, it was the aim to investigate the integrity of the entero-insular axis...

  3. 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.

  4. Changing Endogenous Development: the Territorial Capital

    Directory of Open Access Journals (Sweden)

    Balázs István Tóth

    2011-12-01

    Full Text Available The aim of this research is to analyze territorial capital as a new paradigm to make best use of endogenous assets. The study is dealing with the preconditions, meaning and possible theoretical taxonomies of territorial capital. In this study I emphasize that the cumulative effects of regional potentials are more important than economies of scale and location factors. I present different approaches and interpretations of territorial capital, then make an attempt to create an own model. I try to find answers for questions, such as why territorial capital shows a new perspective of urban and regional development; how cognitive elements of territorial capital provide increasing return; how territorial capital influences competitiveness and what kind of relation it has with cohesion.

  5. Endogenous opioid peptides in uterine fluid.

    Science.gov (United States)

    Petraglia, F; Facchinetti, F; M'Futa, K; Ruspa, M; Bonavera, J J; Gandolfi, F; Genazzani, A R

    1986-08-01

    The present study demonstrates the presence of the endogenous opioid peptides beta-endorphin (beta-EP) and methionine-enkephalin (MET-ENK), in the uterine fluid of fertile women and normally cycling and superovulated cows. The two peptides are undetectable in the uterine fluid of untreated postmenopausal women, whereas they are present following estrogen-progesterone treatment. Immunoreactive (IR) MET-ENK concentrations were higher in the secretory than in the proliferative phase of the menstrual cycle. IR beta-EP and IR MET-ENK are present also in the follicular, oviductal, and uterine fluid of cows, and in the uterine fluid, concentrations of IR MET-ENK are higher in the superovulated than in the control animals. Because opioids play important roles on endocrine and immune functions, the present data support the potential physiologic role of endometrial secretions.

  6. Endogenous Natural Complement Inhibitor Regulates Cardiac Development

    DEFF Research Database (Denmark)

    Mortensen, Simon A; Skov, Louise L; Kjaer-Sorensen, Kasper

    2017-01-01

    Congenital heart defects are a major cause of perinatal mortality and morbidity, affecting >1% of all live births in the Western world, yet a large fraction of such defects have an unknown etiology. Recent studies demonstrated surprising dual roles for immune-related molecules and their effector...... protease (MASP)-3/collectin-L1/K1 hetero-oligomer, which impacts cardiac neural crest cell migration. We used knockdown and rescue strategies in zebrafish, a model allowing visualization and assessment of heart function, even in the presence of severe functional defects. Knockdown of embryonic expression...... of MAp44 caused impaired cardiogenesis, lowered heart rate, and decreased cardiac output. These defects were associated with aberrant neural crest cell behavior. We found that MAp44 competed with MASP-3 for pattern recognition molecule interaction, and knockdown of endogenous MAp44 expression could...

  7. The Glucose Sensor ChREBP Links De Novo Lipogenesis to PPARγ Activity and Adipocyte Differentiation.

    Science.gov (United States)

    Witte, Nicole; Muenzner, Matthias; Rietscher, Janita; Knauer, Miriam; Heidenreich, Steffi; Nuotio-Antar, Alli M; Graef, Franziska A; Fedders, Ronja; Tolkachov, Alexander; Goehring, Isabel; Schupp, Michael

    2015-11-01

    Reduced de novo lipogenesis in adipose tissue, often observed in obese individuals, is thought to contribute to insulin resistance. Besides trapping excess glucose and providing for triglycerides and energy storage, endogenously synthesized lipids can function as potent signaling molecules. Indeed, several specific lipids and their molecular targets that mediate insulin sensitivity have been recently identified. Here, we report that carbohydrate-response element-binding protein (ChREBP), a transcriptional inducer of glucose use and de novo lipogenesis, controls the activity of the adipogenic master regulator peroxisome proliferator-activated receptor (PPAR)γ. Expression of constitutive-active ChREBP in precursor cells activated endogenous PPARγ and promoted adipocyte differentiation. Intriguingly, ChREBP-constitutive-active ChREBP expression induced PPARγ activity in a fatty acid synthase-dependent manner and by trans-activating the PPARγ ligand-binding domain. Reducing endogenous ChREBP activity by either small interfering RNA-mediated depletion, exposure to low-glucose concentrations, or expressing a dominant-negative ChREBP impaired differentiation. In adipocytes, ChREBP regulated the expression of PPARγ target genes, in particular those involved in thermogenesis, similar to synthetic PPARγ ligands. In summary, our data suggest that ChREBP controls the generation of endogenous fatty acid species that activate PPARγ. Thus, increasing ChREBP activity in adipose tissue by therapeutic interventions may promote insulin sensitivity through PPARγ.

  8. tirant, a newly discovered active endogenous retrovirus in Drosophila simulans.

    Science.gov (United States)

    Akkouche, Abdou; Rebollo, Rita; Burlet, Nelly; Esnault, Caroline; Martinez, Sonia; Viginier, Barbara; Terzian, Christophe; Vieira, Cristina; Fablet, Marie

    2012-04-01

    Endogenous retroviruses have the ability to become permanently integrated into the genomes of their host, and they are generally transmitted vertically from parent to progeny. With the exception of gypsy, few endogenous retroviruses have been identified in insects. In this study, we describe the tirant endogenous retrovirus in a subset of Drosophila simulans natural populations. By focusing on the envelope gene, we show that the entire retroviral cycle (transcription, translation, and retrotransposition) can be completed for tirant within one population of this species.

  9. Testosterone is protective against impaired glucose metabolism in male intrauterine growth-restricted offspring.

    Science.gov (United States)

    Intapad, Suttira; Dasinger, John Henry; Fahling, Joel M; Backstrom, Miles A; Alexander, Barbara T

    2017-01-01

    Placental insufficiency alters the intrauterine environment leading to increased risk for chronic disease including impaired glucose metabolism in low birth weight infants. Using a rat model of low birth weight, we previously reported that placental insufficiency induces a significant increase in circulating testosterone in male intrauterine growth-restricted offspring (mIUGR) in early adulthood that is lost by 12 months of age. Numerous studies indicate testosterone has a positive effect on glucose metabolism in men. Female growth-restricted littermates exhibit glucose intolerance at 6 months of age. Thus, the aim of this paper was to determine whether mIUGR develop impaired glucose metabolism, and whether a decrease in elevated testosterone levels plays a role in its onset. Male growth-restricted offspring were studied at 6 and 12 months of age. No impairment in glucose tolerance was observed at 6 months of age when mIUGR exhibited a 2-fold higher testosterone level compared to age-matched control. Fasting blood glucose was significantly higher and glucose tolerance was impaired with a significant decrease in circulating testosterone in mIUGR at 12 compared with 6 months of age. Castration did not additionally impair fasting blood glucose or glucose tolerance in mIUGR at 12 months of age, but fasting blood glucose was significantly elevated in castrated controls. Restoration of elevated testosterone levels significantly reduced fasting blood glucose and improved glucose tolerance in mIUGR. Thus, our findings suggest that the endogenous increase in circulating testosterone in mIUGR is protective against impaired glucose homeostasis.

  10. How Active Are Porcine Endogenous Retroviruses (PERVs?

    Directory of Open Access Journals (Sweden)

    Joachim Denner

    2016-08-01

    Full Text Available Porcine endogenous retroviruses (PERVs represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs, which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated nuclease (CRISPR/Cas technology.

  11. Endogenous Methanol Regulates Mammalian Gene Activity

    Science.gov (United States)

    Komarova, Tatiana V.; Petrunia, Igor V.; Shindyapina, Anastasia V.; Silachev, Denis N.; Sheshukova, Ekaterina V.; Kiryanov, Gleb I.; Dorokhov, Yuri L.

    2014-01-01

    We recently showed that methanol emitted by wounded plants might function as a signaling molecule for plant-to-plant and plant-to-animal communications. In mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase (ADH) converts methanol into toxic formaldehyde. However, the detection of methanol in the blood and exhaled air of healthy volunteers suggests that methanol may be a chemical with specific functions rather than a metabolic waste product. Using a genome-wide analysis of the mouse brain, we demonstrated that an increase in blood methanol concentration led to a change in the accumulation of mRNAs from genes primarily involved in detoxification processes and regulation of the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the maintenance of low methanol concentration in the plasma, we used the specific ADH inhibitor 4-methylpyrazole (4-MP) and showed that intraperitoneal administration of 4-MP resulted in a significant increase in the plasma methanol, ethanol and formaldehyde concentrations. Removal of the intestine significantly decreased the rate of methanol addition to the plasma and suggested that the gut flora may be involved in the endogenous production of methanol. ADH in the liver was identified as the main enzyme for metabolizing methanol because an increase in the methanol and ethanol contents in the liver homogenate was observed after 4-MP administration into the portal vein. Liver mRNA quantification showed changes in the accumulation of mRNAs from genes involved in cell signalling and detoxification processes. We hypothesized that endogenous methanol acts as a regulator of homeostasis by controlling the mRNA synthesis. PMID:24587296

  12. Physiological role of endogenous amines in the modulation of ventricular automaticity in the guinea-pig.

    Science.gov (United States)

    Hume, J; Katzung, B G

    1980-12-01

    1. Current-clamp experiments were carried out with guinea-pig papillary muscles to determine the dependence of depolarization-induced automaticity on endogenous catecholamines. 2. Catecholamine depletion was produced by pre-treatment of animals with 6-hydroxydopamine and confirmed by fluorimetric assay of right ventricular tissue. Papillary muscles from depleted animals demonstrated a marked suppression of depolarization-induced automaticity for maximum diastolic potentials less negative than -55 mV. This suppression was completely reversed by noradrenaline but not by tyramine. 3. In normal tissue, noradrenaline and tyramine had much smaller effects on automaticity arising from maximum diastolic potentials negative to -55 mV than on repetitive activity arising positive to this level. 4. L-propranolol in concentrations of 2-3 x 10(-7) M reduced repetitive activity in the less negative range of maximum diastolic potential. No evidence of direct membrane depression was observed at these doses and the effect was reversed by application of noradrenaline. 5. D-propranolol, the isomer with much lower beta-receptor blocking potency, required twentyfold higher concentrations to depress automaticity and this was accompanied by evidence of direct membrane depression, i.e. reduction of upstroke velocity of action potentials. 6. These results show that automaticity induced in guinea-pig papillary muscles by depolarization positive to -55 mV is strongly dependent upon endogenous catecholamines. 7. The hypothesis that endogenous catecholamines facilitate depolarization-induced automaticity through an increase in calcium conductance was modelled using numerical techniques. It was found that changes in calcium conductance caused changes in the model which closely parallelled the experimental effects of catecholamine depletion and beta-blockade. The effects of changes in delayed rectification in the model did not accurately reproduce the experimental results.

  13. Glucose-6-phosphate dehydrogenase deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000528.htm Glucose-6-phosphate dehydrogenase deficiency To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a condition ...

  14. Sucessfull management of bilateral presumed Candida endogenous endophtalmitis following pancreatitis

    Directory of Open Access Journals (Sweden)

    Ricardo Evangelista Marrocos de Aragão

    2016-06-01

    Full Text Available ABSTRACT Endogenous endophthalmitis is a rare, and frequently devastating, ophthalmic disease. It occurs mostly in immunocompromised patients, or those with diabetes mellitus, cancer or intravenous drugs users. Candida infection is the most common cause of endogenous endophthalmitis. Ocular candidiasis develops within days to weeks of fungemia. The association of treatment for pancreatitis with endophthalmitis is unusual. Treatment with broad-spectrum antibiotics and total parenteral nutrition may explain endogenous endophthalmitis. We report the case of a patient with pancreatitis treated with broad-spectrum antibiotics and total parenteral nutrition who developed bilateral presumed Candida endogenous endophthalmitis that was successfully treated with vitrectomy and intravitreal amphotericin B.

  15. Effects of nadroparin, enoxaparin, and unfractionated heparin on endogenous factor Xa and IIa formation and on thrombelastometry profiles.

    Science.gov (United States)

    Cvirn, Gerhard; Wagner, Thomas; Juergens, Guenther; Koestenberger, Martin

    2009-01-01

    Measurements of anti-FXa or anti-FIIa (thrombin) activities are conventional tests for biological monitoring of low molecular weight heparin (LMWH) or unfractionated heparin treatment. It was the aim of our study to assess the anticoagulant efficacy of the LMWHs nadroparin and enoxaparin and that of unfractionated heparin not by the above-mentioned isolated measurements but in the physiological environment of clotting plasma or whole blood. The effects of increasing amounts of nadroparin, enoxaparin, or unfractionated heparin on the time-course of FXa or FIIa formation were investigated in tissue factor activated platelet-poor plasma using a subsampling technique and chromogenic substrates. Moreover, the anticoagulant efficacy of these drugs was also investigated in whole blood triggered by the physiological relevant activator collagen/endogenous thrombin using thrombelastometry. Nadroparin is as efficient as enoxaparin concerning suppression of endogenous FXa or FIIa formation. The two LMWHs are capable of suppressing the formation of FIIa as efficient as that of FXa. Compared with equivalent anti-FXa activity, unfractionated heparin is markedly more efficient in suppressing the formation of FXa and FIIa than the LMWHs. Corresponding results were obtained in whole blood. The anticoagulant efficacy of nadroparin was comparable with that of enoxaparin and the influence of unfractionated heparin on thrombelastometry parameters was markedly stronger than that of the two LMWHs. We conclude that LMWHs are efficient inhibitors not only of endogenous FXa formation but also of endogenous FIIa formation. Under our experimental conditions, the anticoagulant efficacy of nadroparin was comparable with that of enoxaparin but markedly lower than that of unfractionated heparin.

  16. Ability of higenamine and related compounds to enhance glucose uptake in L6 cells.

    Science.gov (United States)

    Kato, Eisuke; Kimura, Shunsuke; Kawabata, Jun

    2017-12-15

    β2-Adrenergic receptor (β2AR) agonists are employed as bronchodilators to treat pulmonary disorders, but are attracting attention for their modulation of glucose handling and energy expenditure. Higenamine is a tetrahydroisoquinoline present in several plant species and has β2AR agonist activity, but the involvement of each functional groups in β2AR agonist activity and its effectiveness compared with endogenous catecholamines (dopamine, epinephrine, and norepinephrine) has rarely been studied. Glucose uptake of muscle cells are known to be induced through β2AR activation. Here, the ability to enhance glucose uptake of higenamine was compared with that of several methylated derivatives of higenamine or endogenous catecholamines. We found that: (i) the functional groups of higenamine except for the 4'-hydroxy group are required to enhance glucose uptake; (ii) higenamine shows a comparable ability to enhance glucose uptake with that of epinephrine and norepinephrine; (iii) the S-isomer shows a greater ability to enhance glucose uptake compared with that of the R-isomer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Blood glucose in acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj

    2009-01-01

    Blood glucose is often elevated in acute stroke, and higher admission glucose levels are associated with larger lesions, greater mortality and poorer functional outcome. In patients treated with thrombolysis, hyperglycemia is associated with an increased risk of hemorrhagic transformation...... to the risk of inducing potentially harmful hypoglycemia has been raised. Still, basic and observational research is overwhelmingly in support of a causal relationship between blood glucose and stroke outcome and further research on glucose-lowering therapy in acute stroke is highly warranted....

  18. Explosion suppression system

    Science.gov (United States)

    Sapko, Michael J.; Cortese, Robert A.

    1992-01-01

    An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

  19. ORAL GLUCOSE TOLERANCE TEST REVISITED

    African Journals Online (AJOL)

    0 Abnormal previous glucose result of either impaired fasting plasma glucose ... Population studies for epidemiological data are known indications for oral ... Table I : Factors other than diabetes that may influence oral glucose tolerance test 1. Patient's preparation. 0 Duration of fast. Prior carbohydrate intake. Medications.

  20. The GLUT4 Glucose Transporter

    National Research Council Canada - National Science Library

    Huang, Shaohui; Czech, Michael P

    2007-01-01

    ... protein that mediates this uptake is one isoform (Gene name, SLC2A4; protein name: GLUT4) of a family of sugar transporter proteins containing 12-transmembrane domains ( Figure 1 ). The GLUT4 glucose transporter is thus a major mediator of glucose removal from the circulation and a key regulator of whole-body glucose homeostasis. Here, we discus...

  1. THE PROCESSES OF ENDOGENIZING IN THE ENDOGENOUS GROWTH: THE CASE OF TURKEY

    Directory of Open Access Journals (Sweden)

    OSMAN DEMİR

    2013-06-01

    Full Text Available The aim of this study is to state how the main inputs of endogenous growth, i.e. knowledge, human capital and technological progress are made endogenous by education, R&D, university-industry cooperation, learning by doing and diffusion within the production process. Competitiveness of firms and countries would increase as educated people enter into workforce; as R&D produces new technologies which are used in the production process; as theoretical knowledge meets with practice by university-industry cooperation; and as workers have more experience by learning by doing. In empirical analysis for Turkey is made by using data of 1970-2001 term it was found that a positive relationship among labour and capital factors and GNP and a negative relationship among education expenditures and foreign trade volume and capital stock.

  2. Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect.

    Science.gov (United States)

    Saisho, Yoshifumi

    2015-01-01

    Metformin is an oral hypoglycemic agent which is most widely used as first-line therapy for type 2 diabetes. Metformin improves hyperglycemia by suppressing hepatic glucose production and increasing glucose uptake in muscle. Metformin also has been shown to reduce cardiovascular events in randomized controlled trials; however, the underlying mechanism remains to be established. Recent preclinical and clinical studies have suggested that metformin not only improves chronic inflammation through the improvement of metabolic parameters such as hyperglycemia, insulin resistance and atherogenic dyslipidemia, but also has a direct anti-inflammatory action. Studies have suggested that metformin suppresses inflammatory response by inhibition of nuclear factor κB (NFκB) via AMP-activated protein kinase (AMPK)-dependent and independent pathways. This review summarizes the basic and clinical evidence of the anti-inflammatory action of metformin and discusses its clinical implication.

