Evidence connecting old, new and neglected glucose-lowering drugs to bile acid-induced GLP-1 secretion

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Kårhus, Martin L; Brønden, Andreas; Sonne, David P

2017-01-01

Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have...... current evidence connecting established glucose-lowering drugs to bile acid-induced GLP-1 secretion and discusses whether bile acid-induced GLP-1 secretion may constitute a new basis for understanding how metformin, inhibitors of the apical sodium-dependent bile acids transporter, and bile acid...... sequestrants - old, new and neglected glucose-lowering drugs - improve glucose metabolism....

Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents

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Perry, Rachel J; Cardone, Rebecca L; Petersen, Max C

2016-01-01

Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A1c (1-3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase...

[Role of classical oral glucose-lowering medications in current treatment].

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Carramiñana Barrera, F C

2014-07-01

Classical oral glucose were discovered in the mid twentieth century. Despite the time elapsed since then and the lack of large studies to support the use of some of these drugs, they continue to be employed, are indicated in all clinical practice guidelines and consensus documents and, overall, remain among the most widely prescribed drugs in the national health system. The main arguments for their continued use are their widespread and prolonged prescription, their effectiveness, and cost. Their main disadvantages have always been and continue to be their adverse gastrointestinal effects, weight gain, the risk of hypoglycemia and other adverse effects, which have encouraged the development of new glucose-lowering drugs with an improved pharmacological profile that would cover the various mechanisms of hyperglycemia. Currently, deep knowledge of glucose-lowering drugs is required in the patient-centered management of diabetes. Furthermore, this knowledge should be adapted to each individual patient to acquire the experience necessary to achieve effective metabolic control, delay the development of chronic complications, and improve the quality of life and life expectancy of patients with diabetes. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.

Avoiding hypoglycemia: a key to success for glucose-lowering therapy in type 2 diabetes

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Ahrén B

2013-04-01

Full Text Available Bo Ahrén Department of Clinical Sciences, Lund, Faculty of Medicine, Lund University, Lund, Sweden Abstract: Type 2 diabetes carries a risk for hypoglycemia, particularly in patients on an intensive glucose control plan as a glucose-lowering strategy, where hypoglycemia may be a limitation for the therapy and also a factor underlying clinical inertia. Glucose-lowering medications that increase circulating insulin in a glucose-independent manner, such as insulin and sulfonylurea therapy, are the most common cause of hypoglycemia. However, other factors such as a delayed or missed meal, physical exercise, or drug or alcohol consumption may also contribute. Specific risk factors for development of hypoglycemia are old age, long duration of diabetes, some concomitant medication, renal dysfunction, hypoglycemia unawareness, and cognitive dysfunction. Hypoglycemia is associated with acute short-term symptoms related to either counterregulation, such as tachycardia and sweating, or to neuroglycopenia, such as irritability, confusion, and in severe cases stupor, coma, and even death. However, there are also long-term consequences of hypoglycemia such as reduced working capacity, weight gain, loss of self-confidence with reduced quality of life, and increased risk for cardiovascular diseases. For both the patients, the health care system, and the society at large, hypoglycemia carries a high cost. Strategies to mitigate the risk of hypoglycemia include awareness of the condition; education of patients, relatives, and health-care providers; and selecting appropriate glucose-lowering medication that also judges the risk for hypoglycemia to prevent this complication. This article summarizes the current knowledge of hypoglycemia and its consequences with a special emphasis on its consequences for the choice of glucose-lowering therapy. Keywords: type 2 diabetes, hypoglycemia, treatment, sulfonylurea, incretin therapy, insulin

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

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

2015-01-01

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

Fructose replacement of glucose or sucrose in food or beverages lowers postprandial glucose and insulin without raising triglycerides: a systematic review and meta-analysis.

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Evans, Rebecca A; Frese, Michael; Romero, Julio; Cunningham, Judy H; Mills, Kerry E

2017-08-01

Background: Conflicting evidence exists on the effects of fructose consumption in people with type 1 and type 2 diabetes mellitus. No systematic review has addressed the effect of isoenergetic fructose replacement of glucose or sucrose on peak postprandial glucose, insulin, and triglyceride concentrations. Objective: The objective of this study was to review the evidence for postprandial glycemic and insulinemic responses after isoenergetic replacement of either glucose or sucrose in foods or beverages with fructose. Design: We searched the Cochrane Library, MEDLINE, EMBASE, the WHO International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov The date of the last search was 26 April 2016. We included randomized controlled trials measuring peak postprandial glycemia after isoenergetic replacement of glucose, sucrose, or both with fructose in healthy adults or children with or without diabetes. The main outcomes analyzed were peak postprandial blood glucose, insulin, and triglyceride concentrations. Results: Replacement of either glucose or sucrose by fructose resulted in significantly lowered peak postprandial blood glucose, particularly in people with prediabetes and type 1 and type 2 diabetes. Similar results were obtained for insulin. Peak postprandial blood triglyceride concentrations did not significantly increase. Conclusions: Strong evidence exists that substituting fructose for glucose or sucrose in food or beverages lowers peak postprandial blood glucose and insulin concentrations. Isoenergetic replacement does not result in a substantial increase in blood triglyceride concentrations. © 2017 American Society for Nutrition.

The effect of lowering the threshold for diagnosis of impaired fasting glucose.

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Kim, So Hun; Shim, Wan Sub; Kim, Eun A; Kim, Eun Joo; Lee, Seung Hee; Hong, Seong Bin; Kim, Yong Seong; Park, Shin Goo; Leem, Jong Han; Lim, Jong Whan; Lee, Hun-Jae; Nam, Moonsuk

2008-04-30

The aim of this study was to evaluate the effect of lowering the fasting plasma glucose (FPG) criteria for impaired fasting glucose (IFG) on the prevalence of IFG and the risk for the development of diabetes associated with IFG in Koreans. A total of 7,211 subjects who had normal glucose tolerance (NGT) or IFG were recruited. Subjects were evaluated at baseline and after two years follow up. Clinical data including total cholesterol, FPG and blood pressure were examined. Lowering the criteria for IFG from 6.1 mmol/L (110 mg/dL) to 5.6 mmol/L (100 mg/dL) increased the prevalence of IFG from 6.6% (494 subjects) to 24.4% (1829 subjects). After the 2 years follow up period, 91 subjects (1.3%) developed diabetes. Twenty one (0.3%) subjects developed diabetes among 5,382 NGT subjects and 70 (3.8%) subjects developed diabetes among 1,829 IFG (5.6-7.0 mmol/L) subjects. Lowering the IFG threshold from 6.1 mmol/L to 5.6 mmol/L resulted in a 18.4% decrease in specificity and 23.9% increase in sensitivity for predicting diabetes. The baseline FPG for predicting the development of diabetes after 2 years at a point on the receiver operating characteristic curve that was closest to the ideal 100% sensitivity and 100% specificity was 5.7 mmol/L (103 mg/dL). Lowering the FPG criterion of IFG should have benefits in predicting new onset type 2 diabetes mellitus in Koreans. The economic and health benefits of applying the new IFG criteria should be evaluated in future studies.

Recent and emerging therapeutic medications in type 2 diabetes mellitus: incretin-based, Pramlintide, Colesevelam, SGLT2 Inhibitors, Tagatose, Succinobucol.

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Lo, Margaret C; Lansang, M Cecilia

2013-01-01

colesevelam, which is approved by the United States Food and Drug Administration for both type-2 diabetes and hyperlipidemia. It will further review the clinical data on the novel emerging agents of sodium-glucose cotransporter-2 inhibitors, tagatose, and succinobucol, all currently in phase III clinical trials. This review article can serve as an aid for clinicians to identify clinical indications in which these new agents can be applied in the treatment algorithm.

Glucose-lowering effect of whey protein depends upon clinical characteristics of patients with type 2 diabetes.

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Almario, Rogelio U; Buchan, Wendy M; Rocke, David M; Karakas, Sidika E

2017-01-01

Whey protein (WP) intake has been shown to reduce postprandial glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute challenge or weight loss studies. It is not known if WP supplementation can provide sustained glucose lowering. Our goal was to investigate the effects of WP on glycemia comprehensively by using continuous glucose monitoring (CGM) while avoiding the confounding effects of variable food intake through controlled feeding. This double-blinded and placebo (PL)-controlled study included 22 patients with T2DM patients (11 male, 11 female; age 57.1±12.6 years) on diet or metformin monotherapy. First, one serving (21 g) of WP was compared with PL in parallel-armed acute challenge studies. Next, in a crossover design, each patient underwent CGM twice, over 2 consecutive weeks, 3.5 days each week. Identical diets were provided by the study during both CGM periods. During the first CGM, one serving of either WP or PL was consumed before breakfast and another before dinner. During the second CGM, participants switched to the alternate supplement. Order of the supplements was randomized. During acute challenge studies, WP stimulated insulin and glucagon-like peptide (GLP)-1 secretion; suppressed ghrelin (all pObesity, hypertriglyceridemia and high fasting GLP-1 concentrations predicted increased glucose levels. Effects of WP supplementation on glycemia in T2DM depend on the baseline characteristics. Lower body weight, normal triglyceride and lower GLP-1 levels predict glucose lowering. In contrast, obesity, hypertriglyceridemia and high baseline GLP-1 predict increased glucose response.

The acute glucose lowering effect of specific GPR120 activation in mice is mainly driven by glucagon-like peptide 1.

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Linda Sundström

Full Text Available The mechanism behind the glucose lowering effect occurring after specific activation of GPR120 is not completely understood. In this study, a potent and selective GPR120 agonist was developed and its pharmacological properties were compared with the previously described GPR120 agonist Metabolex-36. Effects of both compounds on signaling pathways and GLP-1 secretion were investigated in vitro. The acute glucose lowering effect was studied in lean wild-type and GPR120 null mice following oral or intravenous glucose tolerance tests. In vitro, in GPR120 overexpressing cells, both agonists signaled through Gαq, Gαs and the β-arrestin pathway. However, in mouse islets the signaling pathway was different since the agonists reduced cAMP production. The GPR120 agonists stimulated GLP-1 secretion both in vitro in STC-1 cells and in vivo following oral administration. In vivo GPR120 activation induced significant glucose lowering and increased insulin secretion after intravenous glucose administration in lean mice, while the agonists had no effect in GPR120 null mice. Exendin 9-39, a GLP-1 receptor antagonist, abolished the GPR120 induced effects on glucose and insulin following an intravenous glucose challenge. In conclusion, GLP-1 secretion is an important mechanism behind the acute glucose lowering effect following specific GPR120 activation.

Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes.

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Heise, T; Nosek, L; Bøttcher, S G; Hastrup, H; Haahr, H

2012-10-01

Insulin degludec (IDeg) is a new-generation, ultra-long-acting basal insulin that forms soluble multihexamers upon subcutaneous injection, resulting in a depot from which IDeg is absorbed slowly and continuously into circulation. This double-blind, two-period, incomplete block cross-over trial investigated the pharmacodynamic and pharmacokinetic properties of IDeg at steady state (SS) in people with type 2 diabetes. Forty-nine subjects treated with insulin without concomitant oral anti-diabetic drugs were given IDeg (0.4, 0.6 and/or 0.8 U/kg) once daily for two 6-day periods, separated by an interval of 13-21 days. Following dosing on Day 6, subjects underwent a 26-h euglycaemic glucose clamp (Biostator®; clamp blood glucose level: 90 mg/dl; 5.0 mmol/l). Pharmacokinetic samples were taken until 120 h after last dosing. For all dose levels, the mean glucose infusion rate (GIR) profiles were flat and stable. The glucose-lowering effect of IDeg was evenly distributed over the dosing interval τ, with area under the curve (AUC) for each of the four 6-h intervals being approximately 25% of the total AUC (AUC(GIR) (,τ,) (SS) ). Total glucose-lowering effect increased linearly with increasing dose. The blood glucose levels of all subjects stayed very close to the clamp target until end of clamp. The terminal half-life of IDeg was approximately 25 h at steady state. IDeg was well tolerated and no safety concerns were identified. No injection site reactions were reported. IDeg has a flat and consistent glucose-lowering effect in people with type 2 diabetes. © 2012 Blackwell Publishing Ltd.

Favorable glucose tolerance and lower prevalence of metabolic syndrome in offspring without diabetes mellitus of nonagenarian siblings: the Leiden longevity study.

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Rozing, Maarten P; Westendorp, Rudi G J; de Craen, Anton J M; Frölich, Marijke; de Goeij, Moniek C M; Heijmans, Bastiaan T; Beekman, Marian; Wijsman, Carolien A; Mooijaart, Simon P; Blauw, Gerard-Jan; Slagboom, P Eline; van Heemst, Diana

2010-03-01

To explore measures of metabolic syndrome and glucose metabolism in families with exceptional longevity. Case-control study. A university hospital in Leiden, the Netherlands. One hundred twenty-one offspring of nonagenarian siblings, who were enriched for familial factors promoting longevity, and 113 of their partners. No subject had diabetes mellitus. Prevalence of metabolic syndrome was determined according to the criteria of the Third Report of the National Cholesterol Education Program. Glucose tolerance was assessed according to a 2-hour oral glucose tolerance test. The offspring of nonagenarians siblings had a lower prevalence of metabolic syndrome (P=.03), similar body composition, lower mean fasting blood glucose levels (4.99 vs 5.16 mmol/L; P=.01), lower mean fasting insulin levels (5.81 vs 6.75 mU/L; P=.04), a higher mean homeostasis model assessment of insulin sensitivity (0.78 vs 0.65; P=.02), and a more-favorable glucose tolerance (mean area under the receiver operating characteristic curve for glucose (13.2 vs 14.3; P=.007) than their partners. No significant differences were observed between the offspring and their partners in beta-cell function (insulogenic index 13.6 vs 12.5; P=.38). Despite similar body composition, the offspring of nonagenarian siblings showed a lower prevalence of metabolic syndrome and better glucose tolerance than their partners, centralizing the role of favorable glucose metabolism in familial longevity.

Changing Patterns of Glucose-Lowering Medication Use in VA Nursing Home Residents With Diabetes, 2005 to 2011.

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Lee, Sei J; Stijacic-Cenzer, Irena; Barnhart, Caroline; McClymont, Keelan; Steinman, Michael A

2015-10-01

Although nursing home (NH) residents make up a large and growing proportion of Americans with diabetes mellitus, little is known about how glucose-lowering medications are used in this population. We sought to examine glucose-lowering medication use in Veterans Affairs (VA) NH residents with diabetes between 2005 and 2011. Retrospective cohort study, using linked laboratory, pharmacy, administrative, and NH Minimum Dataset (MDS) 2.0 databases in 123 VA NHs. A total of 9431 long-stay (>90 days) VA NH residents older than 65 followed for 52,313 person-quarters. We identified receipt of glucose-lowering medications, including insulin, metformin, sulfonylureas, thiazolidinediones, and others (alpha-glucosidase inhibitors, meglitinides, glucagonlike peptide-1 analogs, dipeptidyl peptidase-4 inhibitors and amylin analogs) per quarter. The rates of sulfonylurea use in long-stay NH residents dropped dramatically from 24% in 2005 to 12% in 2011 (P use (10% to 2%, P use in 2007 (4% to Metformin use was stable, ranging between 7% and 9% (P = .24). Insulin use increased slightly from 30% to 32% (P Use of other classes of glucose-lowering medications was stable (P = .22) and low, remaining below 1.3%. Between 2005 and 2011, there were dramatic declines in use of sulfonylureas and thiazolidinediones in VA NH residents, suggesting that prescribing practices can be quickly changed in this setting. Published by Elsevier Inc.

Morning cortisol is lower in obese individuals with normal glucose tolerance

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Praveen EP

2011-09-01

Full Text Available Edavan P Praveen1, Jaya Prakash Sahoo1, Bindu Kulshreshtha2, Madan L Khurana3, Nandita Gupta1, Sada Nand Dwivedi3, Guresh Kumar3, Ariachery C Ammini11Department of Endocrinology, All India Institute of Medical Sciences, 2Ram Manohar Lohia Hospital, 3Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, IndiaBackground: There is no consensus on the role of cortisol in the pathogenesis of obesity and metabolic syndrome (MS. This cross-sectional study aimed to analyze the relationship of morning plasma cortisol and adrenocorticotropic hormone (ACTH levels with body mass index (BMI and glucose tolerance.Subjects and methods: The sample frame was the “Offspring of individuals with diabetes study” database. A total of 358 offspring of individuals with type 2 diabetes mellitus (T2DM and 287 individuals without a known family history of T2DM were recruited for the study. Subjects who were ≥10 years of age were selected from the database for analysis. Subjects with T2DM were excluded. All participants underwent a 75 g oral glucose tolerance test (OGTT, and blood samples were collected at 0, 30, 60, and 120 minutes for glucose, insulin and C-peptide. Plasma cortisol, ACTH, and lipid profile were estimated from the fasting sample.Results: Four hundred and ninety-five participants (305 males [62%] and 190 females [38%] were included in the analysis. ACTH and cortisol levels were higher in normal-weight subjects than in overweight/obese subjects. Both ACTH and cortisol increased as fasting plasma glucose increased. Cortisol levels were significantly lower in offspring of T2DM subjects with MS than in offspring of T2DM subjects without MS. When adjusted for BMI, the significance was marginal. In males, cortisol levels were negatively correlated with early insulin secretion during OGTT (insulinogenic index [0–30] and positively with waist circumference and serum high-density lipoprotein cholesterol. In females, fasting

Drug-drug interactions with sodium-glucose cotransporters type 2 (SGLT2) inhibitors, new oral glucose-lowering agents for the management of type 2 diabetes mellitus.

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Scheen, André J

2014-04-01

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment.

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

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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

Social Inclusion Predicts Lower Blood Glucose and Low-Density Lipoproteins in Healthy Adults.

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Floyd, Kory; Veksler, Alice E; McEwan, Bree; Hesse, Colin; Boren, Justin P; Dinsmore, Dana R; Pavlich, Corey A

2017-08-01

Loneliness has been shown to have direct effects on one's personal well-being. Specifically, a greater feeling of loneliness is associated with negative mental health outcomes, negative health behaviors, and an increased likelihood of premature mortality. Using the neuroendocrine hypothesis, we expected social inclusion to predict decreases in both blood glucose levels and low-density lipoproteins (LDLs) and increases in high-density lipoproteins (HDLs). Fifty-two healthy adults provided self-report data for social inclusion and blood samples for hematological tests. Results indicated that higher social inclusion predicted lower levels of blood glucose and LDL, but had no effect on HDL. Implications for theory and practice are discussed.

Investigation of the Blood Glucose Lowering Potential of the Jamaican Momordica charantia (Cerasee) Fruit in Sprague-Dawley Rats

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Burnett, A; McKoy, M-L; Singh, P

2015-01-01

ABSTRACT The Momordica charantia (MC) fruit has been documented to possess antidiabetic properties. However, these studies were not without controversy surrounding the blood glucose-lowering ability and the mechanism of action in diabetes therapy. In an effort to evaluate such claims in the Jamaican MC species known as cerasee, aqueous extracts of the unripe fruit were studied in normal and diabetic rats. Normal male Sprague-Dawley rats were divided into groups (n = 6) orally administered distilled water, 10% dimethyl sulfoxide (DMSO) solution, the aqueous extract (400 mg/kg body weight) and glibenclamide (15 mg/kg body weight), respectively prior to assessment of fasting blood glucose (FBG) concentration. The oral glucose tolerance test (OGTT) was conducted in normoglycaemic rats orally administered distilled water, 10% DMSO solution, glibenclamide (15 mg/kg body weight) or aqueous extracts of the fruit (200 and 400 mg/kg body weight). Blood glucose concentration was also monitored in streptozotocin-induced diabetic rats administered the aqueous extract (250 mg/kg body weight) or water vehicle after an overnight fast. The aqueous extracts showed no hypoglycaemic or antidiabetic activity. However, the administration of the aqueous extracts (200 and 400 mg/kg body weight) resulted in significant improvement in glucose tolerance of glucose-primed normoglycaemic rats during the OGTT. These data suggest that the glucose-lowering mechanism of the Jamaican MC fruit species likely involves altered glucose absorption across the gastrointestinal tract. PMID:26624580

Glycated albumin is set lower in relation to plasma glucose levels in patients with Cushing's syndrome.

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Kitamura, Tetsuhiro; Otsuki, Michio; Tamada, Daisuke; Tabuchi, Yukiko; Mukai, Kosuke; Morita, Shinya; Kasayama, Soji; Shimomura, Iichiro; Koga, Masafumi

2013-09-23

Glycated albumin (GA) is an indicator of glycemic control, which has some specific characters in comparison with HbA1c. Since glucocorticoids (GC) promote protein catabolism including serum albumin, GC excess state would influence GA levels. We therefore investigated GA levels in patients with Cushing's syndrome. We studied 16 patients with Cushing's syndrome (8 patients had diabetes mellitus and the remaining 8 patients were non-diabetic). Thirty-two patients with type 2 diabetes mellitus and 32 non-diabetic subjects matched for age, sex and BMI were used as controls. In the patients with Cushing's syndrome, GA was significantly correlated with HbA1c, but the regression line shifted downwards as compared with the controls. The GA/HbA1c ratio in the patients with Cushing's syndrome was also significantly lower than the controls. HbA1c in the non-diabetic patients with Cushing's syndrome was not different from the non-diabetic controls, whereas GA was significantly lower. In 7 patients with Cushing's syndrome who performed self-monitoring of blood glucose, the measured HbA1c was matched with HbA1c estimated from mean blood glucose, whereas the measured GA was significantly lower than the estimated GA. We clarified that GA is set lower in relation to plasma glucose levels in patients with Cushing's syndrome. Copyright © 2013 Elsevier B.V. All rights reserved.

Caffeic acid as active principle from the fruit of Xanthium strumarium to lower plasma glucose in diabetic rats.

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Hsu, F L; Chen, Y C; Cheng, J T

2000-04-01

The antihyperglycemic effect of caffeic acid, one of the phenolic compounds contained in the fruit of Xanthium strumarium, was investigated. After an intravenous injection of caffeic acid into diabetic rats of both streptozotocin-induced and insulin-resistant models, a dose-dependent decrease of plasma glucose was observed. However, a similar effect was not produced in normal rats. An insulin-independent action of caffeic acid can thus be considered. Otherwise, this compound reduced the elevation of plasma glucose level in insulin-resistant rats receiving a glucose challenge test. Also, glucose uptake into the isolated adipocytes was raised by caffeic acid in a concentration-dependent manner. Increase of glucose utilization by caffeic acid seems to be responsible for the lowering of plasma glucose.

Is there an effect of glucose lowering treatment on incidence and prognosis of tuberculosis?

DEFF Research Database (Denmark)

Jørgensen, Marit Eika; Faurholt-Jepsen, Daniel

2014-01-01

The association between diabetes and incidence of tuberculosis is well established, and observational studies have shown poor treatment outcome in tuberculosis related to hyperglycemia. The WHO recommends screening for diabetes among all patients with tuberculosis and optimized glycemic control...... aiming at improving tuberculosis outcome. However, no intervention studies support this notion. Patients with tuberculosis are often vulnerable with high degree of comorbidity, and, therefore, at high risk of adverse effects of intensive glucose control. Controlled intervention studies of the effect...... of glucose lowering treatment on tuberculosis outcomes are clearly warranted to justify screening for- and tight control of diabetes....

A higher-complex carbohydrate diet in gestational diabetes mellitus achieves glucose targets and lowers postprandial lipids: a randomized crossover study.

Science.gov (United States)

Hernandez, Teri L; Van Pelt, Rachael E; Anderson, Molly A; Daniels, Linda J; West, Nancy A; Donahoo, William T; Friedman, Jacob E; Barbour, Linda A

2014-01-01

The conventional diet approach to gestational diabetes mellitus (GDM) advocates carbohydrate restriction, resulting in higher fat (HF), also a substrate for fetal fat accretion and associated with maternal insulin resistance. Consequently, there is no consensus about the ideal GDM diet. We hypothesized that, compared with a conventional, lower-carbohydrate/HF diet (40% carbohydrate/45% fat/15% protein), consumption of a higher-complex carbohydrate (HCC)/lower-fat (LF) Choosing Healthy Options in Carbohydrate Energy (CHOICE) diet (60/25/15%) would result in 24-h glucose area under the curve (AUC) profiles within therapeutic targets and lower postprandial lipids. Using a randomized, crossover design, we provided 16 GDM women (BMI 34 ± 1 kg/m2) with two 3-day isocaloric diets at 31 ± 0.5 weeks (washout between diets) and performed continuous glucose monitoring. On day 4 of each diet, we determined postprandial (5 h) glucose, insulin, triglycerides (TGs), and free fatty acids (FFAs) following a controlled breakfast meal. There were no between-diet differences for fasting or mean nocturnal glucose, but 24-h AUC was slightly higher (∼6%) on the HCC/LF CHOICE diet (P = 0.02). The continuous glucose monitoring system (CGMS) revealed modestly higher 1- and 2-h postprandial glucose on CHOICE (1 h, 115 ± 2 vs. 107 ± 3 mg/dL, P ≤ 0.01; 2 h, 106 ± 3 vs. 97 ± 3 mg/dL, P = 0.001) but well below current targets. After breakfast, 5-h glucose and insulin AUCs were slightly higher (P diet. This highly controlled study randomizing isocaloric diets and using a CGMS is the first to show that liberalizing complex carbohydrates and reducing fat still achieved glycemia below current treatment targets and lower postprandial FFAs. This diet strategy may have important implications for preventing macrosomia.

Glucose-lowering effect of whey protein depends upon clinical characteristics of patients with type 2 diabetes

OpenAIRE

Almario, Rogelio U; Buchan, Wendy M; Rocke, David M; Karakas, Sidika E

2017-01-01

Objective Whey protein (WP) intake has been shown to reduce postprandial glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute challenge or weight loss studies. It is not known if WP supplementation can provide sustained glucose lowering. Our goal was to investigate the effects of WP on glycemia comprehensively by using continuous glucose monitoring (CGM) while avoiding the confounding effects of variable food intake through controlled feeding. Research design and methods...

Postprandial glucose-lowering effect of premeal consumption of protein-enriched, dietary fiber-fortified bar in individuals with type 2 diabetes mellitus or normal glucose tolerance.

Science.gov (United States)

Bae, Jae Hyun; Kim, Lee Kyung; Min, Se Hee; Ahn, Chang Ho; Cho, Young Min

2018-03-04

Protein preload improves postprandial glycemia by stimulating secretion of insulin and incretin hormones. However, it requires a large dose of protein to produce a significant effect. The present study was carried out to investigate the postprandial glucose-lowering effect of a premeal protein-enriched, dietary fiber-fortified bar (PFB), which contains moderate amounts of protein, in individuals with type 2 diabetes mellitus or normal glucose tolerance (NGT). The participants (15 type 2 diabetes mellitus and 15 NGT) were randomly assigned to either a premeal or postmeal PFB group and underwent two mixed meal tolerance tests, 1 week apart in reverse order. Plasma levels of glucose, insulin, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide were measured. During the mixed meal tolerance tests, the incremental area under the curve from 0 to 180 min of plasma glucose levels was lower with premeal PFB than with postmeal PFB in the type 2 diabetes mellitus (14,723 ± 1,310 mg min/dL vs 19,642 ± 1,367 mg min/dL; P = 0.0002) and NGT participants (3,943 ± 416 mg min/dL vs 4,827 ± 520 mg min/dL, P = 0.0296). In the type 2 diabetes mellitus participants, insulinogenic index and the incremental area under the curve from 0 to 180 min of plasma total glucagon-like peptide-1 levels were higher with premeal PFB than with postmeal PFB, but not in the NGT participants. There was no difference in postprandial glucose-dependent insulinotropic polypeptide levels between premeal and postmeal PFB in both groups. Acute administration of premeal PFB decreased postprandial glucose excursion in both type 2 diabetes mellitus and NGT participants. In the type 2 diabetes mellitus participants, premeal PFB augmented the early-phase insulin secretion, possibly through enhancing glucagon-like peptide-1 secretion. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons

A decision support tool for appropriate glucose-lowering therapy in patients with type 2 diabetes

NARCIS (Netherlands)

Ampudia-Blasco, F.J.; Benhamou, P.Y.; Charpentier, G.; Consoli, A.; Diamant, M.; Gallwitz, B.; Khunti, K.; Mathieu, C.; Ridderstrale, M.; Seufert, J.; Tack, C.J.; Vilsboll, T.; Phan, T.; Stoevelaar, H.

2015-01-01

BACKGROUND: Optimal glucose-lowering therapy in type 2 diabetes mellitus requires a patient-specific approach. Although a good framework, current guidelines are insufficiently detailed to address the different phenotypes and individual needs of patients seen in daily practice. We developed a

Electrical stimulation of human lower extremities enhances energy consumption, carbohydrate oxidation, and whole body glucose uptake.

Science.gov (United States)

Hamada, Taku; Hayashi, Tatsuya; Kimura, Tetsuya; Nakao, Kazuwa; Moritani, Toshio

2004-03-01

Our laboratory has recently demonstrated that low-frequency electrical stimulation (ES) of quadriceps muscles alone significantly enhanced glucose disposal rate (GDR) during euglycemic clamp (Hamada T, Sasaki H, Hayashi T, Moritani T, and Nakao K. J Appl Physiol 94: 2107-2112, 2003). The present study is further follow-up to examine the acute metabolic effects of ES to lower extremities compared with voluntary cycle exercise (VE) at identical intensity. In eight male subjects lying in the supine position, both lower leg (tibialis anterior and triceps surae) and thigh (quadriceps and hamstrings) muscles were sequentially stimulated to cocontract in an isometric manner at 20 Hz with a 1-s on-off duty cycle for 20 min. Despite small elevation of oxygen uptake by 7.3 +/- 0.3 ml x kg(-1) x min(-1) during ES, the blood lactate concentration was significantly increased by 3.2 +/- 0.3 mmol/l in initial period (5 min) after the onset of the ES (P increased anaerobic glycolysis by ES. Furthermore, whole body glucose uptake determined by GDR during euglycemic clamp demonstrated a significant increase during and after the cessation of ES for at least 90 min (P energy consumption, carbohydrate oxidation, and whole body glucose uptake at low intensity of exercise. Percutaneous ES may become a therapeutic utility to enhance glucose metabolism in humans.

Blood glucose lowering effect of ophiopogonis tuber extract and mechanism of anti-insulin-resistance

Directory of Open Access Journals (Sweden)

Meng NING

2013-01-01

Full Text Available Objective 　To study the hypoglycemic effect and insulin sensitization mechanism of ophiopogonis tuber extracts on the 3T3-L1-induced adipocytes, and also in rats with reproduction of type 2 diabetes mellitus (T2DM. Methods 　3T3-L1 cells were induced and differentiated into adipocytes. After the intervention with ophiopogonpolysaccharide (OPSR and ophiopogonin (OPG, glucose consuming rate was detected for screening the extracts which may have effective hypoglycemic effects. The insulin resistance (IR adipocyte model was established by dexamethasone induction, and then it was treated with OPSR. The protein expression levels of leptin, adiponectin and resistin were detected by Western blotting. The T2DM rat model was reproduced and then treated with OPSR for 4 weeks. Body weight (BW, triglyeride (TG, fasting blood glucose (FBG and fasting insulin (FINs of the rats were measured respectively. Results 　OPSR in dosage of 0.5-50mg/L promoted glucose consumption of adipocytes in a dose-dependent manner, the glucose consumption ratios were 32.27%, 75.14% and 90.47% respectively. OPG of 50mg/L showed very weak activity with glucose consumption ratio of only 8.49%. OPSR could significantly promote the protein expression of leptin and adiponectin, and showed an inhibitory effect on the protein expression of resistin (P<0.05. After treatment with OPSR for 4 weeks, the BW of rats increased obviously, while TG, FBG and HOMA-IR decreased significantly (P<0.05 or P<0.01. Conclusions 　OPSR may promote glucose transport and utilization of adipocytes, decrease the level of FBG and TG, and improve the condition of IR in T2DM rats. The mechanism of blood glucose lowering effect may be attributed to secretion of adipokines, such as leptin, adiponectin and resistin by IR adipocytes.

Intraperitoneal lactate/pyruvate ratio and the level of glucose and glycerol concentration differ between patients surgically treated for upper and lower perforations of the gastrointestinal tract

DEFF Research Database (Denmark)

Sabroe, Jonas E; Axelsen, Anne R; Ellebæk, Mark B

2017-01-01

collected every 4th hour for up to 7 postoperative days. Samples were analysed for concentrations of glucose, lactate, pyruvate and glycerol. RESULTS: Microdialysis results showed that patients with upper gastrointestinal tract lesions had significantly higher levels of postoperative intraperitoneal glucose...... and glycerol concentrations, as well as lower lactate/pyruvate ratios and lactate/glucose ratios. In the group with perforation of the lower gastrointestinal tract, those patients with a complicated course showed lower levels of postoperative intraperitoneal glucose concentration and glycerol concentration...... and higher lactate/pyruvate ratios and lactate/glucose ratios than those patients with an uncomplicated course. CONCLUSION: Patients with upper and lower gastrointestinal tract lesions showed differences in postoperative biomarker levels. A difference was also seen between patients with complicated...

Initiation of glucose-lowering treatment decreases international normalized ratio levels among users of vitamin K antagonists

DEFF Research Database (Denmark)

Stage, Tore Bjerregaard; Pottegård, Anton; Henriksen, Daniel Pilsgaard

2016-01-01

-lowering treatment affects international normalized ratio (INR) and dose requirements of the anticoagulant VKAs warfarin and phenprocoumon. PATIENTS/METHODS: We performed a self-controlled retrospective register-based study. A total of 118 patients initiating glucose-lowering treatment while being treated......-lowering treatment reduces the anticoagulant effect of VKA to an extent that is likely to be clinically relevant. This finding needs confirmation and mechanistic explanation. This article is protected by copyright. All rights reserved....