  3. Glucose-6-phosphatase deficiency.

    OpenAIRE

    Labrune Philippe; Gajdos Vincent; Eberschweiler Pascale; Hubert-Buron Aurélie; Petit François; Vianey-Saban Christine; Boudjemline Alix; Piraud Monique; Froissart Roseline

    2011-01-01

    Abstract Glucose-6-phosphatase deficiency (G6P deficiency), or glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, betw...

  4. Glucose Regulates the Expression of the Apolipoprotein A5 Gene

    Energy Technology Data Exchange (ETDEWEB)

    Fruchart, Jamila; Nowak, Maxime; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Moitrot, Emmanuelle; Rommens, Corinne; Pennacchio, Len A.; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2008-04-07

    The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.

  5. Crosstalk between endogenous and synthetic components--synthetic signaling meets endogenous components.

    Science.gov (United States)

    Morey, Kevin J; Antunes, Mauricio S; Barrow, Matt J; Solorzano, Fernando A; Havens, Keira L; Smith, J Jeff; Medford, June

    2012-07-01

    Synthetic biology uses biological components to engineer new functionality in living organisms. We have used the tools of synthetic biology to engineer detector plants that can sense man-made chemicals, such as the explosive trinitrotoluene, and induce a response detectable by eye or instrumentation. A goal of this type of work is to make the designed system orthogonal, that is, able to function independently of systems in the host. In this review, the design and function of two partially synthetic signaling pathways for use in plants is discussed. We describe observed interactions (crosstalk) with endogenous signaling components. This crosstalk can be beneficial, allowing the creation of hybrid synthetic/endogenous signaling pathways, or detrimental, resulting in system noise and/or false positives. Current approaches in the field of synthetic biology applicable to the design of orthogonal signaling systems, including the design of synthetic components, partially synthetic systems that utilize crosstalk to signal through endogenous components, computational redesign of proteins, and the use of heterologous components, are discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Comparison of serum glucose and salivary glucose in diabetic patients

    Directory of Open Access Journals (Sweden)

    Sreedevi

    2008-01-01

    Full Text Available Background and Objectives: The importance of saliva for oral health is well known. Diabetes mellitus affects the salivary gland functioning and thus alters the salivary constituents. For many years the question of the presence of glucose in saliva has been a subject of debate and only few people found correlation between serum glucose and salivary glucose in diabetics. Hence, the purpose of this study was to estimate and correlate salivary glucose concentration and serum glucose concentration in diabetics and healthy controls. Materials and Methods: 60 newly diagnosed diabetic patients and 60 age and sex matched control subjects were included in the study. Blood and saliva samples from both the groups were collected at least two hours after the breakfast. The samples were centrifuged and subjected to glucose analysis using Semiautoanalyzer (BioSystems BTS-310 Photometer. For experimental group, the samples were collected again after the control of diabetes mellitus. The statistical comparisons were performed using paired and unpaired t -test. Results: A highly significant correlation was found between salivary glucose and serum glucose before the treatment and also after the control of diabetes. The correlation between salivary glucose and serum glucose was also highly significant in controls. The levels of salivary glucose did not vary with age and sex. Conclusion and Interpretation: As there was significant correlation between salivary glucose and serum glucose, salivary glucose holds the potential of being a marker in diabetes. Further, it has an added advantage of being non-invasive procedure with no need of special equipments and with fewer compliance problems as compared with collection of blood.

  7. New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) I: Endogenous Angiotensin Converting Enzyme (ACE) Inhibition

    Science.gov (United States)

    Fagyas, Miklós; Úri, Katalin; Siket, Ivetta M.; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Édes, István; Papp, Zoltán; Tóth, Attila

    2014-01-01

    Angiotensin-converting enzyme (ACE) inhibitors represent the fifth most often prescribed drugs. ACE inhibitors decrease 5-year mortality by approximately one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors, which endogenous inhibitory effects are much less characterized than that for the clinically administered ACE inhibitors. Here we aimed to investigate this endogenous ACE inhibition in human sera. It was hypothesized that ACE activity is masked by an endogenous inhibitor, which dissociates from the ACE when its concentration decreases upon dilution. ACE activity was measured by FAPGG hydrolysis first. The specific (dilution corrected) enzyme activities significantly increased by dilution of human serum samples (23.2±0.7 U/L at 4-fold dilution, 51.4±0.3 U/L at 32-fold dilution, n = 3, p = 0.001), suggesting the presence of an endogenous inhibitor. In accordance, specific enzyme activities did not changed by dilution when purified renal ACE was used, where no endogenous inhibitor was present (655±145 U/L, 605±42 U/L, n = 3, p = 0.715, respectively). FAPGG conversion strongly correlated with angiotensin I conversion suggesting that this feature is not related to the artificial substrate. Serum samples were ultra-filtered to separate ACE (MW: 180 kDa) and the hypothesized inhibitor. Filtering through 50 kDa filters was without effect, while filtering through 100 kDa filters eliminated the inhibiting factor (ACE activity after ACE by this endogenous factor. The endogenous inhibitor had higher potency on the C-terminal active site than N-terminal active site of ACE. Finally, this endogenous ACE inhibition was also present in mouse, donkey, goat, bovine sera besides men (increasing of specific ACE activity from 4-fold to 32-fold dilution: 2.8-fold, 1.7-fold, 1.5-fold, 1.8-fold, 2.6-fold, respectively). We report here the existence of an evolutionary conserved

  8. New perspectives in the renin-angiotensin-aldosterone system (RAAS I: endogenous angiotensin converting enzyme (ACE inhibition.

    Directory of Open Access Journals (Sweden)

    Miklós Fagyas

    Full Text Available Angiotensin-converting enzyme (ACE inhibitors represent the fifth most often prescribed drugs. ACE inhibitors decrease 5-year mortality by approximately one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors, which endogenous inhibitory effects are much less characterized than that for the clinically administered ACE inhibitors. Here we aimed to investigate this endogenous ACE inhibition in human sera. It was hypothesized that ACE activity is masked by an endogenous inhibitor, which dissociates from the ACE when its concentration decreases upon dilution. ACE activity was measured by FAPGG hydrolysis first. The specific (dilution corrected enzyme activities significantly increased by dilution of human serum samples (23.2 ± 0.7 U/L at 4-fold dilution, 51.4 ± 0.3 U/L at 32-fold dilution, n = 3, p = 0.001, suggesting the presence of an endogenous inhibitor. In accordance, specific enzyme activities did not changed by dilution when purified renal ACE was used, where no endogenous inhibitor was present (655 ± 145 U/L, 605 ± 42 U/L, n = 3, p = 0.715, respectively. FAPGG conversion strongly correlated with angiotensin I conversion suggesting that this feature is not related to the artificial substrate. Serum samples were ultra-filtered to separate ACE (MW: 180 kDa and the hypothesized inhibitor. Filtering through 50 kDa filters was without effect, while filtering through 100 kDa filters eliminated the inhibiting factor (ACE activity after <100 kDa filtering: 56.4 ± 2.4 U/L, n = 4, control: 26.4 ± 0.7 U/L, n = 4, p<0.001. Lineweaver-Burk plot indicated non-competitive inhibition of ACE by this endogenous factor. The endogenous inhibitor had higher potency on the C-terminal active site than N-terminal active site of ACE. Finally, this endogenous ACE inhibition was also present in mouse, donkey, goat, bovine sera besides men (increasing of specific ACE activity

  9. Suppressing bullfrog larvae with carbon dioxide

    Science.gov (United States)

    Gross, Jackson A.; Ray, Andrew; Sepulveda, Adam J.; Watten, Barnaby J.; Densmore, Christine L.; Layhee, Megan J.; Mark Abbey-Lambert,; ,

    2014-01-01

    Current management strategies for the control and suppression of the American Bullfrog (Lithobates catesbeianus = Rana catesbeiana Shaw) and other invasive amphibians have had minimal effect on their abundance and distribution. This study evaluates the effects of carbon dioxide (CO2) on pre- and prometamorphic Bullfrog larvae. Bullfrogs are a model organism for evaluating potential suppression agents because they are a successful invader worldwide. From experimental trials we estimated that the 24-h 50% and 99% lethal concentration (LC50 and LC99) values for Bullfrog larvae were 371 and 549 mg CO2/L, respectively. Overall, larvae that succumbed to experimental conditions had a lower body condition index than those that survived. We also documented sublethal changes in blood chemistry during prolonged exposure to elevated CO2. Specifically, blood pH decreased by more than 0.5 pH units after 9 h of exposure and both blood partial pressure of CO2 (pCO2) and blood glucose increased. These findings suggest that CO2 treatments can be lethal to Bullfrog larvae under controlled laboratory conditions. We believe this work represents the necessary foundation for further consideration of CO2 as a potential suppression agent for one of the most harmful invaders to freshwater ecosystems.

  10. Glucose hypermetabolism in the thalamus of patients with hemifacial spasm.

    Science.gov (United States)

    Shimizu, Megumi; Suzuki, Yukihisa; Kiyosawa, Motohiro; Wakakura, Masato; Ishii, Kenji; Ishiwata, Kiichi; Mochizuki, Manabu

    2012-04-01

    The purpose of this study was investigate functional alteration in the brains of patients with hemifacial spasm using positron emission tomography (PET). We studied cerebral glucose metabolism using PET with (18) F-fluorodeoxyglucose in 13 patients with right lateral hemifacial spasm and 13 with left lateral hemifacial spasm. All patients underwent 2 PET scans before treatment (active state) and after treatment (suppressive state) with the botulinum neurotoxin type A. At the time of the PET scans, the severity of the spasm was rated according to the Jankovic Disability Rating Scale. We also used magnetic resonance imaging to evaluate the grade of neurovascular compression in each patient using scores of 1 to 3 (1 = mild, 3 = severe). Fifty-two normal volunteers were examined as controls. Compared with controls, patients with right and left hemifacial spasm showed bilateral cerebral glucose hypermetabolism in the thalamus in both the active and suppressive states. However, thalamic glucose metabolism after the suppressive state was significantly reduced compared with that in the active state using region of interest analysis. There was a positive correlation between the severity of the spasm in the active state and the score of neurovascular compression (rs = 0.65) that was estimated using Spearman order correlation coefficient. We observed bilateral cerebral glucose hypermetabolism in the thalamus of patients with hemifacial spasm. The thalamic glucose hypermetabolism may be attributed to multiple sources, including afferent input from the skin and muscle spindle, antidromic conduction of the facial nerve, and secondary alteration in the central nervous system. Copyright © 2012 Movement Disorder Society.

  11. Quantifying rates of glucose production in vivo following an intraperitoneal tracer bolus.

    Science.gov (United States)

    Wang, Sheng-Ping; Zhou, Dan; Yao, Zuliang; Satapati, Santhosh; Chen, Ying; Daurio, Natalie A; Petrov, Aleksandr; Shen, Xiaolan; Metzger, Daniel; Yin, Wu; Nawrocki, Andrea R; Eiermann, George J; Hwa, Joyce; Fancourt, Craig; Miller, Corin; Herath, Kithsiri; Roddy, Thomas P; Slipetz, Deborah; Erion, Mark D; Previs, Stephen F; Kelley, David E

    2016-12-01

    Aberrant regulation of glucose production makes a critical contribution to the impaired glycemic control that is observed in type 2 diabetes. Although isotopic tracer methods have proven to be informative in quantifying the magnitude of such alterations, it is presumed that one must rely on venous access to administer glucose tracers which therein presents obstacles for the routine application of tracer methods in rodent models. Since intraperitoneal injections are readily used to deliver glucose challenges and/or dose potential therapeutics, we hypothesized that this route could also be used to administer a glucose tracer. The ability to then reliably estimate glucose flux would require attention toward setting a schedule for collecting samples and choosing a distribution volume. For example, glucose production can be calculated by multiplying the fractional turnover rate by the pool size. We have taken a step-wise approach to examine the potential of using an intraperitoneal tracer administration in rat and mouse models. First, we compared the kinetics of [U-(13)C]glucose following either an intravenous or an intraperitoneal injection. Second, we tested whether the intraperitoneal method could detect a pharmacological manipulation of glucose production. Finally, we contrasted a potential application of the intraperitoneal method against the glucose-insulin clamp. We conclude that it is possible to 1) quantify glucose production using an intraperitoneal injection of tracer and 2) derive a "glucose production index" by coupling estimates of basal glucose production with measurements of fasting insulin concentration; this yields a proxy for clamp-derived assessments of insulin sensitivity of endogenous production. Copyright © 2016 the American Physiological Society.

  12. Endogene opioider og deres terapeutiske anvendelse i smertebehandling

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, A T

    1990-01-01

    Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients following epidural or intrathecal administration of endogenous opioids. Further...

  13. Government spending in a New Keynesian Endogenous Growth Model

    NARCIS (Netherlands)

    Kuehn, S.; Veen, van A.P. (Tom); Muysken, J.

    2009-01-01

    Standard New Keynesian models cannot generate the widely observed result that private consumption is crowded in by government spending. We use a New Keynesian endogenous growth model with endogenous labour supply to analyse this phenomenon. The presence of small direct productivity effects of

  14. Do Endogenous and Exogenous Action Control Compete for Perception?

    Science.gov (United States)

    Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

    2012-01-01

    Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the…

  15. Susceptibility of human liver cells to porcine endogenous retrovirus.

    Science.gov (United States)

    Lin, Xinzi; Qi, Lin; Li, Zhiguo; Chi, Hao; Lin, Wanjun; Wang, Yan; Jiang, Zesheng; Pan, Mingxin; Gao, Yi

    2013-12-01

    The risk of porcine endogenous retrovirus infection is a major barrier for pig-to-human xenotransplant. Porcine endogenous retrovirus, present in porcine cells, can infect many human and nonhuman primate cells in vitro, but there is no evidence available about in vitro infection of human liver cells. We investigated the susceptibility of different human liver cells to porcine endogenous retrovirus. The supernatant from a porcine kidney cell line was added to human liver cells, including a normal hepatocyte cell line (HL-7702 cells), primary hepatocytes (Phh cells), and a liver stellate cell line (Lx-2 cells), and to human embryonic kidney cells as a reference control. Expression of the porcine endogenous retrovirus antigen p15E in the human cells was evaluated with polymerase chain reaction, reverse transcription-polymerase chain reaction, and Western blot. The porcine endogenous retrovirus antigen p15E was not expressed in any human liver cells (HL-7702, Phh, or Lx-2 cells) that had been exposed to supernatants from porcine kidney cell lines. Porcine endogenous retrovirus-specific fragments were amplified in human kidney cells. Human liver cells tested were not susceptible to infection by porcine endogenous retrovirus. Therefore, not all human cells are susceptible to porcine endogenous retrovirus.

  16. Optimized endogenous post-stratification in forest inventories

    Science.gov (United States)

    Paul L. Patterson

    2012-01-01

    An example of endogenous post-stratification is the use of remote sensing data with a sample of ground data to build a logistic regression model to predict the probability that a plot is forested and using the predicted probabilities to form categories for post-stratification. An optimized endogenous post-stratified estimator of the proportion of forest has been...

  17. Endogenous change : On cooperation and water in ancient history

    NARCIS (Netherlands)

    Pande, S.; Ertsen, M.W.

    2013-01-01

    We propose and test the theory of endogenous change based on historical reconstructions of two ancient civilizations, Indus and Hohokam, in two water scarce basins, the Indus basin in the Indian subcontinent and the Lower Colorado basin in Southwestern United States. The endogenous institutional

  18. The Endogenous-Exogenous Partition in Attribution Theory

    Science.gov (United States)

    Kruglanski, Arie W.

    1975-01-01

    Within lay explanation of actions, several significant inferences are assumed to follow from the partition between endogenous and exogenous attributions. An endogenous action is judged to constitute an end in itself; an exogenous action is judged to serve as a means to some further end. (Editor/RK)

  19. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase

    DEFF Research Database (Denmark)

    Madiraju, Anila K; Erion, Derek M; Rahimi, Yasmeen

    2014-01-01

    Metformin is considered to be one of the most effective therapeutics for treating type 2 diabetes because it specifically reduces hepatic gluconeogenesis without increasing insulin secretion, inducing weight gain or posing a risk of hypoglycaemia. For over half a century, this agent has been...... prescribed to patients with type 2 diabetes worldwide, yet the underlying mechanism by which metformin inhibits hepatic gluconeogenesis remains unknown. Here we show that metformin non-competitively inhibits the redox shuttle enzyme mitochondrial glycerophosphate dehydrogenase, resulting in an altered...... hepatocellular redox state, reduced conversion of lactate and glycerol to glucose, and decreased hepatic gluconeogenesis. Acute and chronic low-dose metformin treatment effectively reduced endogenous glucose production, while increasing cytosolic redox and decreasing mitochondrial redox states. Antisense...

  20. [Effect of combined and local cytokine- and ozone therapy on the indices of lipid peroxidation, endogenous intoxication and ferroproteins in diffuse peritonitis].

    Science.gov (United States)

    Gadzhiev, N Dzh; Nasirov, M Ia; Sushkov, S V; Klimova, E M

    2014-01-01

    The article analyzes the results of effect of combined and local cytokine- and ozone therapy on the indices of lipid peroxidation, endogenous intoxication and ferroproteins in 111 patients with diffuse peritonitis. It was shown, that combined sequential local and systemic cytokine and ozone therapy allows correcting the expression of endogenous intoxication and lipid peroxidation in diffuse peritonitis. This method suppresses an inflammation in the abdominal cavity. At the same time, it accelerates the elimination of intestine atony and thereby potentiates the possibilities of traditional methods of treatment.

  1. Faox enzymes inhibited Maillard reaction development during storage both in protein glucose model system and low lactose UHT milk

    NARCIS (Netherlands)

    Troise, A.D.; Dathan, N.A.; Fiore, A.; Roviello, G.; Fiore, Di A.; Caira, S.; Cuollo, M.; Simone, De G.; Fogliano, V.; Monti, S.M.