Rates of myocardial infarction and stroke in patients initiated on SGLT2-inhibitors versus other glucose-lowering agents in real-world clinical practice

DEFF Research Database (Denmark)

Kosiborod, Mikhail; Birkeland, Kåre I; Cavender, Matthew A

2018-01-01

The multinational, observational CVD-REAL study recently showed that initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2i) was associated with significantly lower rates of death and heart failure vs. other glucose-lowering drugs (oGLDs). This sub-analysis of CVD-REAL sought to determ...

Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats.

Science.gov (United States)

Rasmussen, Brittany A; Breen, Danna M; Luo, Ping; Cheung, Grace W C; Yang, Clair S; Sun, Biying; Kokorovic, Andrea; Rong, Weifang; Lam, Tony K T

2012-04-01

The duodenum senses nutrients to maintain energy and glucose homeostasis, but little is known about the signaling and neuronal mechanisms involved. We tested whether duodenal activation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) is sufficient and necessary for cholecystokinin (CCK) signaling to trigger vagal afferent firing and regulate glucose production. In rats, we selectively activated duodenal PKA and evaluated changes in glucose kinetics during the pancreatic (basal insulin) pancreatic clamps and vagal afferent firing. The requirement of duodenal PKA signaling in glucose regulation was evaluated by inhibiting duodenal activation of PKA in the presence of infusion of the intraduodenal PKA agonist (Sp-cAMPS) or CCK1 receptor agonist (CCK-8). We also assessed the involvement of a neuronal network and the metabolic impact of duodenal PKA activation in rats placed on high-fat diets. Intraduodenal infusion of Sp-cAMPS activated duodenal PKA and lowered glucose production, in association with increased vagal afferent firing in control rats. The metabolic and neuronal effects of duodenal Sp-cAMPS were negated by coinfusion with either the PKA inhibitor H89 or Rp-CAMPS. The metabolic effect was also negated by coinfusion with tetracaine, molecular and pharmacologic inhibition of NR1-containing N-methyl-d-aspartate (NMDA) receptors within the dorsal vagal complex, or hepatic vagotomy in rats. Inhibition of duodenal PKA blocked the ability of duodenal CCK-8 to reduce glucose production in control rats, whereas duodenal Sp-cAMPS bypassed duodenal CCK resistance and activated duodenal PKA and lowered glucose production in rats on high-fat diets. We identified a neural glucoregulatory function of duodenal PKA signaling. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Lower omental t-regulatory cell count is associated with higher fasting glucose and lower β-cell function in adults with obesity.

Science.gov (United States)

Gyllenhammer, Lauren E; Lam, Jonathan; Alderete, Tanya L; Allayee, Hooman; Akbari, Omid; Katkhouda, Namir; Goran, Michael I

2016-06-01

T-lymphocytes are potential initiators and regulators of adipose tissue (AT) inflammation, but there is limited human data on omental AT. The aim of this study was to assess the relationship between T cells, particularly Foxp3+ regulatory T (Treg) cells, in human subcutaneous (subQ) and omental AT and type 2 diabetes risk. SubQ and deep subQ (DsubQ) abdominal and omental AT biopsies were collected from 44 patients (body mass index, BMI ≥25) undergoing elective abdominal surgery. Flow cytometry was used to quantify CD4+ T cell (T effector and Treg) and macrophages (M1 and M2), and systemic inflammation was measured in fasting blood. Tregs were significantly lower in omental versus subQ and DsubQ AT, and M1 cell counts were significantly higher in the omental and DsubQ depot relative to the subQ. Only omental AT Tregs were negatively associated with fasting glucose and MCP-1 and positively associated with homeostasis model assessment (HOMA)-β. M1 and M2 cell counts across multiple depots had significant relationships with HOMA-insulin resistance, tumor necrosis factor-α, insulin, and HOMA-β. All relationships were consistent across ethnicities. Tregs were significantly lower in omental versus both subQ adipose depots. Fewer omental Tregs may have metabolic implications based on depot-specific relationships with higher fasting glucose and lower β-cell function. © 2016 The Obesity Society.

Efficacy of lower doses of vanadium in restoring altered glucose ...

Indian Academy of Sciences (India)

Unknown

Keywords. Antioxidant enzymes; diabetes; glucose metabolism; lens; polyol pathway; Trigonella foenum graecum; vanadate .... mimetic agent by increasing glucose transport and meta- .... way analysis of variance (ANOVA) followed by Dunnet.

Chapter 10: Glucose control: insulin therapy*

African Journals Online (AJOL)

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

Blood glucose lowering effects of brown rice in normal and diabetic subjects.

Science.gov (United States)

Panlasigui, Leonora N; Thompson, Lilian U

2006-01-01

Carbohydrate foods, which produce low glycemic responses, have been shown to be beneficial in the dietary management of chronic diseases such as diabetes and hyperlipidemia. This study determined the starch digestion rate in vitro and, in a randomised crossover design, the postprandial blood glucose response of 10 healthy and nine type 2 diabetic volunteers to brown rice compared to milled rice from the same batch and variety. The total sugar released in vitro was 23.7% lower in brown rice than in milled rice. In healthy volunteers, the glycemic area and glycemic index were, respectively, 19.8% and 12.1% lower (p brown rice than milled rice, while in diabetics, the respective values were 35.2% and 35.6% lower. The effect was partly due to the higher amounts of phytic acid, polyphenols, dietary fiber and oil in brown compared to milled rice and the difference in some physicochemical properties of the rice samples such as minimum cooking time and degree of gelatinisation. In conclusion, brown rice is a more health beneficial food for diabetics and hyperglycemic individuals than milled rice.

Activation of Short and Long Chain Fatty Acid Sensing Machinery in the Ileum Lowers Glucose Production in Vivo.

Science.gov (United States)

Zadeh-Tahmasebi, Melika; Duca, Frank A; Rasmussen, Brittany A; Bauer, Paige V; Côté, Clémence D; Filippi, Beatrice M; Lam, Tony K T

2016-04-15

Evidence continues to emerge detailing the myriad of ways the gut microbiota influences host energy homeostasis. Among the potential mechanisms, short chain fatty acids (SCFAs), the byproducts of microbial fermentation of dietary fibers, exhibit correlative beneficial metabolic effects in humans and rodents, including improvements in glucose homeostasis. The underlying mechanisms, however, remain elusive. We here report that one of the main bacterially produced SCFAs, propionate, activates ileal mucosal free fatty acid receptor 2 to trigger a negative feedback pathway to lower hepatic glucose production in healthy rats in vivo We further demonstrate that an ileal glucagon-like peptide-1 receptor-dependent neuronal network is necessary for ileal propionate and long chain fatty acid sensing to regulate glucose homeostasis. These findings highlight the potential to manipulate fatty acid sensing machinery in the ileum to regulate glucose homeostasis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients

DEFF Research Database (Denmark)

Toft-Nielsen, M B; Madsbad, Sten; Holst, J J

1999-01-01

OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefo....... CONCLUSIONS: We conclude that 48-h continuous subcutaneous infusion of GLP-1 in type 2 diabetic patients 1) lowers fasting as well as meal-related plasma glucose, 2) reduces appetite, 3) has no gastrointestinal side effects, and 4) has no negative effect on blood pressure.......OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefore......, previously shown to lower blood glucose effectively in type 2 diabetic patients. Fasting plasma glucose (day 2) decreased from 14.1 +/- 0.9 (saline) to 12.2 +/- 0.7 mmol/l (GLP-1), P = 0.009, and 24-h mean plasma glucose decreased from 15.4 +/- 1.0 to 13.0 +/- 1.0 mmol/l, P = 0.0009. Fasting and total area...

Intragastric administration of leucine or isoleucine lowers the blood glucose response to a mixed-nutrient drink by different mechanisms in healthy, lean volunteers.

Science.gov (United States)

Ullrich, Sina S; Fitzgerald, Penelope Ce; Schober, Gudrun; Steinert, Robert E; Horowitz, Michael; Feinle-Bisset, Christine

2016-11-01

The branched-chain amino acids leucine and isoleucine lower blood glucose after oral glucose ingestion, and the intraduodenal infusion of leucine decreases energy intake in healthy, lean men. We investigated the effects of the intragastric administration of leucine and isoleucine on the gastric emptying of, and blood glucose responses to, a physiologic mixed-macronutrient drink and subsequent energy intake. In 2 separate studies, 12 healthy, lean subjects received on 3 separate occasions an intragastric infusion of 5 g leucine (leucine-5g) or an intragastric infusion of 10 g leucine (leucine-10g), an intragastric infusion of 5 g isoleucine (isoleucine-5g) or an intragastric infusion of 10 g isoleucine (isoleucine-10g), or a control. Fifteen minutes later, subjects consumed a mixed-nutrient drink (400 kcal, 56 g carbohydrates, 15 g protein, and 12 g fat), and gastric emptying ( 13 C-acetate breath test) and blood glucose, plasma insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (leucine study only) were measured for 60 min. Immediately afterward, energy intake from a cold, buffet-style meal was assessed. Compared with the control, leucine-10g decreased the blood glucose area under the curve (AUC) (P blood glucose (P = 0.07), whereas effects of leucine-5g were NS. Leucine-10g, but not leucine-5g, increased plasma insulin and C-peptide AUCs (P blood glucose AUC and peak blood glucose (P blood glucose AUC. Isoleucine did not affect energy intake. In healthy subjects, both leucine and isoleucine reduced blood glucose in response to a mixed-nutrient drink but did not affect subsequent energy intake. The mechanisms underlying glucose lowering appear to differ; leucine stimulated insulin, whereas isoleucine acted insulin independently. These trials were registered at www.anzctr.org.au as 12613000899741 and 12614000837628. © 2016 American Society for Nutrition.

A combination of l-arabinose and chromium lowers circulating glucose and insulin levels after an acute oral sucrose challenge

Directory of Open Access Journals (Sweden)

Perricone Nicholas V

2011-05-01

Full Text Available Abstract Background A growing body of research suggests that elevated circulating levels of glucose and insulin accelerate risk factors for a wide range of disorders. Low-risk interventions that could suppress glucose without raising insulin levels could offer significant long-term health benefits. Methods To address this issue, we conducted two sequential studies, the first with two phases. In the first phase of Study 1, baseline fasting blood glucose was measured in 20 subjects who consumed 70 grams of sucrose in water and subsequently completed capillary glucose measurements at 30, 45, 60 and 90 minutes (Control. On day-2 the same procedure was followed, but with subjects simultaneously consuming a novel formula containing l-arabinose and a trivalent patented food source of chromium (LA-Cr (Treatment. The presence or absence of the LA-Cr was blinded to the subjects and testing technician. Comparisons of changes from baseline were made between Control and Treatment periods. In the second phase of Study 1, 10 subjects selected from the original 20 competed baseline measures of body composition (DXA, a 43-blood chemistry panel and a Quality of Life Inventory. These subjects subsequently took LA-Cr daily for 4 weeks completing daily tracking forms and repeating the baseline capillary tests at the end of each of the four weeks. In Study 2, the same procedures used in the first phase were repeated for 50 subjects, but with added circulating insulin measurements at 30 and 60 minutes from baseline. Results In both studies, as compared to Control, the Treatment group had significantly lower glucose responses for all four testing times (AUC = P P = Conclusions As compared to a placebo control, consumption of a LA-Cr formula after a 70-gram sucrose challenge was effective in safely lowering both circulating glucose and insulin levels. Trial Registration Clinical Trials.gov, NCT0110743

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.

Lowering glucose level elevates [Ca2+]i in hypothalamic arcuate nucleus NPY neurons through P/Q-type Ca2+ channel activation and GSK3β inhibition

Science.gov (United States)

Chen, Yu; Zhou, Jun; Xie, Na; Huang, Chao; Zhang, Jun-qi; Hu, Zhuang-li; Ni, Lan; Jin, You; Wang, Fang; Chen, Jian-guo; Long, Li-hong

2012-01-01

Aim: To identify the mechanisms underlying the elevation of intracellular Ca2+ level ([Ca2+]i) induced by lowering extracellular glucose in rat hypothalamic arcuate nucleus NPY neurons. Methods: Primary cultures of hypothalamic arcuate nucleus (ARC) neurons were prepared from Sprague-Dawley rats. NPY neurons were identified with immunocytochemical method. [Ca2+]i was measured using fura-2 AM. Ca2+ current was recorded using whole-cell patch clamp recording. AMPK and GSK3β levels were measured using Western blot assay. Results: Lowering glucose level in the medium (from 10 to 1 mmol/L) induced a transient elevation of [Ca2+]i in ARC neurons, but not in hippocampal and cortical neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons depended on extracellular Ca2+, and was blocked by P/Q-type Ca2+channel blocker ω-agatoxin TK (100 nmol/L), but not by L-type Ca2+ channel blocker nifedipine (10 μmol/L) or N-type Ca2+channel blocker ω-conotoxin GVIA (300 nmol/L). Lowering glucose level increased the peak amplitude of high voltage-activated Ca2+ current in ARC neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons was blocked by the AMPK inhibitor compound C (20 μmol/L), and enhanced by the GSK3β inhibitor LiCl (10 mmol/L). Moreover, lowering glucose level induced the phosphorylation of AMPK and GSK3β, which was inhibited by compound C (20 μmol/L). Conclusion: Lowering glucose level enhances the activity of P/Q type Ca2+channels and elevates [Ca2+]i level in hypothalamic arcuate nucleus neurons via inhibition of GSK3β. PMID:22504905

Uncooked rice of relatively low gelatinization degree resulted in lower metabolic glucose and insulin responses compared with cooked rice in female college students.

Science.gov (United States)

Jung, Eun Young; Suh, Hyung Joo; Hong, Wan Soo; Kim, Dong Geon; Hong, Yang Hee; Hong, In Sun; Chang, Un Jae

2009-07-01

Cooking processes that gelatinize granules or disrupt structure might increase the glucose and insulin responses because a disruption of the structure of starch by gelatinization increases its availability for digestion and absorption in the small intestine. We hypothesized that the uncooked form of rice, which has a relatively low degree of gelatinization even though in powder form, would result in lower metabolic glucose and insulin responses compared with cooked rice (CR). To assess the effects of the gelatinization of rice on metabolic response of glucose and insulin, we investigated the glucose and insulin responses to 3 rice meals of different gelatinization degree in female college students (n = 12): CR (76.9% gelatinized), uncooked rice powder (UP; 3.5% gelatinized), and uncooked freeze-dried rice powder (UFP; 5.4% gelatinized). Uncooked rice powders (UP and UFP) induced lower glucose and insulin responses compared with CR. The relatively low gelatinization degree of UPs resulted in low metabolic responses in terms of the glycemic index (CR: 72.4% vs UP: 49.7%, UFP: 59.8%) and insulin index (CR: 94.8% vs UP: 74.4%, UFP: 68.0%). In summary, UPs that were less gelatinized than CR induced low postprandial glucose and insulin responses.

Glucose-lowering agents and the patterns of risk for cancer

DEFF Research Database (Denmark)

van Staa, T P; Patel, D; Gallagher, A M

2012-01-01

. METHODS: The General Practice Research Database (GPRD) was used to identify cohorts of new users. Cancer outcomes were obtained from the GPRD, Hospital Episode Statistics and cancer registries. Relative rates of cancer comparing different glucose-lowering agents were estimated using Poisson regression.......19, 1.51] with sulfonylureas and 1.79 [95% CI 1.53, 2.10] with insulin, compared with metformin). Insulin users had decreasing cancer incidence over time (adjusted relative rate of 0.58 [95% CI 0.50, 0.68] during months 6-24, relative rate of 0.50 [95% CI 0.42, 0.59] during months 25-60 and relative...... rate of 0.48 [95% CI 0.40, 0.59] during months 60+) compared with months 0-6 after starting insulin. Similar patterns were found with sulfonylureas and metformin. There were no increases over time with insulin glargine (A21Gly, B31Arg, B32Arg human insulin; relative rate of 0.70 [95% CI 0.52, 0.95], 0...

Lifestyle factors associated with type 2 diabetes and use of different glucose-lowering drugs: cross-sectional study.

Directory of Open Access Journals (Sweden)

Sinna P Ulrichsen

Full Text Available To examine the lifestyle profile among persons with and without Type 2 diabetes mellitus (DM and among users of different glucose-lowering drugs.We used questionnaire data from a Danish health survey and identified presence of Type 2 DM and use of medications through medical databases. We calculated age- and gender-standardized prevalence ratios (PRs of lifestyle factors according to Type 2 DM and different glucose-lowering drugs.Of 21,637 survey participants aged 25-79 years, 680 (3% had Type 2 DM (median age 63 years with a median diabetes duration of 5 years. Participants with Type 2 DM had a substantially higher prevalence of obesity (36% vs. 13%, PR: 3.1, 95% confidence interval (CI: 2.8-3.6, yet more reported to eat a very healthy diet (25% vs. 21%, PR: 1.2, 95% CI: 1.0-1.4 and to exercise regularly (67% vs. 53%, PR: 1.3, 95% CI: 1.2-1.4. Also, fewer were current smokers or had high alcohol intake. When compared with metformin users, obesity was substantially less prevalent in users of sulfonylurea (PR: 0.5, 95% CI: 0.4-0-8, and insulin and analogues (PR: 0.4, 95% CI: 0.3-0.7. Tobacco smoking was more prevalent in sulfonylurea users (PR: 1.4, 95% CI: 0.9-2.1 compared with metformin users. We found no material differences in physical exercise, diet or alcohol intake according to type of glucose-lowering drug.Type 2 DM patients are substantially more obese than other individuals, but otherwise report to have a healthier lifestyle. Metformin use is strongly associated with obesity, whereas sulfonylurea use tends to be associated with tobacco smoking.

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... how often you should check and what your blood glucose levels should be. Checking your blood and then treating ... I Treat Hyperglycemia? You can often lower your blood glucose level by exercising. However, if your blood glucose is ...

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

NARCIS (Netherlands)

Siegelaar, S.E.

2011-01-01

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

Impact of cancer diagnosis and treatment on glycaemic control among individuals with colorectal cancer using glucose lowering drugs

NARCIS (Netherlands)

Zanders, M.M.J.; van Herk-Sukel, M.P.P.; Herings, R.M.C.; van de Poll-Franse, L.V.; Haak, H.

2016-01-01

Aims This study aims to evaluate the impact of cancer and its treatment on HbA1c values among individuals with colorectal cancer (CRC) using glucose-lowering drugs (GLDs). Methods Patients with primary CRC (1998–2011) were selected from the Eindhoven Cancer Registry and linked to the PHARMO Database

THE EFFECTIVENES OF ETANOL EXTRACT, PARTITION N-HEKSANA, AND CROMATHOGRAPHY FRACTION OF MOMORDICA CHARANTIA L. TO LOWER BLOOD GLUCOSE LEVEL

Directory of Open Access Journals (Sweden)

Ni Luh Putu Kusuma Clara Dewinda

2017-08-01

Full Text Available This study aims to determine the effectiveness of the ethanol extract, partition n-hexane, and chromatography fractions Momordica charantia L. in lowering blood glucose levels in experimental diabetic male rats.  This study used 25 male rats were divided into five treatment groups P0 (negative control, P1 (positive control, P2 (ethanol extract, P3 (partition n-hexane, and P4 (chromatographic fraction the variable observed glucose levels blood for 21 days. Blood glucose levels were analyzed on days -1, 0, 4, 11, 18. The bill, which is used in the form of a completely randomized design (CRD. The data obtained and analyzed by using Split in Time. The results showed of giving chromatographic fractions bitter melon 50 mg / kg body weight can reduce blood glucose levels in hyperglycemic rats better than the ethanol extract 200 mg / kg body weight and partition n-hexane 50 mg / kg body weight.

Lower extremity weakness is associated with elevated blood and cerebrospinal fluid glucose levels following multibranched endovascular aortic aneurysm repair.

Science.gov (United States)

Hiramoto, Jade S; Fernandez, Charlene; Gasper, Warren; Vartanian, Shant; Reilly, Linda; Chuter, Timothy

2017-02-01

Hyperglycemia is associated with worsened clinical outcomes after central nervous system injury. The purpose of this study was to examine the association between lower extremity weakness (LEW) and the glucose levels of blood and cerebrospinal fluid (CSF) in patients undergoing multibranched endovascular aneurysm repair (MBEVAR) of thoracoabdominal and pararenal aortic aneurysms. Blood and CSF samples were collected preoperatively, immediately after aneurysm repair, and on postoperative day 1 in 21 patients undergoing MBEVAR. Data on demographics, operative repair, complications, and outcomes were collected prospectively. There were 21 patients who underwent successful MBEVAR. Two patients had pre-existing paraplegia from prior open aortic surgery and were excluded from the current analysis. The mean age was 73 ± 8 years, and 15 of 19 (79%) were men. In the postoperative period, 7 of 19 (37%) patients developed LEW. This was temporary in 5 of 19 (26%) patients and permanent in 2 of 19 (11%) patients. The LEW group was older than the non-LEW group (77 ± 6 vs 70 ± 9 years, respectively; P = .10), had a lower preoperative glomerular filtration rate (58.6 ± 18.5 vs 71.4 ± 23.5 mL/min per 1.73 m 2 ; P = .24), and was more likely to be taking a statin (100% vs 67%, respectively; P = .13), but these did not reach statistical significance. There was no significant difference in the prevalence of diabetes mellitus, hypertension, coronary artery disease, lung disease, or peripheral artery disease between the LEW and non-LEW groups. There was also no difference in operative time, blood loss, contrast material volume, or fluoroscopy times between the two groups. Preoperative blood and CSF glucose levels were similar in those with and without LEW. During the postoperative period, glucose values in the blood and CSF were significantly higher in those patients who developed LEW compared with those who did not develop LEW. In all patients with LEW, the elevation

A high-throughput colorimetric assay for glucose detection based on glucose oxidase-catalyzed enlargement of gold nanoparticles

Science.gov (United States)

Xiong, Yanmei; Zhang, Yuyan; Rong, Pengfei; Yang, Jie; Wang, Wei; Liu, Dingbin

2015-09-01

We developed a simple high-throughput colorimetric assay to detect glucose based on the glucose oxidase (GOx)-catalysed enlargement of gold nanoparticles (AuNPs). Compared with the currently available glucose kit method, the AuNP-based assay provides higher clinical sensitivity at lower cost, indicating its great potential to be a powerful tool for clinical screening of glucose.We developed a simple high-throughput colorimetric assay to detect glucose based on the glucose oxidase (GOx)-catalysed enlargement of gold nanoparticles (AuNPs). Compared with the currently available glucose kit method, the AuNP-based assay provides higher clinical sensitivity at lower cost, indicating its great potential to be a powerful tool for clinical screening of glucose. Electronic supplementary information (ESI) available: Experimental section and additional figures. See DOI: 10.1039/c5nr03758a

Glucose-lowering effect and glycaemic variability of insulin glargine, insulin detemir and insulin lispro protamine in people with type 1 diabetes.

Science.gov (United States)

Derosa, G; Franzetti, I; Querci, F; Romano, D; D'Angelo, A; Maffioli, P

2015-06-01

To compare, using a continuous glucose monitoring (CGM) system, the effect on glycaemic variability of insulin glargine, detemir and lispro protamine. A total of 49 white people with type 1 diabetes, not well controlled by three times daily insulin lispro, taken for at least 2 months before study and on a stable dose, were enrolled. The study participants were randomized to add insulin glargine, detemir or lispro protamine, once daily, in the evening. We used a CGM system, the iPro Digital Recorder (Medtronic MiniMed, Northridge, CA, USA) for 1 week. Glycaemic control was assessed according to mean blood glucose values, the area under the glucose curve above 3.9 mmol/l (AUC(>3.9)) or above 10.0 mmol/l (AUC(>10.0)), and the percentage of time spent with glucose values >3.9 or >10.0 mmol/l. Intraday glycaemic variability was assessed using standard deviation (s.d.) values, the mean amplitude of glycaemic excursions and continuous overlapping of net glycaemic action. Day-to-day glycaemic variability was assessed using the mean of daily differences. The s.d. was found to be significantly lower with insulin lispro protamine and glargine compared with insulin detemir. AUC(>3.9) was higher and AUC(>10.0) was lower with insulin lispro protamine and glargine compared with detemir. The mean amplitude of glycaemic excursions and continuous overlapping net glycaemic action values were lower with insulin lispro protamine and glargine compared with detemir. In addition, the mean of daily differences was significantly lower with insulin lispro protamine and glargine compared with detemir. Fewer hypoglycaemic events were recorded during the night-time with insulin lispro protamine compared with glargine and detemir. The results suggest that insulin lispro protamine and glargine are more effective than detemir in reducing glycaemic variability and improving glycaemic control in people with type 1 diabetes. Insulin lispro protamine seems to lead to fewer hypoglycaemic

Differences in Body Fat Distribution Play a Role in the Lower Levels of Elevated Fasting Glucose amongst Ghanaian Migrant Women Compared to Men.

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Nicolaou, Mary; Kunst, Anton E; Busschers, Wim B; van Valkengoed, Irene G; Dijkshoorn, Henriette; Boateng, Linda; Brewster, Lizzy M; Snijder, Marieke B; Stronks, Karien; Agyemang, Charles

2013-01-01

Despite higher levels of obesity, West African migrant women appear to have lower rates of type 2 diabetes than their male counterparts. We investigated the role of body fat distribution in these differences. Cross-sectional study of Ghanaian migrants (97 men, 115 women) aged 18-60 years in Amsterdam, the Netherlands. Weight, height, waist and hip circumferences were measured. Logistic regression was used to explore the association of BMI, waist and hip measurements with elevated fasting glucose (glucose≥5.6 mmol/L). Linear regression was used to study the association of the same parameters with fasting glucose. Mean BMI, waist and hip circumferences were higher in women than men while the prevalence of elevated fasting glucose was higher in men than in women, 33% versus 19%. With adjustment for age only, men were non-significantly more likely than women to have an elevated fasting glucose, odds ratio (OR) 1.81, 95% CI: 0.95, 3.46. With correction for BMI, the higher odds among men increased and were statistically significant (OR 2.84, 95% CI: 1.32, 6.10), but with consideration of body fat distribution (by adding both hip and waist in the analysis) differences were no longer significant (OR 1.56 95% CI: 0.66, 3.68). Analysis with fasting glucose as continuous outcome measure showed somewhat similar results. Compared to men, the lower rates of elevated fasting glucose observed among Ghanaian women may be partly due to a more favorable body fat distribution, characterized by both hip and waist measurements.

Differences in Body Fat Distribution Play a Role in the Lower Levels of Elevated Fasting Glucose amongst Ghanaian Migrant Women Compared to Men.

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Mary Nicolaou

Full Text Available Despite higher levels of obesity, West African migrant women appear to have lower rates of type 2 diabetes than their male counterparts. We investigated the role of body fat distribution in these differences.Cross-sectional study of Ghanaian migrants (97 men, 115 women aged 18-60 years in Amsterdam, the Netherlands. Weight, height, waist and hip circumferences were measured. Logistic regression was used to explore the association of BMI, waist and hip measurements with elevated fasting glucose (glucose≥5.6 mmol/L. Linear regression was used to study the association of the same parameters with fasting glucose.Mean BMI, waist and hip circumferences were higher in women than men while the prevalence of elevated fasting glucose was higher in men than in women, 33% versus 19%. With adjustment for age only, men were non-significantly more likely than women to have an elevated fasting glucose, odds ratio (OR 1.81, 95% CI: 0.95, 3.46. With correction for BMI, the higher odds among men increased and were statistically significant (OR 2.84, 95% CI: 1.32, 6.10, but with consideration of body fat distribution (by adding both hip and waist in the analysis differences were no longer significant (OR 1.56 95% CI: 0.66, 3.68. Analysis with fasting glucose as continuous outcome measure showed somewhat similar results.Compared to men, the lower rates of elevated fasting glucose observed among Ghanaian women may be partly due to a more favorable body fat distribution, characterized by both hip and waist measurements.

Correlation between Fasting Glucose, Erectile Dysfunction, and Lower Urinary Tract Symptoms in Benign Prostate Hyperplasia Patients

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Tommie Prasetyo

2017-01-01

Full Text Available This study is aimed to determine the correlation between fasting glucose level, erectile dysfunction,and lower urinary tract symptoms (LUTS in patients diagnosed with benign prostatic hyperplasia (BPH. Weenrolled patients with BPH-related LUTS aged over 50 years old. LUTS and erectile dysfunction (ED wereevaluated using International Prostate Symptom Score (IPSS and International Index of Erectile Function-5(IIEF-5. Diabetes mellitus was established if fasting glucose level was above 126mg/dL. Forty-two patientswere enrolled in this study from outpatient clinic in Kardinah Hospital, Tegal during January–March 2015.Patients’ mean age was 68.8±8.6 years old with most of them suffered from ED (83.3% and also suffered fromsevere LUTS (80.96%. Mean fasting glucose level was 108.3 + 21.1 mg/dl. However, diabetes mellitus wasobserved in 26.2% subjects with mean fasting glucose level was 136.8+7.8mg/dl. IPSS score was correlatedwith fasting glucose level (r=0.879, p<0.001 and IIEF-5 score (r= -0.346, p=0.025. IIEF-5 score showednegative correlation with age (r=-0.31, p=0.046 and fasting glucose level (r=-0.305, p=0.049. Higher fastingglucose level in a man older than 50 years with BPH would increase severity of LUTS and ED. Keywords: Diabetes mellitus, lower urinary tract symptoms, erectile dysfunction   Korelasi antara Glukosa Darah Puasa, Disfungsi Ereksi, dan GejalaSaluran Kemih Bagian Bawah pada PasienBenign Prostatic Hyperplasia AbstrakPenelitian ini bertujuan untuk mengetahui hubungan antara nilai glukosa darah puasa, disfungsi ereksi(DE, dan gejala saluran kemih bagian bawah (LUTS pada pasien dengan pembesaran prostate jinak/benignprostatic hyperplasia (BPH. Subjek adalah pasien berusia lebih dari 50 tahun dengan pembesaran prostatjinak di RS Kardinah, Tegal pada bulan Januari-Maret 2015. LUTS dan DE dievaluasi dengan menggunakanInternational Prostate Symptom Score (IPSS and International Index of Erectile Function-5 (IIEF-5

Blood-Brain Glucose Transfer: Repression in Chronic Hyperglycemia

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Gjedde, Albert; Crone, Christian

1981-10-01

Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients

DEFF Research Database (Denmark)

Toft-Nielsen, M B; Madsbad, Sten; Holst, J J

1999-01-01

OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefore......, previously shown to lower blood glucose effectively in type 2 diabetic patients. Fasting plasma glucose (day 2) decreased from 14.1 +/- 0.9 (saline) to 12.2 +/- 0.7 mmol/l (GLP-1), P = 0.009, and 24-h mean plasma glucose decreased from 15.4 +/- 1.0 to 13.0 +/- 1.0 mmol/l, P = 0.0009. Fasting and total area...... under the curve for insulin and C-peptide levels were significantly higher during the GLP-1 administration, whereas glucagon levels were unchanged. Neither triglycerides nor free fatty acids were affected. GLP-1 administration decreased hunger and prospective food intake and increased satiety, whereas...

Prunus mume leaf extract lowers blood glucose level in diabetic mice.

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Lee, Min Woo; Kwon, Jung Eun; Lee, Young-Jong; Jeong, Yong Joon; Kim, Inhye; Cho, Young Mi; Kim, Yong-Min; Kang, Se Chan

2016-10-01

Context Diabetes is a common metabolic disease with long-term complications. Prunus mume Sieb. et Zucc. (Rosaceae) fruits have shown to ameliorate glucose intolerance. However, the antidiabetic effects of P. mume leaves have not been investigated. Objective This study evaluated the effects of P. mume leaf 70% ethanol extract (PMLE) on alleviating diabetes in vivo and in vitro. Materials and methods PMLE was fractionated into n-hexane, dichloromethane (CH2Cl2), ethyl acetate (EtOAc), n-butanol (BuOH) and water. Polyphenol and flavonoid contents in PMLE fractions were determined using Folin-Ciocalteu reagent and the aluminium chloride colorimetric method, respectively. We evaluated α-glucosidase inhibition using a microplate reader at 400 nm. Adipocyte differentiation by lipid accumulation was measured using Nile Red staining. Male imprinting control region (ICR) mice were injected with streptozotocin (STZ, 100 mg/kg, i.p.). High-fat diets were provided for three weeks prior to PMLE treatments to induce type 2 diabetes. PMLE (0, 5, 25 or 50 mg/kg) was administrated for four weeks with high-fat diets. Results The EtOAc fraction of PMLE inhibited α-glucosidase activity (IC50 = 68.2 μg/mL) and contained 883.5 ± 14.9 mg/g of polyphenols and 820.1 ± 7.7 mg/g of flavonoids. The 50 mg/kg PMLE supplement reduced 40% of blood glucose level compared to obese/diabetes mice. Obese/diabetic mice treated with 50 mg/kg PMLE showed a lower level of triacylglycerol (320.7 ± 20.73 mg/dL) compared to obese/diabetes mice (494.9 ± 14.80 mg/dL). Conclusion The data demonstrate that P. mume leaves exert antidiabetic effects that may be attributable to high concentrations of polyphenols and flavonoids.