    2014-01-01

    Fructosamines, also known asAmadori products, are formed by the condensation of glucose with the amino group of amino acids or proteins. These compounds are precursors of advanced glycation end products (AGEs) that can be formed either endogenously during aging and diabetes, and exogenously in

  2. Validation of a Simulation Model Describing the Glucose-Insulin-Glucagon Pharmacodynamics in Patients with Type 1 Diabetes

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Ranjan, Ajenthen; Møller, Jan Kloppenborg

    Currently, no consensus exists on a model describing endogenous glucose production (EGP) as a function of glucagon concentrations. Reliable simulations to determine the glucagon dose preventing or treating hypoglycemia or to tune a dual-hormone artificial pancreas control algorithm need a validated...

  3. Type of infectious disease affects glucose metabolism and liver glycogen content in Surinamese children: malaria vs. pneumonia

    NARCIS (Netherlands)

    Zijlmans, Wilco; Jitan, Jeetendra; Ackermans, Mariëtte T.; Serlie, Mireille J.; van Kempen, Anne A. M. W.; Sauerwein, Hans P.

    2013-01-01

    Abstract Background and aim: Fasting is an important risk factor for hypoglycemia in children with malaria or pneumonia. Young children are more at risk because of impaired endogenous glucose production presumably due to smaller liver glycogen stores. The aim of this study was to measure the effect

  4. Enterococcus faecalis Endogenous Endophthalmitis from Valvular Endocarditis

    Directory of Open Access Journals (Sweden)

    Sidnei Barge

    2013-01-01

    Full Text Available We report a case of a 74-year-old female, with a mitral heart valve, who presented with pain and blurred vision in the right eye for 2 days. Her visual acuity was light perception (LP in the right eye and 20/40 in the left eye. Slit lamp examination showed corneal edema and hypopyon, and a view of the right fundus was impossible. Echography showed vitreous condensation. One day after presentation, the patient developed acute lung edema requiring hospitalization, so she was not submitted to vitreous tap and intravitreal treatment. The cardiac and systemic evaluations revealed a mitral endocarditis secondary to Enterococcus faecalis. The patient improved systemically with treatment with gentamicin, vancomycin, and linezolid. Her visual acuity remained as no LP, and her intraocular pressure (IOP has been controlled with brimonidine bid despite developing a total cataract with 360° posterior synechia. A cardiac source for endogenous endophthalmitis should be considered in the presence of a prosthetic cardiac valve. The treatment and followup must be made in cooperation with a cardiologist specialist, but the ophthalmologist can play a key role in the diagnosis.

  5. Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes.

    Science.gov (United States)

    Gilbert, C; Meik, J M; Dashevsky, D; Card, D C; Castoe, T A; Schaack, S

    2014-09-22

    We report the discovery of endogenous viral elements (EVEs) from Hepadnaviridae, Bornaviridae and Circoviridae in the speckled rattlesnake, Crotalus mitchellii, the first viperid snake for which a draft whole genome sequence assembly is available. Analysis of the draft assembly reveals genome fragments from the three virus families were inserted into the genome of this snake over the past 50 Myr. Cross-species PCR screening of orthologous loci and computational scanning of the python and king cobra genomes reveals that circoviruses integrated most recently (within the last approx. 10 Myr), whereas bornaviruses and hepadnaviruses integrated at least approximately 13 and approximately 50 Ma, respectively. This is, to our knowledge, the first report of circo-, borna- and hepadnaviruses in snakes and the first characterization of non-retroviral EVEs in non-avian reptiles. Our study provides a window into the historical dynamics of viruses in these host lineages and shows that their evolution involved multiple host-switches between mammals and reptiles. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  6. Retinal photodamage by endogenous and xenobiotic agents.

    Science.gov (United States)

    Wielgus, Albert R; Roberts, Joan E

    2012-01-01

    The human eye is constantly exposed to sunlight and artificial lighting. Light transmission through the eye is fundamental to its unique biological functions of directing vision and circadian rhythm and therefore light absorbed by the eye must be benign. However, exposure to the very intense ambient radiation can pose a hazard particularly if the recipient is over 40 years of age. There are age-related changes in the endogenous (natural) chromophores (lipofuscin, A2E and all-trans-retinal derivatives) in the human retina that makes it more susceptible to visible light damage. Intense visible light sources that do not filter short blue visible light (400-440 nm) used for phototherapy of circadian imbalance (i.e. seasonal affective disorder) increase the risk for age-related light damage to the retina. Moreover, many drugs, dietary supplements, nanoparticles and diagnostic dyes (xenobiotics) absorb ocular light and have the potential to induce photodamage to the retina, leading to transient or permanent blinding disorders. This article will review the underlying reasons why visible light in general and short blue visible light in particular dramatically raises the risk of photodamage to the human retina. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  7. Endogenous Retroviruses: With Us and Against Us

    Science.gov (United States)

    Meyer, Thomas J.; Rosenkrantz, Jimi L.; Carbone, Lucia; Chavez, Shawn L.

    2017-04-01

    Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe the roles ERVs may play in somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.

  8. The role of biological clock in glucose homeostasis 

    Directory of Open Access Journals (Sweden)

    Piotr Chrościcki

    2013-06-01

    Full Text Available The mechanism of the biological clock is based on a rhythmic expression of clock genes and clock-controlled genes. As a result of their transcripto-translational associations, endogenous rhythms in the synthesis of key proteins of various physiological and metabolic processes are created. The major timekeeping mechanism for these rhythms exists in the central nervous system. The master circadian clock, localized in suprachiasmatic nucleus (SCN, regulates multiple metabolic pathways, while feeding behavior and metabolite availability can in turn regulate the circadian clock. It is also suggested that in the brain there is a food entrainable oscillator (FEO or oscillators, resulting in activation of both food anticipatory activity and hormone secretion that control digestion processes. Moreover, most cells and tissues express autonomous clocks. Maintenance of the glucose homeostasis is particularly important for the proper function of the body, as this sugar is the main source of energy for the brain, retina, erythrocytes and skeletal muscles. Thus, glucose production and utilization are synchronized in time. The hypothalamic excited orexin neurons control energy balance of organism and modulate the glucose production and utilization. Deficiency of orexin action results in narcolepsy and weight gain, whereas glucose and amino acids can affect activity of the orexin cells. Large-scale genetic studies in rodents and humans provide evidence for the involvement of disrupted clock gene expression rhythms in the pathogenesis of obesity and type 2 diabetes. In general, the current lifestyle of the developed modern societies disturbs the action of biological clock. 

  9. The effect of caffeine on glucose kinetics in humans - influence of adrenaline

    DEFF Research Database (Denmark)

    Battram, Danielle S.; Graham, Terry E.; Richter, Erik

    2005-01-01

    While caffeine impedes insulin-mediated glucose disposal in humans, its effect on endo-genous glucose production (EGP) remains unknown. In addition, the mechanism involved in these effects is unclear, but may be due to the accompanying increase in adrenaline concentration. We studied the effect...... of caffeine on EGP and glucose infusion rates (GIR), and whether or not adrenaline can account for all of caffeine's effects. Subjects completed three isoglycaemic-hyperinsulinaemic clamps (with 3-[3H]glucose infusion) 30 min after ingesting: (1) placebo capsules (n= 12); (2) caffeine capsules (5 mg kg-1) (n......= 12); and either (3) placebo plus a high-dose adrenaline infusion (HAdr; adrenaline concentration, 1.2 nM; n= 8) or (4) placebo plus a low-dose adrenaline infusion (LAdr; adrenaline concentration, 0.75 nM; n= 6). With caffeine, adrenaline increased to 0.6 nM but no effect on EGP was observed. While...

  10. Novel endogenous type C retrovirus in baboons: complete sequence, providing evidence for baboon endogenous virus gag-pol ancestry

    NARCIS (Netherlands)

    Mang, R.; Goudsmit, J.; van der Kuyl, A. C.

    1999-01-01

    A complete endogenous type C viral genome has been isolated from a baboon genomic library. The provirus, Papio cynocephalus endogenous retrovirus (PcEV), is 8,572 nucleotides long, and 38 to 59 proviral copies per baboon genome are found. The PcEV provirus possesses the typical simple retroviral

  11. Hypoxia induced expression of endogenous markers in vitro is highly influenced by pH

    DEFF Research Database (Denmark)

    Sørensen, Brita Singers; Alsner, Jan; Overgaard, Jens

    2007-01-01

    BACKGROUND: Genes such as carbonic anhydrase IX (Ca9), glucose transporter 1 (Glut1), lactate dehydrogenase A (LDH-A), osteopontin (OPN) and lysyl oxidase (LOX) have been suggested as hypoxic markers, but inconsistent results suggest that factors other than oxygen influence their expression......Ha and FaDu(DD) cells Ca9 and LOX reached the highest level of expression at 1% oxygen. In FaDu(DD) cells, a pH of 6.5 had a medium suppression effect on the hypoxia induced expression of Ca9. pH 6.3 resulted in severe suppression of expression for Ca9 and LOX in both SiHa and FaDu(DD). Glut1 and LDH-A had...

  12. Delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells

    Directory of Open Access Journals (Sweden)

    Seung Eun Song

    2016-04-01

    Full Text Available This study examined the effect of delphinidin on high glucose-induced cell proliferation and collagen synthesis in mesangial cells. Glucose dose-dependently (5.6–25 mM increased cell proliferation and collagen I and IV mRNA levels, whereas pretreatment with delphinidin (50 μM prevented cell proliferation and the increased collagen mRNA levels induced by high glucose (25 mM. High glucose increased reactive oxygen species (ROS generation, and this was suppressed by pretreating delphinidin or the antioxidant N-acetyl cysteine. NADPH oxidase (NOX 1 was upregulated by high glucose, but pretreatment with delphinidin abrogated this upregulation. Increased mitochondrial superoxide by 25 mM glucose was also suppressed by delphinidin. The NOX inhibitor apocynin and mitochondria-targeted antioxidant Mito TEMPO inhibited ROS generation and cell proliferation induced by high glucose. Phosphorylation of extracellular signal regulated kinase (ERK1/2 was increased by high glucose, which was suppressed by delphinidin, apocynin or Mito TEMPO. Furthermore, PD98059 (an ERK1/2 inhibitor prevented the high glucose-induced cell proliferation and increased collagen mRNA levels. Transforming growth factor (TGF-β protein levels were elevated by high glucose, and pretreatment with delphinidin or PD98059 prevented this augmentation. These results suggest that delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells.

  13. [Effects of bagging on pigment, sugar and endogenous hormone contents of Cara Cara orange flesh].

    Science.gov (United States)

    Wang, Guiyuan; Xia, Renxue; Zeng, Xiangguo; Hu, Liming

    2006-02-01

    This paper studied the effects of bagging during the period from young fruit formation to fruit coloration on the contents of pigment, sugar and endogenous hormone in Cara Cara orange flesh. The results showed that bagging could significantly increase the lycopene and beta-carotene contents of matured fruit, but didn't have any effects on its GA and ABA contents. The GA content decreased rapidly during fruit-expanding period, and maintained at a lower level in the period from fruit coloration to maturing. The ABA content reached the maximum when the bag was removed, decreased rapidly then, and there was a small peak before fruit maturation. Glucose and fructose contents were decreased, while sucrose content was increased significantly. No significant change was observed in total sugar content.

  14. Expression and knockdown analysis of glucose phosphate isomerase in chicken primordial germ cells.

    Science.gov (United States)

    Rengaraj, Deivendran; Lee, Sang In; Yoo, Min; Kim, Tae Hyun; Song, Gwonhwa; Han, Jae Yong

    2012-09-01

    Glucose is an important monosaccharide required to generate energy in all cells. After entry into cells, glucose is phosphorylated to glucose-6-phosphate and then transformed into glycogen or metabolized to produce energy. Glucose phosphate isomerase (GPI) catalyzes the reversible isomerization of glucose-6-phosphate and fructose-6-phosphate. Without GPI activity or fructose-6-phosphate, many steps of glucose metabolism would not occur. The requirement for GPI activity for normal functioning of primordial germ cells (PGCs) needs to be identified. In this study, we first examined the expression of chicken GPI during early embryonic development and germ cell development. GPI expression was strongly and ubiquitously detected in chicken early embryos and embryonic tissues at Embryonic Day 6.5 (E6.5). Continuous GPI expression was detected in PGCs and germ cells of both sexes during gonadal development. Specifically, GPI expression was stronger in male germ cells than in female germ cells during embryonic development and the majority of post-hatching development. Then, we used siRNA-1499 to knock down GPI expression in PGCs. siRNA-1499 caused an 85% knockdown in GPI, and PGC proliferation was also affected 48 h after transfection. We further examined the knockdown effects on 28 genes related to the glycolysis/gluconeogenesis pathway and the endogenous glucose level in chicken PGCs. Among genes related to glycolysis/gluconeogenesis, 20 genes showed approximately 3-fold lower expression, 4 showed approximately 10-fold lower, and 2 showed approximately 100-fold lower expression in knockdown PGCs. The endogenous glucose level was significantly reduced in knockdown PGCs. We conclude that the GPI gene is crucial for maintaining glycolysis and supplying energy to developing PGCs.

  15. Endogenous synthesis of corticosteroids in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Shimpei Higo

    Full Text Available BACKGROUND: Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC synthase, cytochrome P450(c21. METHODOLOGY/PRINCIPAL FINDINGS: The expression of P450(c21 was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG was demonstrated by metabolism analysis of (3H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21, P450(2D4, P450(11β1 and 3β-hydroxysteroid dehydrogenase (3β-HSD were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM doses of CORT for 1 h. CONCLUSIONS/SIGNIFICANCE: These results imply the complete pathway of corticosteroid synthesis of 'pregnenolone →PROG→DOC→CORT' in the hippocampal neurons. Both P450(c21 and P450(2D4 can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands.

  16. Endogenous opioids: The downside of opposing stress

    Directory of Open Access Journals (Sweden)

    Rita J. Valentino

    2015-01-01

    Full Text Available Our dynamic environment regularly exposes us to potentially life-threatening challenges or stressors. To answer these challenges and maintain homeostasis, the stress response, an innate coordinated engagement of central and peripheral neural systems is initiated. Although essential for survival, the inappropriate initiation of the stress response or its continuation after the stressor is terminated has pathological consequences that have been linked to diverse neuropsychiatric and medical diseases. Substantial individual variability exists in the pathological consequences of stressors. A theme of this Special Issue is that elucidating the basis of individual differences in resilience or its flipside, vulnerability, will greatly advance our ability to prevent and treat stress-related diseases. This can be approached by studying individual differences in “pro-stress” mediators such as corticosteroids or the hypothalamic orchestrator of the stress response, corticotropin-releasing factor. More recently, the recognition of endogenous neuromodulators with “anti-stress” activity that have opposing actions or that restrain stress-response systems suggests additional bases for individual differences in stress pathology. These “anti-stress” neuromodulators offer alternative strategies for manipulating the stress response and its pathological consequences. This review uses the major brain norepinephrine system as a model stress-response system to demonstrate how co-regulation by opposing pro-stress (corticotropin-releasing factor and anti-stress (enkephalin neuromodulators must be fine-tuned to produce an adaptive response to stress. The clinical consequences of tipping this fine-tuned balance in the direction of either the pro- or anti-stress systems are emphasized. Finally, that each system provides multiple points at which individual differences could confer stress vulnerability or resilience is discussed.

  17. Endophytic fungi associated with endogenous Boswellia sacra

    Directory of Open Access Journals (Sweden)

    SAIFELDIN A.F. EL-NAGERABI

    2014-04-01

    Full Text Available El-Nagerabi SAF, Elshafie AE, AlKhanjari SS. 2014. Endophytic fungi associated with endogenous Boswellia sacra. Biodiversitas 15: 22-28. Endophytic fungi associated with leaves and stem tissues of Boswellia sacra growing in Dhofar Mountains of Oman were investigated from May 2008 through October 2011. The biological diversity, tissue-preference and seasonal variations of fungi were evaluated. Forty-three species and 3 varieties of fungi were recovered as new records from this plant. Of these isolates, 35 species are new reports to the mycoflora of Oman, whereas 12 species were added to the list of fungal flora of the Arabian Peninsula. The genus Alternaria (12 species is the most prevalent genus recovered from 12.5-83.3% of the screened leaves and stem samples, followed by Aspergillus (5 species, 3 varieties, 6.9-86.1%, Mycelia sterilia (76.4%, Rhizopus stolonifer (62.5%, Drechslera (3 species, 40.3-54.2%, Cladosporium (3 species, 20.8-52.8%, Curvularia lunata (38.8%, Chaetomium (2 species, 15.3-26.3%, Penicillim spp. (9.8-27.8%, Fusarium (9 species, 6.9-27.8%, Ulocladium consortiale (27.8%, Mucor hiemalis (19.5%, and the remaining species (Scytalidium thermophilum, Phoma solani, Taeniolella exilis, and Botryodiplodia theobromae exhibited very low levels of incidence (4.2-11.1%. Endophytic colonization of the leaf tissues was greater (43 species, 3 varieties comparable to stem tissues (25 species. This indicates heterogeneity and tissue-preference, with no evidence of seasonal variation. Therefore, the isolation of many fungal species and sterile mycelia supports the biodiversity of the endophytic fungi invading B. sacra and the high possibility of isolating more fungal species using advanced molecular techniques.

  18. Manager's effort and endogenous economic discrimination

    Directory of Open Access Journals (Sweden)

    Jaime Orrillo

    2004-09-01

    Full Text Available Assume a labor supply consisting of two types of workers, 1 and 2. Both workers are equally productive and exhibit supply functions with the same elasticity. We consider a firm (entrepreneur or shareholders that is competitive in the output market and monopsonistic in input markets. The firm uses the services of a manager who has a high human capital and whose wage is given by the market. It is supposed that the manager does not like to work with one type of worker, say type 1. If we allow the manager's effort to be an additional input without any extra (in addition to his salary cost for the firm, then the firm's pricing decision will be different for both workers. That is, there will be a wage differential and therefore endogenous economic discrimination2 in the labor markets.Vamos assumir que a oferta de trabalho consiste de dois tipos de trabalhadores, 1 e 2. Ambos os trabalhadores são igualmente produtivos e exibem funções de oferta com a mesma elasticidade. Consideramos uma firma (empresário ou acionistas, a qual é competitiva no mercado de produtos e monopsonista nos mercados de insumos. A firma usa os serviços de um gerente quem tem um alto capital humano e cujo salário é dado pelo mercado. Suponhamos que o gerente não gosta de trabalhar com um tipo de trabalhador, digamos o tipo 1. Se permitirmos que o esforço do gerente seja um insumo adicional sem nenhum custo extra (além de seu salário, a decisão de salários será diferente para ambos os trabalhadores. Isto é, haverá um diferencial de salários e, em conseqüência, uma discriminação econômica1 endógena nos mercados de trabalho.

  19. Effects of D-allulose on glucose metabolism after the administration of sugar or food in healthy dogs.

    Science.gov (United States)

    Nishii, Naohito; Nomizo, Toru; Takashima, Satoshi; Matsubara, Tatsuya; Tokuda, Masaaki; Kitagawa, Hitoshi

    2016-12-01

    D-allulose is a C-3 epimer of D-fructose and has recently been investigated for its hypoglycemic effects. In the present study, the effects of D-allulose on glucose metabolism were evaluated in healthy dogs administrated sugar or food. The oral administrations of D-allulose decreased plasma glucose concentrations after oral glucose or maltose administration, with a diminished plasma insulin rise. The glucose suppressive effect of D-allulose was also observed after intravenous glucose administrations without increase in plasma insulin concentration. In contrast, D-allulose showed no effect on plasma glucose and insulin concentrations after feeding. The present results suggest that D-allulose administration may be beneficial in dogs with impaired glucose tolerance. Further studies investigating the therapeutic efficacy of D-allulose in diabetic dogs are required.

  20. Characteristics of glucose metabolism in Nordic and South Asian subjects with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Cecilie Wium

    Full Text Available BACKGROUND: Insulin resistance and type 2 diabetes are more prevalent in people of South Asian ethnicity than in people of Western European origin. To investigate the source of these differences, we compared insulin sensitivity, insulin secretion, glucose and lipid metabolism in South Asian and Nordic subjects with type 2 diabetes. METHODS: Forty-three Nordic and 19 South Asian subjects with type 2 diabetes were examined with intra-venous glucose tolerance test, euglycemic clamp including measurement of endogenous glucose production, indirect calorimetry measuring glucose and lipid oxidation, and dual x-ray absorptiometry measuring body composition. RESULTS: Despite younger mean ± SD age (49.7 ± 9.4 vs 58.3 ± 8.3 years, p = 0.001, subjects of South Asian ethnicity had the same diabetes duration (9.3 ± 5.5 vs 9.6 ± 7.0 years, p = 0.86, significantly higher median [inter-quartile range] HbA1c (8.5 [1.6] vs 7.3 [1.6] %, p = 0.024 and lower BMI (28.7 ± 4.0 vs 33.2 ± 4.7 kg/m(2, p<0.001. The South Asian group exhibited significantly higher basal endogenous glucose production (19.1 [9.1] vs 14.4 [6.8] µmol/kgFFM · min, p = 0.003. There were no significant differences between the groups in total glucose disposal (39.1 ± 20.4 vs 39.2 ± 17.6 µmol/kgFFM · min, p = 0.99 or first phase insulin secretion (AUC0-8 min: 220 [302] vs 124 [275] pM, p = 0.35. In South Asian subjects there was a tendency towards positive correlations between endogenous glucose production and resting and clamp energy expenditure. CONCLUSIONS: Subjects of South Asian ethnicity with type 2 diabetes, despite being younger and leaner, had higher basal endogenous glucose production, indicating higher hepatic insulin resistance, and a trend towards higher use of carbohydrates as fasting energy substrate compared to Nordic subjects. These findings may contribute to the understanding of the observed differences in prevalence of type 2 diabetes between the ethnic groups.

  1. Endogenous versus exogenous shocks in systems with memory

    Science.gov (United States)

    Sornette, D.; Helmstetter, A.

    2003-02-01

    Systems with long-range persistence and memory are shown to exhibit different precursory as well as recovery patterns in response to shocks of exogenous versus endogenous origins. By endogenous, we envision either fluctuations resulting from an underlying chaotic dynamics or from a stochastic forcing origin which may be external or be an effective coarse-grained description of the microscopic fluctuations. In this scenario, endogenous shocks result from a kind of constructive interference of accumulated fluctuations whose impacts survive longer than the large shocks themselves. As a consequence, the recovery after an endogenous shock is in general slower at early times and can be at long times either slower or faster than after an exogenous perturbation. This offers the tantalizing possibility of distinguishing between an endogenous versus exogenous cause of a given shock, even when there is no “smoking gun”. This could help in investigating the exogenous versus self-organized origins in problems such as the causes of major biological extinctions, of change of weather regimes and of the climate, in tracing the source of social upheaval and wars, and so on. Sornette et al., Volatility fingerprints of large stocks: endogenous versus exogenous, cond-mat/0204626 has already shown how this concept can be applied concretely to differentiate the effects on financial markets of the 11 September 2001 attack or of the coup against Gorbachev on 19 August 1991 (exogenous) from financial crashes such as October 1987 (endogenous).

  2. Glucose-dependent Insulinotropic Polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel B; Calanna, Salvatore; Holst, Jens Juul

    2014-01-01

    : 6.5 ± 0.1% [48 ± 2 mmol/mol]). INTERVENTION: We infused physiological amounts of GIP (2 pmol × kg(-1) × min(-1)) or saline. MAIN OUTCOME MEASURES: We measured plasma concentrations of glucagon, glucose, insulin, C-peptide, intact GIP, and amounts of glucose needed to maintain glucose clamps. RESULTS...... glucagon levels during the initial 30 minutes, resulting in less glucose needed to be infused to maintain the clamp (29 ± 8 vs 49 ± 12 mg × kg(-1), P hyperglycemia (1.5 × fasting plasma glucose ∼12 mmol/L), GIP augmented insulin secretion throughout the clamp, with slightly less glucagon......, during hyperglycemia, GIP increases glucose disposal through a predominant effect on insulin release....

  3. Modulation of the postprandial phase by beta-glucan in overweight subjects: effects on glucose and insulin kinetics.

    Science.gov (United States)

    Nazare, Julie-Anne; Normand, Sylvie; Oste Triantafyllou, Angeliki; Brac de la Perrière, Aude; Desage, Michel; Laville, Martine

    2009-03-01

    Decreasing the postprandial glucose response is potentially of major importance to public health when low-glycemic index or high-fibre content foods are associated with a decreased risk of diabetes. We investigated in overweight subjects the effect of adding beta-glucan (BG) to a polenta (Pol) meal on postprandial metabolism and glucose bioavailability using stable isotopes. In this single-blind, randomized, crossover trial, 12 subjects ate two meals containing Pol with (Pol + BG) or without (Pol) 5 g BG. Concentrations of glucose, insulin, C-peptide, nonesterified fatty acids, triacylglycerol, total and exogenous glucose kinetics were assessed for 6 h postprandially. The kinetics of total and exogenous glucose importantly differed between the meals, but not the quantity of total and exogenous glucose appearing in plasma. Less total and exogenous glucose appeared during the first 120 min after the Pol + BG meal; the phenomenon was then reversed (both p < 0.0001). After 120 min, glucose and insulin responses declined, but remained higher after the Pol + BG meal (p < 0.05) in parallel to the inhibition of lipolysis. The endogenous glucose production (EGP) was significantly more inhibited after the Pol + BG meal. The addition of BG slowed the appearance of glucose in plasma, resulting in longer-lasting insulin secretion which exerted a prolonged inhibition of EGP and lipolysis.

  4. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

    Science.gov (United States)

    Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram

    2004-01-01

    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (Pnootropics, D-levetiracetam and D-pyroglutamate, have higher antagonist Ki's against pentobarbital inhibition of glucose transport than more potent L-stereoisomers (Pnootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis. PMID:15148255

  5. Evidence that forskolin binds to the glucose transporter of human erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lavis, V.R.; Lee, D.P.; Shenolikar, S.

    1987-10-25

    Binding of (4-/sup 3/H)cytochalasin B and (12-/sup 3/H)forskolin to human erythrocyte membranes was measured by a centrifugation method. Glucose-displaceable binding of cytochalasin B was saturable, with KD = 0.11 microM, and maximum binding approximately 550 pmol/mg of protein. Forskolin inhibited the glucose-displaceable binding of cytochalasin B in an apparently competitive manner, with K1 = 3 microM. Glucose-displaceable binding of (12-/sup 3/H)forskolin was also saturable, with KD = 2.6 microM and maximum binding approximately equal to 400 pmol/mg of protein. The following compounds inhibited binding of (12-/sup 3/H)forskolin and (4-/sup 3/H)cytochalasin B equivalently, with relative potencies parallel to their reported affinities for the glucose transport system: cytochalasins A and D, dihydrocytochalasin B, L-rhamnose, L-glucose, D-galactose, D-mannose, D-glucose, 2-deoxy-D-glucose, 3-O-methyl-D-glucose, phloretin, and phlorizin. A water-soluble derivative of forskolin, 7-hemisuccinyl-7-desacetylforskolin, displaced equivalent amounts of (4-/sup 3/H)cytochalasin B or (12-/sup 3/H)forskolin. Rabbit erythrocyte membranes, which are deficient in glucose transporter, did not bind either (4-/sup 3/H)cytochalasin B or (12-/sup 3/H)forskolin in a glucose-displaceable manner. These results indicate that forskolin, in concentrations routinely employed for stimulation of adenylate cyclase, binds to the glucose transporter. Endogenous ligands with similar specificities could be important modulators of cellular metabolism.

  6. Endogenous ω-3 polyunsaturated fatty acid production confers resistance to obesity, dyslipidemia, and diabetes in mice.

    Science.gov (United States)

    Li, Jie; Li, Fanghong R; Wei, Dong; Jia, Wei; Kang, Jing X; Stefanovic-Racic, Maja; Dai, Yifan; Zhao, Allan Z

    2014-08-01

    Despite the well-documented health benefits of ω-3 polyunsaturated fatty acids (PUFAs), their use in clinical management of hyperglycemia and obesity has shown little success. To better define the mechanisms of ω-3 PUFAs in regulating energy balance and insulin sensitivity, we deployed a transgenic mouse model capable of endogenously producing ω-3 PUFAs while reducing ω-6 PUFAs owing to the expression of a Caenorhabditis elegans fat-1 gene encoding an ω-3 fatty acid desaturase. When challenged with high-fat diets, fat-1 mice strongly resisted obesity, diabetes, hypercholesterolemia, and hepatic steatosis. Endogenous elevation of ω-3 PUFAs and reduction of ω-6 PUFAs did not alter the amount of food intake but led to increased energy expenditure in the fat-1 mice. The requirements for the levels of ω-3 PUFAs as well as the ω-6/ω-3 ratios in controlling blood glucose and obesity are much more stringent than those in lipid metabolism. These metabolic phenotypes were accompanied by attenuation of the inflammatory state because tissue levels of prostaglandin E2, leukotriene B4, monocyte chemoattractant protein-1, and TNF-α were significantly decreased. TNF-α-induced nuclear factor-κB signaling was almost completely abolished. Consistent with the reduction in chronic inflammation and a significant increase in peroxisome proliferator-activated receptor-γ activity in the fat-1 liver tissue, hepatic insulin signaling was sharply elevated. The activities of prolipogenic regulators, such as liver X receptor, stearoyl-CoA desaturase-1, and sterol regulatory element binding protein-1 were sharply decreased, whereas the activity of peroxisome proliferator-activated receptor-α, a nuclear receptor that facilitates lipid β-oxidation, was markedly increased. Thus, endogenous conversion of ω-6 to ω-3 PUFAs via fat-1 strongly protects against obesity, diabetes, inflammation, and dyslipidemia and may represent a novel therapeutic modality to treat these prevalent

  7. Utilizing an endogenous pathway for 1-butanol production in Saccharomyces cerevisiae.

    Science.gov (United States)

    Si, Tong; Luo, Yunzi; Xiao, Han; Zhao, Huimin

    2014-03-01

    Microbial production of higher alcohols from renewable feedstock has attracted intensive attention thanks to its potential as a source for next-generation gasoline substitutes. Here we report the discovery, characterization and engineering of an endogenous 1-butanol pathway in Saccharomyces cerevisiae. Upon introduction of a single gene deletion adh1Δ, S. cerevisiae was able to accumulate more than 120 mg/L 1-butanol from glucose in rich medium. Precursor feeding, ¹³C-isotope labeling and gene deletion experiments demonstrated that the endogenous 1-butanol production was dependent on catabolism of threonine in a manner similar to fusel alcohol production by the Ehrlich pathway. Specifically, the leucine biosynthesis pathway was engaged in the conversion of key 2-keto acid intermediates. Overexpression of the pathway enzymes and elimination of competing pathways achieved the highest reported 1-butanol titer in S. cerevisiae (242.8 mg/L). Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  8. Endogenous cytokinin overproduction modulates ROS homeostasis and decreases salt stress resistance in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Yanping eWang

    2015-11-01

    Full Text Available Cytokinins in plants are crucial for numerous biological processes, including seed germination, cell division and differentiation, floral initiation and adaptation to abiotic stresses. The salt stress can promote reactive oxygen species (ROS production in plants which are highly toxic and ultimately results in oxidative stress. However, the correlation between endogenous cytokinin production and ROS homeostasis in responding to salt stress is poorly understood. In this study, we analyzed the correlation of overexpressing the cytokinin biosynthetic gene AtIPT8 (adenosine phosphate-isopentenyl transferase 8 and the response of salt stress in Arabidopsis. Overproduction of cytokinins, which was resulted by the inducible overexpression of AtIPT8, significantly inhibited the primary root growth and true leaf emergence, especially under the conditions of exogenous salt, glucose and mannitol treatments. Upon cytokinin overproduction, the salt stress resistance was declined, and resulted in less survival rates and chlorophyll content. Interestingly, ROS production was obviously increased with the salt treatment, accompanied by endogenously overproduced cytokinins. The activities of CAT and SOD, which are responsible for scavenging ROS, were also affected. Transcription profiling revealed that the differential expressions of ROS-producing and scavenging related genes, the photosynthesis-related genes and stress responsive genes were existed in transgenic plants of overproducing cytokinins. Our results suggested that broken in the homeostasis of cytokinins in plant cells could modulate the salt stress responses through a ROS-mediated regulation in Arabidopsis.

  9. Vasohibin-1 suppresses colon cancer

    National Research Council Canada - National Science Library

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-01-01

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor.However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown...

  10. Minor Contribution of Endogenous GLP-1 and GLP-2 to Postprandial Lipemia in Obese Men.

    Science.gov (United States)

    Matikainen, Niina; Björnson, Elias; Söderlund, Sanni; Borén, Christofer; Eliasson, Björn; Pietiläinen, Kirsi H; Bogl, Leonie H; Hakkarainen, Antti; Lundbom, Nina; Rivellese, Angela; Riccardi, Gabriele; Després, Jean-Pierre; Alméras, Natalie; Holst, Jens Juul; Deacon, Carolyn F; Borén, Jan; Taskinen, Marja-Riitta

    2016-01-01

    Glucose and lipids stimulate the gut-hormones glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP) but the effect of these on human postprandial lipid metabolism is not fully clarified. To explore the responses of GLP-1, GLP-2 and GIP after a fat-rich meal compared to the same responses after an oral glucose tolerance test (OGTT) and to investigate possible relationships between incretin response and triglyceride-rich lipoprotein (TRL) response to a fat-rich meal. Glucose, insulin, GLP-1, GLP-2 and GIP were measured after an OGTT and after a fat-rich meal in 65 healthy obese (BMI 26.5-40.2 kg/m(2)) male subjects. Triglycerides (TG), apoB48 and apoB100 in TG-rich lipoproteins (chylomicrons, VLDL1 and VLDL2) were measured after the fat-rich meal. Postprandial responses (area under the curve, AUC) for glucose, insulin, GLP-1, GLP-2, GIP in plasma, and TG, apoB48 and apoB100 in plasma and TG-rich lipoproteins. The GLP-1, GLP-2 and GIP responses after the fat-rich meal and after the OGTT correlated strongly (r = 0.73, p<0.0001; r = 0.46, p<0.001 and r = 0.69, p<0.001, respectively). Glucose and insulin AUCs were lower, but the AUCs for GLP-1, GLP-2 and GIP were significantly higher after the fat-rich meal than after the OGTT. The peak value for all hormones appeared at 120 minutes after the fat-rich meal, compared to 30 minutes after the OGTT. After the fat-rich meal, the AUCs for GLP-1, GLP-2 and GIP correlated significantly with plasma TG- and apoB48 AUCs but the contribution was very modest. In obese males, GLP-1, GLP-2 and GIP responses to a fat-rich meal are greater than following an OGTT. However, the most important explanatory variable for postprandial TG excursion was fasting triglycerides. The contribution of endogenous GLP-1, GLP-2 and GIP to explaining the variance in postprandial TG excursion was minor.