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... can often lower your blood glucose level by exercising. However, if your blood glucose is above 240 ... ketones. If you have ketones, do not exercise. Exercising when ketones are present may make your blood ...

A Soxhlet Extract of Gongronema latifolium Retains Moderate Blood Glucose Lowering Effect and Produces Structural Recovery in the Pancreas of STZ-Induced Diabetic Rats

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Bassel Al-Hindi

2016-04-01

Full Text Available Background: Gongronema latifolium Benth. (GL possesses considerable glucose lowering effects able to be utilized on a large-scale. This paper investigates the effects of a Soxhlet extract on hyperglycemia, Langerhans islets and glucose uptake by abdominal muscles. Methods: Ethanol and a Soxhlet apparatus were used to obtain GL ethanolic Soxhlet extract (GLES. It was then administered to randomly-segregated male Sprague-Dawley, normal and STZ-induced diabetic rats, using oral gavage to evaluate blood glucose levels (BGLs, serum lipid profile, insulin levels and the pancreas post-treatment. Results: GLES significantly (p < 0.05 decreased BGLs of normal rats in glucose tolerance testing at a dose of 2 g/kg b.w. but failed to do so in diabetic rats undergoing acute 7-h treatment. Given twice-daily, 1 g/kg b.w. of GLES moderately controlled diabetic BGLs starting from day 10. After 14 days of treatment, 1 g/kg and 0.5 g/kg b.w. of GLES caused 44% and 50% respective increases in the average area of Langerhans islets compared to DC. Using isolated rat abdominal muscle, GLES was found to be a mild insulin-sensitizer. GC-MS analysis revealed the presence of the known glucose-lowering phytosterol, Sitostenone. Conclusion: Despite retaining moderate antidiabetic activity, Soxhlet extraction of Gongronema latifolium probably leads to the destruction of active heat-liable compounds.

Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic)

DEFF Research Database (Denmark)

Birkeland, Kåre I.; Jørgensen, Marit E.; Carstensen, Bendix

2017-01-01

, and atrial fibrillation. We also assessed incidence of severe hypoglycaemia. Findings Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering drug (n=68 490) groups were well balanced at baseline, with a mean follow-up of 0·9 (SD 4·1) years (80 669 patient-years) and mean age of 61 (12·0) years; 40...... with the results of clinical trials in patients at high cardiovascular risk. Funding AstraZeneca....

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

DEFF Research Database (Denmark)

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

2008-01-01

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

Prescribing practices and clinical predictors of glucose-lowering therapy within the first year in people with newly diagnosed Type 2 diabetes

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Mor, Anil; Berencsi, K; Svensson, E

2015-01-01

%) received monotherapy [685 (95%) with metformin], and 133 (12%) received more than one drug. Predictors of receiving any vs. no therapy and combination vs. monotherapy were: age years [RR: 1.29 (95% CI: 1.16-1.44) and 3.60 (95% CI: 2.36-5.50)]; high Charlson Comorbidity Index [RRs: 1.20 (95% CI: 1......AIM: To examine prescribing practices and predictors of glucose-lowering therapy within the first year following diagnosis of Type 2 diabetes mellitus in a clinical care setting. METHODS: We followed people enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort from...... outpatient hospital clinics and general practices throughout Denmark in 2010-2013. We used Poisson regression to compute age- and gender-adjusted risk ratios (RRs). RESULTS: Among 1158 new Type 2 diabetes mellitus patients, 302 (26%) did not receive glucose-lowering therapy within the first year, 723 (62...

Blood glucose lowering effect of aqueous extract of Graptophyllum ...

African Journals Online (AJOL)

... 10 mg/kg body weight metformin, a well known hypoglycemic drug, while group 5 served as control and received the vehicle of administration (distilled water). The fasting blood glucose level (FBGL) of the rats was checked before commencement of treatment and weekly during the drug administration period using Roche ...

The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

Energy Technology Data Exchange (ETDEWEB)

Conde, Vanessa R. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Oliveira, Pedro F. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto – UMIB/ICBAS/UP (Portugal); Nunes, Ana R.; Rocha, Cátia S. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Ramalhosa, Elsa; Pereira, José A. [Mountain Research Centre (CIMO), School of Agriculture, Polytechnic Institute of Bragança (Portugal); Alves, Marco G., E-mail: alvesmarc@gmail.com [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Silva, Branca M., E-mail: bmcms@ubi.pt [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal)

2015-07-01

Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression.

Glucose hypometabolism is highly localized, but lower cortical thickness and brain atrophy are widespread in cognitively normal older adults.

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Nugent, Scott; Castellano, Christian-Alexandre; Goffaux, Philippe; Whittingstall, Kevin; Lepage, Martin; Paquet, Nancy; Bocti, Christian; Fulop, Tamas; Cunnane, Stephen C

2014-06-01

Several studies have suggested that glucose hypometabolism may be present in specific brain regions in cognitively normal older adults and could contribute to the risk of subsequent cognitive decline. However, certain methodological shortcomings, including a lack of partial volume effect (PVE) correction or insufficient cognitive testing, confound the interpretation of most studies on this topic. We combined [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43 anatomically defined brain regions from a group of cognitively normal younger (25 ± 3 yr old; n = 25) and older adults (71 ± 9 yr old; n = 31). After correcting for PVE, we observed 11-17% lower CMRg in three specific brain regions of the older group: the superior frontal cortex, the caudal middle frontal cortex, and the caudate (P ≤ 0.01 false discovery rate-corrected). In the older group, cortical volumes and cortical thickness were 13-33 and 7-18% lower, respectively, in multiple brain regions (P ≤ 0.01 FDR correction). There were no differences in CMRg between individuals who were or were not prescribed antihypertensive medication. There were no significant correlations between CMRg and cognitive performance or metabolic parameters measured in fasting plasma. We conclude that highly localized glucose hypometabolism and widespread cortical thinning and atrophy can be present in older adults who are cognitively normal, as assessed using age-normed neuropsychological testing measures. Copyright © 2014 the American Physiological Society.

Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats.

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Legette, Leecole L; Luna, Arlyn Y Moreno; Reed, Ralph L; Miranda, Cristobal L; Bobe, Gerd; Proteau, Rosita R; Stevens, Jan F

2013-07-01

Obesity contributes to increased risk for several chronic diseases including cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses of xanthohumol at 0, 1.86, 5.64, and 16.9 mg/kg BW for 6 weeks. All rats were maintained on a high fat (60% kcal) AIN-93G diet for 3 weeks to induce severe obesity followed by a normal AIN-93G (15% kcal fat) diet for the last 3 weeks of the study. Weekly food intake and body weight were recorded. Plasma cholesterol, glucose, insulin, triglyceride, and monocyte chemoattractant protein-1 (MCP-1) levels were assessed using commercial assay kits. Plasma and liver tissue levels of XN and its metabolites were determined by liquid-chromatography tandem mass spectrometry. Plasma and liver tissue levels of xanthohumol were similar between low and medium dose groups and significantly (peffect on body weight and plasma glucose levels. The highest dose group (n=6) had significantly lower plasma glucose levels compared to the control group (n=6) in male but not female rats. There was also a significant decrease in body weight for male rats in the highest dose group (16.9 mg/kg BW) compared to rats that received no xanthohumol, which was also not seen for female rats. Plasma cholesterol, insulin, triglycerides, and MCP-1 as well as food intake were not affected by treatment. The findings suggest that xanthohumol has beneficial effects on markers of metabolic syndrome. Copyright © 2012. Published by Elsevier Ltd.

Possible increase in insulin resistance and concealed glucose-coupled potassium-lowering mechanisms during acute coronary syndrome documented by covariance structure analysis.

Science.gov (United States)

Ito, Satoshi; Nagoshi, Tomohisa; Minai, Kosuke; Kashiwagi, Yusuke; Sekiyama, Hiroshi; Yoshii, Akira; Kimura, Haruka; Inoue, Yasunori; Ogawa, Kazuo; Tanaka, Toshikazu D; Ogawa, Takayuki; Kawai, Makoto; Yoshimura, Michihiro

2017-01-01

Although glucose-insulin-potassium (GIK) therapy ought to be beneficial for ischemic heart disease in general, variable outcomes in many clinical trials of GIK in acute coronary syndrome (ACS) had a controversial impact. This study was designed to examine whether "insulin resistance" is involved in ACS and to clarify other potential intrinsic compensatory mechanisms for GIK tolerance through highly statistical procedure. We compared the degree of insulin resistance during ACS attack and remission phase after treatment in individual patients (n = 104). During ACS, homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly increased (Pcovariance structure analysis with a strong impact (β: 0.398, P = 0.015). Intriguingly, a higher incidence of myocardial infarction relative to unstable angina pectoris, as well as a longer hospitalization period were observed in patients with larger ΔK, indicating that ΔK also reflects disease severity of ACS. Insulin resistance most likely increases during ACS; however, ΔK was positively correlated with plasma glucose level, which overwhelmed insulin resistance condition. The present study with covariance structure analysis suggests that there are potential endogenous glucose-coupled potassium lowering mechanisms, other than insulin, regulating glucose metabolism during ACS.

GLP-1 secretion is increased by inflammatory stimuli in an IL-6-dependent manner, leading to hyperinsulinemia and blood glucose lowering.

Science.gov (United States)

Kahles, Florian; Meyer, Christina; Möllmann, Julia; Diebold, Sebastian; Findeisen, Hannes M; Lebherz, Corinna; Trautwein, Christian; Koch, Alexander; Tacke, Frank; Marx, Nikolaus; Lehrke, Michael

2014-10-01

Hypoglycemia and hyperglycemia are both predictors for adverse outcome in critically ill patients. Hyperinsulinemia is induced by inflammatory stimuli as a relevant mechanism for glucose lowering in the critically ill. The incretine hormone GLP-1 was currently found to be induced by endotoxin, leading to insulin secretion and glucose lowering under inflammatory conditions in mice. Here, we describe GLP-1 secretion to be increased by a variety of inflammatory stimuli, including endotoxin, interleukin-1β (IL-1β), and IL-6. Although abrogation of IL-1 signaling proved insufficient to prevent endotoxin-dependent GLP-1 induction, this was abolished in the absence of IL-6 in respective knockout animals. Hence, we found endotoxin-dependent GLP-1 secretion to be mediated by an inflammatory cascade, with IL-6 being necessary and sufficient for GLP-1 induction. Functionally, augmentation of the GLP-1 system by pharmacological inhibition of DPP-4 caused hyperinsulinemia, suppression of glucagon release, and glucose lowering under endotoxic conditions, whereas inhibition of the GLP-1 receptor led to the opposite effect. Furthermore, total GLP-1 plasma levels were profoundly increased in 155 critically ill patients presenting to the intensive care unit (ICU) in comparison with 134 healthy control subjects. In the ICU cohort, GLP-1 plasma levels correlated with markers of inflammation and disease severity. Consequently, GLP-1 provides a novel link between the immune system and the gut with strong relevance for metabolic regulation in context of inflammation. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Postprandial glucose response to selected tropical fruits in normal glucose-tolerant Nigerians.

Science.gov (United States)

Edo, A; Eregie, A; Adediran, O; Ohwovoriole, A; Ebengho, S

2011-01-01

The glycemic response to commonly eaten fruits in Nigeria has not been reported. Therefore, this study assessed the plasma glucose response to selected fruits in Nigeria. Ten normal glucose-tolerant subjects randomly consumed 50 g carbohydrate portions of three fruits: banana (Musa paradisiaca), pineapple (Ananus comosus), and pawpaw (Carica papaya), and a 50-g glucose load at 1-week intervals. Blood samples were collected in the fasting state and half-hourly over a 2-h period post-ingestion of the fruits or glucose. The samples were analyzed for plasma glucose concentrations. Plasma glucose responses were assessed by the peak plasma glucose concentration, maximum increase in plasma glucose, 2-h postprandial plasma glucose level, and incremental area under the glucose curve and glycemic index (GI). The results showed that the blood glucose response to these three fruits was similar in terms of their incremental areas under the glucose curve, maximum increase in plasma glucose, and glycemic indices (GIs). The 2-h postprandial plasma glucose level of banana was significantly higher than that of pineapple, P < 0.025. The mean ± SEM GI values were as follows: pawpaw; 86 ± 26.8%; banana, 75.1 ± 21.8%; pineapple, 64.5 ± 11.3%. The GI of glucose is taken as 100. The GI of pineapple was significantly lower than that of glucose (P < 0.05). Banana, pawpaw, and pineapple produced a similar postprandial glucose response. Measured portions of these fruits may be used as fruit exchanges with pineapple having the most favorable glycemic response.

A decision support tool for appropriate glucose-lowering therapy in patients with type 2 diabetes.

Science.gov (United States)

Ampudia-Blasco, F Javier; Benhamou, Pierre Yves; Charpentier, Guillaume; Consoli, Agostino; Diamant, Michaela; Gallwitz, Baptist; Khunti, Kamlesh; Mathieu, Chantal; Ridderstråle, Martin; Seufert, Jochen; Tack, Cees; Vilsbøll, Tina; Phan, Tra-Mi; Stoevelaar, Herman

2015-03-01

Optimal glucose-lowering therapy in type 2 diabetes mellitus requires a patient-specific approach. Although a good framework, current guidelines are insufficiently detailed to address the different phenotypes and individual needs of patients seen in daily practice. We developed a patient-specific decision support tool based on a systematic analysis of expert opinion. Based on the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) 2012 position statement, a panel of 12 European experts rated the appropriateness (RAND/UCLA Appropriateness Method) of treatment strategies for 930 clinical scenarios, which were permutations of clinical variables considered relevant to treatment choice. These included current treatment, hemoglobin A1c difference from individualized target, risk of hypoglycemia, body mass index, life expectancy, and comorbidities. Treatment options included addition of a second or third agent, drug switches, and replacement by monotherapies if the patient was metformin-intolerant. Treatment costs were not considered. Appropriateness (appropriate, inappropriate, uncertain) was based on the median score and expert agreement. The panel recommendations were embedded in an online decision support tool (DiaScope(®); Novo Nordisk Health Care AG, Zürich, Switzerland). Treatment appropriateness was associated with (combinations of) the patient variables mentioned above. As second-line agents, dipeptidyl peptidase-4 inhibitors were considered appropriate in all scenarios, followed by glucagon-like peptide-1 receptor agonists (50%), insulins (33%), and sulfonylureas (25%), but not pioglitazone (0%). Ratings of third-line combinations followed a similar pattern. Disagreement was highest for regimens including pioglitazone, sulfonylureas, or insulins and was partly due to differences in panelists' opinions and in drug availability and reimbursement across European countries (although costs were disregarded in the rating process

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.

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

Science.gov (United States)

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

2016-12-01

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

Small intestinal glucose delivery affects the glucose-lowering effect of acute vildagliptin in type 2 diabetes

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Wu, T; Zhang, X; Trahair, LG

2016-01-01

of the DPP-4 inhibitor, vildagliptin (VILD), during intraduodenal (ID) glucose infusion at 2 different rates within the physiological range of gastric emptying, in type 2 diabetes. Participants and Design: A total of 16 diet-controlled type 2 diabetic patients were studied on 4 separate days in double...

Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in patients with type 2 diabetes.

Science.gov (United States)

Temizkan, S; Deyneli, O; Yasar, M; Arpa, M; Gunes, M; Yazici, D; Sirikci, O; Haklar, G; Imeryuz, N; Yavuz, D G

2015-02-01

Artificial sweeteners were thought to be metabolically inactive, but after demonstrating that the gustatory mechanism was also localized in the small intestine, suspicions about the metabolic effects of artificial sweeteners have emerged. The objective of this study was to determine the effect of artificial sweeteners (aspartame and sucralose) on blood glucose, insulin, c-peptide and glucagon-like peptide-1 (GLP-1) levels. Eight newly diagnosed drug-naive type 2 diabetic patients (mean age 51.5±9.2 years; F/M: 4/4) and eight healthy subjects (mean age 45.0±4.1 years; F/M: 4/4) underwent 75 g oral glucose tolerance test (OGTT). During OGTT, glucose, insulin, c-peptide and GLP-1 were measured at 15- min intervals for 120 min. The OGTTs were performed at three settings on different days, where subjects were given 72 mg of aspartame and 24 mg of sucralose in 200 ml of water or 200 ml of water alone 15 min before OGTT in a single-blinded randomized order. In healthy subjects, the total area under the curve (AUC) of glucose was statistically significantly lower in the sucralose setting than in the water setting (P=0.002). There was no difference between the aspartame setting and the water setting (P=0.53). Total AUC of insulin and c-peptide was similar in aspartame, sucralose and water settings. Total AUC of GLP-1 was significantly higher in the sucralose setting than in the water setting (P=0.04). Total AUC values of glucose, insulin, c-peptide and GLP-1 were not statistically different in three settings in type 2 diabetic patients. Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in newly diagnosed type 2 diabetic patients.

Assessment of insulin action in insulin-dependent diabetes mellitus using [6(14)C]glucose, [3(3)H]glucose, and [2(3)H]glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used

International Nuclear Information System (INIS)

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

1986-01-01

To determine whether [2(3)H], [3(3)H], and [6(14)C]glucose provide an equivalent assessment of glucose turnover in insulin-dependent diabetes mellitus (IDDM) and nondiabetic man, glucose utilization rates were measured using a simultaneous infusion of these isotopes before and during hyperinsulinemic euglycemic clamps. In the nondiabetic subjects, glucose turnover rates determined with [6(14)C]glucose during insulin infusion were lower (P less than 0.02) than those determined with [2(3)H]glucose and higher (P less than 0.01) than those determined with [3(3)H]glucose. In IDDM, glucose turnover rates measured with [6(14)C]glucose during insulin infusion were lower (P less than 0.05) than those determined with [2(3)H]glucose, but were not different from those determined with [3(3)H]glucose. All three isotopes indicated the presence of insulin resistance. However, using [3(3)H]glucose led to the erroneous conclusion that glucose utilization was not significantly decreased at high insulin concentrations in the diabetic patients. [6(14)C] and [3(3)H]glucose but not [2(3)H]glucose indicated impairment in insulin-induced suppression of glucose production. These results indicate that tritiated isotopes do not necessarily equally reflect the pattern of glucose metabolism in diabetic and nondiabetic man

Nonsuppressed Glucagon After Glucose Challenge as a Potential Predictor for Glucose Tolerance.

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Wagner, Róbert; Hakaste, Liisa H; Ahlqvist, Emma; Heni, Martin; Machann, Jürgen; Schick, Fritz; Van Obberghen, Emmanuel; Stefan, Norbert; Gallwitz, Baptist; Tuomi, Tiinamaija; Häring, Hans-Ulrich; Groop, Leif; Fritsche, Andreas

2017-05-01

Glucagon levels are classically suppressed after glucose challenge. It is still not clear as to whether a lack of suppression contributes to hyperglycemia and thus to the development of diabetes. We investigated the association of postchallenge change in glucagon during oral glucose tolerance tests (OGTTs), hypothesizing that higher postchallenge glucagon levels are observed in subjects with impaired glucose tolerance (IGT). Glucagon levels were measured during OGTT in a total of 4,194 individuals without diabetes in three large European cohorts. Longitudinal changes in glucagon suppression were investigated in 50 participants undergoing a lifestyle intervention. Only 66-79% of participants showed suppression of glucagon at 120 min (fold change glucagon 120/0 change glucagon 120/0 ≥1). Participants with nonsuppressed glucagon 120 had a lower risk of IGT in all cohorts (odds ratio 0.44-0.53, P change glucagon 120/0 was associated with an improvement in insulin sensitivity ( P = 0.003). We characterize nonsuppressed glucagon 120 during the OGTT. Lower glucagon suppression after oral glucose administration is associated with a metabolically healthier phenotype, suggesting that it is not an adverse phenomenon. © 2017 by the American Diabetes Association.

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

DEFF Research Database (Denmark)

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

2013-01-01

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

A tripeptide Diapin effectively lowers blood glucose levels in male type 2 diabetes mice by increasing blood levels of insulin and GLP-1.

Directory of Open Access Journals (Sweden)

Jifeng Zhang

Full Text Available The prevalence of type 2 diabetes (T2D is rapidly increasing worldwide. Effective therapies, such as insulin and Glucagon-like peptide-1 (GLP-1, require injections, which are costly and result in less patient compliance. Here, we report the identification of a tripeptide with significant potential to treat T2D. The peptide, referred to as Diapin, is comprised of three natural L-amino acids, GlyGlyLeu. Glucose tolerance tests showed that oral administration of Diapin effectively lowered blood glucose after oral glucose loading in both normal C57BL/6J mice and T2D mouse models, including KKay, db/db, ob/ob mice, and high fat diet-induced obesity/T2D mice. In addition, Diapin treatment significantly reduced casual blood glucose in KKay diabetic mice in a time-dependent manner without causing hypoglycemia. Furthermore, we found that plasma GLP-1 and insulin levels in diabetic models were significantly increased with Diapin treatment compared to that in the controls. In summary, our findings establish that a peptide with minimum of three amino acids can improve glucose homeostasis and Diapin shows promise as a novel pharmaceutical agent to treat patients with T2D through its dual effects on GLP-1 and insulin secretion.

Lowering blood glucose during hip surgery does not influence coagulation activation

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Marjolein K. Sechterberger

2015-06-01

Conclusion: Although the human GLP-1 analogue liraglutide moderately reduced post-operative blood glucose levels in non-diabetic and prediabetic obese patients undergoing elective hip surgery, no changes were observed with respect to coagulation activation.

Accuracy evaluation of contour next compared with five blood glucose monitoring systems across a wide range of blood glucose concentrations occurring in a clinical research setting.

Science.gov (United States)

Klaff, Leslie J; Brazg, Ronald; Hughes, Kristen; Tideman, Ann M; Schachner, Holly C; Stenger, Patricia; Pardo, Scott; Dunne, Nancy; Parkes, Joan Lee

2015-01-01

This study evaluated the accuracy of Contour(®) Next (CN; Bayer HealthCare LLC, Diabetes Care, Whippany, NJ) compared with five blood glucose monitoring systems (BGMSs) across a wide range of clinically occurring blood glucose levels. Subjects (n=146) were ≥ 18 years and had type 1 or type 2 diabetes. Subjects' glucose levels were safely lowered or raised to provide a wide range of glucose values. Capillary blood samples were tested on six BGMSs and a YSI glucose analyzer (YSI Life Sciences, Inc., Yellow Springs, OH) as the reference. Extreme glucose values were achieved by glucose modification of the blood sample. System accuracy was assessed by mean absolute difference (MAD) and mean absolute relative difference (MARD) across several glucose ranges, with glucose range (Abbott Diabetes Care, Inc., Alameda, CA), 2.77 mg/dL; OneTouch(®) Ultra(®) 2 (LifeScan, Inc., Milpitas, CA), 10.20 mg/dL; OneTouch(®) Verio(®) Pro (LifeScan, Inc.), 4.53 mg/dL; and Truetrack(®) (Nipro Diagnostics, Inc., Fort Lauderdale, FL), 11.08 mg/dL. The lowest MAD in the low glucose range, from CN, was statistically significantly lower than those of the other BGMSs with the exception of the FSL. CN also had a statistically significantly lower MARD than all other BGMSs in the low glucose range. In the overall glucose range (21-496 mg/dL), CN yielded the lowest MAD and MARD values, which were statistically significantly lower in comparison with the other BGMSs. When compared with other BGMSs, CN demonstrated the lowest mean deviation from the reference value (by MAD and MARD) across multiple glucose ranges.

A Decision Support Tool for Appropriate Glucose-Lowering Therapy in Patients with Type 2 Diabetes

DEFF Research Database (Denmark)

Ampudia-Blasco, F Javier; Benhamou, Pierre Yves; Charpentier, Guillaume

2014-01-01

Abstract Background: Optimal glucose-lowering therapy in type 2 diabetes mellitus requires a patient-specific approach. Although a good framework, current guidelines are insufficiently detailed to address the different phenotypes and individual needs of patients seen in daily practice. We developed...... a patient-specific decision support tool based on a systematic analysis of expert opinion. Materials and Methods: Based on the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) 2012 position statement, a panel of 12 European experts rated the appropriateness (RAND....... The panel recommendations were embedded in an online decision support tool (DiaScope(®); Novo Nordisk Health Care AG, Zürich, Switzerland). Results: Treatment appropriateness was associated with (combinations of) the patient variables mentioned above. As second-line agents, dipeptidyl peptidase-4 inhibitors...

CSF glucose test

Science.gov (United States)

... in the space surrounding the spinal cord and brain. ... Abnormal results include higher and lower glucose levels. Abnormal results may be due to: Infection (bacterial or fungus) Inflammation of the central nervous system Tumor

Concomitant Intake of Quercetin with a Grain-Based Diet Acutely Lowers Postprandial Plasma Glucose and Lipid Concentrations in Pigs

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Silvia Wein

2014-01-01

Full Text Available Treatment goals of diabetes mellitus type 2 (DMT2 include glycemic control and reduction of nonglycemic risk factors, for example, dyslipidemia. Quercetin, a plant-derived polyphenol, often discussed for possible antidiabetic effects, was investigated for acute postprandial glucose- and lipid-lowering effects in healthy growing pigs. Male pigs (n = 16, body weight = BW 25–30 kg were fed flavonoid-poor grain-based meals without (GBM or with quercetin (GBMQ. In a first experiment, postprandial plasma concentrations of glucose, nonesterified fatty acids (NEFA, and triacylglycerols were analyzed in 8 pigs receiving 500 g of either GBM or GBMQ (10 mg/kg BW in a cross-over design. Blood samples were collected before, and up to 5 h every 30 min, as well as 6 and 8 h after the feeding. In the second experiment, 2 h after ingestions of 1000 g of either GBM or GBMQ (50 mg/kg BW animals were sacrificed; gastric content was collected and analyzed for dry matter content. Quercetin ingestion reduced postprandial glucose, NEFA, and TG concentration, but two hours after ingestion of the meal no effect on gastric emptying was observed. Our results point to inhibitory effects of quercetin on nutrient absorption, which appear not to be attributable to delayed gastric emptying.

Efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose: Results of a randomized controlled trial.

Science.gov (United States)

Göke, R; Eschenbach, P; Dütting, E D

2015-06-01

This study compared the efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose (FPG) as single-pill combinations (SPCs) with metformin. The randomized crossover, open-label, active-controlled study design assessed the FPG-lowering abilities of a vildagliptin/metformin (50/1000 mg twice daily) SPC compared with a sitagliptin/metformin (50/1000 mg twice daily) SPC after 2 weeks of treatment in 99 type 2 diabetes patients uncontrolled by stable metformin therapy (1000-2000 mg/day). The change in FPG from baseline to day 14 was significantly greater (P vildagliptin [-21.9 mg/dL (SD 27.0)] than with sitagliptin [-14.5 mg/dL (SD 23.0)]. After 14 days of treatment, the mean FPG was 137.8 mg/dL (SD 28.5) with vildagliptin and 140.1mg/dL (SD 26.5) with sitagliptin (P vildagliptin produced a significantly greater reduction in FPG vs baseline compared with sitagliptin, which may translate into clinical relevance. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia.

Science.gov (United States)

Strilka, Richard J; Stull, Mamie C; Clemens, Michael S; McCaver, Stewart C; Armen, Scott B

2016-01-27

The critically ill can have persistent dysglycemia during the "subacute" recovery phase of their illness because of altered gene expression; it is also not uncommon for these patients to receive continuous enteral nutrition during this time. The optimal short-acting subcutaneous insulin therapy that should be used in this clinical scenario, however, is unknown. Our aim was to conduct a qualitative numerical study of the glucose-insulin dynamics within this patient population to answer the above question. This analysis may help clinicians design a relevant clinical trial. Eight virtual patients with stress hyperglycemia were simulated by means of a mathematical model. Each virtual patient had a different combination of insulin resistance and insulin deficiency that defined their unique stress hyperglycemia state; the rate of gluconeogenesis was also doubled. The patients received 25 injections of subcutaneous regular or Lispro insulin (0-6 U) with 3 rates of continuous nutrition. The main outcome measurements were the change in mean glucose concentration, the change in glucose variability, and hypoglycemic episodes. These end points were interpreted by how the ultradian oscillations of glucose concentration were affected by each insulin preparation. Subcutaneous regular insulin lowered both mean glucose concentrations and glucose variability in a linear fashion. No hypoglycemic episodes were noted. Although subcutaneous Lispro insulin lowered mean glucose concentrations, glucose variability increased in a nonlinear fashion. In patients with high insulin resistance and nutrition at goal, "rebound hyperglycemia" was noted after the insulin analog was rapidly metabolized. When the nutritional source was removed, hypoglycemia tended to occur at higher Lispro insulin doses. Finally, patients with severe insulin resistance seemed the most sensitive to insulin concentration changes. Subcutaneous regular insulin consistently lowered mean glucose concentrations and glucose

Glucose patterns during an oral glucose tolerance test and associations with future diabetes, cardiovascular disease and all-cause mortality rate

DEFF Research Database (Denmark)

Hulman, Adam; Vistisen, Dorte; Glümer, Charlotte

2018-01-01

classes. Results: Four distinct glucose patterns during the OGTT were identified. One pattern was characterised by high 30 min but low 2 h glucose values. Participants with this pattern had an increased risk of developing diabetes compared with participants with lower 30 min and 2 h glucose levels (HR 4...

Hyperglycemia (High Blood Glucose)

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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 ...

Ficus Deltoidea Enhance Glucose Uptake Activity in Cultured Muscle Cells

International Nuclear Information System (INIS)

Zainah Adam; Shafii Khamis; Amin Ismail; Muhajir Hamid

2015-01-01

Ficus deltoidea or locally known as Mas cotek is one of the common medicinal plants used in Malaysia. Our previous studies showed that this plant have blood glucose lowering effect. Glucose uptake into muscle and adipocytes cells is one of the known mechanisms of blood glucose lowering effect. This study was performed to evaluate the effect of Ficus deltoidea on glucose uptake activity into muscle cells. The cells were incubated with Ficus deltoidea extracts either alone or combination with insulin. Amount of glucose uptake by L6 myotubes was determined using glucose tracer, 2-deoxy-(1- 3 H 1 )-glucose. The results showed that Ficus deltoidea extracts at particular doses enhanced basal or insulin-mediated glucose uptake into muscle cells significantly. Hot aqueous extract enhanced glucose uptake at the low concentration (10 μg/ ml) whereas methanolic extract enhanced glucose uptake at low and high concentrations. Methanolic extract also mimicked insulin activity during enhancing glucose uptake into L^ muscle cells. Glucose uptake activity of Ficus deltoidea could be attributed by the phenolic compound presence in the plant. This study had shown that Ficus deltoidea has the ability to enhance glucose uptake into muscle cells which is partly contributed the antidiabetic activity of this plant. (author)

Hyperglycemia (High Blood Glucose)

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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 Advisor Tools ...

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...... resistance. Postabsorptive glucose production (P = 0.64) and the fractional....... Hepatic GE was lower during cortisol than during saline infusion (2.39 +/- 0.24 vs. 3.82 +/- 0.51 ml.kg-1.min-1; P

Initiation and persistence to statin treatment in patients with diabetes receiving glucose-lowering medications 1997- 2006

DEFF Research Database (Denmark)

Dominguez, H; Schramm, T K; Norgaard, M L

2009-01-01

AIMS: Since 2001 guidelines recommend statin treatment in most patients with diabetes. We investigated secular changes in initiation and persistence to statin treatment during a 10-year period in a nationwide cohort of patients initiating glucose-lowering medication (GLM). METHODS: All Danish...... citizens 30 years and older who claimed prescriptions of GLM between 1997 and 2006 were identified from nationwide registers of drug dispensing from pharmacies and hospitalizations, and followed until 2006. Statin treatment was registered if a prescription was claimed during the period. By logistic...... regression we analyzed factors related to initiation and persistence to statin treatment. RESULTS: In total 128,106 patients were included. In 1997 only 7% of the patients receiving GLM claimed statins within the first year after GLM initiation. Despite increasing statin prescriptions the following years...

Hyperglycemia (High Blood Glucose)

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Full Text Available ... 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 ...

Amperometric Bioelectronic Tongue for glucose determination

Directory of Open Access Journals (Sweden)

Yazan Al-Issa

2015-03-01

Full Text Available An amperometric Bioelectronic Tongue is reported for glucose determination that contains eight sensor electrodes constructed using different metal electrodes (Pt, Au, oxidoreductase enzymes (glucose oxidase, ascorbate oxidase, uricase, and membrane coatings (Nafion, chitosan. The response to varying concentrations of glucose, ascorbic acid, uric acid, and acetaminophen was tested for two models, concentration determination by current density measurements at individual electrodes and concentration determination by a linear regression model for the entire electrode array. The reduced chi-squared for the full array model was found to be about one order of magnitude lower than that for the individual-electrode model. Discrimination of glucose from chemical interference by the other three species is accomplished through a combination of enzyme catalysis, metal electrocatalysis, and membrane surface charge. The benefit of incorporating enzyme electrodes into the sensor array is illustrated by the lower correlation coefficients between different enzyme electrodes relative to non-enzyme coated electrodes. This approach can be more generally applied to detection of other substrates of oxidoreductase enzymes.

Impact of sex and glucose-lowering treatments on hypoglycaemic symptoms in people with type 2 diabetes and chronic kidney disease. The French Chronic Kidney Disease - Renal Epidemiology and Information Network (CKD-REIN) Study.

Science.gov (United States)

Balkau, B; Metzger, M; Andreelli, F; Frimat, L; Speyer, E; Combe, C; Laville, M; Jacquelinet, C; Briançon, S; Ayav, C; Massy, Z; Pisoni, R L; Stengel, B; Fouque, D

2018-04-06

To describe current practices of glucose-lowering treatments in people with diabetes and chronic kidney disease (CKD), the associated glucose control and hypoglycaemic symptoms, with an emphasis on sex differences. Among the 3033 patients with CKD stages 3-5 recruited into the French CKD-REIN study, 645 men and 288 women had type 2 diabetes and were treated by glucose-lowering drugs. Overall, 31% were treated only with insulin, 28% with combinations of insulin and another drug, 42% with non-insulin glucose-lowering drugs. In CKD stage 3, 40% of patients used metformin, 12% at stages 4&5, similar for men and women; in CKD stage 3, 53% used insulin, similar for men and women, but at stages 4&5, 59% of men and 77% of women used insulin. Patients were reasonably well controlled, with a median HbA1c of 7.1% (54mmol/mol) in men, 7.4% (57mmol/mol) in women (P=0.0003). Hypoglycaemic symptoms were reported by 40% of men and 59% of women; they were not associated with the estimated glomerular filtration rate, nor with albuminuria or with HbA1c in multivariable analyses, but they were more frequent in people treated with insulin, particularly with fast-acting and pre-mixed insulins. Glucose-lowering treatment, HbA1c and hypoglycaemic symptoms were sex dependent. Metformin use was similar in men and women, but unexpectedly low in CKD stage 3; its use could be encouraged rather than resorting to insulin. Hypoglycaemic symptoms were frequent and need to be more closely monitored, with appropriate patient-education, especially in women. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Study on kinetics of glucose uptake by some species of plankton

Science.gov (United States)

Li, Wenquan; Wang, Xian; Zhang, Yaohua

1993-03-01

The rates of glucose uptake by some species of plankton were determined by3H-glucose tracer method. Experimental results indicated that the observed glucose uptake at natural seawater concentrations by Platymonas subcordiformis and Brachionus plicatilis was principally a metabolic process fitted with the Michaelis-Menten equation in the range of adaptive temperatures. Heterotrophic uptake by Platymonas subcordiformis was mainly dependent on diffusion at high glucose levels. The uptake by Brachionus plicatilis showed active transport even at high glucose levels, indicating its high heterotrophic activity. The uptake rate by Artemia salina was lower, and its V m/K ratio was lower than those of the other two species of plankton.

Decreased serum glucose and glycosylated hemoglobin levels in patients with Chuvash polycythemia: a role for HIF in glucose metabolism

Science.gov (United States)

McClain, Donald A.; Abuelgasim, Khadega A.; Nouraie, Mehdi; Salomon-Andonie, Juan; Niu, Xiaomei; Miasnikova, Galina; Polyakova, Lydia A.; Sergueeva, Adelina; Okhotin, Daniel J.; Cherqaoui, Rabia; Okhotin, David; Cox, James E.; Swierczek, Sabina; Song, Jihyun; Simon, M.Celeste; Huang, Jingyu; Simcox, Judith A.; Yoon, Donghoon; Prchal, Josef T.; Gordeuk, Victor R.

2012-01-01

In Chuvash polycythemia, a homozygous 598C>T mutation in the von Hippel-Lindau gene (VHL) leads to an R200W substitution in VHL protein, impaired degradation of α-subunits of hypoxia inducible factor (HIF)-1 and HIF-2, and augmented hypoxic responses during normoxia. Chronic hypoxia of high altitude is associated with decreased serum glucose and insulin concentrations. Other investigators reported that HIF-1 promotes cellular glucose uptake by increased expression of GLUT1 and increased glycolysis by increased expression of enzymes such as PDK. On the other hand, inactivation of Vhl in murine liver leads to hypoglycemia associated with a HIF-2-related decrease in the expression of the gluconeogenic enzymes genes Pepck, G6pc, and Glut2. We therefore hypothesized that glucose concentrations are decreased in individuals with Chuvash polycythemia. We found that 88 Chuvash VHLR200W homozygotes had lower random glucose and glycosylated hemoglobin A1c levels than 52 Chuvash subjects with wildtype VHL alleles. Serum metabolomics revealed higher glycerol and citrate levels in the VHLR200W homozygotes. We expanded these observations in VHLR200W homozygote mice and found that they had lower fasting glucose values and lower glucose excursions than wild-type control mice but no change in fasting insulin concentrations. Hepatic expression of Glut2 and G6pc but not Pdk2 was decreased and skeletal muscle expression of Glut1, Pdk1 and Pdk4 was increased. These results suggest that both decreased hepatic gluconeogenesis and increased skeletal uptake and glycolysis contribute to the decreased glucose concentrations. Further study is needed to determine whether pharmacologically manipulating HIF expression might be beneficial for treatment of diabetic patients. PMID:23015148

Coexistence of insulin resistance and increased glucose tolerance in pregnant rats: a physiological mechanism for glucose maintenance.

Science.gov (United States)

Carrara, Marcia Aparecida; Batista, Márcia Regina; Saruhashi, Tiago Ribeiro; Felisberto, Antonio Machado; Guilhermetti, Marcio; Bazotte, Roberto Barbosa

2012-06-06

The contribution of insulin resistance (IR) and glucose tolerance to the maintenance of blood glucose levels in non diabetic pregnant Wistar rats (PWR) was investigated. PWR were submitted to conventional insulin tolerance test (ITT) and glucose tolerance test (GTT) using blood sample collected 0, 10 and 60 min after intraperitoneal insulin (1 U/kg) or oral (gavage) glucose (1g/kg) administration. Moreover, ITT, GTT and the kinetics of glucose concentration changes in the fed and fasted states were evaluated with a real-time continuous glucose monitoring system (RT-CGMS) technique. Furthermore, the contribution of the liver glucose production was investigated. Conventional ITT and GTT at 0, 7, 14 and 20 days of pregnancy revealed increased IR and glucose tolerance after 20 days of pregnancy. Thus, this period of pregnancy was used to investigate the kinetics of glucose changes with the RT-CGMS technique. PWR (day 20) exhibited a lower (pinsulin sensitivity and/or glucose tolerance during late pregnancy. In contrast to the general view that IR is a pathological process associated with gestational diabetes, a certain degree of IR may represent an important physiological mechanism for blood glucose maintenance during fasting. Copyright © 2012 Elsevier Inc. All rights reserved.

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

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Emmanouil Apostolidis

2013-07-01

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

Evidence for brain glucose dysregulation in Alzheimer's disease.

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

2018-03-01

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

Effect of levulose containing sweets on blood and salivary glucose levels.

Science.gov (United States)

Subramaniam, Priya; K L, Girish Babu; Gona, Harsha

2015-06-01

It is common that many diabetic patients crave for sweets which are normally prohibited. To satisfy their desire to have sweets, alternative sweeteners have been introduced to provide sweetness to some items of their diabetic diet. To (1) assess the effect of sweets containing levulose on glucose levels in blood and saliva, and (2) compare it with effect of sweets containing sucrose on blood and saliva levels of glucose. The study consisted of 20 healthy participants, aged 17-20 years. Two sweet preparations of 36 g each were selected for the study. One preparation was sweetened with levulose (diabetic sweet; Group I) and the other with sucrose (regular sweet; Group II). Blood sugar and salivary glucose levels were estimated before and after the consumption of diabetic and regular sweets. The mean increase in salivary glucose level was lower in Group I than in Group II. Similarly, increase in blood glucose levels in Group I was lower and highly significant. In comparison with regular sweets, consumption of levulose containing sweet resulted in significantly lower blood and salivary glucose levels.

Glucose kinetics at rest and during exercise in gluconeogenesis-inhibited rats

International Nuclear Information System (INIS)

Turcotte, L.P.

1988-01-01

To evaluate the role played by gluconeogenesis in blood glucose homeostasis, untrained and trained rats were injected with mercaptopicolinic acid (MPA), a known inhibitor of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase. Glucose turnover, recycling and oxidation rates were assessed by primed-continuous infusion of [U- 14 C]- and [6- 3 H] glucose at rest and during submaximal exercise at 13.4 m/min on level grade. When compared to the untrained sham-injected animals, the untrained MPA-treated animals had 22% lower and 44% higher resting blood glucose and lactate concentrations, respectively. Resting glucose turnover, calculated from [6- 3 H]glucose, was 32% lower in the MPA-treated animals than in the sham-injected animals. During exercise, turnover increased in the sham-injected animals but remained unchanged in the MPA-treated animals. MPA-treated animals had no glucose recycling at rest or during exercise. Exercise further decreased blood glucose concentration and increased blood lactate concentration in the MPA-treated animals, but MPA treatment did not change the exercise-induced increases in glucose oxidation rate, % total VCO 2 arising from glucose oxidation and metabolic clearance rate of glucose

Hyperglycemia (High Blood Glucose)

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Hyperglycemia (High Blood Glucose)

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Hyperglycemia (High Blood Glucose)

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Hyperglycemia (High Blood Glucose)

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Glucose-induced effects and joker function of glucose: endocrine or genotoxic prevalence?

Science.gov (United States)

Berstein, L M; Vasilyev, D A; Poroshina, T E; Kovalenko, I G

2006-10-01

The steady increase in chronic "glycemic load" is characteristic for modern times. Among myriad of glucose functions, two principals can be emphasized: first, endocrine (in particular, ability to induce insulin secretion) and second, DNA-damaging related to formation of reactive oxygen species (ROS). It was suggested by us earlier that a shift in the ratio of mentioned functions reflects a possible "joker" role of glucose as an important modifier of human pathology. Therefore, we embarked on a study to investigate an individual effect of peroral glucose challenge on serum insulin level and ROS generation by mononuclears (luminol-dependent/latex-induced chemiluminescence) in 20 healthy people aged between 28-75. Concentrations of glucose, blood lipids, carbonylated proteins, malondialdehyde, leptin and TNF-alpha were determined as well. On the basis of received data two separate groups could be distinguished: one (n=8), in which glucose stimulation of ROS generation by mononuclears was increased and relatively prevailed over induction of insulin secretion (state of the so called glucose-induced genotoxicity, GIGT), and another (n=12), in which signs of GIGT were not revealed. People who belonged to the first group were characterized with a tendency to lower body mass index, blood leptin and cholesterol and to higher TNF-alpha concentration. Thus, if joker function of glucose is realized in "genotoxic mode", the phenotype (and probably genotype) of subjects may be rather distinctive to the one discovered in glucose-induced "endocrine prevalence". Whether such changes may serve as a pro-mutagenic or pro-endocrine basis for the rise of different chronic diseases or, rather, different features/aggressiveness of the same disease warrants further study.

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

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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.

Cardiovascular effects of sodium glucose cotransporter 2 inhibitors

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Cavaiola, Tricia Santos; Pettus, Jeremy

2018-01-01

As the first cardiovascular (CV) outcome trial of a glucose-lowering agent to demonstrate a reduction in the risk of CV events in patients with type 2 diabetes mellitus (T2DM), the EMPAgliflozin Removal of Excess Glucose: Cardiovascular OUTCOME Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME®) trial, which investigated the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, has generated great interest among health care professionals. CV outcomes data for another SGLT2 inhibitor, canagliflozin, have been published recently in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program, as have CV data from the retrospective real-world study Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL), which compared SGLT2 inhibitors with other classes of glucose-lowering drugs. This review discusses the results of these three studies and, with a focus on EMPA-REG OUTCOME, examines the possible mechanisms by which SGLT2 inhibitors may reduce CV risk in patients with T2DM. PMID:29695924

Hyperglycemia (High Blood Glucose)

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Glucose Homeostasis During Short-term and Prolonged Exposure to High Altitudes

Science.gov (United States)

Ader, Marilyn; Bergman, Richard N.

2015-01-01

Most of the literature related to high altitude medicine is devoted to the short-term effects of high-altitude exposure on human physiology. However, long-term effects of living at high altitudes may be more important in relation to human disease because more than 400 million people worldwide reside above 1500 m. Interestingly, individuals living at higher altitudes have a lower fasting glycemia and better glucose tolerance compared with those who live near sea level. There is also emerging evidence of the lower prevalence of both obesity and diabetes at higher altitudes. The mechanisms underlying improved glucose control at higher altitudes remain unclear. In this review, we present the most current evidence about glucose homeostasis in residents living above 1500 m and discuss possible mechanisms that could explain the lower fasting glycemia and lower prevalence of obesity and diabetes in this population. Understanding the mechanisms that regulate and maintain the lower fasting glycemia in individuals who live at higher altitudes could lead to new therapeutics for impaired glucose homeostasis. PMID:25675133

Intestinal glucose transport and salinity adaptation in a euryhaline teleost

International Nuclear Information System (INIS)

Reshkin, S.J.; Ahearn, G.A.

1987-01-01

Glucose transport by upper and lower intestinal brush-border membrane vesicles of the African tilapia (Oreochromis mossambicus) was characterized in fish acclimated to either freshwater of full-strength sea water. D-[ 3 H]-glucose uptake by vesicles was stimulated by a transmembrane Na gradient, was electrogenic, and was enhanced by countertransport of either D-glucose or D-galactose. Glucose transport was greater in the upper intestine than in the lower intestine and in sea water animals rather than in fish acclimated to freshwater. Glucose influx (10-s uptake) involved both saturable and nonsaturable transport components. Sea water adaptation increased apparent glucose influx K/sub t/, J/sub max/, apparent diffusional permeability (P), and the apparent Na affinity of the cotransport system in both intestinal segments, but the stoichiometry of Na-glucose transfer (1:1) was unaffected by differential saline conditions or gut region. It is suggested that increased sugar transport in sea water animals is due to the combination of enhanced Na-binding properties and an increase in number or transfer rate of the transport proteins. Freshwater animals compensate for reduced Na affinity of the coupled process by markedly increasing the protein affinity for glucose

Resistant starch lowers postprandial glucose and leptin in overweight adults consuming a moderate-to-high-fat diet: a randomized-controlled trial.

Science.gov (United States)

Maziarz, Mindy Patterson; Preisendanz, Sara; Juma, Shanil; Imrhan, Victorine; Prasad, Chandan; Vijayagopal, Parakat

2017-02-21

High-amylose maize resistant starch type 2 (HAM-RS2) stimulates gut-derived satiety peptides and reduces adiposity in animals. Human studies have not supported these findings despite improvements in glucose homeostasis and insulin sensitivity after HAM-RS2 intake which can lower adiposity-related disease risk. The primary objective of this study was to evaluate the impact of HAM-RS2 consumption on blood glucose homeostasis in overweight, healthy adults. We also examined changes in biomarkers of satiety (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], and leptin) and body composition determined by anthropometrics and dual-energy x-ray absorptiometry, dietary intake, and subjective satiety measured by a visual analogue scale following HAM-RS2 consumption. Using a randomized-controlled, parallel-arm, double-blind design, 18 overweight, healthy adults consumed either muffins enriched with 30 g HAM-RS2 (n = 11) or 0 g HAM-RS2 (control; n = 7) daily for 6 weeks. The HAM-RS2 and control muffins were similar in total calories and available carbohydrate. At baseline, total PYY concentrations were significantly higher 120 min following the consumption of study muffins in the HAM-RS2 group than control group (P = 0.043). Within the HAM-RS2 group, the area under the curve (AUC) glucose (P = 0.028), AUC leptin (P = 0.022), and postprandial 120-min leptin (P = 0.028) decreased independent of changes in body composition or overall energy intake at the end of 6 weeks. Fasting total PYY increased (P = 0.033) in the HAM-RS2 group, but changes in insulin or total GLP-1 were not observed. Mean overall change in subjective satiety score did not correlate with mean AUC biomarker changes suggesting the satiety peptides did not elicit a satiation response or change in overall total caloric intake. The metabolic response from HAM-RS2 occurred despite the habitual intake of a moderate-to-high-fat diet (mean range 34.5% to 39.4% of total calories). Consuming 30�

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Hyperglycemia (High Blood Glucose)

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Cardiovascular effects of sodium glucose cotransporter 2 inhibitors

Directory of Open Access Journals (Sweden)

Santos Cavaiola T

2018-04-01

Full Text Available Tricia Santos Cavaiola, Jeremy Pettus Division of Endocrinology and Metabolism, University of California San Diego, San Diego, CA, USA Abstract: As the first cardiovascular (CV outcome trial of a glucose-lowering agent to demonstrate a reduction in the risk of CV events in patients with type 2 diabetes mellitus (T2DM, the EMPAgliflozin Removal of Excess Glucose: Cardiovascular OUTCOME Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME® trial, which investigated the sodium glucose cotransporter 2 (SGLT2 inhibitor empagliflozin, has generated great interest among health care professionals. CV outcomes data for another SGLT2 inhibitor, canagliflozin, have been published recently in the CANagliflozin CardioVascular Assessment Study (CANVAS Program, as have CV data from the retrospective real-world study Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL, which compared SGLT2 inhibitors with other classes of glucose-lowering drugs. This review discusses the results of these three studies and, with a focus on EMPA-REG OUTCOME, examines the possible mechanisms by which SGLT2 inhibitors may reduce CV risk in patients with T2DM. Keywords: canagliflozin, cardiovascular outcomes, dapagliflozin, empagliflozin, mechanisms, sodium glucose cotransporter 2 inhibitors

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

Directory of Open Access Journals (Sweden)

Antoine E Roux

2009-03-01

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

Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control

NARCIS (Netherlands)

Vos, Rimke C; van Avendonk, Mariëlle JP; Jansen, Hanneke; Goudswaard, Alexander N; van den Donk, Maureen; Gorter, Kees; Kerssen, Anneloes; Rutten, Guy EHM

2016-01-01

BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of

Separation of glucose and fructose by freezing crystallization

Energy Technology Data Exchange (ETDEWEB)

Silva, A.T.C.R.; Martinez, K.C.L. [Federal University of Sao Carlos, Chemical Engineering Department, Industrial Crystallization Laboratory - Rod. Washington Luis km 235, P.O. Box 676, CEP:13565-905, Sao Carlos-SP (Brazil); Brito, A.B.N. [Federal University of Espirito Santo, Engineering and Computing Dept. - Rodovia BR 101 Norte, Km. 60, Bairro Litoraneo, CEP 29932-540, Sao Mateus-ES (Brazil); Giulietti, M. [Laboratory of Chemical Process and Particle Technology of Institute for Technological Research, Av. Prof. Almeida Prado 532 -Universitary City, CEP:05508-901, Sao Paulo-SP (Brazil)

2010-10-15

This work comprises the implementation of a methodology for the study of an industrial crystallization process by freezing and cooling to be applied in the separation of sugars with industrial relevance (glucose and fructose). The main interest is the production of fructose. This sugar is obtained by sucrose hydrolysis in acidic solutions, which yields an equimolar mixture of glucose and fructose. The developed separation process is based on the solubility difference between the sugars. Experiments were carried out in a jacketed glass crystallizer where the solution coming from the sucrose acid inversion was submitted to a slow cooling. Since glucose has lower solubility than fructose, it crystallizes in the bulk as the temperature is lowered, thus it can be removed from the solution by filtration or centrifugation. Best fructose-glucose separation was achieved for a total sugar concentration of 50 wt%. (copyright 2010 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Glucose effectiveness is a critical pathogenic factor leading to glucose intolerance and type 2 diabetes: An ignored hypothesis.

Science.gov (United States)

Alford, F P; Henriksen, J E; Rantzau, C; Beck-Nielsen, H

2018-02-16

Although the ability of glucose to mediate its own in vivo metabolism is long documented, the quantitative measurement of whole body glucose-mediated glucose disposal at basal insulin levels (glucose effectiveness [GE]), followed the introduction of the Minimal Model intravenous glucose tolerance test technique. A literature review, combined with our own studies, of the role of GE in glucose metabolism in normal and "at risk" individuals, was undertaken to determine GE's contribution to glucose homeostasis. GE accounts for ~45% to 65% of glucose disposal in man. A negative association between GE and insulin meditated glucose disposal (Si), is present in normal subjects without a family history of type 2 diabetes mellitus but is absent in normoglycaemic "at risk" relatives with a positive family history of diabetes mellitus. Intracellular GE disposal is mediated by mass action of glucose through the skeletal muscle membrane via facilitated Glut 4 transporters. However, GE is frequently forgotten as a significant contributor to the development of glucose intolerance in "at risk" individuals. Only limited studies have examined the role of a lower GE in such normoglycemic subjects with preexisting mild insulin resistance and β-cell dysfunction. These studies demonstrate that in "at risk" individuals, an initial low GE is a key contributor and predictor of future glucose intolerance, whereas an initial raised GE is protective against future glucose intolerance. In "at risk" individuals, a low GE and genetically determined vulnerable β-cell function are more critical determinants of future glucose intolerance than their preexisting insulin-resistant state. Copyright © 2018 John Wiley & Sons, Ltd.

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

Science.gov (United States)

Wu, Jing; Sun, Qiuhong; Yang, Hua

2015-05-19

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

Is Insulin Action in the Brain Relevant in Regulating Blood Glucose in Humans?

Science.gov (United States)

Dash, Satya; Xiao, Changting; Morgantini, Cecilia; Koulajian, Khajag; Lewis, Gary F

2015-07-01

In addition to its direct action on the liver to lower hepatic glucose production, insulin action in the central nervous system (CNS) also lowers hepatic glucose production in rodents after 4 hours. Although CNS insulin action (CNSIA) modulates hepatic glycogen synthesis in dogs, it has no net effect on hepatic glucose output over a 4-hour period. The role of CNSIA in regulating plasma glucose has recently been examined in humans and is the focus of this review. Intransal insulin (INI) administration increases CNS insulin concentration. Hence, INI can address whether CNSIA regulates plasma glucose concentration in humans. We and three other groups have sought to answer this question, with differing conclusions. Here we will review the critical aspects of each study, including its design, which may explain these discordant conclusions. The early glucose-lowering effect of INI is likely due to spillover of insulin into the systemic circulation. In the presence of simultaneous portal and CNS hyperinsulinemia, portal insulin action is dominant. INI administration does lower plasma glucose independent of peripheral insulin concentration (between ∼3 and 6 h after administration), suggesting that CNSIA may play a role in glucose homeostasis in the late postprandial period when its action is likely greatest and portal insulin concentration is at baseline. The potential physiological role and purpose of this pathway are discussed in this review. Because the effects of INI are attenuated in patients with type 2 diabetes and obesity, this is unlikely to be of therapeutic utility.

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

Science.gov (United States)

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

2017-03-01

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

effect of adrenaline on glucose uptake by the canine large bowel

African Journals Online (AJOL)

lower metabolic activity in the colon. From the results we concluded that the colon is involved in glucose homeostasis and that the colonic increase in glucose uptake in response to adrenaline is mediated by alpha and beta adrenergic receptors. KEYWORDS: :Adrenaline, glucose uptake, colon, dog, adrenergic receptors.

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

Science.gov (United States)

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

2015-10-01

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

Regional brain glucose use in unstressed rats after two days of starvation

International Nuclear Information System (INIS)

Mans, A.M.; Davis, D.W.; Hawkins, R.A.

1987-01-01

Regional brain glucose use was measured in conscious, unrestrained, fed rats and after 2 days of starvation, using quantitative autoradiography and [6- 14 C]glucose. Plasma glucose, lactate, and ketone body concentrations and brain glucose and lactate content were measured in separate groups of rats. Glucose concentrations were lower in starved rats in both plasma and brain; plasma ketone body concentrations were elevated. Glucose use was found to be lower throughout the brain by about 12%. While some areas seemed to be affected more than others, statistical analysis showed that none were exceptionally different. The results could not be explained by increased loss of 14 C as lactate or pyruvate during the experimental period, because the arteriovenous differences of these species were insignificant. The calculated contribution by ketone bodies to the total energy consumption was between 3 and 9% for the brain as a whole in the starved rats and could, therefore, partially account for the depression seen in glucose use. It was concluded that glucose oxidation is slightly depressed throughout the brain after 2 days of starvation

Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth.

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Tirabanchasak, Sirapassorn; Siripunthana, Sukumarn; Supornsilchai, Vichit; Wacharasindhu, Suttipong; Sahakitrungruang, Taninee

2015-09-01

Subjects with impaired glucose tolerance (IGT) are at risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. The predictors of IGT in obese youth are not well described. We studied 115 obese Thai children who underwent an oral glucose tolerance test (OGTT). Plasma glucose and insulin levels were calculated for assessment of β-cell function. Hemoglobin A1c (HbA1c), lipid profile, and clinical parameters were also used to determine predictors of IGT. We found that three patients had T2DM and 30 subjects had IGT. IGT patients had significantly higher fasting glucose (FG), 1-h postload glucose, 2-h postload insulin, and lower whole-body insulin sensitivity indices than in normal glucose tolerance subjects whereas other indices were comparable. By ROC curve analyses, 1-h postload glucose was the best predictor of IGT, but FG or HbA1c represented a poor diagnostic tool for prediabetes screening. Subjects with 1-h OGTT glucose > 155 mg/dL had significantly lower high-density lipoprotein levels, lower insulin sensitivity, and more insulin resistance than those with 1-h postload glucose of ≤ 155 mg/dL. Abnormal glucose tolerance is highly prevalent in obese Thai youth. Several fasting indices and HbA1c fail to predict IGT. An 1-h OGTT glucose of > 155 mg/dL appears to be more associated with adverse insulin dynamics and metabolic profile than 2-h postload glucose.

Hyperglycemia (High Blood Glucose)

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Full Text Available ... 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 Tools To Know Your Risk Alert Day Diabetes Basics ...

Impact of glucose-lowering agents on the risk of cancer in type 2 diabetic patients. The Barcelona case-control study.

Directory of Open Access Journals (Sweden)

Rafael Simó

Full Text Available BACKGROUND: The aim of the present study is to evaluate the impact of glucose-lowering agents in the risk of cancer in a large type 2 diabetic population. METHODS: A nested case-control study was conducted within a defined cohort (275,164 type 2 diabetic patients attending 16 Primary Health Care Centers of Barcelona. Cases (n = 1,040 comprised those subjects with any cancer diagnosed between 2008 and 2010, registered at the Cancer Registry of Hospital Vall d'Hebron (Barcelona. Three control subjects for each case (n = 3,120 were matched by age, sex, diabetes duration, and geographical area. The treatments analyzed (within 3 years prior to cancer diagnosis were: insulin glargine, insulin detemir, human insulin, fast-acting insulin and analogues, metformin, sulfonylureas, repaglinide, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and alpha glucosidase inhibitors. Conditional logistic regressions were used to calculate the risk of cancer associated with the use of each drug adjusted by age, BMI, dose and duration of treatment, alcohol use, smoking habit, and diabetes duration. RESULTS: No differences were observed between case and control subjects for the proportion, dose or duration of exposure to each treatment. None of the types of insulin and oral agents analyzed showed a significant increase in the risk of cancer. Moreover, no cancer risk was observed when glargine was used alone or in combination with metformin. CONCLUSIONS: Our results suggest that diabetes treatment does not influence the risk of cancer associated with type 2 diabetes. Therefore, an eventual increase of cancer should not be a reason for biasing the selection of any glucose-lowering treatment in type 2 diabetic population.

Brain glucose content in fetuses of ethanol-fed rats

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

1986-03-01

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

Glucose metabolism of lactobacillus divergens

International Nuclear Information System (INIS)

De Bruyn, I.N.

1987-02-01

The aim of this study was to compile an optimal growth and selective medium for Lactobacillus divergens and to determine the pathway by which it metabolised glucose. The optimum growth temperature is 25 o C which is lower than that of most other lactobacilli. Citrate stimulates growth up to a concentration of 1% while acetate inhibits the organism at neutral pH, but it stimulates growth at pH 8.5 up to a concentration of 0.8%. MRS medium was therefore modified in order to obtain maximum growth of the organism. The acetate was omitted, sucrose was substituted for glucose and the pH was adjusted to 8.5. Sucrose was used, since a neutral pH is obtained after sterilisation of glucose in alkaline (pH ≥ 7.5) solution due to the degradation of glucose by the Maillard reaction. Various inhibitors and dyes were tested in order to formulate a selective medium. In the present study differently labelled glucose precursors were fermented by L. divergens and the fermentation products isolated by HPLC. The concentrations of acetate and formate were determined by comparison to a standard while the concentration of lactate and glucose was determined by enzymic assay. The radioactivity was determined by liquid scintillation counting and the positional labelling in lactate and acetate by chemical degradation. Fermentation of D-[U- 14 C]-glucose was included to correct for endogenous product dilution

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

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

2016-11-01

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

Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies1234

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Hruby, Adela; Ngwa, Julius S.; Renström, Frida; Wojczynski, Mary K.; Ganna, Andrea; Hallmans, Göran; Houston, Denise K.; Jacques, Paul F.; Kanoni, Stavroula; Lehtimäki, Terho; Lemaitre, Rozenn N.; Manichaikul, Ani; North, Kari E.; Ntalla, Ioanna; Sonestedt, Emily; Tanaka, Toshiko; van Rooij, Frank J. A.; Bandinelli, Stefania; Djoussé, Luc; Grigoriou, Efi; Johansson, Ingegerd; Lohman, Kurt K.; Pankow, James S.; Raitakari, Olli T.; Riserus, Ulf; Yannakoulia, Mary; Zillikens, M. Carola; Hassanali, Neelam; Liu, Yongmei; Mozaffarian, Dariush; Papoutsakis, Constantina; Syvänen, Ann-Christine; Uitterlinden, André G.; Viikari, Jorma; Groves, Christopher J.; Hofman, Albert; Lind, Lars; McCarthy, Mark I.; Mikkilä, Vera; Mukamal, Kenneth; Franco, Oscar H.; Borecki, Ingrid B.; Cupples, L. Adrienne; Dedoussis, George V.; Ferrucci, Luigi; Hu, Frank B.; Ingelsson, Erik; Kähönen, Mika; Kao, W. H. Linda; Kritchevsky, Stephen B.; Orho-Melander, Marju; Prokopenko, Inga; Rotter, Jerome I.; Siscovick, David S.; Witteman, Jacqueline C. M.; Franks, Paul W.; Meigs, James B.; McKeown, Nicola M.; Nettleton, Jennifer A.

2013-01-01

Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = −0.009 mmol/L (95% CI: −0.013, −0.005), P magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted. PMID:23343670

Exenatide improves glucocorticoid-induced glucose intolerance in mice

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Ruiying Zhao

2011-01-01

Full Text Available Ruiying Zhao1,2*, Enrique Fuentes-Mattei1,2*, Guermarie Velazquez-Torres1,3, Chun-Hui Su1,2, Jian Chen1, Mong-Hong Lee1,2, Sai-Ching Jim Yeung4,51Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Program in Genes and Development, 3Program in Cancer Biology, Graduate School of Biomedical Sciences, University of Texas Health Science Center in Houston, Houston, TX, USA; 4Department of Endocrine Neoplasia and Hormonal Disorders, 5Department of Emergency Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA *Both authors contributed equally.Abstract: Exenatide is an incretin mimetic that is recently available in the US for the treatment of diabetes. There is a paucity of information on the effects of exenatide in glucocorticoid (GC-induced diabetes. Although the effect of continuous intravenous infusion of exenatide on GC-induced glucose intolerance has been investigated before in healthy human males receiving oral prednisolone, we investigated the efficacy of a single subcutaneous dose of exenatide (3 µg/kg in lowering blood glucose in GC-induced glucose intolerance in C57BL/6 mice. In a longitudinal experiment, the area under the curve (AUC of oral glucose tolerance tests (OGTT significantly increased after dexamethasone (P = 0.004, which was subsequently decreased by exenatide (P < 0.001. A cross-sectional experiment showed that exenatide improved glucose tolerance compared with placebo in a mouse model of dexamethasone-induced glucose intolerance. AUC of OGTT in the exenatide group were significantly (P < 0.001 lower than in the placebo group. Insulin tolerance tests (ITT demonstrated that exenatide decreased the ability of the mice to tolerate insulin compared with placebo. The AUC of ITT in the exenatide group were also significantly (P = 0.006 lower than in the placebo group. In conclusion, a single dose of exenatide was able to decrease glucose intolerance and

Cranberry juice consumption lowers markers of cardiometabolic risk, including blood pressure and circulating C-reactive protein, triglyceride, and glucose concentrations in adults.