  11. Minor Contribution of Endogenous GLP-1 and GLP-2 to Postprandial Lipemia in Obese Men.

    Directory of Open Access Journals (Sweden)

    Niina Matikainen

    Full Text Available Glucose and lipids stimulate the gut-hormones glucagon-like peptide (GLP-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP but the effect of these on human postprandial lipid metabolism is not fully clarified.To explore the responses of GLP-1, GLP-2 and GIP after a fat-rich meal compared to the same responses after an oral glucose tolerance test (OGTT and to investigate possible relationships between incretin response and triglyceride-rich lipoprotein (TRL response to a fat-rich meal.Glucose, insulin, GLP-1, GLP-2 and GIP were measured after an OGTT and after a fat-rich meal in 65 healthy obese (BMI 26.5-40.2 kg/m(2 male subjects. Triglycerides (TG, apoB48 and apoB100 in TG-rich lipoproteins (chylomicrons, VLDL1 and VLDL2 were measured after the fat-rich meal.Postprandial responses (area under the curve, AUC for glucose, insulin, GLP-1, GLP-2, GIP in plasma, and TG, apoB48 and apoB100 in plasma and TG-rich lipoproteins.The GLP-1, GLP-2 and GIP responses after the fat-rich meal and after the OGTT correlated strongly (r = 0.73, p<0.0001; r = 0.46, p<0.001 and r = 0.69, p<0.001, respectively. Glucose and insulin AUCs were lower, but the AUCs for GLP-1, GLP-2 and GIP were significantly higher after the fat-rich meal than after the OGTT. The peak value for all hormones appeared at 120 minutes after the fat-rich meal, compared to 30 minutes after the OGTT. After the fat-rich meal, the AUCs for GLP-1, GLP-2 and GIP correlated significantly with plasma TG- and apoB48 AUCs but the contribution was very modest.In obese males, GLP-1, GLP-2 and GIP responses to a fat-rich meal are greater than following an OGTT. However, the most important explanatory variable for postprandial TG excursion was fasting triglycerides. The contribution of endogenous GLP-1, GLP-2 and GIP to explaining the variance in postprandial TG excursion was minor.

  12. Amplification and chromosomal dispersion of human endogenous retroviral sequences

    Energy Technology Data Exchange (ETDEWEB)

    Steele, P.E.; Martin, M.A.; Rabson, A.B.; Bryan, T.; O' Brien, S.J.

    1986-09-01

    Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification and dispersion events may be linked.

  13. Aldosterone aggravates glucose intolerance induced by high fructose.

    Science.gov (United States)

    Sherajee, Shamshad J; Rafiq, Kazi; Nakano, Daisuke; Mori, Hirohito; Kobara, Hideki; Hitomi, Hirofumi; Fujisawa, Yoshihide; Kobori, Hiroyuki; Masaki, Tsutomu; Nishiyama, Akira

    2013-11-15

    We previously reported that aldosterone impaired vascular insulin signaling in vivo and in vitro. Fructose-enriched diet induces metabolic syndrome including hypertension, insulin resistance, hyperlipidemia and diabetes in animal. In the current study, we hypothesized that aldosterone aggravated fructose feeding-induced glucose intolerance in vivo. Rats were divided into five groups for six-week treatment; uninephrectomy (Unx, n=8), Unx+aldosterone (aldo, 0.75 µg/h, s.c., n=8), Unx+fructose (fruc, 10% in drinking water, n=8), Unx+aldo+fruc, (aldo+fruc, n=8), and Unx+aldo+fruc+spironolactone, a mineralocorticoid receptor antagonist (aldo+fruc+spiro, 20mg/kg/day, p.o., n=8). Aldo+fruc rats manifested the hypertension, and induced glucose intolerance compared to fruc intake rats assessed by oral glucose tolerance test, homeostasis model assessment of insulin resistance and hyperinsulinemic-euglycemic clamp study. Spironolactone, significantly improved the aldosterone-accelerated glucose intolerance. Along with improvement in insulin resistance, spironolactone suppressed upregulated mineralocorticoid receptor (MR) target gene, serum and glucocorticoid-regulated kinases-1 mRNA expression in skeletal muscle in aldo+fruc rats. In conclusion, these data suggested that aldosterone aggravates fructose feeding-induced glucose intolerance through MR activation. © 2013 Published by Elsevier B.V.

  14. High Protein Diet Maintains Glucose Production During Exercise-Induced Energy Deficit: A Controlled Trial

    Science.gov (United States)

    2011-04-28

    www.biomedcentral.com/ Nutrition & Metabolism © 2011 Smith et al. ; licensee BioMed Central Ltd. This is an open access article distr buted under the terms of... Osteopathic Medicine, 1310 Johnson Lane, Mare Island, Vallejo, CA 94592, United States of America 4 Jean Mayer USDA Human Nutrition Research...endogenous glucose production declines in response to energy deficit produced by an abrupt increase in 5 energy expenditure and to ascertain if

  15. Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions

    Directory of Open Access Journals (Sweden)

    Jie Sha

    2014-09-01

    Full Text Available BackgroundThe role of small GTPase molecules is poorly understood under high glucose conditions.MethodsWe analyzed the expression pattern of Vav3 in skeletal muscle C2C12 cells under high glucose culture condition with reverse transcription-polymerase chain reaction and Western blot analysis. We also measured glucose uptake using isotope-labelled glucose.ResultsWe showed that expression of Vav3 (a guanine nucleotide exchange factor for RhoA increased. mRNA and protein levels in skeletal muscle C2C12 cells under high glucose conditions. The AMP-activated protein kinase (AMPK activator AMPK agonist 5-aminoimidazole-4-carboxy-amide-1-d-ribofuranoside (AICAR suppressed high glucose-induced Vav3 induction. In addition, exposure of cells to high glucose concentration increased the phosphorylation of PAK-1, a molecule downstream of RhoA. The phosphorylation of paxillin, a downstream molecule of PAK-1, was also increased by exposure to high glucose. Phosphorylation of these molecules was not observed in the presence of AICAR, indicating that AMPK is involved in the RhoA signal pathway under high glucose conditions. Knock down of Vav3 enhances metformin-mediated glucose uptake. Inhibition of AMPK blocked the increases of Vav3 knock down-induced glucose uptake. Metformin-mediated Glut4 translocation was also increased by Vav3 knock-down, suggesting that Vav3 is involved in metformin-mediated glucose uptake.ConclusionThese results demonstrate that Vav3 is involved in the process of metformin-mediated glucose regulation.

  16. CNC-bZIP protein Nrf1-dependent regulation of glucose-stimulated insulin secretion.

    Science.gov (United States)

    Zheng, Hongzhi; Fu, Jingqi; Xue, Peng; Zhao, Rui; Dong, Jian; Liu, Dianxin; Yamamoto, Masayuki; Tong, Qingchun; Teng, Weiping; Qu, Weidong; Zhang, Qiang; Andersen, Melvin E; Pi, Jingbo

    2015-04-01

    The inability of pancreatic β-cells to secrete sufficient insulin in response to glucose stimulation is a major contributing factor to the development of type 2 diabetes (T2D). We investigated both the in vitro and in vivo effects of deficiency of nuclear factor-erythroid 2-related factor 1 (Nrf1) in β-cells on β-cell function and glucose homeostasis. Silencing of Nrf1 in β-cells leads to a pre-T2D phenotype with disrupted glucose metabolism and impaired insulin secretion. Specifically, MIN6 β-cells with stable knockdown of Nrf1 (Nrf1-KD) and isolated islets from β-cell-specific Nrf1-knockout [Nrf1(b)-KO] mice displayed impaired glucose responsiveness, including elevated basal insulin release and decreased glucose-stimulated insulin secretion (GSIS). Nrf1(b)-KO mice exhibited severe fasting hyperinsulinemia, reduced GSIS, and glucose intolerance. Silencing of Nrf1 in MIN6 cells resulted in oxidative stress and altered glucose metabolism, with increases in both glucose uptake and aerobic glycolysis, which is associated with the elevated basal insulin release and reduced glucose responsiveness. The elevated glycolysis and reduced glucose responsiveness due to Nrf1 silencing likely result from altered expression of glucose metabolic enzymes, with induction of high-affinity hexokinase 1 and suppression of low-affinity glucokinase. Our study demonstrated a novel role of Nrf1 in regulating glucose metabolism and insulin secretion in β-cells and characterized Nrf1 as a key transcription factor that regulates the coupling of glycolysis and mitochondrial metabolism and GSIS. Nrf1 plays critical roles in regulating glucose metabolism, mitochondrial function, and insulin secretion, suggesting that Nrf1 may be a novel target to improve the function of insulin-secreting β-cells.

  17. Glucose metabolism and metabolic flexibility in cultured skeletal muscle cells is related to exercise status in young male subjects

    DEFF Research Database (Denmark)

    Lund, Jenny; S Tangen, Daniel; Wiig, Håvard

    2017-01-01

    deoxyglucose accumulation and fractional glucose oxidation (glucose oxidation relative to glucose uptake), and were also more sensitive to the suppressive action of acutely added oleic acid to the cells. Despite lack of correlation of fibre types between skeletal muscle biopsies and cultured cells, myotubes......We hypothesised that skeletal muscles of healthy young people have a large variation in oxidative capacity and fibre-type composition, and aimed therefore to investigate glucose metabolism in biopsies and myotubes isolated from musculus vastus lateralis from healthy males with varying degrees...

  18. Fine structure of endogenous stages of Eimeria turcicus developing ...

    African Journals Online (AJOL)

    1988-05-06

    ANDERSEN, A.,. HUTCHINSON, W.M. & SlIM, J. Chr. 1977b. Ultrastructural studies on the endogenous development of. Eimeria brunetti IV. Formation and structure of the oocyst wall. Acta path. microbiol. scand. Sect. B 85: 201-211.

  19. Modulation of macrophage antitumor cytostasis by endogenous leukotrienes

    NARCIS (Netherlands)

    J.J. van Hilten (Jacobus)

    1990-01-01

    textabstractUsing resident peritoneal macrophages, this study was focussed on the activating role of endogenous leukotrienes in the regulation of macrophage antitumor cytostatic activity in response to inflammatory stimuli. Inhibitors and inducers of leukotrienes synthesis were used to modulate

  20. Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation

    Science.gov (United States)

    Gorog, Diana A.

    2017-01-01

    The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions. PMID:28841147

  1. Endogenous cardiac glycosides, a new class of steroid hormones

    National Research Council Canada - National Science Library

    Schoner, Wilhelm

    2002-01-01

    The search for endogenous digitalis has led to the isolation of ouabain as well as several additional cardiotonic steroids of the cardenolide and bufadienolide type from blood, adrenals, and hypothalamus...

  2. Detection and distribution of endogenous steroids in human stratum corneum

    Directory of Open Access Journals (Sweden)

    Shu-Ping Tseng

    2014-03-01

    Conclusion: The results demonstrate that, with the achievable sensitivity of current analytical technology, physiological concentrations of endogenous steroids, such as hydrocortisone and cortisone, can be found in the SC of some individuals.

  3. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...... factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...

  4. Evidence that endogenous SST inhibits ACTH and ghrelin expression by independent pathways.

    Science.gov (United States)

    Luque, Raul M; Gahete, Manuel D; Hochgeschwender, Ute; Kineman, Rhonda D

    2006-08-01

    Corticosterone and total ghrelin levels are increased in somatostatin (SST) knockout mice (Sst-/-) compared with SST-intact controls (Sst+/+). Because exogenous ghrelin can increase glucocorticoids, the question arises whether elevated levels of ghrelin contribute to elevated corticosterone levels in Sst-/- mice. We report that Sst-/- mice had elevated mRNA levels for pituitary proopiomelanocortin (POMC), the precursor of adrenocorticotropic hormone (ACTH), whereas mRNA levels for hypothalamic corticotropin-releasing hormone (CRH) did not differ from Sst+/+ mice. Furthermore, SST suppressed pituitary POMC mRNA levels and ACTH release in vitro independently of CRH actions. In contrast, it has been reported that ghrelin increases glucocorticoids via a central effect on CRH secretion and that n-octanoyl ghrelin is the form of ghrelin that activates the GHS-R1a and modulates CRH neuronal activity. Consistent with elevations in total ghrelin levels, Sst-/- mice displayed an increase in stomach ghrelin mRNA levels, whereas hypothalamic and pituitary expression of ghrelin was not altered. Despite the increase in total ghrelin levels, circulating levels of n-octanoyl ghrelin were not altered in Sst-/- mice. Because glucocorticoids and ghrelin increase in response to fasting, we examined the impact of fasting on the adrenal axis and ghrelin in Sst+/+ and Sst-/- mice and found that endogenous SST does not significantly contribute to this adaptive response. We conclude that endogenous SST inhibits basal ghrelin gene expression in a tissue specific manner and independently and directly inhibits pituitary ACTH synthesis and release. Thus endogenous SST exerts an inhibitory effect on ghrelin synthesis and on the adrenal axis through independent pathways.

  5. Independent circadian and sleep/wake regulation of adipokines and glucose in humans.

    Science.gov (United States)

    Shea, Steven A; Hilton, Michael F; Orlova, Christine; Ayers, R Timothy; Mantzoros, Christos S

    2005-05-01

    Leptin and adiponectin play important physiological roles in regulating appetite, food intake, and energy balance and have pathophysiological roles in obesity and anorexia nervosa. To assess the relative contributions of day/night patterns in behaviors (sleep/wake cycle and food intake) and of the endogenous circadian pacemaker on observed day/night patterns of adipokines, in six healthy subjects we measured circulating leptin, soluble leptin receptor, adiponectin, glucose, and insulin levels throughout a constant routine protocol (38 h of wakefulness with constant posture, temperature, and dim light, as well as identical snacks every 2 h) and throughout sleep and fasting periods before and after the constant routine. There were significant endogenous circadian rhythms in leptin, glucose, and insulin, with peaks around the usual time of awakening. Sleep/fasting resulted in additional systematic decreases in leptin, glucose, and insulin, whereas wakefulness/food intake resulted in a systematic increase in leptin. Thus, the day/night pattern in leptin is likely caused by combined effects from the endogenous circadian pacemaker and day/night patterns in behaviors. Our data imply that alterations in the sleep/wake schedule would lead to an increased daily range in circulating leptin, with lowest leptin upon awakening, which, by influencing food intake and energy balance, could be implicated in the increased prevalence of obesity in the shift work population.

  6. Glucose Plus Fructose Ingestion for Post-Exercise Recovery—Greater than the Sum of Its Parts?

    Science.gov (United States)

    Gonzalez, Javier T.; Fuchs, Cas J.; Betts, James A.; van Loon, Luc J. C.

    2017-01-01

    Carbohydrate availability in the form of muscle and liver glycogen is an important determinant of performance during prolonged bouts of moderate- to high-intensity exercise. Therefore, when effective endurance performance is an objective on multiple occasions within a 24-h period, the restoration of endogenous glycogen stores is the principal factor determining recovery. This review considers the role of glucose–fructose co-ingestion on liver and muscle glycogen repletion following prolonged exercise. Glucose and fructose are primarily absorbed by different intestinal transport proteins; by combining the ingestion of glucose with fructose, both transport pathways are utilised, which increases the total capacity for carbohydrate absorption. Moreover, the addition of glucose to fructose ingestion facilitates intestinal fructose absorption via a currently unidentified mechanism. The co-ingestion of glucose and fructose therefore provides faster rates of carbohydrate absorption than the sum of glucose and fructose absorption rates alone. Similar metabolic effects can be achieved via the ingestion of sucrose (a disaccharide of glucose and fructose) because intestinal absorption is unlikely to be limited by sucrose hydrolysis. Carbohydrate ingestion at a rate of ≥1.2 g carbohydrate per kg body mass per hour appears to maximise post-exercise muscle glycogen repletion rates. Providing these carbohydrates in the form of glucose–fructose (sucrose) mixtures does not further enhance muscle glycogen repletion rates over glucose (polymer) ingestion alone. In contrast, liver glycogen repletion rates are approximately doubled with ingestion of glucose–fructose (sucrose) mixtures over isocaloric ingestion of glucose (polymers) alone. Furthermore, glucose plus fructose (sucrose) ingestion alleviates gastrointestinal distress when the ingestion rate approaches or exceeds the capacity for intestinal glucose absorption (~1.2 g/min). Accordingly, when rapid recovery of

  7. A new approach to establish a cell line with reduced risk of endogenous retroviruses.

    Directory of Open Access Journals (Sweden)

    Aiko Fukuma

    Full Text Available Endogenous retroviruses (ERVs are integrated as DNA proviruses in the genomes of all mammalian species. Several ERVs are replication-competent and produced as fully infectious viruses from host cell. Thus, live-attenuated vaccines and biological substances have been prepared using the cell lines which may produce ERV. Indeed, we recently reported that several commercial live-attenuated vaccines for pets were contaminated with the infectious feline endogenous retrovirus, RD-114. In this study, to establish a cell line for vaccine manufacture with reduced risk of ERVs, we generated a cell line stably expressing human tetherin (Teth-CRFK cells. The release of infectious ERV from Teth-CRFK cells was suppressed to undetectable levels, while the production of parvovirus in Teth-CRFK cells was similar to that in parental CRFK cells. These observations suggest that Teth-CRFK cells will be useful as a cell line for the manufacture of live-attenuated vaccines or biological substances with reduced risk of ERV.

  8. Contamination of live attenuated vaccines with an infectious feline endogenous retrovirus (RD-114 virus).

    Science.gov (United States)

    Yoshikawa, Rokusuke; Shimode, Sayumi; Sakaguchi, Shoichi; Miyazawa, Takayuki

    2014-03-01

    Retroviruses are classified as exogenous and endogenous retroviruses according to the mode of transmission. Endogenous retroviruses (ERVs) are retroviruses which have been integrated into germ-line cells and inherited from parents to offspring. Most ERVs are inactivated by deletions and mutations; however, certain ERVs maintain their infectivity and infect the same host and new hosts as exogenous retroviruses. All domestic cats have infectious ERVs, termed RD-114 virus. Several canine and feline attenuated vaccines are manufactured using RD-114 virus-producing cell lines such as Crandell-Rees feline kidney cells; therefore, it is possible that infectious RD-114 virus contaminates live attenuated vaccines. Recently, Japanese and UK research groups found that several feline and canine vaccines were indeed contaminated with infectious RD-114 virus. This was the first incidence of contamination of 'infectious' ERVs in live attenuated vaccines. RD-114 virus replicates efficiently in canine cell lines and primary cells. Therefore, it is possible that RD-114 virus infects dogs following inoculation with contaminated vaccines and induces proliferative diseases and immune suppression, if it adapts to grow efficiently in dogs. In this review, we summarize the incidence of contamination of RD-114 virus in live attenuated vaccines and potential risks of infection with RD-114 virus in dogs.