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Novotny, Janet A; Baer, David J; Khoo, Christina; Gebauer, Sarah K; Charron, Craig S

2015-06-01

Cardiometabolic risk is the risk of cardiovascular disease (CVD), diabetes, or stroke, which are leading causes of mortality and morbidity worldwide. The objective of this study was to determine the potential of low-calorie cranberry juice (LCCJ) to lower cardiometabolic risk. A double-blind, placebo-controlled, parallel-arm study was conducted with controlled diets. Thirty women and 26 men (mean baseline characteristics: 50 y; weight, 79 kg; body mass index, 28 kg/m(2)) completed an 8-wk intervention with LCCJ or a flavor/color/energy-matched placebo beverage. Twice daily volunteers consumed 240 mL of LCCJ or the placebo beverage, containing 173 or 62 mg of phenolic compounds and 6.5 or 7.5 g of total sugar per 240-mL serving, respectively. Fasting serum triglycerides (TGs) were lower after consuming LCCJ and demonstrated a treatment × baseline interaction such that the participants with higher baseline TG concentrations were more likely to experience a larger treatment effect (1.15 ± 0.04 mmol/L vs. 1.25 ± 0.04 mmol/L, respectively; P = 0.027). Serum C-reactive protein (CRP) was lower for individuals consuming LCCJ than for individuals consuming the placebo beverage [ln transformed values of 0.522 ± 0.115 ln(mg/L) vs. 0.997 ± 0.120 ln(mg/L), P = 0.0054, respectively, and equivalent to 1.69 mg/L vs. 2.71 mg/L back-transformed]. LCCJ lowered diastolic blood pressure (BP) compared with the placebo beverage (69.2 ± 0.8 mm Hg for LCCJ vs. 71.6 ± 0.8 mm Hg for placebo; P = 0.048). Fasting plasma glucose was lower (P = 0.03) in the LCCJ group (5.32 ± 0.03 mmol/L) than in the placebo group (5.42 ± 0.03 mmol/L), and LCCJ had a beneficial effect on homeostasis model assessment of insulin resistance for participants with high baseline values (P = 0.035). LCCJ can improve several risk factors of CVD in adults, including circulating TGs, CRP, and glucose, insulin resistance, and diastolic BP. This trial was registered at clinicaltrials.gov as NCT01295684. © 2015

Comparison of glucose concentration and glucose absorption from the GI-tract in pigs in whole blood and in plasma

DEFF Research Database (Denmark)

Theil, Peter Kappel; Jørgensen, Henry; Larsen, Torben

2010-01-01

using a biosensitive electrode (Exp. 1) or a standard colourimetric method (Exp. 2). In general, glucose measured in whole blood was 7-11% lower than in plasma at low glucose levels (3.5-5 mM), whereas the methods agreed well at high glucose levels (10-14 mM). Evaluation of the regression lines between......The present investigation was undertaken to compare glucose absorption from the gastro-intestinal tract quantified in either whole blood or plasma using the arterio-venous differences and portal blood flow measurements. Pigs were surgically modified with catheters in the portal vein...... three different diets with similar contents of starch (470-506 g/kg DM). The diets in both studies differed regarding amount and solubility of fibre. Blood samples were collected repeatedly 0-10 h after morning feeding. Glucose was measured in whole blood using a glucometer (Accu-Chek®) and in plasma...

Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-d-glucose in normal and ischemic brain.

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Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

2018-05-01

Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-d-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-d-glucose showed comparable chemical exchange properties with d-glucose and 2-deoxy-d-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-d-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (Δ R 1 ρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/kg 3-O-methyl-d-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-d-glucose were linearly correlated with Δ R 1 ρ. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-d-glucose injection at 1 h after stroke onset showed reduced Δ R 1 ρ in the ischemic core but higher Δ R 1 ρ in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-d-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.

Characteristics of cerebral glucose utilization in dementia

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Matsuzawa, Taiju; Matsui, Hiroshige; Meguro, Kenichi; Ueda, Masamichi; Yamada, Kenji; Yamaguchi, Tatsuo; Itoh, Masatoshi; Hatazawa, Jun; Kinomura, Shigeo (Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis and Cancer)

1990-12-01

To make clear the characteristics of cerebral glucose utilization in dementia, PET studies with 18F-FDG were carried out. Taking the pattern of 18F-FDG utilization, dementia can be subdivided into two types. One type shows a simultaneous and symmetrical reduction glucose utilization in the posterior part of neocortex covering the temporal, parietal and occipital association cortices. This is referred to as type I. Although this type constitutes only about 1/5 of all dementia patients, it is considered the fundamental type of dementia. Aside from this, there is type wherein a simultaneous and symmetrical reduction in glucose utilization of the neocortex. This is type II. It constitutes about 4/5 of all dementia patients which is far more type I. There are no essential difference in the characteristics of cerebral glucose utilization in AD and MID. However, with regards the mean, AD is lower than MID. Various organic defect in neocortex do not correlate with the global reduction in glucose utilization in dementia patients. These results suggest that the reduction in glucose utilization in dementia may be functional disorder. (author).

Characteristics of cerebral glucose utilization in dementia

International Nuclear Information System (INIS)

Matsuzawa, Taiju; Matsui, Hiroshige; Meguro, Kenichi; Ueda, Masamichi; Yamada, Kenji; Yamaguchi, Tatsuo; Itoh, Masatoshi; Hatazawa, Jun; Kinomura, Shigeo

1990-01-01

To make clear the characteristics of cerebral glucose utilization in dementia, PET studies with 18F-FDG were carried out. Taking the pattern of 18F-FDG utilization, dementia can be subdivided into two types. One type shows a simultaneous and symmetrical reduction glucose utilization in the posterior part of neocortex covering the temporal, parietal and occipital association cortices. This is referred to as type I. Although this type constitutes only about 1/5 of all dementia patients, it is considered the fundamental type of dementia. Aside from this, there is type wherein a simultaneous and symmetrical reduction in glucose utilization of the neocortex. This is type II. It constitutes about 4/5 of all dementia patients which is far more type I. There are no essential difference in the characteristics of cerebral glucose utilization in AD and MID. However, with regards the mean, AD is lower than MID. Various organic defect in neocortex do not correlate with the global reduction in glucose utilization in dementia patients. These results suggest that the reduction in glucose utilization in dementia may be functional disorder. (author)

A highly sensitive electrochemical glucose sensor structuring with nickel hydroxide and enzyme glucose oxidase

International Nuclear Information System (INIS)

Mathew, Manjusha; Sandhyarani, N.

2013-01-01

Graphical abstract: A combination of Ni 2+ /Ni 3+ redox couple and glucose oxidase has successfully been exploited for the realization of a highly sensitive glucose sensor for the first time. -- Highlights: • A multilayered glucose biosensor with enhanced sensitivity was fabricated. • Combination of Ni 2+ /Ni 3+ redox couple and glucose oxidase has been exploited for the first time. • Exhibits a lower detection limit of 100 nM with a high sensitivity of 16,840 μA mM −1 cm −2 . • The surface shows a low Michaelis–Menten constant value of 2.4 μM. • Detailed mechanism of sensing was proposed and justified. -- Abstract: A multilayered glucose biosensor with enhanced electron transport was fabricated via the sequential electrodeposition of chitosan gold nanocomposite (CGNC) and nickel hydroxide (Ni(OH) 2 ) on a bare gold electrode and subsequent immobilization of glucose oxidase. A thin film of Ni(OH) 2 deposited on CGNC modified gold electrode serves as an electrochemical redox probe as well as a matrix for the immobilization of glucose oxidase retaining its activity. Electron transport property of CGNC has been exploited to enhance the electron transport between the analyte and electrode. Electrochemical characteristics of the biosensor were studied by cyclic voltammetry and chronoamperometry. Under optimal conditions the biosensor exhibits a linear range from 1 μM to 100 μM with a limit of detection (lod) down to 100 nM. The sensor shows a low Michaelis-Menten constant value of 2.4 μM indicates the high affinity of enzyme to the analyte points to the retained activity of enzyme after immobilization. The present glucose sensor with the high selectivity, sensitivity and stability is promising for practical clinical applications

Shikonin increases glucose uptake in skeletal muscle cells and improves plasma glucose levels in diabetic Goto-Kakizaki rats.

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Anette I Öberg

Full Text Available BACKGROUND: There is considerable interest in identifying compounds that can improve glucose homeostasis. Skeletal muscle, due to its large mass, is the principal organ for glucose disposal in the body and we have investigated here if shikonin, a naphthoquinone derived from the Chinese plant Lithospermum erythrorhizon, increases glucose uptake in skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: Shikonin increases glucose uptake in L6 skeletal muscle myotubes, but does not phosphorylate Akt, indicating that in skeletal muscle cells its effect is medaited via a pathway distinct from that used for insulin-stimulated uptake. Furthermore we find no evidence for the involvement of AMP-activated protein kinase in shikonin induced glucose uptake. Shikonin increases the intracellular levels of calcium in these cells and this increase is necessary for shikonin-mediated glucose uptake. Furthermore, we found that shikonin stimulated the translocation of GLUT4 from intracellular vesicles to the cell surface in L6 myoblasts. The beneficial effect of shikonin on glucose uptake was investigated in vivo by measuring plasma glucose levels and insulin sensitivity in spontaneously diabetic Goto-Kakizaki rats. Treatment with shikonin (10 mg/kg intraperitoneally once daily for 4 days significantly decreased plasma glucose levels. In an insulin sensitivity test (s.c. injection of 0.5 U/kg insulin, plasma glucose levels were significantly lower in the shikonin-treated rats. In conclusion, shikonin increases glucose uptake in muscle cells via an insulin-independent pathway dependent on calcium. CONCLUSIONS/SIGNIFICANCE: Shikonin increases glucose uptake in skeletal muscle cells via an insulin-independent pathway dependent on calcium. The beneficial effects of shikonin on glucose metabolism, both in vitro and in vivo, show that the compound possesses properties that make it of considerable interest for developing novel treatment of type 2 diabetes.

The glucose oxidase-peroxidase assay for glucose

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The glucose oxidase-peroxidase assay for glucose has served as a very specific, sensitive, and repeatable assay for detection of glucose in biological samples. It has been used successfully for analysis of glucose in samples from blood and urine, to analysis of glucose released from starch or glycog...

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

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

2015-09-01

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

Six and 12 Weeks of Caloric Restriction Increases β Cell Function and Lowers Fasting and Postprandial Glucose Concentrations in People with Type 2 Diabetes123

Science.gov (United States)

Sathananthan, Matheni; Shah, Meera; Edens, Kim L; Grothe, Karen B; Piccinini, Francesca; Farrugia, Luca P; Micheletto, Francesco; Man, Chiara Dalla; Cobelli, Claudio; Rizza, Robert A; Camilleri, Michael; Vella, Adrian

2015-01-01

Background: Caloric restriction alone has been shown to improve insulin action and fasting glucose metabolism; however, the mechanism by which this occurs remains uncertain. Objective: We sought to quantify the effect of caloric restriction on β cell function and glucose metabolism in people with type 2 diabetes. Methods: Nine subjects (2 men, 7 women) with type 2 diabetes [BMI (in kg/m2): 40.6 ± 1.4; age: 58 ± 3 y; glycated hemoglobin: 6.9% ± 0.2%] were studied using a triple-tracer mixed meal after withdrawal of oral diabetes therapy. The oral minimal model was used to measure β cell function. Caloric restriction limited subjects to a pureed diet (restriction. Results: Fasting glucose concentrations decreased significantly from baseline after 6 wk of caloric restriction with no further reduction after a further 6 wk of caloric restriction (9.8 ± 1.3, 5.9 ± 0.2, and 6.2 ± 0.3 mmol/L at baseline and after 6 and 12 wk of caloric restriction, respectively; P = 0.01) because of decreased fasting endogenous glucose production (EGP: 20.4 ± 1.1, 16.2 ± 0.8, and 17.4 ± 1.1 μmol · kg−1 · min−1 at baseline and after 6 and 12 wk of caloric restriction, respectively; P = 0.03). These changes were accompanied by an improvement in β cell function measured by the disposition index (189 ± 51, 436 ± 68, and 449 ± 67 10−14 dL · kg−1 · min−2 · pmol−1 at baseline and after 6 and 12 wk of caloric restriction, respectively; P = 0.01). Conclusions: Six weeks of caloric restriction lowers fasting glucose and EGP with accompanying improvements in β cell function in people with type 2 diabetes. An additional 6 wk of caloric restriction maintained the improvement in glucose metabolism. This trial was registered at clinicaltrials.gov as NCT01094054. PMID:26246321

Glucocorticoid receptor polymorphism in obesity and glucose homeostasis.

Science.gov (United States)

Majer-Łobodzińska, Agnieszka; Adamiec-Mroczek, Joanna

2017-01-01

Glucocorticoid receptor (GR) activity plays a significant role in the etiology of obesity and is essential for glucose homeostasis, the development of hyperinsulinaemia and subsequent increased fat deposition. Several polymorphisms in the GR gene have been described, and at least three of them seem to be associated with altered glucocorticoid sensitivity and changes in glucose homeostasis, and other metabolic parameters. The N363S polymorphism has been associated with increased sensitivity to glucocorticoides, increased insulin response to dexamethasone and increased plasma glucose level. BclI polymorphism is associated with increased abdominal obesity, hyperinsulinaemia and increased insulin resistance. Another polymorphism, ER22/23EK, in contrast to the others, is associated with relative resistance to glucocoricides actions and more beneficial metabolic profile-lower insulin resistance level, decreased lower cardiovascular risk and subseuent prolongation of life time. More research is still needed to understand the mechanisms behind these associations at the molecular level.

Differential effects of vildagliptin and glimepiride on glucose fluctuations in patients with type 2 diabetes mellitus assessed using continuous glucose monitoring.

Science.gov (United States)

He, Y L; Foteinos, G; Neelakantham, S; Mattapalli, D; Kulmatycki, K; Forst, T; Taylor, A

2013-12-01

To assess whether there is a difference in the effects of vildagliptin and glimepiride on glucose fluctuation in patients with type 2 diabetes mellitus (T2DM) using continuous glucose monitoring (CGM). This was an open-label, randomized cross-over study conducted in T2DM patients. A total of 24 patients (age: 58.3 ± 5.56 years, baseline HbA1c: 7.6 ± 0.50%) who were on stable metformin monotherapy (500-3000 mg) were enrolled, and all completed the study. Each patient received two 5-day treatments (vildagliptin 50 mg b.i.d. or glimepiride 2 mg q.d.) in a cross-over manner. Various biomarkers and blood glucose concentrations were measured following breakfast. The 24-h glucose profiles were also measured using the CGM device at baseline and after 5 days of treatment, and fluctuations in glucose levels were estimated from CGM data. Both vildagliptin and glimepiride reduced postprandial glucose levels, based on both CGM data (15% vs. 16%) and measured plasma glucose (13% vs.17%). Vildagliptin showed lower glucose fluctuations than glimepiride as measured by mean amplitude of glycaemic excursions (MAGE, p = 0.1076), standard deviation (s.d., p = 0.1346) of blood glucose rate of change, but did not reach statistical significance attributed to the small sample size. MAGE was reduced by ∼20% with vildagliptin versus glimepiride. Vildagliptin led to statistically significant lowering of the rate of change in the median curve (RCMC) and interquartile range (IQR) of glucose. Treatment with vildagliptin significantly increased the levels of active glucagon-like peptide-1 by 2.36-fold (p ≤ 0.0001) and suppressed glucagon by 8% (p = 0.01), whereas glimepiride significantly increased the levels of insulin and C-peptide by 21% (p = 0.012) and 12% (p = 0.003), respectively. Vildagliptin treatment was associated with less fluctuation of glucose levels than glimepiride treatment as assessed by 24-h CGM device, suggesting vildagliptin may

Luminol, horseradish peroxidase, and glucose oxidase ternary functionalized graphene oxide for ultrasensitive glucose sensing.

Science.gov (United States)

Li, Fang; Ma, Wenjing; Liu, Jiachang; Wu, Xiang; Wang, Yan; He, Jianbo

2018-01-01

Luminol, horseradish peroxidase (HRP), and glucose oxidase (GOx) ternary functionalized graphene oxide (HRP/GOx-luminol-GO) with excellent chemiluminescence (CL) activity and specific enzymatic property was prepared via a simple and general strategy for the first time. In this approach, luminol functionalized GO (luminol-GO) was prepared by gently stirring GO with luminol. Then HRP and GOx were further co-immobilized onto the surface of luminol-GO by storing HRP and GOx with luminol-GO at 4 °C overnight, to form HRP/GOx-luminol-GO bionanocomposites. The synthesized HRP/GOx-luminol-GO could react with H 2 O 2 generated from GOx catalyzed glucose oxidization reaction, to produce strong CL emission in the presence of co-immobilized HRP. Thus, we developed an ultrasensitive, homogeneous, reagentless, selective, and simple CL sensing system for glucose detection. The resulting biosensors exhibited ultra-wide linear range from 5.0 nM to 5.0 mM, and an ultra-low detection limit of 1.2 nM, which was more than 3 orders of magnitude lower than previously reported methods. Furthermore, the sensing system was successfully applied for the detection of glucose in human blood samples.

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... You At Risk? Diabetes Basics Living with Diabetes Food & Fitness In My Community Advocacy Research & Practice Ways to Give Close Are You at Risk? Home ... work with your doctor to find the safest way for you to lower your blood glucose ... down on the amount of food you eat might also help. Work with your ...

Comparison of the effect of sorbitol and glucose on calcium absorption in postmenopausal women

International Nuclear Information System (INIS)

Francis, R.M.; Peacock, M.; Barkworth, S.A.; Marshall, D.H.

1986-01-01

It has been suggested that the oral administration of sorbitol promotes calcium absorption, while glucose has no effect. We have therefore compared the effect of oral sorbitol and glucose on the absorption of radiocalcium from low and high carrier loads in healthy postmenopausal women. In a control group of 20 women given neither sorbitol nor glucose, the mean +/- SEM fractional radiocalcium absorption rate from a low carrier load was 0.65 +/- 0.05 (fraction of dose/h). In a second group of 10 women the fractional absorption rate from the low carrier load was lower (p less than 0.05) with 10 g sorbitol (0.48 +/- 0.05) than with 10 g glucose (0.65 +/- 0.08). Fractional absorption of radiocalcium from a high carrier load measured in a third group of seven women using two isotopes (oral 45Ca, IV 47Ca) was also lower (p less than 0.001) with 10 g sorbitol (0.22 +/- 0.01, fraction/3 h) than with 10 g glucose (0.29 +/- 0.02). The results suggest that calcium absorption from a low carrier load is unaltered by glucose but that absorption of calcium from both low and high carrier loads is lower with sorbitol than with glucose

Blood glucose in acute stroke

DEFF Research Database (Denmark)

Olsen, Tom Skyhøj

2009-01-01

of infarcts. For a number of years, tight glycemic control has been regarded as beneficial in critically illness, but recent research has been unable to support this notion. The only completed randomized study on glucose-lowering therapy in stroke has failed to demonstrate effect, and concerns relating...

Glucose kinetics in gluconeogenesis-inhibited rats during rest and exercise

International Nuclear Information System (INIS)

Turcotte, L.P.; Rovner, A.S.; Roark, R.R.; Brooks, G.A.

1990-01-01

To evaluate the role played by gluconeogenesis in blood glucose homeostasis, female Sprague-Dawley rats were injected with mercaptopicolinic acid (MPA), a gluconeogenic inhibitor. Glucose kinetics were assessed by primed, continuous infusion of [U-14C]- and [6(-3)H]glucose via an indwelling jugular catheter at rest and during submaximal exercise at 13.4 m/min on level grade. Blood samples were taken from carotid catheters and analyzed for glucose and lactate concentrations and specific activities. Tissue glycogen samples were obtained from rats after exercise as well as from unexercised animals. When compared with the sham-injected animals, MPA-treated animals had 22% lower (5.92 +/- 0.36 vs. 7.62 +/- 0.21 mM) and 44% higher (1.90 +/- 0.11 vs. 1.32 +/- 0.09 mM) resting arterial glucose and lactate concentrations, respectively. Resting glucose appearance (Ra) rates were 20% lower in the MPA-treated animals (57.2 +/- 7.5 mumol.kg-1.min-1) than in the sham-injected animals (71.1 +/- 12.1 mumol.kg-1.min-1). During exercise, Ra increased to 174.7 +/- 32.8 mumol.kg-1.min-1 in sham-injected animals. In the MPA-treated animals, there was a 35% increase during the first 15 min of exercise, followed by a decrease to the resting values. MPA-treated animals had no measurable glucose recycling at rest or during exercise. Exercise decreased blood glucose concentration (35%) and increased blood lactate concentration (160%) in the MPA-treated animals. Exercising sham-injected animals had increased blood glucose (9.8%) but no change in blood lactate concentration. Moderate depletions in liver and skeletal muscle glycogen contents were observed after exercise

Metabolism of tritiated D-glucose in rat erythrocytes

International Nuclear Information System (INIS)

Manuel y Keenoy, B.; Malaisse-Lagae, F.; Malaisse, W.J.

1991-01-01

The metabolism of D-[U-14C]glucose, D-[1-14C]glucose, D-[6-14C]glucose, D-[1-3H]glucose, D-[2-3H]glucose, D-[3-3H]glucose, D-[3,4-3H]glucose, D-[5-3H]glucose, and D-[6-3H]glucose was examined in rat erythrocytes. There was a fair agreement between the rate of 3HOH production from either D-[3-3H]glucose and D-[5-3H]glucose, the decrease in the 2,3-diphosphoglycerate pool, its fractional turnover rate, the production of 14C-labeled lactate from D-[U-14C]glucose, and the total lactate output. The generation of both 3HOH and tritiated acidic metabolites from D-[3,4-3H]glucose indicated incomplete detritiation of the C4 during interconversion of fructose-1,6-bisphosphate and triose phosphates. Erythrocytes unexpectedly generated 3HOH from D-[6-3H]glucose, a phenomenon possibly attributable to the detritiation of [3-3H]pyruvate in the reaction catalyzed by glutamate pyruvate transaminase. The production of 3HOH from D-[2-3H]glucose was lower than that from D-[5-3H]glucose, suggesting enzyme-to-enzyme tunneling of glycolytic intermediates in the hexokinase/phosphoglucoisomerase/phosphofructokinase sequence. The production of 3HOH from D-[1-3H]glucose largely exceeded that of 14CO2 from D-[1-14C]glucose, a situation tentatively ascribed to the generation of 3HOH in the phosphomannoisomerase reaction. It is further speculated that the adjustment in specific radioactivity of D-[1-3H]glucose-6-phosphate cannot simultaneously match the vastly different degrees of isotopic discrimination in velocity at the levels of the reactions catalyzed by either glucose-6-phosphate dehydrogenase or phosphoglucoisomerase. The interpretation of the present findings thus raises a number of questions, which are proposed as a scope for further investigations

Effect of emulin on blood glucose in type 2 diabetics.

Science.gov (United States)

Ahrens, Milton Joseph; Thompson, Daryl L

2013-03-01

Emulin™ is a patented blend of chlorogenic acid, myricetin, and quercetin that has shown efficacy in reducing midday and post-oral glucose tolerance test (OGTT) area under the curve (AUC) glucose in streptozotocin-treated rats. The purpose of this study was to determine if similar effects would be evident in type 2 diabetic humans. Forty human subjects with confirmed type 2 diabetes (10 each in 4 groups: placebo/no medication, Emulin/no medication, placebo/metformin and Emulin/metformin) were evaluated. At the end of 1 week, fasting blood glucose, 2 h postprandial, actual peak glucose, and AUC (post-50 g OGTT) were determined. The placebo-only group had a large (5%-13%) increase in all parameters. The Emulin group and those on metformin performed similarly with reductions between 1% and 5%, with Emulin slightly outperforming the medication-alone group. The most significant reduction occurred in the Emulin/metformin group, with decreases in the parameters by up to 20%. These results suggest that Emulin, if consumed regularly, could not only have the acute effect of lowering the glycemic impact of foods, but chronically lower background blood glucose levels of type 2 diabetics.

Patterns of glucose lowering drugs utilization in Portugal and in the Netherlands. Trends over time.

Science.gov (United States)

Torre, Carla; Guerreiro, José; de Oliveira Martins, Sofia; Raposo, João Filipe; Martins, Ana Paula; Leufkens, Hubert

2015-12-01

To compare the temporal trends in the consumption patterns of glucose lowering drugs (GLD) between Portugal and the Netherlands from 2004 to 2013 and to examine possible reasons behind the cross-national variation found. All GLD (ATC pharmacological subgroup A10B) were selected for analysis. Consumption data were obtained for the 10-year period. Portuguese and Dutch drug estimates were obtained from nationwide databases. The consumption of GLD increased in Portugal from 52.9 defined daily dose per 1000 inhabitants per day (DHD) in 2004 to 70.0 DHD in 2013 and in the Netherlands from 44.9 DHD in 2004 to 50.7 DHD in 2013. In Portugal, the use of fixed-dose combinations, especially with dipeptidyl peptidase-4 inhibitors (DPP-4) increased remarkably and in 2013 represented almost a quarter of total GLD consumption. In the Netherlands, the use of combinations was residual. The consumption of GLD rose over the 10-year period in both countries. However, Portuguese overall consumption and costs of GLD were higher. The differentially rapid uptake of DPP-4 inhibitors in Portugal was the main driver of the cost difference. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Analysis of Continuous Glucose Monitoring in Pregnant Women With Diabetes

DEFF Research Database (Denmark)

Law, Graham R; Ellison, George T H; Secher, Anna L

2015-01-01

with diabetes. RESEARCH DESIGN AND METHODS: Functional data analysis (FDA) was applied to 1.68 million glucose measurements from 759 measurement episodes, obtained from two previously published randomized controlled trials of CGM in pregnant women with diabetes. A total of 117 women with type 1 diabetes (n = 89...... developed LGA. LGA was associated with lower mean glucose (7.0 vs. 7.1 mmol/L; P FDA showed that glucose was significantly lower midmorning (0900-1100 h) and early...... evening (1900-2130 h) in trimester 1, significantly higher early morning (0330-0630 h) and throughout the afternoon (1130-1700 h) in trimester 2, and significantly higher during the evening (2030-2330 h) in trimester 3 in women whose infants were LGA. CONCLUSIONS: FDA of CGM data identified specific times...

Exercising Tactically for Taming Postmeal Glucose Surges

Directory of Open Access Journals (Sweden)

Elsamma Chacko

2016-01-01

Full Text Available This review seeks to synthesize data on the timing, intensity, and duration of exercise found scattered over some 39 studies spanning 3+ decades into optimal exercise conditions for controlling postmeal glucose surges. The results show that a light aerobic exercise for 60 min or moderate activity for 20–30 min starting 30 min after meal can efficiently blunt the glucose surge, with minimal risk of hypoglycemia. Exercising at other times could lead to glucose elevation caused by counterregulation. Adding a short bout of resistance exercise of moderate intensity (60%–80%  VO2max to the aerobic activity, 2 or 3 times a week as recommended by the current guidelines, may also help with the lowering of glucose surges. On the other hand, high-intensity exercise (>80%  VO2max causes wide glucose fluctuations and its feasibility and efficacy for glucose regulation remain to be ascertained. Promoting the kind of physical activity that best counters postmeal hyperglycemia is crucial because hundreds of millions of diabetes patients living in developing countries and in the pockets of poverty in the West must do without medicines, supplies, and special diets. Physical activity is the one tool they may readily utilize to tame postmeal glucose surges. Exercising in this manner does not violate any of the current guidelines, which encourage exercise any time.

Exercising Tactically for Taming Postmeal Glucose Surges.

Science.gov (United States)

Chacko, Elsamma

2016-01-01

This review seeks to synthesize data on the timing, intensity, and duration of exercise found scattered over some 39 studies spanning 3+ decades into optimal exercise conditions for controlling postmeal glucose surges. The results show that a light aerobic exercise for 60 min or moderate activity for 20-30 min starting 30 min after meal can efficiently blunt the glucose surge, with minimal risk of hypoglycemia. Exercising at other times could lead to glucose elevation caused by counterregulation. Adding a short bout of resistance exercise of moderate intensity (60%-80%  VO2max) to the aerobic activity, 2 or 3 times a week as recommended by the current guidelines, may also help with the lowering of glucose surges. On the other hand, high-intensity exercise (>80%  VO2max) causes wide glucose fluctuations and its feasibility and efficacy for glucose regulation remain to be ascertained. Promoting the kind of physical activity that best counters postmeal hyperglycemia is crucial because hundreds of millions of diabetes patients living in developing countries and in the pockets of poverty in the West must do without medicines, supplies, and special diets. Physical activity is the one tool they may readily utilize to tame postmeal glucose surges. Exercising in this manner does not violate any of the current guidelines, which encourage exercise any time.

Brain glucose and acetoacetate metabolism: a comparison of young and older adults.

Science.gov (United States)

Nugent, Scott; Tremblay, Sebastien; Chen, Kewei W; Ayutyanont, Napatkamon; Roontiva, Auttawut; Castellano, Christian-Alexandre; Fortier, Melanie; Roy, Maggie; Courchesne-Loyer, Alexandre; Bocti, Christian; Lepage, Martin; Turcotte, Eric; Fulop, Tamas; Reiman, Eric M; Cunnane, Stephen C

2014-06-01

The extent to which the age-related decline in regional brain glucose uptake also applies to other important brain fuels is presently unknown. Ketones are the brain's major alternative fuel to glucose, so we developed a dual tracer positron emission tomography protocol to quantify and compare regional cerebral metabolic rates for glucose and the ketone, acetoacetate. Twenty healthy young adults (mean age, 26 years) and 24 healthy older adults (mean age, 74 years) were studied. In comparison with younger adults, older adults had 8 ± 6% (mean ± SD) lower cerebral metabolic rates for glucose in gray matter as a whole (p = 0.035), specifically in several frontal, temporal, and subcortical regions, as well as in the cingulate and insula (p ≤ 0.01, false discovery rate correction). The effect of age on cerebral metabolic rates for acetoacetate in gray matter did not reach significance (p = 0.11). Rate constants (min(-1)) of glucose (Kg) and acetoacetate (Ka) were significantly lower (-11 ± 6%; [p = 0.005], and -19 ± 5%; [p = 0.006], respectively) in older adults compared with younger adults. There were differential effects of age on Kg and Ka as seen by significant interaction effects in the caudate (p = 0.030) and post-central gyrus (p = 0.023). The acetoacetate index, which expresses the scaled residuals of the voxel-wise linear regression of glucose on ketone uptake, identifies regions taking up higher or lower amounts of acetoacetate relative to glucose. The acetoacetate index was higher in the caudate of young adults when compared with older adults (p ≤ 0.05 false discovery rate correction). This study provides new information about glucose and ketone metabolism in the human brain and a comparison of the extent to which their regional use changes during normal aging. Copyright © 2014 Elsevier Inc. All rights reserved.

Glucose Synthesis in a Protein-Based Artificial Photosynthesis System.

Science.gov (United States)

Lu, Hao; Yuan, Wenqiao; Zhou, Jack; Chong, Parkson Lee-Gau

2015-09-01

The objective of this study was to understand glucose synthesis of a protein-based artificial photosynthesis system affected by operating conditions, including the concentrations of reactants, reaction temperature, and illumination. Results from non-vesicle-based glyceraldehyde-3-phosphate (GAP) and glucose synthesis showed that the initial concentrations of ribulose-1,5-bisphosphate (RuBP) and adenosine triphosphate (ATP), lighting source, and temperature significantly affected glucose synthesis. Higher initial concentrations of RuBP and ATP significantly enhanced GAP synthesis, which was linearly correlated to glucose synthesis, confirming the proper functions of all catalyzing enzymes in the system. White fluorescent light inhibited artificial photosynthesis and reduced glucose synthesis by 79.2 % compared to in the dark. The reaction temperature of 40 °C was optimum, whereas lower or higher temperature reduced glucose synthesis. Glucose synthesis in the vesicle-based artificial photosynthesis system reconstituted with bacteriorhodopsin, F 0 F 1 ATP synthase, and polydimethylsiloxane-methyloxazoline-polydimethylsiloxane triblock copolymer was successfully demonstrated. This system efficiently utilized light-induced ATP to drive glucose synthesis, and 5.2 μg ml(-1) glucose was synthesized in 0.78-ml reaction buffer in 7 h. Light-dependent reactions were found to be the bottleneck of the studied artificial photosynthesis system.

Influence of gastrointestinal factors on glucose metabolism in patients with cirrhosis

DEFF Research Database (Denmark)

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

2015-01-01

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

Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study.

Science.gov (United States)

Bianchi, Cristina; Miccoli, Roberto; Trombetta, Maddalena; Giorgino, Francesco; Frontoni, Simona; Faloia, Emanuela; Marchesini, Giulio; Dolci, Maria A; Cavalot, Franco; Cavallo, Gisella; Leonetti, Frida; Bonadonna, Riccardo C; Del Prato, Stefano

2013-05-01

In subjects with normal glucose tolerance (NGT) 1-hour postload plasma glucose (1-h oral glucose tolerance test [OGTT]) of >155 mg/dL predicts type 2 diabetes (T2DM) and is associated with subclinical atherosclerosis. The purpose of this study was to evaluate β-cell function, insulin resistance, and cardiovascular risk profile in subjects with NGT with a 1-h OGTT glucose of >155 mg/dL. The GENFIEV (Genetics, PHYsiopathology, and Evolution of Type 2 diabetes) study is a multicenter study recruiting individuals at high risk of T2DM. A total of 926 subjects underwent a 75-g OGTT for assessment of plasma glucose and C-peptide for mathematical modeling of β-cell function (derivative and proportional control). Fasting insulin, lipid profile, and clinical parameters were determined as well. A 1-hour OGTT glucose of >155 mg/dL was found in 39% of subjects with NGT, 76% with impaired fasting glucose (IFG), 90% with impaired glucose tolerance (IGT), and 99% and 98% with IFG + IGT or newly diagnosed T2DM, respectively. Among subjects with NGT (n = 474), those with 1-hour OGTT glucose of >155 mg/dL were more insulin-resistant and had worse β-cell function than those with 1-hour OGTT glucose of ≤155 mg/dL. Moreover, glycosylated hemoglobin, blood pressure, low-density lipoprotein cholesterol, and triglycerides were higher in subjects with NGT with 1-hour OGTT glucose of >155 mg/dL, whereas high-density lipoprotein cholesterol was lower compared with that in subjects with NGT with 1-hour OGTT glucose of ≤155 mg/dL. Compared with subjects with IGT, those with NGT with 1-hour OGTT glucose of >155 mg/dL had comparable cardiovascular risk profile and insulin resistance but slightly better β-cell function. Among subjects with NGT, those with 1-hour OGTT glucose of >155 mg/dL showed lower insulin sensitivity, impaired β-cell function, and worse cardiovascular risk profile and therefore are at greater risk of developing T2DM and cardiovascular disease.