  9. An auxin-responsive endogenous peptide regulates root development in Arabidopsis.

    Science.gov (United States)

    Yang, Fengxi; Song, Yu; Yang, Hao; Liu, Zhibin; Zhu, Genfa; Yang, Yi

    2014-07-01

    Auxin plays critical roles in root formation and development. The components involved in this process, however, are not well understood. Here, we newly identified a peptide encoding gene, auxin-responsive endogenous polypeptide 1 (AREP1), which is induced by auxin, and mediates root development in Arabidopsis. Expression of AREP1 was specific to the cotyledon and to root and shoot meristem tissues. Amounts of AREP1 transcripts and AREP1-green fluorescent protein fusion proteins were elevated in response to indoleacetic acid treatment. Suppression of AREP1 through RNAi silencing resulted in reduction of primary root length, increase of lateral root number, and expansion of adventitious roots, compared to the observations in wild-type plants in the presence of auxin. By contrast, transgenic plants overexpressing AREP1 showed enhanced growth of the primary root under auxin treatment. Additionally, root morphology, including lateral root number and adventitious roots, differed greatly between transgenic and wild-type plants. Further analysis indicated that the expression of auxin-responsive genes, such as IAA3, IAA7, IAA17, GH3.2, GH3.3, and SAUR-AC1, was significantly higher in AREP1 RNAi plants, and was slightly lower in AREP1 overexpressing plants than in wild-type plants. These results suggest that the novel endogenous peptide AREP1 plays an important role in the process of auxin-mediated root development. © 2014 Institute of Botany, Chinese Academy of Sciences.

  10. Novel Role of Endogenous Catalase in Macrophage Polarization in Adipose Tissue.

    Science.gov (United States)

    Park, Ye Seul; Uddin, Md Jamal; Piao, Lingjuan; Hwang, Inah; Lee, Jung Hwa; Ha, Hunjoo

    2016-01-01

    Macrophages are important components of adipose tissue inflammation, which results in metabolic diseases such as insulin resistance. Notably, obesity induces a proinflammatory phenotypic switch in adipose tissue macrophages, and oxidative stress facilitates this switch. Thus, we examined the role of endogenous catalase, a key regulator of oxidative stress, in the activity of adipose tissue macrophages in obese mice. Catalase knockout (CKO) exacerbated insulin resistance, amplified oxidative stress, and accelerated macrophage infiltration into epididymal white adipose tissue in mice on normal or high-fat diet. Interestingly, catalase deficiency also enhanced classical macrophage activation (M1) and inflammation but suppressed alternative activation (M2) regardless of diet. Similarly, pharmacological inhibition of catalase activity using 3-aminotriazole induced the same phenotypic switch and inflammatory response in RAW264.7 macrophages. Finally, the same phenotypic switch and inflammatory responses were observed in primary bone marrow-derived macrophages from CKO mice. Taken together, the data indicate that endogenous catalase regulates the polarization of adipose tissue macrophages and thereby inhibits inflammation and insulin resistance.

  11. Invasive fungal infections in endogenous Cushing’s syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Selbach Scheffel

    2010-06-01

    Full Text Available Cushing’s syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing’s original description of the disease. We describe here a patient with endo-genous Cushing’s syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease.

  12. Endogenous growth, backstop technology adoption and optimal jumps

    OpenAIRE

    Valente, Simone

    2009-01-01

    This paper analyzes a two-phase endogenous growth model in which the adoption of a backstop technology (e.g., solar) yields a sustained supply of essential energy inputs previously obtained from exhaustible resources (e.g., oil). Growth is knowledge-driven and the optimal timing of technology switching is determined by welfare maximization. The optimal path exhibits discrete jumps in endogenous variables: technology switching implies sudden reductions in consumption and output, an increase in...

  13. Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS.

    Science.gov (United States)

    Vieira-Marques, Claudia; Arbo, Bruno Dutra; Cozer, Aline Gonçalves; Hoefel, Ana Lúcia; Cecconello, Ana Lúcia; Zanini, Priscila; Niches, Gabriela; Kucharski, Luiz Carlos; Ribeiro, Maria Flávia M

    2017-07-01

    DHEA is a neuroactive steroid, due to its modulatory actions on the central nervous system (CNS). DHEA is able to regulate neurogenesis, neurotransmitter receptors and neuronal excitability, function, survival and metabolism. The levels of DHEA decrease gradually with advancing age, and this decline has been associated with age related neuronal dysfunction and degeneration, suggesting a neuroprotective effect of endogenous DHEA. There are significant sex differences in the pathophysiology, epidemiology and clinical manifestations of many neurological diseases. The aim of this study was to determine whether DHEA can alter glucose metabolism in different structures of the CNS from male and female rats, and if this effect is sex-specific. The results showed that DHEA decreased glucose uptake in some structures (cerebral cortex and olfactory bulb) in males, but did not affect glucose uptake in females. When compared, glucose uptake in males was higher than females. DHEA enhanced the glucose oxidation in both males (cerebral cortex, olfactory bulb, hippocampus and hypothalamus) and females (cerebral cortex and olfactory bulb), in a sex-dependent manner. In males, DHEA did not affect synthesis of glycogen, however, glycogen content was increased in the cerebral cortex and olfactory bulb. DHEA modulates glucose metabolism in a tissue-, dose- and sex-dependent manner to increase glucose oxidation, which could explain the previously described neuroprotective role of this hormone in some neurodegenerative diseases. Copyright © 2016. Published by Elsevier Ltd.

  14. Oxytocin Improves β-Cell Responsivity and Glucose Tolerance in Healthy Men.

    Science.gov (United States)

    Klement, Johanna; Ott, Volker; Rapp, Kristina; Brede, Swantje; Piccinini, Francesca; Cobelli, Claudio; Lehnert, Hendrik; Hallschmid, Manfred

    2017-02-01

    In addition to its pivotal role in psychosocial behavior, the hypothalamic neuropeptide oxytocin contributes to metabolic control by suppressing eating behavior. Its involvement in glucose homeostasis is less clear, although pilot experiments suggest that oxytocin improves glucose homeostasis. We assessed the effect of intranasal oxytocin (24 IU) administered to 29 healthy, fasted male subjects on glucose homeostasis measured by means of an oral glucose tolerance test. Parameters of glucose metabolism were analyzed according to the oral minimal model. Oxytocin attenuated the peak excursion of plasma glucose and augmented the early increases in insulin and C-peptide concentrations in response to the glucose challenge, while slightly blunting insulin and C-peptide peaks. Oral minimal model analyses revealed that oxytocin compared with placebo induced a pronounced increase in β-cell responsivity (PHItotal) that was largely due to an enhanced dynamic response (PHId), and a more than twofold improvement in glucose tolerance (disposition index). Adrenocorticotropic hormone (ACTH), cortisol, glucagon, and nonesterified fatty acid (NEFA) concentrations were not or were only marginally affected. These results indicate that oxytocin plays a significant role in the acute regulation of glucose metabolism in healthy humans and render the oxytocin system a potential target of antidiabetic treatment. © 2017 by the American Diabetes Association.

  15. Glucose uptake stimulatory potential and antidiabetic activity of the Arnebin-1 from Arnabia nobelis.

    Science.gov (United States)

    Pandeti, Sukanya; Arha, Deepti; Mishra, Akansha; Reddy, Sabbu Sathish; Srivastava, Arvind K; Narender, Tadigoppula; Tamrakar, Akhilesh K

    2016-10-15

    The enhanced disposal of glucose by the peripheral tissue is an important mechanism to regulate hyperglycemia. Here, we investigated the effect of Arnebin-1 from Arnebia nobilis, on glucose disposal in skeletal muscle cells and explored its in vivo antihyperglycemic potential. In L6 myotubes, Arnebin-1 stimulated glucose uptake, mediated through the enhanced translocation of the glucose transporter-4 (GLUT4) to plasma membrane, without changing the amount of GLUT4 or GLUT1. These effects of Arnebin-1 were synergistic with that of insulin. The effect of Arnebin-1 on glucose uptake was abolished in presence of wortmannin, and Arnebin-1 significantly stimulated the phosphorylation of Akt and downstream marker GSK-3β. Moreover, treatment with Arnebin-1 lowered postprandial blood glucose levels in streptozotocin-induced diabetic rats, and improved glucose tolerance and suppressed the rises in the fasting blood glucose, serum insulin, triglycerides, and total cholesterol in db/db mice, associated with enhanced expression of the major marker of the PI-3-Kinase-mediated signaling cascade in skeletal muscle. These findings suggest that Arnebin-1 exert antihyperglycemic activity through stimulating glucose disposal in peripheral tissues via PI-3-Kinase-dependent pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Differential suppression of background mammalian lysosomal β-galactosidase increases the detection sensitivity of LacZ-marked leukemic cells

    NARCIS (Netherlands)

    P.J. Hendrikx (P. Jan); A.C.M. Martens (Anton); J.W.M. Visser (Jan); A. Hagenbeek (Anton)

    1994-01-01

    textabstractA method is described for the detection of Escherichia coli β-galactosidase-expressing leukemic cells in ex vivo bone marrow samples. 4-Methylumbelliferyl-β-D-galactopyranoside is used as a substrate in a kinetic assay. D-Galactose is used to suppress endogenous lysosomal β-galactosidase

  17. Glucose-dependent insulinotropic polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel; Vedtofte, Louise; Holst, Jens Juul

    2011-01-01

    OBJECTIVE To evaluate the glucose dependency of glucose-dependent insulinotropic polypeptide (GIP) effects on insulin and glucagon release in 10 healthy male subjects ([means ± SEM] aged 23 ± 1 years, BMI 23 ± 1 kg/m2, and HbA1c 5.5 ± 0.1%). RESEARCH DESIGN AND METHODS Saline or physiological doses...

  18. Glucose repression in Saccharomyces cerevisiae

    National Research Council Canada - National Science Library

    Kayikci, Ömur; Nielsen, Jens; Bolotin-Fukuhara, Monique

    2015-01-01

    ...-transcriptional and post-translational levels. This review describes effects of glucose repression on yeast carbon metabolism with a focus on roles of the Snf3/Rgt2 glucose-sensing pathway and Snf1 signal transduction in establishment and relief...

  19. Glucose repression in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Kayikci, Omur; Nielsen, Jens

    2015-01-01

    and gluconeogenesis. This dominant effect of glucose on yeast carbon metabolism is coordinated by several signaling and metabolic interactions that mainly regulate transcriptional activity but are also effective at post-transcriptional and post-translational levels. This review describes effects of glucose repression...

  20. In situ tissue regeneration: chemoattractants for endogenous stem cell recruitment.

    Science.gov (United States)

    Vanden Berg-Foels, Wendy S

    2014-02-01

    Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration.

  1. Glucose tolerance test - non-pregnant

    Science.gov (United States)

    Oral glucose tolerance test - non-pregnant; OGTT - non-pregnant; Diabetes - glucose tolerance test; Diabetic - glucose tolerance test ... The most common glucose tolerance test is the oral glucose tolerance test (OGTT). Before the test begins, a sample of blood will be ...

  2. ASIATIC ACID INFLUENCES GLUCOSE HOMEOSTASIS IN P. BERGHEI MURINE MALARIA INFECTED SPRAGUE-DAWLEY RATS.

    Science.gov (United States)

    Alfred, Mavondo Greanious; Nkazimulo, Mkhwananzi Blessing; Vuyisile, Mabandla Musa; Tagumirwa, Musabayane Cephas

    2016-01-01

    Glucose homeostasis derangement is a common pathophysiology of malaria whose aetiology is still controversial. The Plasmodium parasite, immunological and inflammatory responses, as well as chemotherapeutics currently used cause hypoglycaemia in malaria. Anti-parasitic and anti-disease drugs are required to combat malaria while ameliorating the pathophysiology of the infection. Asiatic acid has anti-hyperglycaemic, antioxidant, pro-oxidant properties useful in glucose homeostasis but its influence in malaria is yet to be reported. Here we present findings on the influence of asiatic acid on glucose metabolism in vivo using P. berghei-infected Sprague Dawley rats. Acute as well as sub-chronic studies were carried out in vivo where physicochemical properties and glucose homeostasis were monitored after administration of asiatic acid (10mg/kg) in both non-infected and infected animals. Glucose metabolism associated biochemical changes in malaria were also investigated. In acute studies, asiatic acid improved oral glucose response while in the sub-chronic state it maintained food and water intake and suppressed parasitaemia. Normoglycaemic control was maintained in infected animals through insulin suppression and increasing glucagon secretion, in both acute and chronic studies. Asiatic acid administration curtailed lactate concentration towards normal. Per oral post-infection asiatic acid administration preserved drinking and eating habits, inhibited sickness behaviour while suppressing parasitaemia. Reciprocal relationship between insulin and glucagon concentrations was maintained influencing glucose homeostasis positively and inhibition of hyperlactaemia in malaria. Abbreviations: ip -intraperitoneal, po -per oral, ig -intragastric, AA-Asciatic acid, OGTT-oral glucose tolerance test, OS-oxidative stress, ROS-reactive oxygen species, NO-nitric oxide, ONOO- - peroxynitrite, BRU-Biomedical Research Unit, SD-Sprague Dawley.

  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. Acute effects of ghrelin administration on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Djurhuus, Christian Born; Gjedsted, Jakob

    2007-01-01

    CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate metabolism. DESIGN: This was a randomized, single......-blind, placebo-controlled two-period crossover study. SETTING: The study was performed in a university clinical research laboratory. PARTICIPANTS: Eight healthy men aged 27.2 +/- 0.9 yr with a body mass index of 23.4 +/- 0.5 kg/m(2) were included in the study. INTERVENTION: Subjects received infusion of ghrelin...... the final 2 h of each infusion. RESULTS: Basal and insulin-stimulated glucose disposal decreased with ghrelin [basal: 1.9 +/- 0.1 (ghrelin) vs. 2.3 +/- 0.1 mg x kg(-1) x min(-1), P = 0.03; clamp: 3.9 +/- 0.6 (ghrelin) vs. 6.1 +/- 0.5 mg x kg(-1) x min(-1), P = 0.02], whereas endogenous glucose production...

  5. Skeletal muscle glucose uptake during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    2005-01-01

    The increase in skeletal muscle glucose uptake during exercise results from a coordinated increase in rates of glucose delivery (higher capillary perfusion), surface membrane glucose transport, and intracellular substrate flux through glycolysis. The mechanism behind the movement of GLUT4...

  6. Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice

    Science.gov (United States)

    Niki, Mayu; Jyotaki, Masafumi; Yoshida, Ryusuke; Yasumatsu, Keiko; Shigemura, Noriatsu; DiPatrizio, Nicholas V; Piomelli, Daniele; Ninomiya, Yuzo

    2015-01-01

    Leptin is an anorexigenic mediator that reduces food intake by acting on hypothalamic receptor Ob-Rb. In contrast, endocannabinoids are orexigenic mediators that act via cannabinoid CB1 receptors in hypothalamus, limbic forebrain, and brainstem. In the peripheral taste system, leptin administration selectively inhibits behavioural, taste nerve and taste cell responses to sweet compounds. Opposing the action of leptin, endocannabinoids enhance sweet taste responses. However, potential roles of endogenous leptin and endocannabinoids in sweet taste remain unclear. Here, we used pharmacological antagonists (Ob-Rb: L39A/D40A/F41A (LA), CB1: AM251) and examined the effects of their blocking activation of endogenous leptin and endocannabinoid signalling on taste responses in lean control, leptin receptor deficient db/db, and diet-induced obese (DIO) mice. Lean mice exhibited significant increases in chorda tympani (CT) nerve responses to sweet compounds after LA administration, while they showed no significant changes in CT responses after AM251. In contrast, db/db mice showed clear suppression of CT responses to sweet compounds after AM251, increased endocannabinoid (2-arachidonoyl-sn-glycerol (2-AG)) levels in the taste organ, and enhanced expression of a biosynthesizing enzyme (diacylglycerol lipase α (DAGLα)) of 2-AG in taste cells. In DIO mice, the LA effect was gradually decreased and the AM251 effect was increased during the course of obesity. Taken together, our results suggest that circulating leptin, but not local endocannabinoids, may be a dominant modulator for sweet taste in lean mice; however, endocannabinoids may become more effective modulators of sweet taste under conditions of deficient leptin signalling, possibly due to increased production of endocannabinoids in taste tissue. Key points Potential roles of endogenous leptin and endocannabinoids in sweet taste were examined by using pharmacological antagonists and mouse models including leptin receptor

  7. Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice.