Incompatibility between fasting and postprandial plasma glucose in patients with Cushing's syndrome.

Science.gov (United States)

Otsuki, Michio; Kitamura, Tetsuhiro; Tamada, Daisuke; Tabuchi, Yukiko; Mukai, Kosuke; Morita, Shinya; Kasayama, Soji; Shimomura, Iichiro; Koga, Masafumi

2016-11-30

It is shown that glucocorticoids have discordant effects on plasma glucose concentration through their effects on hepatic glycogen deposition, gluconeogenesis and peripheral insulin resistance. Cushing's syndrome caused by cortisol overproduction is frequently accompanied with diabetes mellitus, but fasting plasma glucose (FPG) and post-glucose load plasma glucose levels are not examined in patients with Cushing's syndrome. The aim of this study was to investigate FPG, HbA1c and oral glucose tolerance test (OGTT) 2-h PG and their relationship in patients with Cushing's syndrome, in comparison with control subjects. Sixteen patients with Cushing's syndrome (ACTH-dependent 31%, ACTH-independent 69% and diabetes mellitus 50%) and 64 controls (32 patients with type 2 diabetes mellitus and 32 non-diabetic subjects matched for age, sex and BMI) were enrolled in this study. HbA1c and FPG in the patients with Cushing's syndrome were not different from the controls, whereas the FPG/HbA1c ratio was significantly lower in the patients with Cushing's syndrome than the controls. OGTT 2-h PG was significantly higher in the non-diabetic patients with Cushing's syndrome than the non-diabetic controls, while HbA1c was not different between both groups and FPG was significantly lower in the patients with Cushing's syndrome than the controls. HOMA-β but not HOMA-R was significantly higher in the patients with Cushing's syndrome than the controls. In conclusion, FPG was rather lower in the patients with Cushing's syndrome than the controls. Postprandial PG or post-glucose loaded PG, but not FPG, is useful to evaluate the abnormality of glucose metabolism in patients with Cushing's syndrome.

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

Science.gov (United States)

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

2009-09-01

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

Sodium-Glucose Linked Transporter-2 Inhibitors in Chronic Kidney Disease

Directory of Open Access Journals (Sweden)

L. Zanoli

2015-01-01

Full Text Available SGLT2 inhibitors are new antihyperglycaemic agents whose ability to lower glucose is directly proportional to GFR. Therefore, in chronic kidney disease (CKD the blood glucose lowering effect is reduced. Unlike many current therapies, the mechanism of action of SGLT2 inhibitors is independent of insulin action or beta-cell function. In addition, the mechanism of action of SGLT2 inhibitors is complementary and not alternative to other antidiabetic agents. SGLT2 inhibitors could be potentially effective in attenuating renal hyperfiltration and, consequently, the progression of CKD. Moreover, the reductions in intraglomerular pressure, systemic blood pressure, and uric acid levels induced by SGLT inhibition may potentially be of benefit in CKD subjects without diabetes. However, at present, only few clinical studies were designed to evaluate the effects of SGLT2 inhibitors in CKD. Consequently, safety and potential efficacy beyond blood glucose lowering should be better clarified in CKD. In this paper we provide an updated review of the use of SGLT2 inhibitors in clinical practice, with particular attention on subjects with CKD.

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...

Trigonella Foenum-Graecum Seeds Lowers Postprandial Blood Glucose in Overweight and Obese Individuals

Directory of Open Access Journals (Sweden)

Sathyasurya Daniel Robert

2014-01-01

Full Text Available This study determined the effects of fenugreek on postprandial plasma glucose (PPG and satiety among overweight and obese individuals. Fourteen subjects were studied in the morning after overnight fasts on four separate occasions. Glycaemic responses elicited by 50 g carbohydrate portions of white bread and jam with or without 5.5 g of fenugreek and fried rice with or without 5.5 g fenugreek were determined over 2 h. The primary endpoint was the incremental area under the plasma glucose response curve (IAUC. Adding fenugreek to both foods significantly reduced the IAUC compared to the food alone: white bread and jam, 180 ± 22 versus 271 ± 23 mmol × min/L (P = 0.001; fried rice, 176 ± 20 versus 249 ± 25 mmol × min/L (P = 0.001. Fenugreek also significantly reduced the area under the satiety curve for white bread with jam (134 ± 27 versus 232 ± 33 mm × hr, P = 0.01 and fried rice (280 ± 37 versus 379 ± 36 mm × hr, P = 0.01. It is concluded that fenugreek significantly decreased the PPG response and increased satiety among overweight and obese individuals.

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

DEFF Research Database (Denmark)

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

1990-01-01

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

Lifestyle may modify the glucose-raising effect of genetic loci. A study in the Greek population.

Science.gov (United States)

Marouli, E; Kanoni, S; Dimitriou, M; Kolovou, G; Deloukas, P; Dedoussis, G

2016-03-01

Lifestyle habits including dietary intake and physical activity are closely associated with multiple body processes including glucose metabolism and are known to affect human health. Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with glucose levels. The hypothesis tested here is whether a healthy lifestyle assessed via a score is associated with glycaemic traits and whether there is an interaction between the lifestyle and known glucose-raising genetic variants in association with glycaemic traits. Participants of Greek descent from the THISEAS study were included in this analysis. We developed a glucose preventive score (GPS) including dietary and physical activity characteristics. We also modelled a weighted genetic risk score (wGRS), based on 20 known glucose-raising loci, in order to investigate the impact of lifestyle-gene interaction on glucose levels. The GPS was observed to be significantly associated with lower glucose concentrations (β ± SE: -0.083 ± 0.021 mmol/L, P = 1.6 × 10(-04)) and the wGRS, as expected, with increased glucose levels (β ± SE: 0.020 ± 0.007 mmol/L, P = 8.4 × 10(-3)). The association of the wGRS with glucose levels was attenuated after interaction with the GPS. A higher GPS indicated decreasing glucose levels in the presence of an increasing wGRS (β interaction ± SE: -0.019 ± 0.007 mmol/L, P = 0.014). Our results indicate that lower glucose levels underlie a healthier lifestyle and also support an interaction between the wGRS for known glycaemic loci and GPS associated with lower glucose levels. These scores could be useful tools for monitoring glucose metabolism. Copyright © 2016. Published by Elsevier B.V.

Effects of oral glucose-lowering drugs on long term outcomes in patients with diabetes mellitus following myocardial infarction not treated with emergent percutaneous coronary intervention--a retrospective nationwide cohort study

DEFF Research Database (Denmark)

Jørgensen, Casper H; Gislason, Gunnar H; Andersson, Charlotte

2010-01-01

The optimum oral pharmacological treatment of diabetes mellitus to reduce cardiovascular disease and mortality following myocardial infarction has not been established. We therefore set out to investigate the association between individual oral glucose-lowering drugs and cardiovascular outcomes...... following myocardial infarction in patients with diabetes mellitus not treated with emergent percutaneous coronary intervention....

Metabolic Effects of Glucose-Fructose Co-Ingestion Compared to Glucose Alone during Exercise in Type 1 Diabetes

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Lia Bally

2017-02-01

Full Text Available This paper aims to compare the metabolic effects of glucose-fructose co-ingestion (GLUFRU with glucose alone (GLU in exercising individuals with type 1 diabetes mellitus. Fifteen male individuals with type 1 diabetes (HbA1c 7.0% ± 0.6% (53 ± 7 mmol/mol underwent a 90 min iso-energetic continuous cycling session at 50% VO2max while ingesting combined glucose-fructose (GLUFRU or glucose alone (GLU to maintain stable glycaemia without insulin adjustment. GLUFRU and GLU were labelled with 13C-fructose and 13C-glucose, respectively. Metabolic assessments included measurements of hormones and metabolites, substrate oxidation, and stable isotopes. Exogenous carbohydrate requirements to maintain stable glycaemia were comparable between GLUFRU and GLU (p = 0.46. Fat oxidation was significantly higher (5.2 ± 0.2 vs. 2.6 ± 1.2 mg·kg−1·min−1, p < 0.001 and carbohydrate oxidation lower (18.1 ± 0.8 vs. 24.5 ± 0.8 mg·kg−1·min−1 p < 0.001 in GLUFRU compared to GLU, with decreased muscle glycogen oxidation in GLUFRU (10.2 ± 0.9 vs. 17.5 ± 1.0 mg·kg−1·min−1, p < 0.001. Lactate levels were higher (2.2 ± 0.2 vs. 1.8 ± 0.1 mmol/L, p = 0.012 in GLUFRU, with comparable counter-regulatory hormones between GLUFRU and GLU (p > 0.05 for all. Glucose and insulin levels, and total glucose appearance and disappearance were comparable between interventions. Glucose-fructose co-ingestion may have a beneficial impact on fuel metabolism in exercising individuals with type 1 diabetes without insulin adjustment, by increasing fat oxidation whilst sparing glycogen.

Natural History of Impaired Glucose Tolerance in Japanese Americans: Change in Visceral Adiposity is Associated with Remission from Impaired Glucose Tolerance to Normal Glucose Tolerance.

Science.gov (United States)

Onishi, Yukiko; Hayashi, Tomoshige; Sato, Kyoko K; Leonetti, Donna L; Kahn, Steven E; Fujimoto, Wilfred Y; Boyko, Edward J

2018-05-30

To describe the roles of intra-abdominal fat and its change in the remission of impaired glucose tolerance (IGT) to normal glucose tolerance (NGT). We followed 157 Japanese Americans with IGT at baseline for 10-11 years without external intervention. We measured intra-abdominal and abdominal subcutaneous fat area (IAFA and ASFA) by computed tomography at baseline and at 5-6 years of follow-up. Change in IAFA and ASFA (ΔIAFA and ΔASFA) were calculated by subtracting baseline fat area from 5-6 year follow-up fat area. Glucose and insulin at fasting and during a 75-g oral glucose tolerance test, insulinogenic index (IGI [Δinsulin/Δglucose (30-0 min)]) and homeostasis model assessment for insulin resistance (HOMA-IR) were measured at baseline. Fourty-four subjects remitted to NGT. Among those with lower IAFA (≤median 91.31 cm 2 ) and the lowest tertile of ΔIAFA, 45% remitted, while with higher IAFA (>91.31 cm 2 ) and the highest tertile of ΔIAFA, only 12.5% remitted. ΔIAFA was significantly associated with remission to NGT (multiple-adjusted odd ratio [1-SD decrease] 1.93, 95% CI 1.10-3.36) independent of IAFA, ASFA, ΔASFA, IGI, HOMA-IR, age, sex, and family history of diabetes. In the natural history of IGT, change in intra-abdominal fat was associated with remission to NGT. Copyright © 2018. Published by Elsevier B.V.

Thermogenic Effect of Glucose in Hypothyroid Subjects

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Agnieszka Kozacz

2014-01-01

Full Text Available The importance of thyroid hormone, catecholamines, and insulin in modification of the thermogenic effect of glucose (TEG was examined in 34 healthy and 32 hypothyroid subjects. We calculated the energy expenditure at rest and during oral glucose tolerance test. Blood samples for determinations of glucose, plasma insulin, adrenaline (A, and noradrenaline (NA were collected. It was found that TEG was lower in hypothyroid than in control group (19.68±3.90 versus 55.40±7.32 kJ, resp., P<0.0004. Mean values of glucose and insulin areas under the curve were higher in women with hypothyroidism than in control group (286.79±23.65 versus 188.41±15.84 mmol/L·min, P<0.003 and 7563.27±863.65 versus 4987.72±583.88 mU/L·min, P<0.03 resp.. Maximal levels of catecholamines after glucose ingestion were higher in hypothyroid patients than in control subjects (Amax—0.69±0.08 versus 0.30±0.07 nmol/L, P<0.0001, and NAmax—6.42±0.86 versus 2.54±0.30 nmol/L, P<0.0002. It can be concluded that in hypothyroidism TEG and glucose tolerance are decreased while the adrenergic response to glucose administration is enhanced. Presumably, these changes are related to decreased insulin sensitivity and responsiveness to catecholamine action.

Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes.

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Jabbour, S A; Goldstein, B J

2008-08-01

The kidney plays a central role in the regulation of plasma glucose levels, although until recently this has not been widely appreciated or considered a target for therapeutic intervention. The sodium glucose co-transporter type 2 (SGLT2) located in the plasma membrane of cells lining the proximal tubule mediates the majority of renal glucose reabsorption from the tubular fluid, which normally prevents the loss of glucose in the urine. Competitive inhibitors of SGLT2 that provoke the renal excretion of glucose have been discovered, thereby providing a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. To explore the physiology of SGLT2 action and discuss several SGLT2 inhibitors that have entered early clinical development. All publicly available data were identified by searching the internet for 'SGLT2' and 'SGLT2 inhibitor' through 1 November 2007. Published articles, press releases and abstracts presented at national and international meetings were considered. Sodium glucose co-transporter type 2 inhibition is a novel treatment option for diabetes, which has been studied in preclinical models and a few potent and selective SGLT2 inhibitors have been reported and are currently in clinical development. These agents appear to be safe and generally well tolerated, and will potentially be a beneficial addition to the growing battery of oral antihyperglycaemic agents.

Mechanocatalytic Production of Lactic Acid from Glucose by Ball Milling

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Luyang Li

2017-06-01

Full Text Available A solvent-free process was developed for the direct production of lactic acid from glucose in a mechanocatalytic process in the presence of Ba(OH2, and a moderate lactic acid yield of 35.6% was obtained. Glucose conversion and lactic acid formation were favorable at higher catalyst/glucose mass ratios. However, at relatively lower catalyst/glucose mass ratios, they were greatly inhibited, and the promotion of fructose formation was observed. The mechanocatalytic process was applicable for various carbohydrates such as C5 sugars, C6 sugars, and disaccharides with 20–36% lactic acid yields achieved. This work provides a new pathway for the production of value-added chemicals from biomass resources.

Effects of dehydroepiandrosterone (DHEA) on glucose metabolism in isolated hepatocytes from Zucker rats

International Nuclear Information System (INIS)

Finan, A.; Cleary, M.P.

1986-01-01

DHEA has been shown to competitively inhibit the pentose phosphate shunt (PPS) enzyme glucose-6-phosphate dehydrogenase (G6PD) when added in vitro to supernatants or homogenates prepared from mammalian tissues. However, no consistent effect on G6PD activity has been determined in tissue removed from DHEA-treated rats. To explore the effects of DHEA on PPS, glucose utilization was measured in hepatocytes from lean and obese male Zucker rats (8 wks of age) following 1 wk of DHEA treatment (0.6% in diet). Incubation of isolated hepatocytes from treated lean Zucker rats with either [1- 14 C] glucose or [6- 14 C] glucose resulted in significant decreases in CO 2 production and total glucose utilization. DHEA-lean rats also had lowered fat pad weights. In obese rats, there was no effect of 1 wk of treatment on either glucose metabolism or fat pad weight. The calculated percent contribution of the PPS to glucose metabolism in hepatocytes was not changed for either DHEA-lean or obese rats when compared to control rats. In conclusion, 1 wk of DHEA treatment lowered overall glucose metabolism in hepatocytes of lean Zucker rats, but did not selectively affect the PPS. The lack of an effect of short-term treatment in obese rats may be due to differences in their metabolism or storage/release of DHEA in tissues in comparison to lean rats

Glucose variability negatively impacts long-term functional outcome in patients with traumatic brain injury.

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Matsushima, Kazuhide; Peng, Monica; Velasco, Carlos; Schaefer, Eric; Diaz-Arrastia, Ramon; Frankel, Heidi

2012-04-01

Significant glycemic excursions (so-called glucose variability) affect the outcome of generic critically ill patients but has not been well studied in patients with traumatic brain injury (TBI). The purpose of this study was to evaluate the impact of glucose variability on long-term functional outcome of patients with TBI. A noncomputerized tight glucose control protocol was used in our intensivist model surgical intensive care unit. The relationship between the glucose variability and long-term (a median of 6 months after injury) functional outcome defined by extended Glasgow Outcome Scale (GOSE) was analyzed using ordinal logistic regression models. Glucose variability was defined by SD and percentage of excursion (POE) from the preset range glucose level. A total of 109 patients with TBI under tight glucose control had long-term GOSE evaluated. In univariable analysis, there was a significant association between lower GOSE score and higher mean glucose, higher SD, POE more than 60, POE 80 to 150, and single episode of glucose less than 60 mg/dL but not POE 80 to 110. After adjusting for possible confounding variables in multivariable ordinal logistic regression models, higher SD, POE more than 60, POE 80 to 150, and single episode of glucose less than 60 mg/dL were significantly associated with lower GOSE score. Glucose variability was significantly associated with poorer long-term functional outcome in patients with TBI as measured by the GOSE score. Well-designed protocols to minimize glucose variability may be key in improving long-term functional outcome. Copyright © 2012 Elsevier Inc. All rights reserved.

Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes

DEFF Research Database (Denmark)

Zander, M; Taskiran, M; Toft-Nielsen, M B

2001-01-01

) alternating with GLP-1 (continuous subcutaneous infusion of 2.4 pmol x kg(-1) x min(-1)) alternating with a combination of metformin and GLP-1 for 48 h. Under fixed energy intake, we examined the effects on plasma glucose, insulin, C-peptide, glucagon, and appetite. RESULTS: Fasting plasma glucose (day 2...... this study to investigate the effect of a combination therapy with GLP-1 and metformin, which could theoretically be additive, in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a semiblinded randomized crossover study, seven patients received treatment with metformin (1,500 mg daily orally......) and 11.7 +/- 0.8 (GLP-1) to 9.8 +/- 0.5 (combination) (P = 0.02, no difference between GLP-1 and metformin). Insulin levels were similar between the three regimens, but glucagon levels were significantly reduced with GLP-1 compared with metformin (P = 0.0003). Combination therapy had no additional effect...

Significance of Glucose Addition on Chitosan-Glycerophosphate Hydrogel Properties

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Dian Susanthy

2016-03-01

Full Text Available Chitosan-glycerophosphate hydrogel can be used as dental scaffold due to its thermosensitivity, gelation performance at body temperature, suitable acidity for body condition, biocompatibility, and ability to provide good environment for cell proliferation and differentiation. Previous study showed that glucose addition to the chitosan solution before steam sterilization improved its hydrogel mechanical strength. However, the effectiveness of glucose addition was still doubted because glucose might undergo Maillard reaction in that particular condition. The aims of this study are to confirm whether the glucose addition can increase the hydrogel mechanical strength and gelation rate effectively and also to compare their performance to be dental scaffold. This research was performed through several steps, namely preparation of chitosan-glycerophosphate solution, addition of glucose, gelation time test, gel mechanical strength measurement, functional group analysis, and physical properties measurements (pH, viscosity, and pore size. The result showed that glucose addition did not improve the hydrogel mechanical strength and gelation rate, neither when it was added before nor after steam sterilization. Glucose addition before steam sterilization seemed to trigger Maillard reaction or browning effect, while glucose addition after steam sterilization increased the amount of free water molecules in the hydrogel. Chitosan and glycerophosphate interact physically, but interaction between chitosan and glucose seems to occur chemically and followed by the formation of free water molecules. Glucose addition decreases the solution viscosity and hydrogel pore size so the hydrogel performance as dental scaffold is lowered.

The importance of sensitive screening for abnormal glucose metabolism in patients with IgA nephropathy.

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Jia, Xiaoyuan; Pan, Xiaoxia; Xie, Jingyuan; Shen, Pingyan; Wang, Zhaohui; Li, Ya; Wang, Weiming; Chen, Nan

2016-01-01

To investigate the prevalence of abnormal glucose metabolism, insulin resistance (IR) and the related risk factors in IgA nephropathy (IgAN) patients. We analyzed oral glucose tolerance test (OGTT) and clinical data of 107 IgAN patients and 106 healthy controls. Glucose metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) and the insulin sensitivity index (ISI) of both groups were evaluated. The prevalence of abnormal glucose metabolism was significantly higher in the IgAN group than in the control group (41.12% vs. 9.43%, p glucose, fasting insulin, OGTT 2-hour blood glucose, OGTT 2-hour insulin, HOMA-IR, and lower ISI than healthy controls. Triglyceride (OR = 2.55), 24-hour urine protein excretion (OR = 1.39), and age (OR = 1.06) were independent risk factors for abnormal glucose metabolism in IgAN patients. BMI, eGFR, 24-hour urine protein excretion, triglyceride, fasting blood glucose, fasting insulin, OGTT 2-hour blood glucose, and OGTT 2-hour insulin were significantly higher in IgAN patients with IR than in IgAN patients without IR, while HDL and ISI were significantly lower. BMI, serum albumin, and 24-hour urine protein excretion were correlated factors of IR in IgAN patients. Our study highlighted that abnormal glucose metabolism was common in IgAN patients. Triglyceride and 24-hour urine protein excretion were significant risk factors for abnormal glucose metabolism. Therefore, sensitive screening for glucose metabolism status and timely intervention should be carried out in clinical work.

Umbilical cord blood glucose levels in full-term newborns

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A. L. Karpova

2014-01-01

Full Text Available The purpose of the investigation was to determine the umbilical cord venous blood level of glucose in full-term newborns and its relationship to the mode of delivery. The investigation included 102 full-term newborn infants, including 33 and 69 babies born via cesar-ean and vaginal delivery, respectively. Umbilical cord serum glucose levels were determined by the glucose oxidase test using a Sap-phire-400 biochemical analyzer. In healthy full-term newborns, the mean umbilical cord blood glucose levels were 4,29±0,88 mmol/1 (minimum, 2,9 mmol/1 and maximum, 5,9 mmol/1. In the babies born via cesarean delivery, the umbilical cord blood concentration of glucose was ascertained to be significantly lower than in those born vaginally (3,84+0,71 mmol/1 versus 4,51+0,87 mmol/1; /><0,0001. Abdominal delivery can be apparently considered to be a risk factor for hypoglycemia in neonatal infants.

Underestimation of glucose turnover measured with [6-3H]- and [6,6-2H]- but not [6-14C]glucose during hyperinsulinemia in humans

International Nuclear Information System (INIS)

McMahon, M.M.; Schwenk, W.F.; Haymond, M.W.; Rizza, R.A.

1989-01-01

Recent studies indicate that hydrogen-labeled glucose tracers underestimate glucose turnover in humans under conditions of high flux. The cause of this underestimation is unknown. To determine whether the error is time-, pool-, model-, or insulin-dependent, glucose turnover was measured simultaneously with [6-3H]-, [6,6-2H2]-, and [6-14C]glucose during a 7-h infusion of either insulin (1 mU.kg-1.min-1) or saline. During the insulin infusion, steady-state glucose turnover measured with both [6-3H]glucose (8.0 +/- 0.5 mg.kg-1.min-1) and [6,6-2H2]glucose (7.6 +/- 0.5 mg.kg-1.min-1) was lower (P less than .01) than either the glucose infusion rate required to maintain euglycemia (9.8 +/- 0.7 mg.kg-1.min-1) or glucose turnover determined with [6-14C]glucose and corrected for Cori cycle activity (9.8 +/- 0.7 mg.kg-1.min-1). Consequently negative glucose production rates (P less than .01) were obtained with either [6-3H]- or [6,6-2H2]- but not [6-14C]glucose. The difference between turnover estimated with [6-3H]glucose and actual glucose disposal (or 14C glucose flux) did not decrease with time and was not dependent on duration of isotope infusion. During saline infusion, estimates of glucose turnover were similar regardless of the glucose tracer used. High-performance liquid chromatography of the radioactive glucose tracer and plasma revealed the presence of a tritiated nonglucose contaminant. Although the contaminant represented only 1.5% of the radioactivity in the [6-3H]glucose infusate, its clearance was 10-fold less (P less than .001) than that of [6-3H]glucose. This resulted in accumulation in plasma, with the contaminant accounting for 16.6 +/- 2.09 and 10.8 +/- 0.9% of what customarily is assumed to be plasma glucose radioactivity during the insulin or saline infusion, respectively (P less than .01)

Spatial relationship between tumor perfusion and endogeneous glucose distribution

International Nuclear Information System (INIS)

Schroeder, T.; Larrier, N.; Viglianti, B.; Rabbani, Z.N.; Peltz, C.; Vujascovic, Z.; Dewhirst, M.W.

2003-01-01

Earlier studies detecting glucose in tissue and solid tumors by bioluminescence imaging suggested, that glucose distribution patterns may be spatially related to functional vascularity. The purpose of this study was to evaluate this relationship by comparing glucose distribution patterns as determined by bioluminescence imaging to perfusion patterns of endogeneous Hoechst 33342 in rats bearing mammary carcinomas. R 3230 mammary carcinoma cells have been implanted subcutaneously into 7 female Fischer 344 rats. Two months post implantation, after injection of Hoechst 33342 the tumors were removed and snap frozen to conserve metabolite levels. Concomitantly, blood was sampled from the animals for analysis of glucose concentrations using a micodialysis analyzer. Cryosections of the tumors have been prepared, and every slice has been analyzed for both, Hoechst binding by fluorescence microscopy, and for glucose distribution patterns using bioluminescence imaging. In many cases vascular structures could be retrieved by the spatial pattern of glucose distribution. In some cases however, higher glucose concentrations could be found independent from Hoechst signal. On the other hand, regions of high Hoechst signal are not necessarily correlated with high glucose concentrations. When comparing blood and tissue glucose levels, tissue glucose content as measured with bioluminescence imaging (1.9-3.5 mM) is considerably lower than blood glucose (5.6-8.0 mM), demonstrating the expected gradient from blood to tissue. This study demonstrates the feasibility of monitoring glucose gradients in relation to functional vasculature throughout the body, from blood down to tissue or tumor and further, throughout the microenvironment of the solid tumor. Glucose distribution patterns may be an important tool in perfusion studies, e. g. in detecting the direction of blood flow in ex-vivo samples or in estimating glucose consumption rates of tumor cells adjacent to or in between perfused

Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

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Reed JW

2016-10-01

Full Text Available James W Reed Morehouse School of Medicine, Atlanta, GA, USA Abstract: SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM. These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin on BP in patients with T2DM. Boolean searches were conducted that included terms related to BP or hypertension with terms for SGLT2 inhibitors, canagliflozin, dapagliflozin, or empagliflozin using PubMed, Google, and Google Scholar. Data from numerous randomized controlled trials of SGLT2 inhibitors in patients with T2DM demonstrated clinically relevant reductions in both systolic and diastolic BP, assessed via seated office measurements and 24-hour ambulatory BP monitoring. Observed BP lowering was not associated with compensatory increases in heart rate. Circadian BP rhythm was also maintained. The mechanism of SGLT2 inhibitor-associated BP reduction is not fully understood, but is assumed to be related to osmotic diuresis and natriuresis. Other factors that may also contribute to BP reduction include SGLT2 inhibitor-associated decreases in body weight and reduced arterial stiffness. Local inhibition of the renin–angiotensin–aldosterone system secondary to increased delivery of sodium to the juxtaglomerular apparatus during SGLT2 inhibition has also been postulated. Although SGLT2 inhibitors are not indicated as BP-lowering agents, the modest decreases in systolic and diastolic BP observed with SGLT2 inhibitors may provide an extra clinical advantage for the majority of patients with T2DM, in addition to improving blood glucose

Continuous glucose monitoring, oral glucose tolerance, and insulin - glucose parameters in adolescents with simple obesity.

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El Awwa, A; Soliman, A; Al-Ali, M; Yassin, M; De Sanctis, V

2012-09-01

In obese adolescents pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type2 diabetes (T2DM To assess oral glucose tolerance, 72-h continuous blood glucose concentrations (CGM) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in 13 adolescents with simple obesity (BMI SDS=4 ± 1.06). OGTT performed in 13 obese adolescents (13.47 ± 3 years) revealed 3 cases (23%) with impaired fasting glucose (IFG: fasting glucose >5.6 mmol/L), 4 cases (30%) with impaired glucose tolerance (IGT: 2h blood glucose >7.8 continuous glucose monitoring system ( CGMS), IFG was detected in 4 cases, the maximum serum blood glucose (BG : 2h or more after meal) was >7.8 and 11.1 mmol/L (diabetes) in one case (7.6%). Five cases had a minimum BG recorded of 2.6 and QUICKI values obese adolescents, CGMS is superior to OGTT and HbA1C in detecting glycemic abnormalities, which appears to be secondary to insulin resistance.

Effect of somatostatin on glucose homeostasis in conscious long-fasted dogs

International Nuclear Information System (INIS)

Stevenson, R.W.; Steiner, K.E.; Hendrick, G.K.; Cherrington, A.D.

1987-01-01

The effects of somatostatin plus intraportal insulin and glucagon replacement (pancreatic clamp) on carbohydrate metabolism were studied in conscious dogs fasted for 7 days so that gluconeogenesis was a major contributor to total glucose production. By use of [3- 3 H]glucose, glucose production (R a ) and utilization (R d ) and glucose clearance were assessed before and after implementation of the pancreatic clamp. After an initial control period, somatostatin (0.8 μg·kg -1 ·min -1 ) was infused with intraportal replacement amounts of glucagon and insulin. The insulin infusion rate was varied to maintain euglycemia and then kept constant for 250 min. Plasma glucagon was similar before and during somatostatin infusion, while plasma insulin was lower. Plasma glucose levels remained similar while R a and R d and the ratio of glucose clearance to plasma insulin were significantly increased. Net hepatic lactate uptake and [ 14 C]alanine plus [ 14 C]lactate conversion to [ 14 C]glucose increased. In conclusion, somatostatin alters glucose clearance in 7-day fasted dogs, resulting in changes in several indices of carbohydrate metabolism

Impaired glucose-induced thermogenesis in skeletal muscle in obesity. The role of the sympathoadrenal system

DEFF Research Database (Denmark)

Astrup, A; Andersen, T; Henriksen, O

1987-01-01

tests showed that all patients in the HEI group and the lean controls had normal glucose tolerance, whereas it was abnormal in all subjects in the LEI group. The fasting metabolic rate did not differ between the obese groups but was significantly lower in the lean group. The glucose......From a 7-day food recording in 29 morbidly obese patients two groups of six patients each were selected: a high-energy-intake group (HEI) and a low-energy-intake group (LEI). The groups were otherwise comparable. Five lean subjects served as controls for some observations. Oral glucose tolerance......-induced thermogenesis during 180 min expressed as a percentage of the energy content of the glucose load was lower in both obese groups compared with the lean controls (lean: +11.5 per cent, HEI: +5.3 per cent and LEI: -4.2 per cent, HEI vs lean: P = 0.04 and LEI vs lean: P = 0.005), and lower in the LEI group compared...

Decrease of Plasma Glucose by Hibiscus taiwanensis in Type-1-Like Diabetic Rats

Science.gov (United States)

Wang, Lin-Yu; Chung, Hsien-Hui

2013-01-01

Hibiscus taiwanensis (Malvaceae) is widely used as an alternative herb to treat disorders in Taiwan. In the present study, it is used to screen the effect on diabetic hyperglycemia in streptozotocin-induced diabetic rats (STZ-diabetic rats). The extract of Hibiscus taiwanensis showed a significant plasma glucose-lowering action in STZ-diabetic rats. Stems of Hibiscus taiwanensis are more effective than other parts to decrease the plasma glucose in a dose-dependent manner. Oral administration of Hibiscus taiwanensis three times daily for 3 days into STZ-diabetic rats increased the sensitivity to exogenous insulin showing an increase in insulin sensitivity. Moreover, similar repeated administration of Hibiscus taiwanensis for 3 days in STZ-diabetic rats produced a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver and an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle. Taken together, our results suggest that Hibiscus taiwanensis has the ability to lower plasma glucose through an increase in glucose utilization via elevation of skeletal GLUT 4 and decrease of hepatic PEPCK in STZ-diabetic rats. PMID:23690841

Impaired glucose-induced glucagon suppression after partial pancreatectomy

DEFF Research Database (Denmark)

Schrader, Henning; Menge, Bjoern A; Breuer, Thomas G K

2009-01-01

INTRODUCTION: The glucose-induced decline in glucagon levels is often lost in patients with type 2 diabetes. It is unclear whether this is due to an independent defect in alpha-cell function or secondary to the impairment in insulin secretion. We examined whether a partial pancreatectomy in humans...... would also impair postchallenge glucagon concentrations and, if so, whether this could be attributed to the reduction in insulin levels. PATIENTS AND METHODS: Thirty-six patients with pancreatic tumours or chronic pancreatitis were studied before and after approximately 50% pancreatectomy with a 240-min...... oral glucose challenge, and the plasma concentrations of glucose, insulin, C-peptide, and glucagon were determined. RESULTS: Fasting and postchallenge insulin and C-peptide levels were significantly lower after partial pancreatectomy (P

Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

Science.gov (United States)

Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

2006-03-01

Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

Predicting glucose intolerance with normal fasting plasma glucose by the components of the metabolic syndrome

International Nuclear Information System (INIS)

Pei, D.; Lin, J.; Kuo, S.; Wu, D.; Li, J.; Hsieh, C.; Wu, C.; Hung, Y.; Kuo, K.