    Science.gov (United States)

    Niki, Mayu; Jyotaki, Masafumi; Yoshida, Ryusuke; Yasumatsu, Keiko; Shigemura, Noriatsu; DiPatrizio, Nicholas V; Piomelli, Daniele; Ninomiya, Yuzo

    2015-06-01

    Potential roles of endogenous leptin and endocannabinoids in sweet taste were examined by using pharmacological antagonists and mouse models including leptin receptor deficient (db/db) and diet-induced obese (DIO) mice. Chorda tympani (CT) nerve responses of lean mice to sweet compounds were increased after administration of leptin antagonist (LA) but not affected by administration of cannabinoid receptor antagonist (AM251). db/db mice showed clear suppression of CT responses to sweet compounds after AM251, increased endocannabinoid levels in the taste organ, and enhanced expression of a biosynthesizing enzyme of endocannabinoids in taste cells. The effect of LA was gradually decreased and that of AM251 was increased during the course of obesity in DIO mice. These findings suggest that circulating leptin, but not local endocannabinoids, is a dominant modulator for sweet taste in lean mice and endocannabinoids become more effective modulators of sweet taste under conditions of deficient leptin signalling. Leptin is an anorexigenic mediator that reduces food intake by acting on hypothalamic receptor Ob-Rb. In contrast, endocannabinoids are orexigenic mediators that act via cannabinoid CB1 receptors in hypothalamus, limbic forebrain, and brainstem. In the peripheral taste system, leptin administration selectively inhibits behavioural, taste nerve and taste cell responses to sweet compounds. Opposing the action of leptin, endocannabinoids enhance sweet taste responses. However, potential roles of endogenous leptin and endocannabinoids in sweet taste remain unclear. Here, we used pharmacological antagonists (Ob-Rb: L39A/D40A/F41A (LA), CB1 : AM251) and examined the effects of their blocking activation of endogenous leptin and endocannabinoid signalling on taste responses in lean control, leptin receptor deficient db/db, and diet-induced obese (DIO) mice. Lean mice exhibited significant increases in chorda tympani (CT) nerve responses to sweet compounds after LA

  8. Dual Regulation of Gluconeogenesis by Insulin and Glucose in the Proximal Tubules of the Kidney.

    Science.gov (United States)

    Sasaki, Motohiro; Sasako, Takayoshi; Kubota, Naoto; Sakurai, Yoshitaka; Takamoto, Iseki; Kubota, Tetsuya; Inagi, Reiko; Seki, George; Goto, Moritaka; Ueki, Kohjiro; Nangaku, Masaomi; Jomori, Takahito; Kadowaki, Takashi

    2017-09-01

    Growing attention has been focused on the roles of the proximal tubules (PTs) of the kidney in glucose metabolism, including the mechanism of regulation of gluconeogenesis. In this study, we found that PT-specific insulin receptor substrate 1/2 double-knockout mice, established by using the newly generated sodium-glucose cotransporter 2 (SGLT2)-Cre transgenic mice, exhibited impaired insulin signaling and upregulated gluconeogenic gene expression and renal gluconeogenesis, resulting in systemic insulin resistance. In contrast, in streptozotocin-treated mice, although insulin action was impaired in the PTs, the gluconeogenic gene expression was unexpectedly downregulated in the renal cortex, which was restored by administration of an SGLT1/2 inhibitor. In the HK-2 cells, the gluconeogenic gene expression was suppressed by insulin, accompanied by phosphorylation and inactivation of forkhead box transcription factor 1 (FoxO1). In contrast, glucose deacetylated peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α), a coactivator of FoxO1, via sirtuin 1, suppressing the gluconeogenic gene expression, which was reversed by inhibition of glucose reabsorption. These data suggest that both insulin signaling and glucose reabsorption suppress the gluconeogenic gene expression by inactivation of FoxO1 and PGC1α, respectively, providing insight into novel mechanisms underlying the regulation of gluconeogenesis in the PTs. © 2017 by the American Diabetes Association.

  9. Hyperglycemia and Perioperative Glucose Management

    Science.gov (United States)

    Duncan, Andra E.

    2013-01-01

    Hyperglycemia is associated with increased mortality and morbidity in critically ill patients. Surgical patients commonly develop hyperglycemia related to the hypermetabolic stress response, which increases glucose production and causes insulin resistance. Although hyperglycemia is associated with worse outcomes, the treatment of hyperglycemia with insulin infusions has not provided consistent benefits. Despite early results, which suggested decreased mortality and other advantages of “tight” glucose control, later investigations found no benefit or increased mortality when hyperglycemia was aggressively treated with insulin. Because of these conflicting data, the optimal glucose concentration to improve outcomes in critically ill patients is unknown. There is agreement, however, that hypoglycemia is an undesirable complication of intensive insulin therapy and should be avoided. In addition, the risk of increased glucose variability should be recognized, because of the associated increased risk for worse outcomes. Patients with diabetes mellitus experience chronic hyperglycemia and often require more intensive perioperative glucose management. When diabetic patients are evaluated before surgery, appropriate management of oral hypoglycemic agents is necessary as several of these agents warrant special consideration. Current recommendations for perioperative glucose management from national societies are varied, but, most suggest that tight glucose control may not be beneficial, while mild hyperglycemia appears to be well-tolerated. PMID:22762467

  10. Effect of Buddleja officinalis on high-glucose-induced vascular inflammation in human umbilical vein endothelial cells.

    Science.gov (United States)

    Lee, Yun Jung; Kang, Dae Gill; Kim, Jin Sook; Lee, Ho Sub

    2008-06-01

    In this study, we aimed to investigate whether an aqueous extract of Buddleja officinalis (ABO) suppresses high-glucose-induced vascular inflammatory processes in the primary cultured human umbilical vein endothelial cells (HUVEC). The high-glucose-induced increase in expression of cell adhesion molecules (CAMs) such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-selectin (E-selectin) was significantly attenuated by pretreatment with ABO in a dose-dependent manner. Enhanced cell adhesion caused by high glucose in co-cultured U937 and HUVEC was also blocked by pretreatment with ABO. Pretreatment with ABO also blocked formation of high-glucose-induced reactive oxygen species (ROS). In addition, ABO suppressed the transcriptional activity of NF-kappaB and IkappaB phosphorylation under high-glucose conditions. Pretreatment with N(G)-nitro-l-arginine methyl ester (L-NAME), an endothelial nitric oxide (NO) synthase inhibitor, attenuated the protective action of ABO on high-glucose-induced CAM expression, suggesting a potential role of NO signaling. The present data suggest that ABO could suppress high-glucose-induced vascular inflammatory processes, and ABO may be closely related with the inhibition of ROS and NF-kappaB activation in HUVEC.

  11. Profiles of Everyday Thought Suppression

    OpenAIRE

    Ie, Amanda Yen Lin

    2014-01-01

    The present research assessed whether levels of depression, anxiety and worry, obsessive-compulsive distress, and psychopathy were differentially related to distinct thought suppression profiles. As a means to achieving this goal, the Profiles of Everyday Thought Suppression (PETS) scale was constructed to measure the frequencies with which various target thoughts are suppressed. The PETS scale demonstrated good internal consistency and test-retest reliability, and scores were positively co...

  12. Glucose Binding Protein as a Novel Optical Glucose Nanobiosensor

    Directory of Open Access Journals (Sweden)

    Majed DWEIK

    2009-11-01

    Full Text Available Development of an in vivo optical sensor requires the utilization of Near Infra Red (NIR fluorophores due to their ability to operate within the biological tissue window. Alexa Fluor 750 (AF750 and Alexa Fluor 680 (AF680 were examined as potential NIR fluorophores for an in vivo fluorescence resonance energy transfer (FRET glucose biosensor. AF680 and AF750 found to be a FRET pair and percent energy transfer was calculated. Next, the tested dye pair was utilized in a competitive binding assay in order to detect glucose. Concanavalin A (Con A and dextran have binding affinity, but in the presence of glucose, glucose displaces dextran due to its higher affinity to Con A than dextran. Finally, the percent signal transfer through porcine skin was examined. The results showed with approximately 4.0 mm porcine skin thickness, 1.98 % of the fluorescence was transmitted and captured by the detector.

  13. Sex differences in glucose levels

    DEFF Research Database (Denmark)

    Faerch, K; Borch-Johnsen, Knut; Vaag, A

    2010-01-01

    We aimed to examine whether sex differences in fasting plasma glucose (FPG), 2 h post-OGTT plasma glucose (2hPG) and HbA(1c) could be explained by differences in body size and/or body composition between men and women in a general non-diabetic Danish population. Moreover, we aimed to study to what...... degree the newly suggested high-risk HbA(1c) criteria overlapped with the current OGTT-based criteria of glucose intolerance....

  14. Conversion of glucose to sorbose

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Mark E.; Gounder, Rajamani

    2016-02-09

    The present invention is directed to methods for preparing sorbose from glucose, said method comprising: (a) contacting the glucose with a silica-containing structure comprising a zeolite having a topology of a 12 membered-ring or larger, an ordered mesoporous silica material, or an amorphous silica, said structure containing Lewis acidic Ti.sup.4+ or Zr.sup.4+ or both Ti.sup.4+ and Zr.sup.4+ framework centers, said contacting conducted under reaction conditions sufficient to isomerize the glucose to sorbose. The sorbose may be (b) separated or isolated; or (c) converted to ascorbic acid.

  15. How to measure blood glucose

    OpenAIRE

    Dianne Pickering; Janet Marsden

    2014-01-01

    The level of glucose in the blood can be measured by applying a drop of blood to a chemically treated, disposable ‘test-strip’, which is then inserted into an electronic blood glucose meter. The reaction between the test strip and the blood is detected by the meter and displayed in units of mg/dL or mmol/L. There are a number of different types of meters available, and all are slightly different. Take care when applying the general principles described in this article to the specific glucose ...

  16. “Start” Mutants of Saccharomyces cerevisiae Are Suppressed in Carbon Catabolite-Derepressing Medium

    OpenAIRE

    Shuster, Jeffrey R.

    1982-01-01

    Temperature-sensitive cell division “start” mutants cdc28, cdc36, cdc37, and cdc39 of the yeast Saccharomyces cerevisiae arrested cell division in the G1 phase of the cell cycle in glucose medium. I report here that cdc28, cdc36, and cdc39 mutants were suppressed when grown in carbon catabolite-derepressing medium.

  17. Diazoxide-mediated insulin suppression in obese men: a dose-response study.

    NARCIS (Netherlands)

    Schreuder, T.; Karreman, M.; Rennings, A.J.M.; Ruinemans-Koerts, J.; Jansen, M.; Boer, H.D. de

    2005-01-01

    BACKGROUND: It has been suggested that diazoxide (DZX)-mediated insulin suppression may be useful to promote weight loss in obese subjects. AIM: To assess the DZX-dose range that is safe to use in obese hyperinsulinaemic men. METHODS: Assessment of DZX efficacy and safety was based on plasma glucose

  18. Suppressive effect of resistant maltodextrin on postprandial blood triacylglycerol elevation.

    Science.gov (United States)

    Kishimoto, Yuka; Oga, Hiroshi; Tagami, Hiroyuki; Okuma, Kazuhiro; Gordon, Dennis T

    2007-04-01

    As the physiological functions of soluble dietary fibre, the favourable efficacy, such as attenuating the absorption of saccharides or lipids, is expected. Resistant maltodextrin, a soluble dietary fibre, was investigated and found that it delays the glucose absorption and attenuates the postprandial rise in the blood glucose levels, however, the efficacy of resistant maltodextrin on lipid metabolism is not yet reported. We conducted an animal experiment and a human experiment to investigate the effect of resistant maltodextrin on postprandial blood triacylglycerol elevation. 1. Rats were fed corn oil with or without resistant maltodextrin and the postprandial changes in triacylglycerol were examined. 2. We then conducted a dietary loading experiment on 13 healthy adult male and female subjects using a meal containing approximately 50 g fat. A beverage not containing resistant maltodextrin was used as a placebo; subjects consumed the loading meal and a beverage containing either 5 g or 10 g resistant maltodextrin; blood was periodically collected to see the changes in serum constituents. 1. The corn oil administration experiment using rats showed that resistant maltodextrin dose-dependently suppressed elevation of blood triacylglycerol levels after corn oil administration. 2. The dietary loading experiment on 13 healthy subjects with 5 or 10 g of resistant maltodextrin showed that; in each administration group, resistant maltodextrin significantly suppressed postprandial elevation of blood triacylglycerol, RLP-cholesterol and insulin. These results indicate that resistant maltodextrin ingested with fatty meals suppresses the postprandial elevation of blood triacylglycerol levels.

  19. Screening for suppression in young children : the Polaroid Suppression test

    NARCIS (Netherlands)

    Pott, JWR; Oosterveen, DK; Van Hof-van Duin, J

    1998-01-01

    Background: Assessment of monocular visual impairment during screening of young children is often hampered by lack of cooperation. Because strabismus, amblyopia, or anisometropia may lead to monocular suppression during binocular viewing conditions, a test was developed to screen far suppression in

  20. Tissue-specific tagging of endogenous loci in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Kate Koles

    2016-01-01

    Full Text Available Fluorescent protein tags have revolutionized cell and developmental biology, and in combination with binary expression systems they enable diverse tissue-specific studies of protein function. However these binary expression systems often do not recapitulate endogenous protein expression levels, localization, binding partners and/or developmental windows of gene expression. To address these limitations, we have developed a method called T-STEP (tissue-specific tagging of endogenous proteins that allows endogenous loci to be tagged in a tissue specific manner. T-STEP uses a combination of efficient CRISPR/Cas9-enhanced gene targeting and tissue-specific recombinase-mediated tag swapping to temporally and spatially label endogenous proteins. We have employed this method to GFP tag OCRL (a phosphoinositide-5-phosphatase in the endocytic pathway and Vps35 (a Parkinson's disease-implicated component of the endosomal retromer complex in diverse Drosophila tissues including neurons, glia, muscles and hemocytes. Selective tagging of endogenous proteins allows, for the first time, cell type-specific live imaging and proteomics in complex tissues.

  1. Staphylococcal endogenous endophthalmitis in association with pyogenic vertebral osteomyelitis.

    Science.gov (United States)

    Steeples, L R; Jones, N P

    2016-01-01

    PURPOSE To describe pyogenic vertebral osteomyelitis as a rare infection associated with endogenous endophthalmitis.METHODS A retrospective review of three patients with endogenous endophthalmitis and sepsis due to underlying Staphylococcal vertebral osteomyelitis presenting during a 21-month time period. The ophthalmic and systemic features and management and outcomes are presented.RESULTS One patient developed unilateral endophthalmitis with cervical spine osteomyelitis, Staphylococcus aureus being isolated from blood cultures. The second presented with bilateral endophthalmitis with disseminated Methicillin-resistant S. aureus (MRSA) infection, with thoracic and lumbar discitis and para-spinal abscesses. MRSA was cultured from vitreous, blood, and synovial fluid. Both patients received prolonged courses of intravenous antibiotics. Intravitreal antibiotic therapy was used in the second patient. Excellent visual and systemic outcomes were achieved in both cases with no ocular complications. The third patient developed lumbar osteomyelitis following spinal surgery and presented with disseminated S. aureus sepsis including unilateral endogenous endophthalmitis. Despite systemic antibiotics and intensive care the patient died.CONCLUSIONS Endogenous endophthalmitis should be suspected in septic patients developing eye symptoms. Endogenous endophthalmitis with staphylococcal bone infection is a rare but serious condition. Osteomyelitis should be considered as an infective source in any such patient reporting bone pain or reduced spinal mobility. Prompt investigation and treatment can achieve favourable visual and systemic outcomes.

  2. Glucose-6-phosphatase deficiency

    Directory of Open Access Journals (Sweden)

    Labrune Philippe

    2011-05-01

    Full Text Available Abstract Glucose-6-phosphatase deficiency (G6P deficiency, or glycogen storage disease type I (GSDI, is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea. Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty, generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency. GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib. Mutations in the genes G6PC (17q21 and SLC37A4 (11q23 respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most

  3. Short-term starvation is a strategy to unravel the cellular capacity of oxidizing specific exogenous/endogenous substrates in mitochondria.

    Science.gov (United States)

    Zeidler, Julianna D; Fernandes-Siqueira, Lorena O; Carvalho, Ana S; Cararo-Lopes, Eduardo; Dias, Matheus H; Ketzer, Luisa A; Galina, Antonio; Da Poian, Andrea T

    2017-08-25

    Mitochondrial oxidation of nutrients is tightly regulated in response to the cellular environment and changes in energy demands. In vitro studies evaluating the mitochondrial capacity of oxidizing different substrates are important for understanding metabolic shifts in physiological adaptations and pathological conditions, but may be influenced by the nutrients present in the culture medium or by the utilization of endogenous stores. One such influence is exemplified by the Crabtree effect (the glucose-mediated inhibition of mitochondrial respiration) as most in vitro experiments are performed in glucose-containing media. Here, using high-resolution respirometry, we evaluated the oxidation of endogenous or exogenous substrates by cell lines harboring different metabolic profiles. We found that a 1-h deprivation of the main energetic nutrients is an appropriate strategy to abolish interference of endogenous or undesirable exogenous substrates with the cellular capacity of oxidizing specific substrates, namely glutamine, pyruvate, glucose, or palmitate, in mitochondria. This approach primed mitochondria to immediately increase their oxygen consumption after the addition of the exogenous nutrients. All starved cells could oxidize exogenous glutamine, whereas the capacity for oxidizing palmitate was limited to human hepatocarcinoma Huh7 cells and to C2C12 mouse myoblasts that differentiated into myotubes. In the presence of exogenous glucose, starvation decreased the Crabtree effect in Huh7 and C2C12 cells and abrogated it in mouse neuroblastoma N2A cells. Interestingly, the fact that the Crabtree effect was observed only for mitochondrial basal respiration but not for the maximum respiratory capacity suggests it is not caused by a direct effect on the electron transport system. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Endogenous n-3 Fatty Acids Alleviate Carbon-Tetrachloride-Induced Acute Liver Injury in Fat-1 Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Ruibing Feng

    2016-01-01

    Full Text Available n-3 polyunsaturated fatty acids (PUFAs are beneficial for numerous models of liver diseases. The probable protective effects of n-3 PUFA against carbon-tetrachloride- (CCl4- induced acute liver injury were evaluated in a fat-1 transgenic mouse that synthesizes endogenous n-3 from n-6 PUFA. Fat-1 mice and their WT littermates were fed a modified AIN93 diet containing 10% corn oil and were injected intraperitoneally with a single dose of CCl4 or vehicle. CCl4 challenge caused severe liver injury in WT mice, as indicated by serum parameters and histopathological changes, which were remarkably ameliorated in fat-1 mice. Endogenous n-3 PUFA decreased the elevation of oxidative stress induced by CCl4 challenge, which might be attributed to the activation of Nrf2/keap1 pathway. Additionally, endogenous n-3 PUFA reduces hepatocyte apoptosis via suppressing MAPK pathway. These findings indicate that n-3 PUFA has potent protective effects against acute liver injury induced by CCl4 in mice, suggesting that n-3 PUFA can be used for the prevention and treatment of liver injury.

  5. Endogenous nerve growth factor regulates collagen expression and bladder hypertrophy through Akt and MAPK pathways during cystitis.

    Science.gov (United States)

    Chung, Chul-Won; Zhang, Qing L; Qiao, Li-Ya

    2010-02-05

    Type I collagen forms the main constituent of the extracellular matrix in visceral organs. We reported here that cyclophosphamide (CYP)-induced cystitis significantly increased the production of type I collagen in the inflamed bladder leading to increases in the bladder weight and the thickness of the bladder wall. The endogenous nerve growth factor (NGF) in the urinary bladder regulated type I collagen expression because the neutralizing NGF antibody attenuated cystitis-induced type I collagen up-regulation in the inflamed bladder. Neutralizing NGF antibody also subsequently reversed cystitis-induced increases in bladder weight. Further studies on the intermediate signaling pathways mediating NGF-induced type I collagen expression in the inflamed bladder during cystitis revealed that Akt, JNK, and ERK1/2 activities were increased in the inflamed bladder, whereas p38 MAPK remained unchanged. Suppression of endogenous NGF level with neutralizing NGF antibody significantly blocked the increased activity of Akt, JNK, and ERK1/2 in the inflamed bladder during cystitis. These results indicate that endogenous NGF plays an important role in the activation of Akt and MAPK in the urinary bladder and in bladder hypertrophy during cystitis.

  6. Tumor glucose metabolism imaged in vivo in small animals with whole-body photoacoustic computed tomography

    Science.gov (United States)

    Chatni, Muhammad Rameez; Xia, Jun; Sohn, Rebecca; Maslov, Konstantin; Guo, Zijian; Zhang, Yu; Wang, Kun; Xia, Younan; Anastasio, Mark; Arbeit, Jeffrey; Wang, Lihong V.

    2012-07-01

    With the increasing use of small animals for human disease studies, small-animal whole-body molecular imaging plays an important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose molecular information, leading to higher costs of building dual-modality systems. Even with image co-registration, the spatial resolution of the molecular imaging modality is not improved. Utilizing a ring-shaped confocal photoacoustic computed tomography system, we demonstrate, for the first time, that both anatomy and glucose uptake can be imaged in a single modality. Anatomy was imaged with the endogenous hemoglobin contrast, and glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose.

  7. Glucose-Dependent Insulinotropic Polypeptide (GIP) Inhibits Bone Resorption Independently of Insulin and Glycemia

    DEFF Research Database (Denmark)

    Christensen, Mikkel B; Lund, Asger; Calanna, Salvatore

    2018-01-01

    Context: The gut hormone glucose-dependent insulinotropic polypeptide (GIP) causes postprandial insulin release and inhibits bone resorption assessed by carboxy-terminal collagen crosslinks (CTX). Objective: To study if GIP affects bone homeostasis biomarkers independently of insulin release...... and glycemic level. Design: Randomized, double-blinded, crossover study with 5 study days. Patients: Ten male C-peptide-negative patients with type 1 diabetes. Interventions: On 3 matched days with "low glycemia" (plasma glucose in the interval 3 to 7 mmol/L for 120 minutes), we administered intravenous (IV...... of endogenous insulin secretion and during both elevated and low plasma glucose, but have no effect on P1NP or PTH after 90 minutes....

  8. Level of dietary protein intake affects glucose turnover in endurance-trained men

    Directory of Open Access Journals (Sweden)

    Pasiakos Stefan M

    2011-11-01

    Full Text Available Abstract Background To examine the effects of higher-protein diets on endogenous glucose metabolism in healthy, physically active adults, glucose turnover was assessed in five endurance-trained men (age 21.3 ± 0.3 y, VO2peak 70.6 ± 0.1 mL kg-1 min-1 who consumed dietary protein intakes spanning the current dietary reference intakes. Findings Using a randomized, crossover design, volunteers consumed 4 week eucaloric diets providing either a low (0.8 g kg-1 d-1; LP, moderate (1.8 g kg-1 d-1; MP, or high (3.6 g kg-1 d-1; HP level of dietary protein. Glucose turnover (Ra, glucose rate of appearance; and Rd glucose rate of disappearance was assessed under fasted, resting conditions using primed, constant infusions of [6,6-2H2] glucose. Glucose Ra and Rd (mg kg-1 min-1 were higher for MP (2.8 ± 0.1 and 2.7 ± 0.1 compared to HP (2.4 ± 0.1 and 2.3 ± 0.2, P P P > 0.05 between LP (4.6 ± 0.1, MP (4.8 ± 0.1, and HP (4.7 ± 0.1 diets. Conclusions Level of protein consumption influenced resting glucose turnover in endurance athletes in a state of energy balance with a higher rate of turnover noted for a protein intake of 1.8 g kg-1 d-1. Findings suggest that consumption of protein in excess of the recommended dietary allowance but within the current acceptable macronutrient distribution range may contribute to the regulation of blood glucose when carbohydrate intake is reduced by serving as a gluconeogenic substrate in endurance-trained men.

  9. 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....... Furthermore, the body has also glucose sensors in the intestine, the brain, the portal vein, and to some extent the liver, and they sense very different glucose concentrations. All sensors are incorporated in a dynamic network that is interconnected by both hormones and the nervous system. Regarding glucose...... 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...

  10. Lymphomas that recur after MYC suppression continue to exhibit oncogene addiction.

    Science.gov (United States)

    Choi, Peter S; van Riggelen, Jan; Gentles, Andrew J; Bachireddy, Pavan; Rakhra, Kavya; Adam, Stacey J; Plevritis, Sylvia K; Felsher, Dean W

    2011-10-18

    The suppression of oncogenic levels of MYC is sufficient to induce sustained tumor regression associated with proliferative arrest, differentiation, cellular senescence, and/or apoptosis, a phenomenon known as oncogene addiction. However, after prolonged inactivation of MYC in a conditional transgenic mouse model of Eμ-tTA/tetO-MYC T-cell acute lymphoblastic leukemia, some of the tumors recur, recapitulating what is frequently observed in human tumors in response to targeted therapies. Here we report that these recurring lymphomas express either transgenic or endogenous Myc, albeit in many cases at levels below those in the original tumor, suggesting that tumors continue to be addicted to MYC. Many of the recurring lymphomas (76%) harbored mutations in the tetracycline transactivator, resulting in expression of the MYC transgene even in the presence of doxycycline. Some of the remaining recurring tumors expressed high levels of endogenous Myc, which was associated with a genomic rearrangement of the endogenous Myc locus or activation of Notch1. By gene expression profiling, we confirmed that the primary and recurring tumors have highly similar transcriptomes. Importantly, shRNA-mediated suppression of the high levels of MYC in recurring tumors elicited both suppression of proliferation and increased apoptosis, confirming that these tumors remain oncogene addicted. These results suggest that tumors induced by MYC remain addicted to overexpression of this oncogene.

  11. Changes in glucose-induced plasma active glucagon-like peptide-1 levels by co-administration of sodium–glucose cotransporter inhibitors with dipeptidyl peptidase-4 inhibitors in rodents

    Directory of Open Access Journals (Sweden)

    Takahiro Oguma

    2016-12-01

    Full Text Available We investigated whether structurally different sodium–glucose cotransporter (SGLT 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4 inhibitors, could enhance glucagon-like peptide-1 (GLP-1 secretion during oral glucose tolerance tests (OGTTs in rodents. Three different SGLT inhibitors—1-(β-d-Glucopyranosyl-4-chloro-3-[5-(6-fluoro-2-pyridyl-2-thienylmethyl]benzene (GTB, TA-1887, and canagliflozin—were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1 elevation and suppressed glucose excursions in both normal and diabetic rodents. In DPP4-deficient rats, GTB enhanced glucose-induced aGLP-1 elevation without affecting the basal level, whereas metformin, previously reported to enhance GLP-1 secretion, increased both the basal level and glucose-induced elevation. Oral treatment with canagliflozin and TA-1887 also enhanced glucose-induced aGLP-1 elevation when co-administered with either teneligliptin or sitagliptin. These data suggest that structurally different SGLT2 inhibitors enhance plasma aGLP-1 elevation and suppress glucose excursions during OGTT when co-administered with DPP4 inhibitors, regardless of the difference in chemical structure. Combination treatment with DPP4 inhibitors and SGLT2 inhibitors having moderate SGLT1 inhibitory activity may be a promising therapeutic option for improving glycemic control in patients with type 2 diabetes mellitus.

  12. Modulation of glucose postprandiale phase

    OpenAIRE

    Nazare, Julie-Anne

    2009-01-01

    The reduction of the postprandial glycemic excursions has been proposed as to limit risk of type 2 diabetes. There has been growing interest in the development of dietary ingredients that could potentially modulate carbohydrates bioavailability and thus their impact on postprandial glycemia. The aim of this thesis was to investigate the effects of the the modulation of glucose bioavailability by different ingredients on 2-hour glycemic response but also on glucose kinetics (total, exogenous a...

  13. Muscle-specific loss of Bmal1 leads to disrupted tissue glucose metabolism and systemic glucose homeostasis.

    Science.gov (United States)

    Harfmann, Brianna D; Schroder, Elizabeth A; Kachman, Maureen T; Hodge, Brian A; Zhang, Xiping; Esser, Karyn A

    2016-01-01

    Diabetes is the seventh leading cause of death in the USA, and disruption of circadian rhythms is gaining recognition as a contributing factor to disease prevalence. This disease is characterized by hyperglycemia and glucose intolerance and symptoms caused by failure to produce and/or respond to insulin. The skeletal muscle is a key insulin-sensitive metabolic tissue, taking up ~80 % of postprandial glucose. To address the role of the skeletal muscle molecular clock to insulin sensitivity and glucose tolerance, we generated an inducible skeletal muscle-specific Bmal1 (-/-) mouse (iMSBmal1 (-/-)). Progressive changes in body composition (decreases in percent fat) were seen in the iMSBmal1 (-/-) mice from 3 to 12 weeks post-treatment as well as glucose intolerance and non-fasting hyperglycemia. Ex vivo analysis of glucose uptake revealed that the extensor digitorum longus (EDL) muscles did not respond to either insulin or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) stimulation. RT-PCR and Western blot analyses demonstrated a significant decrease in mRNA expression and protein content of the muscle glucose transporter (Glut4). We also found that both mRNA expression and activity of two key rate-limiting enzymes of glycolysis, hexokinase 2 (Hk2) and phosphofructokinase 1 (Pfk1), were significantly reduced in the iMSBmal1 (-/-) muscle. Lastly, results from metabolomics analyses provided evidence of decreased glycolytic flux and uncovered decreases in some tricarboxylic acid (TCA) intermediates with increases in amino acid levels in the iMSBmal1 (-/-) muscle. These findings suggest that the muscle is relying predominantly on fat as a fuel with increased protein breakdown to support the TCA cycle. These data support a fundamental role for Bmal1, the endogenous circadian clock, in glucose metabolism in the skeletal muscle. Our findings have implicated altered molecular clock dictating significant changes in altered substrate metabolism in the absence of feeding

  14. Endogenous infection and hospital's civil liability - a case study.

    Science.gov (United States)

    Wąsik, D; Wąsik, N; Sygit, B; Dubiel, M

    2014-01-01

    The subject matter of this publication is the legal assessment of endogenous infection - the specific type of hospital infections. The main aim of the publication is to answer the question of whether medical and legal grounds exist for civil liability for endogenous infections and for treating those infections as cases of medical malpractice or medical events. The research method adopted is a case study. The authors have analysed a civil lawsuit for compensation instituted by an infected patient against a Polish hospital, adjudicated in 2013. The main conclusion of the publication is to postulate distinguishing medical malpractice from complications resulting from the reactions of the human body to treatment. The authors argue that endogenous infections should be treated as the latter-mentioned of these two cases.

  15. Public procurement of innovation; endogenous institutions in user producer interaction

    DEFF Research Database (Denmark)

    Hjaltadóttir, Rannveig Edda

    2013-01-01

    This article sets out to explore endogenous institutions as the rules that govern the interaction between users and producers in public procurement of innovation in a regional context. It further aims to study how this interaction influences the results of the procurement process by investigating...... possible institutional barriers and what can be done to fence against them. The article addresses the question: How do endogenous institutions in the context of user-producer interaction affect performance in public procurement of innovation? Innovation is an interactive learning process...... and the participants in this interaction need a common code of communication to efficiently work together. The institutions that govern user-producer interaction have therefore been seen as a possible explanation for success or failure in public procurement of innovation. Endogenous institutions were found...

  16. Exercise effects on postprandial glucose metabolism in type 1 diabetes: a triple-tracer approach.

    Science.gov (United States)

    Mallad, Ashwini; Hinshaw, Ling; Schiavon, Michele; Dalla Man, Chiara; Dadlani, Vikash; Basu, Rita; Lingineni, Ravi; Cobelli, Claudio; Johnson, Matthew L; Carter, Rickey; Kudva, Yogish C; Basu, Ananda

    2015-06-15

    To determine the effects of exercise on postprandial glucose metabolism and insulin action in type 1 diabetes (T1D), we applied the triple tracer technique to study 16 T1D subjects on insulin pump therapy before, during, and after 75 min of moderate-intensity exercise (50% V̇o2max) that started 120 min after a mixed meal containing 75 g of labeled glucose. Prandial insulin bolus was administered as per each subject's customary insulin/carbohydrate ratio adjusted for meal time meter glucose and the level of physical activity. Basal insulin infusion rates were not altered. There were no episodes of hypoglycemia during the study. Plasma dopamine and norepinephrine concentrations rose during exercise. During exercise, rates of endogenous glucose production rose rapidly to baseline levels despite high circulating insulin and glucose concentrations. Interestingly, plasma insulin concentrations increased during exercise despite no changes in insulin pump infusion rates, implying increased mobilization of insulin from subcutaneous depots. Glucagon concentrations rose before and during exercise. Therapeutic approaches for T1D management during exercise will need to account for its effects on glucose turnover, insulin mobilization, glucagon, and sympathetic response and possibly other blood-borne feedback and afferent reflex mechanisms to improve both hypoglycemia and hyperglycemia. Copyright © 2015 the American Physiological Society.

  17. Assessing the bioequivalence of analogues of endogenous substances (‘endogenous drugs’): considerations to optimize study design

    Science.gov (United States)

    Dissanayake, Sanjeeva

    2010-01-01

    BACKGROUND Assessment of the bioequivalence of generic versions of certain reference drugs is complicated by the presence of endogenous levels of said compounds which cannot be distinguished from externally derived compound levels following drug administration. If unaccounted for, the presence of endogenous compound biases towards equivalence in bioequivalence studies of these drugs. Bioequivalence assessments may be complicated further as disposition of the exogenous analogue can be subject to various endogenous processes resulting in nonlinear pharmacokinetics. To overcome these inherent biases a number of different strategies have been employed. AIMS To critically review methods used to overcome confounding biases in bioequivalence studies of ‘endogenous’ drugs. METHODS A literature search of the EMBASE and PubMed databases was performed. RESULTS The following strategies were identified: ablation/modulation of baseline endogenous substance levels; recruitment of ‘substance-deficient’ populations; restriction of dietary intake of the relevant substance; standardization of conditions with the potential to affect relevant homeostatic mechanisms; correction for baseline substance levels; and administration of supra-therapeutic drug doses. CONCLUSIONS On the basis of this review key study design concepts, intended to optimize the design of future bioequivalence studies of these so-called ‘endogenous drugs’, are described. The dual stable isotope method, which could be used in a specific context, is also discussed. PMID:20233194

  18. An Alternative to Thought Suppression?

    Science.gov (United States)

    Boice, Robert

    2012-01-01

    Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

  19. Insulin resistance of protein anabolism accompanies that of glucose metabolism in lean, glucose-tolerant offspring of persons with type 2 diabetes.

    Science.gov (United States)

    Burgos, Sergio A; Chandurkar, Vikram; Tsoukas, Michael A; Chevalier, Stéphanie; Morais, José A; Lamarche, Marie; Marliss, Errol B

    2016-01-01

    To test whether protein anabolic resistance is an early defect in type 2 diabetes (T2D). Seven lean, normoglycemic T2D offspring (T2D-O) and eight matched participants without family history (controls; C) underwent a 3-hour hyperinsulinemic (40 mU/m2/min), euglycemic (5.5 mmol/L) and isoaminoacidemic clamp. Whole-body glucose and protein kinetics were measured with d-[3-3H]glucose and l-[l-13C]leucine, respectively. Plasma amino acids were measured by liquid chromatography-tandem mass spectrometry. Fasting glycemia and glucose kinetic variables did not differ between groups. Clamp decreases in glucose rate of appearance were not different, but rate of disappearance increased 29% less in T2D-O, to a significantly lower rate. Fasting leucine was higher in T2D-O, but kinetics did not differ. Clamp increases in leucine oxidation and decreases in endogenous rate of appearance (protein breakdown) were equal, but in T2D-O, non-oxidative rate of disappearance (protein synthesis) did not increase and net balance (synthesis-breakdown) did not become positive as in C. Resistance of whole-body protein anabolism (synthesis and net balance) accompanies resistance of glucose uptake in T2D-O. Mechanisms responsible, possible roles in the increased risk of developing diabetes, and its potential impact on long-term protein balance require definition.

  20. Remodeling of oxidative energy metabolism by galactose improves glucose handling and metabolic switching in human skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Eili Tranheim Kase

    Full Text Available Cultured human myotubes have a low mitochondrial oxidative potential. This study aims to remodel energy metabolism in myotubes by replacing glucose with galactose during growth and differentiation to ultimately examine the consequences for fatty acid and glucose metabolism. Exposure to galactose showed an increased [(14C]oleic acid oxidation, whereas cellular uptake of oleic acid uptake was unchanged. On the other hand, both cellular uptake and oxidation of [(14C]glucose increased in myotubes exposed to galactose. In the presence of the mitochondrial uncoupler carbonylcyanide p-trifluormethoxy-phenylhydrazone (FCCP the reserve capacity for glucose oxidation was increased in cells grown with galactose. Staining and live imaging of the cells showed that myotubes exposed to galactose had a significant increase in mitochondrial and neutral lipid content. Suppressibility of fatty acid oxidation by acute addition of glucose was increased compared to cells grown in presence of glucose. In summary, we show that cells grown in galactose were more oxidative, had increased oxidative capacity and higher mitochondrial content, and showed an increased glucose handling. Interestingly, cells exposed to galactose showed an increased suppressibility of fatty acid metabolism. Thus, galactose improved glucose metabolism and metabolic switching of myotubes, representing a cell model that may be valuable for metabolic studies related to insulin resistance and disorders involving mitochondrial impairments.