2007-01-01

Surprisingly it is estimated that about half of type 2 diabetics remain undetected. The possible causes may be partly attributable to people with normal fasting plasma glucose (FPG) but abnormal postprandial hyperglycemia. We attempted to develop an effective predictive model by using the metabolic syndrome (MeS) components as parameters to identify such persons. All participants received a standard 75 gm oral glucose tolerance test which showed that 106 had normal glucose tolerance, 61 had impaired glucose tolerance and 6 had diabetes on isolated postchallenge hyperglycemia. We tested five models which included various MeS components. Model 0: FPG; Model 1 (Clinical history model): family history (FH), FPG, age and sex; Model 2 (MeS model): Model 1 plus triglycerides, high-density lipoprotein cholesterol, body mass index, systolic blood pressure and diastolic blood pressure; Model 3: Model 2 plus fasting plasma insulin (FPI); Model 4: Model 3 plus homeostasis model assessment of insulin resistance. A receiver-operating characteristic (ROC) curve was used to determine the predictive discrimination of these models. The area under the ROC curve of the Model 0 was significantly larger than the area under the diagonal reference line. All the other 4 models had a larger area under the ROC curve than Model 0. Considering the simplicity and lower cost of Model 2, it would be the best model to use. Nevertheless, Model 3 had the largest area under the ROC curve. We demonstrated that Model 2 and 3 have a significantly better predictive discrimination to identify persons with normal FPG at high risk for glucose intolerance. (author)

A new blood glucose management algorithm for type 2 diabetes: a position statement of the Australian Diabetes Society.

Science.gov (United States)

Gunton, Jenny E; Cheung, N Wah; Davis, Timothy M E; Zoungas, Sophia; Colagiuri, Stephen

2014-12-11

Lowering blood glucose levels in people with type 2 diabetes has clear benefits for preventing microvascular complications and potential benefits for reducing macrovascular complications and death. Treatment needs to be individualised for each person with diabetes. This should start with selecting appropriate glucose and glycated haemoglobin targets, taking into account life expectancy and the patient's wishes. For most people, early use of glucose-lowering therapies is warranted. A range of recently available therapies has added to the options for lowering glucose levels, but this has made the clinical pathway for treating diabetes more complicated. This position statement from the Australian Diabetes Society outlines the risks, benefits and costs of the available therapies and suggests a treatment algorithm incorporating the older and newer agents.

Improved glucose tolerance after high-load strength training in patients undergoing dialysis

DEFF Research Database (Denmark)

Mølsted, Stig; Harrison, Adrian Paul; Eidemak, Inge

2013-01-01

glucose tolerance (n = 9). Conclusion: The conducted strength training was associated with a significant improvement in glucose tolerance in patients with impaired glucose tolerance or type 2 diabetes undergoing dialysis. The effect was apparently not associated with muscle hypertrophy, whereas the muscle...... a week. Muscle fiber size, composition and capillary density were analyzed in biopsies obtained in the vastus lateralis muscle. Glucose tolerance and the insulin response were measured by a 2-hour oral glucose tolerance test. Results: All outcome measures remained unchanged during the control period....... After strength training the relative area of type 2X fibers was decreased. Muscle fiber size and capillary density remained unchanged. After the strength training, insulin concentrations were significantly lower in patients with impaired glucose tolerance or type 2 diabetes (n = 14) (fasting insulin...

Is fasting glucose sufficient to define diabetes? Epidemiological data from 20 European studies

NARCIS (Netherlands)

DECODE-study group, [Unknown

1999-01-01

Aims/hypothesis. The World Health Organization Consultation recommended new diagnostic criteria for diabetes mellitus including: lowering of the diagnostic fasting plasma glucose to 7.0 mmol/l and introduction of a new category: impaired fasting glycaemia. The diagnostic 2-h glucose concentrations

Decreased cerebral glucose metabolism associated with mental deterioration in multi-infarct dementia

International Nuclear Information System (INIS)

Meguro, K.; Doi, C.; Yamaguchi, T.; Sasaki, H.; Matsui, H.; Yamada, K.; Kinomura, S.; Tohoku Univ.; Itoh, M.

1991-01-01

Cerebral glucose metabolism of 18 patients with multi-infarct dementia (MID) and 10 age-matched normal subjects were examined with positron emission tomography and the 18 -F-fluoro-deoxy-glucose technique. MID patients had significantly lower glucose metabolsim in all the grey matter regions measured and were also characterized by more individuality in metabolic pattern. MID patients were also evaluated as to intelligence quotient (IQ). A positive correlation between IQ as shown by the Tanaka-Binet test and glucose metabolism for the entire grey matter was found. The clinical applicability of this test for predicting cerebral metabolism is discussed. (orig.)

Effect of adrenaline on glucose kinetics during exercise in adrenalectomised humans

DEFF Research Database (Denmark)

Howlett, K.; Galbo, Henrik; Lorentsen, J.

1999-01-01

for 45 min at 68 +/- 1 % maximum pulmonary O2 uptake (VO2,max), followed by 15 min at 84 +/- 2 % VO2, max without (-ADR) or with (+ADR) adrenaline infusion, which elevated plasma adrenaline levels (45 min, 4.49 +/- 0.69 nmol l-1; 60 min, 12.41 +/- 1.80 nmol l-1; means +/- s.e.m.). Glucose kinetics were...... measured using [3-3H]glucose. 3. Euglycaemia was maintained during exercise in CON and -ADR, whilst in +ADR plasma glucose was elevated. The exercise-induced increase in hepatic glucose production was similar in +ADR and -ADR; however, adrenaline infusion augmented the rise in hepatic glucose production...... early in exercise. Glucose uptake increased during exercise in +ADR and -ADR, but was lower and metabolic clearance rate was reduced in +ADR. 4. During exercise noradrenaline and glucagon concentrations increased, and insulin and cortisol concentrations decreased, but plasma levels were similar between...

Relation of Adiponectin to Glucose Tolerance Status, Adiposity, and Cardiovascular Risk Factor Load

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N. Wolfson

2012-01-01

Full Text Available Objective. Adiponectin has anti-atherogenic and anti-inflammatory properties. We investigated the influence of adiponectin on glucose tolerance status, adiposity and cardiovascular risk factors (CVRFs. Design and Patients. Study consisted of 107 subjects: 55 with normal glucose tolerance (NGT and 52 with impaired glucose regulation (IGR who were divided into two groups: 24 subjects with impaired fasting glucose (IFG Group and 28 patients with type 2 diabetes mellitus (DM Group. In additional analysis, study participants were divided into two groups, according to CVRFs: low and high risk. Measurements: Patients were evaluated for glucose, HbA1C, insulin, lipids, CRP, HOMA-IR and adiponectin. Measurements. Patients were evaluated for glucose, HbA1C, insulin, lipids, CRP, HOMA-IR and adiponectin. Results. Adiponectin was significantly higher in NGT group than in IFG (=0.003 and DM (=0.01 groups. Adiponectin was significantly, positively associated with HDL and inversely associated with glucose, HbA1c, ALT, AST, TG, HOMA-IR. Patients with higher CVRFs load have lesser adiponectin compared to patients with low cardiovascular risk <0.0001. Adiponectin was inversely associated with the number of risk factors (=−0.430, =0.0001. Conclusions. Circulating adiponectin was significantly lower in subjects with different degree of IGR compared to subjects with normal glucose homeostasis. Adiponectin was significantly lower in high risk group than low risk group and decreased concurrently with increased number of CVRFs.

Loss of sugar detection by GLUT2 affects glucose homeostasis in mice.

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Emilie Stolarczyk

Full Text Available BACKGROUND: Mammals must sense the amount of sugar available to them and respond appropriately. For many years attention has focused on intracellular glucose sensing derived from glucose metabolism. Here, we studied the detection of extracellular glucose concentrations in vivo by invalidating the transduction pathway downstream from the transporter-detector GLUT2 and measured the physiological impact of this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We produced mice that ubiquitously express the largest cytoplasmic loop of GLUT2, blocking glucose-mediated gene expression in vitro without affecting glucose metabolism. Impairment of GLUT2-mediated sugar detection transiently protected transgenic mice against starvation and streptozotocin-induced diabetes, suggesting that both low- and high-glucose concentrations were not detected. Transgenic mice favored lipid oxidation, and oral glucose was slowly cleared from blood due to low insulin production, despite massive urinary glucose excretion. Kidney adaptation was characterized by a lower rate of glucose reabsorption, whereas pancreatic adaptation was associated with a larger number of small islets. CONCLUSIONS/SIGNIFICANCE: Molecular invalidation of sugar sensing in GLUT2-loop transgenic mice changed multiple aspects of glucose homeostasis, highlighting by a top-down approach, the role of membrane glucose receptors as potential therapeutic targets.

Pleocytosis is not fully responsible for low CSF glucose in meningitis.

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Baud, Maxime O; Vitt, Jeffrey R; Robbins, Nathaniel M; Wabl, Rafael; Wilson, Michael R; Chow, Felicia C; Gelfand, Jeffrey M; Josephson, S Andrew; Miller, Steve

2018-01-01

The mechanism of hypoglycorrhachia-low CSF glucose-in meningitis remains unknown. We sought to evaluate the relative contribution of CSF inflammation vs microorganisms (bacteria and fungi) in lowering CSF glucose levels. We retrospectively categorized CSF profiles into microbial and aseptic meningitis and analyzed CSF leukocyte count, glucose, and protein concentrations. We assessed the relationship between these markers using multivariate and stratified linear regression analysis for initial and repeated CSF sampling. We also calculated the receiver operating characteristics of CSF glucose and CSF-to-serum glucose ratios to presumptively diagnose microbial meningitis. We found that increasing levels of CSF inflammation were associated with decreased CSF glucose levels in the microbial but not aseptic category. Moreover, elevated CSF protein levels correlated more strongly than the leukocyte count with low CSF glucose levels on initial ( R 2 = 36%, p CSF sampling ( R 2 = 46%, p CSF glucose and CSF-to-serum glucose ratios had similar low sensitivity and moderate-to-high specificity in diagnosing microbial meningitis at thresholds commonly used. The main driver of hypoglycorrhachia appears to be a combination of microbial meningitis with moderate to high degrees of CSF inflammation and proteins, suggesting that the presence of microorganisms capable of catabolizing glucose is a determinant of hypoglycorrhachia in meningitis. A major notable exception is neurosarcoidosis. Low CSF glucose and CSF-to-serum glucose ratios are useful markers for the diagnosis of microbial meningitis.

Glucose rapidly induces different forms of excitatory synaptic plasticity in hypothalamic POMC neurons.

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Jun Hu

Full Text Available Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+, EPSC(-, and EPSC(+/- based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs, using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+ neurons, but increased it in EPSC(- neurons. Unlike EPSC(+ and EPSC(- neurons, EPSC(+/- neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/- neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals.

Glucose rapidly induces different forms of excitatory synaptic plasticity in hypothalamic POMC neurons.

Science.gov (United States)

Hu, Jun; Jiang, Lin; Low, Malcolm J; Rui, Liangyou

2014-01-01

Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+), EPSC(-), and EPSC(+/-)) based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs), using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(-) neurons. Unlike EPSC(+) and EPSC(-) neurons, EPSC(+/-) neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/-) neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals.

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

International Nuclear Information System (INIS)

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

1990-01-01

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

A Disposable Tear Glucose Biosensor—Part 2: System Integration and Model Validation

Science.gov (United States)

La Belle, Jeffrey T.; Bishop, Daniel K.; Vossler, Stephen R.; Patel, Dharmendra R.; Cook, Curtiss B.

2010-01-01

Background We presented a concept for a tear glucose sensor system in an article by Bishop and colleagues in this issue of Journal of Diabetes Science and Technology. A unique solution to collect tear fluid and measure glucose was developed. Individual components were selected, tested, and optimized, and system error modeling was performed. Further data on prototype testing are now provided. Methods An integrated fluidics portion of the prototype was designed, cast, and tested. A sensor was created using screen-printed sensors integrated with a silicone rubber fluidics system and absorbent polyurethane foam. A simulated eye surface was prepared using fluid-saturated poly(2-hydroxyethyl methacrylate) sheets, and the disposable prototype was tested for both reproducibility at 0, 200, and 400 μM glucose (n = 7) and dynamic range of glucose detection from 0 to 1000 μM glucose. Results From the replicated runs, an established relative standard deviation of 15.8% was calculated at 200 μM and a lower limit of detection was calculated at 43.4 μM. A linear dynamic range was demonstrated from 0 to 1000 μM with an R2 of 99.56%. The previously developed model predicted a 14.9% variation. This compares to the observed variance of 15.8% measured at 200 μM glucose. Conclusion With the newly designed fluidics component, an integrated tear glucose prototype was assembled and tested. Testing of this integrated prototype demonstrated a satisfactory lower limit of detection for measuring glucose concentration in tears and was reproducible across a physiological sampling range. The next step in the device design process will be initial animal studies to evaluate the current prototype for factors such as eye irritation, ease of use, and correlation with blood glucose. PMID:20307390

A disposable tear glucose biosensor-part 2: system integration and model validation.

Science.gov (United States)

La Belle, Jeffrey T; Bishop, Daniel K; Vossler, Stephen R; Patel, Dharmendra R; Cook, Curtiss B

2010-03-01

We presented a concept for a tear glucose sensor system in an article by Bishop and colleagues in this issue of Journal of Diabetes Science and Technology. A unique solution to collect tear fluid and measure glucose was developed. Individual components were selected, tested, and optimized, and system error modeling was performed. Further data on prototype testing are now provided. An integrated fluidics portion of the prototype was designed, cast, and tested. A sensor was created using screen-printed sensors integrated with a silicone rubber fluidics system and absorbent polyurethane foam. A simulated eye surface was prepared using fluid-saturated poly(2-hydroxyethyl methacrylate) sheets, and the disposable prototype was tested for both reproducibility at 0, 200, and 400 microM glucose (n = 7) and dynamic range of glucose detection from 0 to 1000 microM glucose. From the replicated runs, an established relative standard deviation of 15.8% was calculated at 200 microM and a lower limit of detection was calculated at 43.4 microM. A linear dynamic range was demonstrated from 0 to 1000 microM with an R(2) of 99.56%. The previously developed model predicted a 14.9% variation. This compares to the observed variance of 15.8% measured at 200 microM glucose. With the newly designed fluidics component, an integrated tear glucose prototype was assembled and tested. Testing of this integrated prototype demonstrated a satisfactory lower limit of detection for measuring glucose concentration in tears and was reproducible across a physiological sampling range. The next step in the device design process will be initial animal studies to evaluate the current prototype for factors such as eye irritation, ease of use, and correlation with blood glucose. (c) 2010 Diabetes Technology Society.

Blood glucose level reconstruction as a function of transcapillary glucose transport.

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Koutny, Tomas

2014-10-01

A diabetic patient occasionally undergoes a detailed monitoring of their glucose levels. Over the course of a few days, a monitoring system provides a detailed track of their interstitial fluid glucose levels measured in their subcutaneous tissue. A discrepancy in the blood and interstitial fluid glucose levels is unimportant because the blood glucose levels are not measured continuously. Approximately five blood glucose level samples are taken per day, and the interstitial fluid glucose level is usually measured every 5min. An increased frequency of blood glucose level sampling would cause discomfort for the patient; thus, there is a need for methods to estimate blood glucose levels from the glucose levels measured in subcutaneous tissue. The Steil-Rebrin model is widely used to describe the relationship between blood and interstitial fluid glucose dynamics. However, we measured glucose level patterns for which the Steil-Rebrin model does not hold. Therefore, we based our research on a different model that relates present blood and interstitial fluid glucose levels to future interstitial fluid glucose levels. Using this model, we derived an improved model for calculating blood glucose levels. In the experiments conducted, this model outperformed the Steil-Rebrin model while introducing no additional requirements for glucose sample collection. In subcutaneous tissue, 26.71% of the calculated blood glucose levels had absolute values of relative differences from smoothed measured blood glucose levels less than or equal to 5% using the Steil-Rebrin model. However, the same difference interval was encountered in 63.01% of the calculated blood glucose levels using the proposed model. In addition, 79.45% of the levels calculated with the Steil-Rebrin model compared with 95.21% of the levels calculated with the proposed model had 20% difference intervals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of exercise training on glucose control, lipid metabolism, and insulin sensitivity in hypertriglyceridemia and non-insulin dependent diabetes mellitus.

Science.gov (United States)

Lampman, R M; Schteingart, D E

1991-06-01

Exercise training has potential benefits for patients with hyperlipidemia and/or non-insulin dependent diabetes mellitus. In nondiabetic, nonobese subjects with hypertriglyceridemia, exercise training alone increased insulin sensitivity, improved glucose tolerance, and lowered serum triglyceride and cholesterol levels. These improvements did not occur when exercise training alone was given to similar patients with impaired glucose tolerance. In severely obese (X = 125 kg) subjects without diabetes melitus, a 600 calorie diet alone decreased glucose and insulin concentrations and improved glucose tolerance but did not increase insulin sensitivity. The addition of exercise training improved insulin sensitivity. Obese, non-insulin dependent diabetes mellitus subjects on sulfonylurea therapy alone increased insulin levels but failed to improve insulin sensitivity or glucose levels. In contrast, the addition of exercise training to this medication resulted in improved insulin sensitivity and lowered glucose levels. We conclude that exercise training has major effects on lowering triglyceride levels in hyperlipidemic subjects and can potentiate the effect of diet or drug therapy on glucose metabolism in patients with non-insulin dependent diabetes mellitus.

Effects of Panax ginseng, consumed with and without glucose, on blood glucose levels and cognitive performance during sustained 'mentally demanding' tasks.

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Reay, Jonathon L; Kennedy, David O; Scholey, Andrew B

2006-11-01

Single doses of the traditional herbal treatment Panax ginseng have recently been shown to lower blood glucose levels and elicit cognitive improvements in healthy, overnight-fasted volunteers. The specific mechanisms responsible for these effects are not known. However, cognitive improvements may be related to the glycaemic properties of Panax ginseng. Using a double-blind, placebo-controlled, balanced-crossover design, 27 healthy young adults completed a 10 minute "cognitive demand" test battery at baseline. They then consumed capsules containing either ginseng (extract G115) or a placebo and 30 minutes later a drink containing glucose or placebo. A further 30 minutes later (i.e. 60 minutes post-baseline/capsules) they completed the "cognitive demand" battery six times in immediate succession. Depending on the condition to which the participant was allocated on that particular day, the combination of capsules/drink treatments corresponded to a dose of: 0mg G115/0 mg glucose (placebo); 200mg G115/0 mg glucose (ginseng); 0 mg G115/25 g glucose (glucose) or 200 mg G115/25 g glucose (ginseng/glucose combination). The 10 minute "cognitive demand" battery comprised a Serial Threes subtraction task (2 min); a Serial Sevens subtraction task (2 min); a Rapid Visual Information Processing task (5 min); and a "mental fatigue" visual analogue scale. Blood glucose levels were measured prior to the day's treatment, and before and after the post-dose completions of the battery. The results showed that both Panax ginseng and glucose enhanced performance of a mental arithmetic task and ameliorated the increase in subjective feelings of mental fatigue experienced by participants during the later stages of the sustained, cognitively demanding task performance. Accuracy of performing the Rapid Visual Information Processing task (RVIP) was also improved following the glucose load. There was no evidence of a synergistic relationship between Panax ginseng and exogenous glucose ingestion

Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

Science.gov (United States)

Reed, James W

2016-01-01

SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM). These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP) lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin) on BP in patients with T2DM. Boolean searches were conducted that included terms related to BP or hypertension with terms for SGLT2 inhibitors, canagliflozin, dapagliflozin, or empagliflozin using PubMed, Google, and Google Scholar. Data from numerous randomized controlled trials of SGLT2 inhibitors in patients with T2DM demonstrated clinically relevant reductions in both systolic and diastolic BP, assessed via seated office measurements and 24-hour ambulatory BP monitoring. Observed BP lowering was not associated with compensatory increases in heart rate. Circadian BP rhythm was also maintained. The mechanism of SGLT2 inhibitor-associated BP reduction is not fully understood, but is assumed to be related to osmotic diuresis and natriuresis. Other factors that may also contribute to BP reduction include SGLT2 inhibitor-associated decreases in body weight and reduced arterial stiffness. Local inhibition of the renin–angiotensin–aldosterone system secondary to increased delivery of sodium to the juxtaglomerular apparatus during SGLT2 inhibition has also been postulated. Although SGLT2 inhibitors are not indicated as BP-lowering agents, the modest decreases in systolic and diastolic BP observed with SGLT2 inhibitors may provide an extra clinical advantage for the majority of patients with T2DM, in addition to improving blood glucose control. PMID:27822054

Acute effects of light and dark roasted coffee on glucose tolerance

DEFF Research Database (Denmark)

Rakvaag, Elin; Dragsted, Lars Ove

2016-01-01

PURPOSE: Epidemiological evidence suggests that coffee consumption is associated with a lower risk of type 2 diabetes. Coffee contains caffeine and several other components that may modulate glucose regulation. The chlorogenic acids (CGA) in coffee have been indicated as constituents that may help...... to normalize the acute glucose response after a carbohydrate challenge. The aim of this study was to investigate whether two coffee beverages that differ in CGA content due to different roasting degrees will differentially affect glucose regulation. METHODS: In a controlled crossover trial, 11 healthy fasted...... volunteers consumed 300 mL of either light (LIR) or dark (DAR) roasted coffee, or water, followed 30 min later by a 75-g oral glucose tolerance test (OGTT). Blood samples were drawn at baseline, 30, 60, and 120 min. Differences in glucose and insulin responses and insulin sensitivity index (ISI) were...

Measuring brain glucose phosphorylation with labeled glucose

International Nuclear Information System (INIS)

Brondsted, H.E.; Gjedde, A.

1988-01-01

This study tested whether glucose labeled at the C-6 position generates metabolites that leave brain so rapidly that C-6-labeled glucose cannot be used to measure brain glucose phosphorylation (CMRGlc). In pentobarbital-anesthetized rats, the parietal cortex uptake of [ 14 C]glucose labeled in the C-6 position was followed for times ranging from 10 s to 60 min. We subtracted the observed radioactivity from the radioactivity expected with no loss of labeled metabolites from brain by extrapolation of glucose uptake in an initial period when loss was negligible. The observed radioactivity was a monoexponentially declining function of the total radioactivity expected in the absence of metabolite loss. The constant of decline was 0.0077.min-1 for parietal cortex. Metabolites were lost from the beginning of the experiment. However, with correction for the loss of labeled metabolites, it was possible to determine an average CMRGlc between 4 and 60 min of circulation of 64 +/- 4 (SE; n = 49) mumol.hg-1.min-1

Metabolic and energetic aspects of the growth of Clostridium butyricum on glucose in chemostat culture.

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Crabbendam, P M; Neijssel, O M; Tempest, D W

1985-09-01

The influence of a number of environmental parameters on the fermentation of glucose, and on the energetics of growth of Clostridium butyricum in chemostat culture, have been studied. With cultures that were continuously sparged with nitrogen gas, glucose was fermented primarily to acetate and butyrate with a fixed stoichiometry. Thus, irrespective of the growth rate, input glucose concentration, specific nutrient limitation and, within limits, the culture pH value, the acetate/butyrate molar ratio in the culture extracellular fluids was uniformly 0.74 +/- 0.07. Thus, the efficiency with which ATP was generated from glucose catabolism also was constant at 3.27 +/- 0.02 mol ATP/mol glucose fermented. However, the rate of glucose fermentation at a fixed growth rate, and hence the rate of ATP generation, varied markedly under some conditions, leading to changes in the Y glucose and YATP values. In general, glucose-sufficient cultures expressed lower yield values than a corresponding glucose-limited culture, and this was particularly marked with a potassium-limited culture. However, with a glucose-limited culture increasing the input glucose concentration above 40 g glucose X 1(-1) also led to a significant decrease in the yield values that could be partially reversed by increasing the sparging rate of the nitrogen gas. Finally glucose-limited cultures immediately expressed an increased rate of glucose fermentation when relieved of their growth limitation. Since the rate of cell synthesis did not increase instantaneously, again the yield values with respect to glucose consumed and ATP generated transiently decreased. Two conditions were found to effect a change in the fermentation pattern with a lowering of the acetate/butyrate molar ratio. First, a significant decrease in this ratio was observed when a glucose-limited culture was not sparged with nitrogen gas; and second, a substantial (and progressive) decrease was observed to follow addition of increasing amounts of

Use of continuous glucose monitoring as an outcome measure in clinical trials.

Science.gov (United States)

Beck, Roy W; Calhoun, Peter; Kollman, Craig

2012-10-01

Although developed to be a management tool for individuals with diabetes, continuous glucose monitoring (CGM) also has potential value for the assessment of outcomes in clinical studies. We evaluated using CGM as such an outcome measure. Data were analyzed from six previously completed inpatient studies in which both CGM (Freestyle Navigator™ [Abbott Diabetes Care, Alameda, CA] or Guardian(®) [Medtronic, Northridge, CA]) and reference glucose measurements were available. The analyses included 97 days of data from 93 participants with type 1 diabetes (age range, 5-57 years; mean, 18 ± 12 years). Mean glucose levels per day were similar for the CGM and reference measurements (median, 148 mg/dL vs. 143 mg/dL, respectively; P = 0.92), and the correlation of the two was high (r = 0.89). Similarly, most glycemia metrics showed no significant differences comparing CGM and reference values, except that the nadir glucose tended to be slightly lower and peak glucose slightly higher with reference measurements than CGM measurements (respective median, 59 mg/dL vs. 66 mg/dL [P = 0.05] and 262 mg/dL vs. 257 mg/dL [P = 0.003]) and glucose variability as measured with the coefficient of variation was slightly lower with CGM than reference measurements (respective median, 31% vs. 35%; Pblood glucose measurements. CGM inaccuracy and underestimation of the extremes of hyperglycemia and hypoglycemia can be accounted for in a clinical trial's study design. Thus, in appropriate settings, CGM can be a very meaningful and feasible outcome measure for clinical trials.

Suboptimal nutrient balancing despite dietary choice in glucose-averse German cockroaches, Blattella germanica.

Science.gov (United States)

Jensen, Kim; Schal, Coby; Silverman, Jules

2015-10-01

Insects have evolved fine-tuned gustatory and post-ingestive physiological mechanisms that enable them to self-select an optimal composition of macronutrients. Their ability to forage optimally among multiple food sources and maximize fitness parameters depends on their ability not only to taste and perceive the nutritional value of potential foods but also to avoid deleterious components; the strength of such avoidance should reflect the severity of the perceived hazard. In German cockroaches (Blattella germanica), glucose aversion has evolved in some populations in response to anthropogenic selection with glucose-containing insecticidal baits. In four feeding treatments, we gave newly eclosed glucose-averse female cockroaches free choice to feed from two artificial, nutritionally complementary foods varying in protein and carbohydrate composition, with glucose or fructose as the sole carbohydrate source in either food. After 6days of feeding, we measured diet consumption and the length of basal oocytes as an estimate of sexual maturation. The females did not compromise on their aversion to glucose in order to balance their protein and carbohydrate intake, and experienced lower sexual maturation rates as a consequence. Nutrient specific hunger via feedback mechanisms, and adjustments to gustatory sensitivity thus do not override the deterrence of glucose, likely due to strong selection against ingesting even small amounts of toxin associated with glucose in baits. In the absence of baits, glucose aversion would be expected to incur a fitness cost compared to wild-type individuals due to lower overall food availability but also to larger difficulty in attaining a nutritionally balanced diet. Copyright © 2015 Elsevier Ltd. All rights reserved.

Glucose metabolism in gamma-irradiated rice seeds

International Nuclear Information System (INIS)

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

1980-01-01

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

Bread making technology influences postprandial glucose response: a review of the clinical evidence.

Science.gov (United States)

Stamataki, Nikoleta S; Yanni, Amalia E; Karathanos, Vaios T

2017-04-01

Lowering postprandial glucose and insulin responses may have significant beneficial implications for prevention and treatment of metabolic disorders. Bread is a staple food consumed worldwide in a daily basis, and the use of different baking technologies may modify the glucose and insulin response. The aim of this review was to critically record the human studies examining the application of different bread making processes on postprandial glucose and insulin response to bread. Literature is rich of results which show that the use of sourdough fermentation instead of leavening with Saccharomyces cerevisiae is able to modulate glucose response to bread, whereas evidence regarding its efficacy on lowering postprandial insulin response is less clear. The presence of organic acids is possibly involved, but the exact mechanism of action is still to be confirmed. The reviewed data also revealed that the alteration of other processing conditions (method of cooking, proofing period, partial baking freezing technology) can effectively decrease postprandial glucose response to bread, by influencing physical structure and retrogradation of starch. The development of healthier bread products that benefit postprandial metabolic responses is crucial and suggested baking conditions can be used by the bread industry for the promotion of public health.

Lower Doses of Fructose Extend Lifespan in Caenorhabditis elegans.

Science.gov (United States)

Zheng, Jolene; Gao, Chenfei; Wang, Mingming; Tran, Phuongmai; Mai, Nancy; Finley, John W; Heymsfield, Steven B; Greenway, Frank L; Li, Zhaoping; Heber, David; Burton, Jeffrey H; Johnson, William D; Laine, Roger A

2017-05-04

Epidemiological studies indicate that the increased consumption of sugars including sucrose and fructose in beverages correlate with the prevalence of obesity, type-2 diabetes, insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension in humans. A few reports suggest that fructose extends lifespan in Saccharomyces cerevisiae. In Anopheles gambiae, fructose, glucose, or glucose plus fructose also extended lifespan. New results presented here suggest that fructose extends lifespan in Caenorhabditis elegans (C. elegans) wild type (N2). C. elegans were fed standard laboratory food source (E. coli OP50), maintained in liquid culture. Experimental groups received additional glucose (111 mM), fructose (55 mM, 111 mM, or 555 mM), sucrose (55 mM, 111 mM, or 555 mM), glucose (167 mM) plus fructose (167 mM) (G&F), or high fructose corn syrup (HFCS, 333 mM). In four replicate experiments, fructose dose-dependently increased mean lifespan at 55 mM or 111 m Min N2, but decreased lifespan at 555 mM (P Glucose reduced lifespan (P fructose (555 mM), glucose (111 mM), and sucrose (55 mM, 111 mM, and 555 mM). Here we report a biphasic effect of fructose increasing lifespan at lower doses and shortening lifespan at higher doses with an inverse effect on IFD. In view of reports that fructose increases lifespan in yeast, mosquitoes and now nematodes, while decreasing fat deposition (in nematodes) at lower concentrations, further research into the relationship of fructose to lifespan and fat accumulation in vertebrates and mammals is indicated.

A Mixed-Methods Study on Acceptability, Tolerability, and Substitution of Brown Rice for White Rice to Lower Blood Glucose Levels among Nigerian Adults

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Sally N. Adebamowo

2017-07-01

Full Text Available BackgroundWhole-grain products such as brown rice have been associated with lower risk of metabolic disorders including diabetes. We examined the acceptability and tolerability of substituting brown rice for white rice and the feasibility of introducing brown rice into the diet through a long-term trial to lower the risk of type 2 diabetes.MethodsFifty-one adults residing in Abuja, Nigeria, participated in this study. Using purposeful sampling for focus group discussions (FGDs, participants were enrolled based on their age (19–25 vs. 40–60 years and body mass index (BMI (normal weight vs. overweight/obese. Participants tasted four meals with different constitution of brown and white rice (25:75%, 50:50%, 75:25%, and 100% brown rice. Twelve FGDs were conducted, six before and six after the food tasting. Two-hour postprandial blood glucose was measured after consumption of each rice meal.ResultsThe mean age of the participants was 39 (±14 years, their mean BMI was 25.6 (±5.2 and about half of them were male. Most of the participants (61% reported that rice was their main source of carbohydrate and 67% consumed rice at least five times/week. Before the food tasting, participants considered white polished rice superior to brown rice with regard to quality, taste, and nutritional value. After the food tasting, most of the participants (49% indicated a preference for the 100% brown rice, 19% preferred the 25% brown rice, 18% preferred the 50% brown rice, and 7% preferred the 75% brown rice meals. Factors that may affect the acceptability of brown rice include its appearance, longer cooking time, cost, limited availability, and poor appreciation of its nutritional value. In general, 2-h postprandial glucose levels were lower, after consumption of meals with higher proportion of brown rice.ConclusionThis study provides valuable insight into the acceptability of brown rice as a substitute for white rice in Nigeria. If confirmed in larger studies

Glucose Rapidly Induces Different Forms of Excitatory Synaptic Plasticity in Hypothalamic POMC Neurons

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Hu, Jun; Jiang, Lin; Low, Malcolm J.; Rui, Liangyou

2014-01-01

Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+), EPSC(−), and EPSC(+/−)) based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs), using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(−) neurons. Unlike EPSC(+) and EPSC(−) neurons, EPSC(+/−) neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/−) neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals. PMID:25127258

Glucose Metabolism in High-Risk Subjects for Type 2 Diabetes Carrying the rs7903146 TCF7L2 Gene Variant.

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Daniele, Giuseppe; Gaggini, Melania; Comassi, Mario; Bianchi, Cristina; Basta, Giuseppina; Dardano, Angela; Miccoli, Roberto; Mari, Andrea; Gastaldelli, Amalia; Del Prato, Stefano

2015-08-01

The mechanisms responsible for contribution of variants in the gene TFC7L2 to the risk for type 2 diabetes (T2DM) remains far from being completely understood, and available studies have generated nonunivocal results. We investigated the postprandial glucose metabolism in subjects at risk for T2DM carrying the TCF7L2 risk allele. Twenty-three subjects carrying the risk-conferring TCF7L2 genotypes (11 TT and 12 CT at rs7901346) and 13 subjects with wild-type genotype (CC) underwent a standard mixed-meal test (MMT) in combination with stable isotope tracers. We evaluated endogenous and exogenous glucose fluxes and hormonal responses. Fasting plasma glucose, insulin, C-peptide, glycated hemoglobin, endogenous glucose production, and plasma glucose clearance were similar in the three groups, whereas plasma glucagon levels were lower in both CT and TT than in CC (64 ± 20, 63 ± 18 and 90 ± 29 pg/mL, respectively; both P = .01). In response to the MMT, TT subjects had lower plasma glucose levels than CC subjects [mean area under the time-concentration curve (AUC) 6.1 ± 3.9 vs 7.1 ± 12.0 mmol/L, P = .04] and lower insulin secretion rate (mean AUC 385 ± 95 vs 530 ± 159 pmol/m(2) · min, P = .02). Initial (0-60 min) rate of appearance (Ra) of oral glucose was lower in TT compared with CT/CC (AUC 2.7 ± 1.1 vs 3.8 ± 1.2 μmol/kg · min, P = .02) with no difference among the three groups in endogenous glucose production. The AUC0-60min for Ra of exogenous glucose (Raex) was positively correlated with the plasma glucose AUC0-60min. Total Raex AUC0-120min was correlated with total AUC0-120min of plasma glucose (r = 0.45, P glucose-dependent insulinotropic peptide levels in response to the MMT were not affected by genotype. In subjects at risk for T2DM, the TCF7L2 polymorphisms were associated with reduced Raex into systemic circulation, causing reduced postprandial blood glucose increase and, in turn, lower insulin secretion rate with no impairment in β-cell function

Ratiometric glucose sensing based on fluorescent oxygen films and glucose oxidase

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Fengyu Su

2017-06-01

Full Text Available A new two-layer sensor film was constructed for sensing glucose based on glucose oxidase and oxygen sensing material. The first layer of film containing the oxygen sensor and intra-reference material was polymerized, then the second layer of glucose oxidase and glutaraldehyde was formed on the oxygen sensor layer. The two-layer sensor film has a resolution up to 0.05 mM and a detection range from 0 to 5 mM to glucose. The effects of pH and temperature on the sensing performance were systematically investigated. The selective detection of glucose among other monosaccharides, such as fructose, mannose and galactose indicated that the sensing film has excellent selectivity. The prepared sensor was successfully applied for glucose sample detection of glucose concentration in artificial tears. Keywords: Glucose sensor, Glucose oxidase, Fluorescence, Oxygen film, Diabetes

Dietary fructose and glucose differentially affect lipid and glucose homeostasis.

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

2009-06-01

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

Glucose turnover, oxidation, and indices of recycling in severely traumatized patients

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Jeevanandam, M.; Young, D.H.; Schiller, W.R. (St. Joseph' s Hospital Medical Center, Phoenix, AZ (USA))

1990-05-01

Hyperglycemia is often seen in trauma patients and its etiology is not clearly understood. We have determined parameters of glucose metabolism by using simultaneous primed-constant intravenous infusion of both (6-3H) glucose and (U-14C) glucose in ten severely traumatized hypermetabolic subjects during the early flow phase of injury and in six post-absorptive normal volunteers. The mean rate of glucose production (determined by means of (6-3H) glucose) was 3.96 +/- 0.40 mg/kg/min in trauma patients, which was significantly (p = 0.025) higher than the value of 2.75 +/- 0.13 observed in normal volunteers. Glucose turnover rates determined with (U-14C) glucose as tracer were lower in all subjects. The difference between the turnover rates determined by the two tracers represents an index of recycling of glucose through three-carbon fragments. This recycling index was similar in both groups of subjects in amount (0.24 +/- 0.07 vs. 0.26 +/- 0.08 mg glucose/kg/min) but different when expressed as percentage of total glucose turnover (5.6 +/- 1.4% vs. 9.8 +/- 1.7%; p = 0.05). The absolute rates of glucose clearance, oxidation, and recycling were similar in stressed trauma patients and unstressed controls although the rate of production was increased by 44% due to injury. Post-trauma hyperglycemia was mainly due to an increased hepatic output of glucose and not due to a decreased ability of the tissue to extract glucose from the plasma. Hyperglycemia may be the driving force in the metabolic effects of injury.

Glucose turnover, oxidation, and indices of recycling in severely traumatized patients

International Nuclear Information System (INIS)

Jeevanandam, M.; Young, D.H.; Schiller, W.R.

1990-01-01

Hyperglycemia is often seen in trauma patients and its etiology is not clearly understood. We have determined parameters of glucose metabolism by using simultaneous primed-constant intravenous infusion of both [6-3H] glucose and [U-14C] glucose in ten severely traumatized hypermetabolic subjects during the early flow phase of injury and in six post-absorptive normal volunteers. The mean rate of glucose production (determined by means of [6-3H] glucose) was 3.96 +/- 0.40 mg/kg/min in trauma patients, which was significantly (p = 0.025) higher than the value of 2.75 +/- 0.13 observed in normal volunteers. Glucose turnover rates determined with [U-14C] glucose as tracer were lower in all subjects. The difference between the turnover rates determined by the two tracers represents an index of recycling of glucose through three-carbon fragments. This recycling index was similar in both groups of subjects in amount (0.24 +/- 0.07 vs. 0.26 +/- 0.08 mg glucose/kg/min) but different when expressed as percentage of total glucose turnover (5.6 +/- 1.4% vs. 9.8 +/- 1.7%; p = 0.05). The absolute rates of glucose clearance, oxidation, and recycling were similar in stressed trauma patients and unstressed controls although the rate of production was increased by 44% due to injury. Post-trauma hyperglycemia was mainly due to an increased hepatic output of glucose and not due to a decreased ability of the tissue to extract glucose from the plasma. Hyperglycemia may be the driving force in the metabolic effects of injury

Associations of fatty acids in cerebrospinal fluid with peripheral glucose concentrations and energy metabolism.

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Reiner Jumpertz

Full Text Available Rodent experiments have emphasized a role of central fatty acid (FA species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT followed by measurements of 24 hour (24EE and sleep energy expenditure (SLEEP as well as respiratory quotient (RQ in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16:1, C18:1 and very-long-chain saturated (C24:0, C26:0 FAs.Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.

Blood pressure effects of sodium-glucose co-transport 2 (SGLT2) inhibitors.

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Oliva, Raymond V; Bakris, George L

2014-05-01

Management of hypertension in diabetes is critical for reduction of cardiovascular mortality and morbidity. While blood pressure (BP) control has improved over the past two decades, the control rate is still well below 50% in the general population of patients with type 2 diabetes mellitus (T2DM). A new class of oral glucose-lowering agents has recently been approved; the sodium-glucose co-transporter 2 (SGLT2) inhibitors, which act by eliminating large amounts of glucose in the urine. Two agents, dapagliflozin and canagliflozin, are currently approved in the United States and Europe, and empagliflozin and ipragliflozin have reported Phase 3 trials. In addition to glucose lowering, SGLT2 inhibitors are associated with weight loss and act as osmotic diuretics, resulting in a lowering of BP. While not approved for BP-lowering, they may potentially aid BP goal achievement in people within 7-10 mm Hg of goal. It should be noted that the currently approved agents have side effects that include an increased incidence of genital infections, predominantly in women. The approved SGLT2 inhibitors have limited use based on kidney function and should be used only in those with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 for dapagliflozin and ≥45 mL/min/1.73 m2 for canagliflozin. Cardiovascular outcome trials are ongoing with these agents and will be completed within the next 4-5 years. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

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

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

2005-10-01

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

Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production

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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.

The Brain–to–Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions

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Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C.; Ali, Almas; Tamarina, Natalia; Philipson, Louis H.; Enquist, Lynn W.; Myers, Martin G.

2016-01-01

The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. PMID:27207534

The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

Science.gov (United States)

Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

2016-09-01

The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes

DEFF Research Database (Denmark)

Meier, Juris J; Weyhe, Dirk; Michaely, Mark

2004-01-01

of GLP-1 (1.2 pmol x kg x min) and placebo over 8 hrs, each administered in randomized order in the fasting state. C-reactive protein concentrations of 4.9+/-4.2 mg/dL indicated a systemic inflammation. Blood was drawn in 30-min intervals for glucose (glucose oxidase), insulin, C-peptide, glucagon...... practicability and the risk of hypoglycemia. Therefore, the glucose-lowering effect of the incretin hormone glucagon-like peptide 1 (GLP-1) was investigated in patients with type 2 diabetes after major surgery. DESIGN: Randomised clinical study. SETTING: A surgical unit of a university hospital. PATIENTS......, and GLP-1 (specific immunoassays). Statistics were done with repeated-measures analysis of variance and Duncan's post hoc tests. MAIN RESULTS: During the intravenous infusion of GLP-1, plasma glucose concentrations were significantly lowered, reaching the normoglycemic fasting glucose range within 150...

Altered glucose kinetics in diabetic rats during Gram-negative infection

International Nuclear Information System (INIS)

Lang, C.H.; Dobrescu, C.; Bagby, G.J.; Spitzer, J.J.

1987-01-01

The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced severe diabetes, whereas the lower dose of streptozotocin produced a miler, latent diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of [6- 3 H]- and [U- 14 C]glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats. Thus the present study suggests that the imposition of nonlethal Gram-negative sepsis on severe diabetic animals does not further impair glucose homeostasis and that the milder latent diabetes was not converted to a more severe diabetic state by the septic challenge

Cooperation between brain and islet in glucose homeostasis and diabetes

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Schwartz, Michael W.; Seeley, Randy J.; Tschöp, Matthias H.; Woods, Stephen C.; Morton, Gregory J.; Myers, Martin G.; D'Alessio, David

2014-01-01

Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficient to explain glucose homeostasis, and that diabetes results from defects of insulin secretion, action or both. However, insulin-independent mechanisms, referred to as ‘glucose effectiveness’, account for roughly 50% of overall glucose disposal, and reduced glucose effectiveness also contributes importantly to diabetes pathogenesis. Although mechanisms underlying glucose effectiveness are poorly understood, growing evidence suggests that the brain can dynamically regulate this process in ways that improve or even normalize glycaemia in rodent models of diabetes. Here we present evidence of a brain-centred glucoregulatory system (BCGS) that can lower blood glucose levels via both insulin-dependent and -independent mechanisms, and propose a model in which complex and highly coordinated interactions between the BCGS and pancreatic islets promote normal glucose homeostasis. Because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. Consequently, therapies that target the BCGS in addition to conventional approaches based on enhancing insulin effects may have the potential to induce diabetes remission, whereas targeting just one typically does not. PMID:24201279

Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

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Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

2011-01-01

OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

Influence of the time of day and fasting duration on glucose level following a 1-hour, 50-gram glucose challenge test in pregnant women.

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Panchalli Wang

Full Text Available BACKGROUND: Previous studies have shown that the time of day (TD of glucose measurement and the fasting duration (FD influence the glucose levels in adults. Few studies have examined the effects of the TD and FD on the glucose level following a 1-hour, 50-gram glucose challenge test (GCT in pregnant women in screening for or diagnosing gestational diabetes mellitus (GDM. The objective of this study was to investigate the influence of the TD (morning, afternoon, night and the FD (the time of the last food ingestion as follows: ≤1 hour, 1-2 hours, and >2 hours by examining their combined effects on the glucose levels following a 50-gram GCT in pregnant women. METHODS AND RESULTS: We analyzed the data of 1,454 non-diabetic pregnant Taiwanese women in a prospective study. Multiple linear regression and multiple logistic regression were used to estimate the relationships between the 9 TD-FD groups and the continuous and binary glucose levels (cut-off at 140 mg/dL following a 50-gram GCT, after adjusting for maternal age, nulliparity, pre-pregnancy body mass index, and weight gain. Different TD and FD groups were associated with variable glucose responses to the 50-gram GCT, some of which were significant. The estimate coefficients (β of the TD-FD groups "night, ≤1 hr" and "night, 1-2 hr" revealed significantly lower glucose concentrations [β (95% confidence interval [CI]: -6.46 (-12.53, -0.38 and -6.85 (-12.50, -1.20] compared with the "morning, >2 hr" group. The TD-FD groups "afternoon, ≤1 hr" and "afternoon, 1-2 hr" showed significantly lower odds ratios (OR of a positive GCT; the adjusted ORs (95% CI were 0.54 (0.31-0.95 and 0.58 (0.35-0.96, respectively. CONCLUSIONS: Our findings demonstrate the importance of standardizing the TD and FD for the 1-hour, 50-gram GCT. In screening for and diagnosing GDM, the TD and FD are modifiable factors that should be considered in clinical practice and epidemiological studies.

A review of metabolism of labeled glucoses for use in measuring glucose recycling

International Nuclear Information System (INIS)

Russell, R.W.; Young, J.W.

1990-01-01

The fate of tritium from each carbon of D-glucose and the metabolism of L-glucose and 2-deoxy-D-glucose are known. Differences in metabolism of labeled glucoses can be used to quantify physical and chemical recycling of glucose. Only physical recycling is measured by [1- 3 H]-L-glucose, whereas [U- 14 C]-D-glucose measures total recycling. The difference between [1- 3 H]-L-glucose and [U- 14 C]-D-glucose, therefore, is chemical recycling. Recycling from extracellular binding sites and hepatic glucose 6-phosphate can be measured by difference between [1,2- 3 H]-2-deoxy-D-glucose and [1- 3 H]-L-glucose, and the difference in irreversible loss of the two will measure extrahepatic uptake of D-glucose. Recycling via Cori-alanine cycle plus CO 2 is the difference in irreversible loss measured by using [6- 3 H]-glucose and [U- 14 C]-D-glucose. Recycling via the hexose monophosphate pathway can be determined by difference in irreversible loss between [1- 3 H]-D-glucose and [6- 3 H]-D-glucose. Recycling via CO 2 and glycerol must be measured directly with [U- 14 C]glucose, bicarbonate, and glycerol. Recycling via hepatic glycogen can be estimated by subtracting all other measured chemical recycling from total chemical recycling. This review describes means to quantify glucose recycling in vivo, enabling studies of mechanisms for conservation and utilization of glucose. 54 references

The association between Western and Prudent dietary patterns and fasting blood glucose levels in type 2 diabetes and normal glucose metabolism in older Australian adults.

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Walsh, Erin I; Jacka, Felice N; Butterworth, Peter; Anstey, Kaarin J; Cherbuin, Nicolas

2017-06-01

High blood glucose and type 2 diabetes are associated with a range of adverse health and cognitive outcomes. One factor that contributes to high blood glucose and type 2 diabetes is dietary intake. This study investigated the relationship between dietary patterns, fasting blood glucose and diabetes status in a sample of 209 participants aged 60-65. Blood plasma glucose was measured from venous blood samples. Individual Prudent and Western dietary patterns were estimated from a self-completed food frequency questionnaire. The relationship between dietary patterns, diabetes, and blood glucose was assessed via general linear model analyses controlling for age, sex, height, and total caloric intake. Results indicated that there was no association between Prudent diet and fasting blood glucose levels, or type 2 diabetes. In contrast, an individual in the upper tertile for Western dietary score had a significantly higher risk of having diabetes than an individual in the lower tertile for Western dietary score. However, there was no significant association between Western diet and fasting blood glucose. Western diet may be associated with type 2 diabetes through mechanisms beyond impacting blood plasma glucose directly. The fact that the association between Western diet and type 2 diabetes remained even when total caloric intake was controlled for highlights the need for policy and population health interventions targeting the reduction of unhealthy food consumption.

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.

The Acute Impact of Ingestion of Sourdough and Whole-Grain Breads on Blood Glucose, Insulin, and Incretins in Overweight and Obese Men

Directory of Open Access Journals (Sweden)

Anita Mofidi

2012-01-01

Full Text Available Consumption of whole-grain and sourdough breads is associated with improved glucose homeostasis. We examined the impact of commercial breads on biomarkers of glucose homeostasis in subjects at risk for glucose intolerance. In a randomized, crossover study, overweight or obese males ingested 11-grain, sprouted-grain, 12-grain, sourdough, or white bread on different occasions, matched for available carbohydrate (50 g in part 1 (n=12 and bread mass (107 g in part 2 (n=11, and blood glucose, insulin and glucose-dependent insulinotropic polypeptide (GIP and glucagon-like peptide-1 (GLP-1 were determined for 3 h. In part 1, glucose response for sprouted-grain was lower than 11-grain, sourdough, and white breads. Insulin area under the curve (AUC for sourdough and white was lower than 11-grain and sprouted-grain breads. GLP-1 response to sourdough was lower than all breads. In part 2, glucose and insulin AUC for sourdough was greater than 11-grain, sprouted-grain, and 12-grain breads. Sprouted-grain bread improved glycemia by lowering glucose response and increasing GLP-1 response. In overweight and obese men, the glycemic response to sprouted grain bread was reduced in both parts 1 and 2 while the other whole-grain test breads did not improve metabolic responses in the acute postprandial state.

Pseudo-bi-enzyme glucose sensor: ZnS hollow spheres and glucose oxidase concerted catalysis glucose.

Science.gov (United States)

Shuai, Ying; Liu, Changhua; Wang, Jia; Cui, Xiaoyan; Nie, Ling

2013-06-07

This work creatively uses peroxidase-like ZnS hollow spheres (ZnS HSs) to cooperate with glucose oxidase (GOx) for glucose determinations. This approach is that the ZnS HSs electrocatalytically oxidate the enzymatically generated H2O2 to O2, and then the O2 circularly participates in the previous glucose oxidation by glucose oxidase. Au nanoparticles (AuNPs) and carbon nanotubes (CNTs) are used as electron transfer and enzyme immobilization matrices, respectively. The biosensor of glucose oxidase-carbon nanotubes-Au nanoparticles-ZnS hollow spheres-gold electrode (GOx-CNT-AuNPs-ZnS HSs-GE) exhibits a rapid response, a low detection limit (10 μM), a wide linear range (20 μM to 7 mM) as well as good anti-interference, long-term longevity and reproducibility.

Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

DEFF Research Database (Denmark)

Richter, Erik; Hansen, B F; Hansen, S A

1988-01-01

in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation.......The ability of glucose and insulin to modify insulin-stimulated glucose transport and uptake was investigated in perfused skeletal muscle. Here we report that perfusion of isolated rat hindlimbs for 5 h with 12 mM-glucose and 20,000 microunits of insulin/ml leads to marked, rapidly developing...

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

SCAPIS Pilot Study: Sitness, Fitness and Fatness - Is Sedentary Time Substitution by Physical Activity Equally Important for Everyone's Markers of Glucose Regulation?

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Ekblom-Bak, Elin; Ekblom, Örjan; Bolam, Kate A; Ekblom, Björn; Bergström, Göran; Börjesson, Mats

2016-07-01

Although moderate-to-vigorous physical activity (MVPA) is mainly recommended for glucose control, light physical activity (LIPA) may also have the potential to induce favorable changes. We investigated sedentary time (SED) substitution with equal time in LIPA and MVPA, and the association with markers of glucose regulation and insulin sensitivity after stratification by waist circumference, fitness and fasting glucose levels. A total of 654 men and women, 50 to 64 years, from the SCAPIS pilot study were included. Daily SED, LIPA and MVPA were assessed using hip-worn accelerometers. Fasting plasma glucose, insulin and HOMA-IR were determined. Substituting 30 min of SED with LIPA was significantly associated with 3.0% lower fasting insulin values and 3.1% lower HOMA-IR values, with even lower levels when substituting SED with MVPA. Participants with lower fitness and participants with high fasting glucose levels benefited significantly more from substituting 30 min of SED with LIPA compared with participants with normal to high fitness levels and participants with normal glucose levels, respectively. LIPA, and not only MVPA, may have beneficial associations with glucose regulation. This is of great clinical and public health importance, not least because it may confer a higher compliance rate to regular PA.

Relative accuracy of the BD Logic and FreeStyle blood glucose meters.

Science.gov (United States)

2007-04-01

The BD Logic((R)) (Becton, Dickinson and Co., Franklin Lakes, NJ) and FreeStyle((R)) (Abbott Diabetes Care, Alameda, CA) meters are used to transmit data directly to insulin pumps for calculation of insulin doses and to calibrate continuous glucose sensors as well as to monitor blood glucose levels. The accuracy of the two meters was evaluated in two inpatient studies conducted by the Diabetes Research in Children Network (DirecNet). In both studies, meter glucose measurements made with either venous or capillary blood were compared with reference glucose measurements made by the DirecNet Central Laboratory at the University of Minnesota using a hexokinase enzymatic method. The BD Logic tended to read lower than the laboratory reference regardless of whether venous (median difference = -9 mg/dL) or capillary blood (median difference = -7 mg/dL) was used. This resulted in lower accuracy of the BD Logic compared with the FreeStyle meter based on the median relative absolute difference (RAD) for both venous blood (median RAD, 9% vs. 5%, P blood (median RAD, 11% vs. 6%, P = 0.008). The greatest discrepancy in the performance of the two meters was at higher reference glucose values. Accuracy was not significantly different when the reference was < or = 70 mg/dL. The BD Logic meter is less accurate than the FreeStyle meter.

Glucose metabolism in critically ill patients

DEFF Research Database (Denmark)

Nielsen, Signe Tellerup; Krogh-Madsen, Rikke; Møller, Kirsten

2015-01-01

glucose (BG). This is taken advantage of in the treatment of patients with T2DM, for whom GLP-1 analogs have been introduced during the recent years. Infusion of GLP-1 also lowers the BG level in critically ill patients without causing severe hypoglycemia. The T2DM and critical illness share similar......, stimulates insulin secretion and inhibits glucagon release both in healthy individuals and in patients with type 2 diabetes (T2DM). Compared to insulin, GLP-1 appears to be associated with a lower risk of severe hypoglycemia, probably because the magnitude of its insulinotropic action is dependent on blood...

Glucose allostasis

DEFF Research Database (Denmark)

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

2003-01-01

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......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...... 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...

Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle.

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Santiago, Ammy M; Clegg, Deborah J; Routh, Vanessa H

2016-12-01

17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs). These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed. The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application. These data suggest that physiological

Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle

Science.gov (United States)

Santiago, Ammy M.; Clegg, Deborah J.; Routh, Vanessa H.

2016-01-01

Objective 17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs). Methods These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed. Results The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application. Conclusion

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

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

2018-01-01

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

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

Science.gov (United States)

Kosse, C; Gonzalez, A; Burdakov, D

2015-01-01

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

Estimation of gluconeogenesis and glucose utilization in carbohydate deficient growing rats

International Nuclear Information System (INIS)

Hill, F.W.; Egtesadi, S.; Rucker, R.B.

1986-01-01

A carbohydrate deficient diet based on food grade oleic acid and soybean oil and a minimally adequate level of casein protein was supplemented with graded levels of glucose (0, 4, 10, 65%), and casein protein (12% basal level plus 4, 6, 20%). Weanling rats were fed the respective diets for 28 days. Under anesthesia in fed state, the right jugular vein and left carotid artery were cannulated. NaH 14 CO 3 and 3 H-glucose labelled on C 6 were injected into aorta via carotid and blood samples taken from vena cava via jugular over a period of 30 minutes. Rate of increase of blood 14 C-glucose was the indicator of gluconeogenesis (GLNG). Disappearance of blood 3 H-glucose was the measure of glucose flux. Relative rate of GLNG was very high in basal unsupplemented rats, and glucose flux was very low. Rats growing rapidly with minimum supplementation (4% glucose or 6% casein) showed the lowest relative rate of GLNG and maximum glucose flux, of the order of 10 mg min -1 kg -1 . GLNG increased with higher levels of glucose and casein, but flux did not increase. The fed state glucose flux extrapolated to 24 hour basis was approximately 2X greater than the dietary intake of glucose and its equivalent of glucogenic precursors in rats fed the basal diet and low levels of supplements. Adjustment for lower flux in post absorptive state, based on flux in fasted rats, reduced the differences between observed flux and intake

Comparison electrical stimulation and passive stretching for blood glucose control type 2 diabetes mellitus patients

Science.gov (United States)

Arsianti, Rika Wahyuni; Parman, Dewy Haryanti; Lesmana, Hendy

2018-04-01

Physical exercise is one of the cornerstones for management and treatment type 2 diabetes mellitus. But not all people are able to perform physical exercise because of their physical limitation condition. The strategy for those people in this study is electrical stimulation and passive stretching. The aim of this study is to find out the effect of electrical stimulation and passive stretching to lowering blood glucose level. 20 subjects is divided into electrical stimulation and passive stretching group. The provision of electrical stimulation on lower extremities muscles for 30 minutes for electrical stimulation group (N=10). And other underwent passive stretching for 30 minutes (N=10). The result shows that blood glucose level is decrease from 192.9 ± 10.7087 mg/dL to 165.3 ± 10.527 mg/dL for electrical stimulation intervention group while for the passive stretching group the blood glucose decrease from 153 ± 12.468 mg/dL to 136.1 ± 12.346 mg/dL. Both electrical stimulation and passive stretching are effective to lowering blood glucose level and can be proposed for those people restricted to perform exercise.

High environmental temperature increases glucose requirement in the developing chicken embryo.

Directory of Open Access Journals (Sweden)

Roos Molenaar

Full Text Available Environmental conditions during the perinatal period influence metabolic and developmental processes in mammals and avian species, which could impact pre- and postnatal survival and development. The current study investigated the effect of eggshell temperature (EST on glucose metabolism in broiler chicken embryos. Broiler eggs were incubated at a high (38.9°C or normal (37.8°C EST from day 10.5 of incubation onward and were injected with a bolus of [U-(13C]glucose in the chorio-allantoic fluid at day 17.5 of incubation. After [U-(13C]glucose administration, (13C enrichment was determined in intermediate pools and end-products of glucose metabolism. Oxidation of labeled glucose occurred for approximately 3 days after injection. Glucose oxidation was higher in the high than in the normal EST treatment from day 17.6 until 17.8 of incubation. The overall recovery of (13CO2 tended to be 4.7% higher in the high than in the normal EST treatment. An increase in EST (38.9°C vs 37.8°C increased (13C enrichment in plasma lactate at day 17.8 of incubation and (13C in hepatic glycogen at day 18.8 of incubation. Furthermore, high compared to normal EST resulted in a lower yolk-free body mass at day 20.9 (-2.74 g and 21.7 (-3.81 g of incubation, a lower hepatic glycogen concentration at day 18.2 (-4.37 mg/g and 18.8 (-4.59 mg/g of incubation, and a higher plasma uric acid concentration (+2.8 mg/mL/+43% at day 21.6 of incubation. These results indicate that the glucose oxidation pattern is relatively slow, but the intensity increased consistently with an increase in developmental stage of the embryo. High environmental temperatures in the perinatal period of chicken embryos increased glucose oxidation and decreased hepatic glycogen prior to the hatching process. This may limit glucose availability for successful hatching and could impact body development, probably by increased gluconeogenesis from glucogenic amino acids to allow anaerobic glycolysis.

Furfural and glucose can enhance conversion of xylose to xylitol by Candida magnoliae TISTR 5663.

Science.gov (United States)

Wannawilai, Siwaporn; Lee, Wen-Chien; Chisti, Yusuf; Sirisansaneeyakul, Sarote

2017-01-10

Xylitol production from xylose by the yeast Candida magnoliae TISTR 5663 was enhanced by supplementing the fermentation medium with furfural (300mg/L) and glucose (3g/L with an initial mass ratio of glucose to xylose of 1:10) together under oxygen limiting conditions. In the presence of furfural and glucose, the final concentration of xylitol was unaffected relative to control cultures but the xylitol yield on xylose increased by about 5%. Supplementation of the culture medium with glucose alone at an initial concentration of 3g/L, stimulated the volumetric and specific rates of xylose consumption and the rate of xylitol production from xylose. In a culture medium containing 30g/L xylose, 300mg/L furfural and 3g/L glucose, the volumetric production rate of xylitol was 1.04g/L h and the specific production rate was 0.169g/g h. In the absence of furfural and glucose, the volumetric production rate of xylitol was ∼35% lower and the specific production rate was nearly 30% lower. In view of these results, xylose-containing lignocellulosic hydrolysates contaminated with furfural can be effectively used for producing xylitol by fermentation so long as the glucose-to-xylose mass ratio in the hydrolysate does not exceed 1:10 and the furfural concentration is ≤300mg/L. Copyright © 2016 Elsevier B.V. All rights reserved.

Prefrontal glucose deficits in murderers lacking psychosocial deprivation.

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Raine, A; Phil, D; Stoddard, J; Bihrle, S; Buchsbaum, M

1998-01-01

Previous research has suggested that links between autonomic nervous system functioning and violence are strongest in those who come from benign home backgrounds, but there appears to be no similar research using brain-imaging measures of central nervous system functioning. It was hypothesized that murderers who had no early psychosocial deprivation (e.g., no childhood abuse, family neglect) would demonstrate lower prefrontal glucose metabolism than murderers with early psychosocial deprivation and a group of normal controls. Murderers from a previous study, which showed prefrontal deficits in murderers, were assessed for psychosocial deprivation and divided into those with and without deprivation. Murderers without any clear psychosocial deficits were significantly lower on prefrontal glucose metabolism than murderers with psychosocial deficits and controls. These results suggest that murderers lacking psychosocial deficits are characterized by prefrontal deficits. It is argued that among violent offenders without deprived home backgrounds, the "social push" to violence is minimized, and consequently, brain abnormalities provide a relatively stronger predisposition to violence in this group.

Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism.

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Langsetmo, Lisa; Barr, Susan I; Dasgupta, Kaberi; Berger, Claudie; Kovacs, Christopher S; Josse, Robert G; Adachi, Jonathan D; Hanley, David A; Prior, Jerilynn C; Brown, Jacques P; Morin, Suzanne N; Davison, Kenneth S; Goltzman, David; Kreiger, Nancy

2016-04-01

We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk. Copyright © 2016 Elsevier Inc. All rights reserved.

Sequential Injection Determination of D-Glucose by Chemiluminescence Using an Open Tubular Immobilised Enzyme Reactor

DEFF Research Database (Denmark)

Liu, Xuezhu; Hansen, Elo Harald

1996-01-01

A sequential injection analysis system is described that incorporates a nylon tubular reactor containing immobilised glucose oxidase, allowing determination of D-glucose by means of subsequent luminol chemiluminescence detection of the hydrogen peroxide generated in the enzymatic reaction....... The operating parameters were optimised by fractional factorial screening and response surface modelling. The linear range of D-glucose determination was 30-600 mu M, With a detection limit of 15 mu M using a photodiode detector. The sampling frequency was 54 h(-1). Lower LOD (0.5 mu M D-glucose) could...

Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM: Crossover pilot study (J-VICTORIA study

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Sakamoto Masaya

2012-08-01

Full Text Available Abstract Background No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM and cardiovascular parameters. Methods Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1 mean (± standard deviation 24-hour blood glucose level, 2 mean amplitude of glycemic excursions (MAGE, 3 fasting blood glucose level, 4 highest postprandial blood glucose level and time, 5 increase in blood glucose level after each meal, 6 area under the curve (AUC for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7 area over the curve (AOC for daily blood glucose level Results The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012. In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040, the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015, the AUC (≥180 mg/dL within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025, and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008 than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. Conclusions CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There

Impaired brain energy gain upon a glucose load in obesity.

Science.gov (United States)

Wardzinski, Ewelina K; Kistenmacher, Alina; Melchert, Uwe H; Jauch-Chara, Kamila; Oltmanns, Kerstin M

2018-03-06

There is evidence that the brain's energy status is lowered in obesity despite of chronic hypercaloric nutrition. The underlying mechanisms are unknown. We hypothesized that the brain of obese people does not appropriately generate energy in response to a hypercaloric supply. Glucose was intravenously infused in 17 normal weights and 13 obese participants until blood glucose concentrations reached the postprandial levels of 7 mmol/L and 10 mmol/L. Changes in cerebral adenosine triphosphate (ATP) and phosphocreatine (PCr) content were measured by 31 phosphorus magnetic resonance spectroscopy and stress hormonal measures regulating glucose homeostasis were monitored. Because vitamin C is crucial for a proper neuronal energy synthesis we determined circulating concentrations during the experimental testing. Cerebral high-energy phosphates were increased at blood glucose levels of 7 mmol/L in normal weights, which was completely missing in the obese. Brain energy content moderately raised only at blood glucose levels of 10 mmol/L in obese participants. Vitamin C concentrations generally correlated with the brain energy content at blood glucose concentrations of 7 mmol/L. Our data demonstrate an inefficient cerebral energy gain upon a glucose load in obese men, which may result from a dysfunctional glucose transport across the blood-brain barrier or a downregulated energy synthesis in mitochondrial oxidation processes. Our finding offers an explanation for the chronic neuroenergetic deficiency and respectively missing satiety perception in obesity. Copyright © 2018. Published by Elsevier Inc.

Effects of Cr methionine on glucose metabolism, plasma metabolites, meat lipid peroxidation, and tissue chromium in Mahabadi goat kids.

Science.gov (United States)

Emami, A; Ganjkhanlou, M; Zali, A

2015-03-01

This study was designed to investigate the effects of chromium methionine (Cr-Met) on glucose metabolism, blood metabolites, meat lipid peroxidation, and tissue chromium (Cr) in Mahabadi goat kids. Thirty-two male kids (16.5 ± 2.8 kg BW, 4-5 months of age) were fed for 90 days in a completely randomized design with four treatments. Treatments were supplemented with 0 (control), 0.5, 1, and 1.5 mg Cr as Cr-Met/animal/daily. Blood samples were collected via heparin tubes from the jugular vein on 0, 21, 42, 63, and 90 days of experiment. On day 70, an intravenous glucose tolerance test (IVGTT) was conducted. At the end of the feeding trial, the kids were slaughtered, and the liver, kidney, and longissimus dorsi (LD) muscle samples were collected. Plasma glucose, insulin, and triglyceride concentrations were decreased by Cr supplementation (P glucose concentrations at 30 and 60 min after glucose infusion were lower in the kids fed 1.5 mg Cr diet than the kids fed control diet (P glucose clearance rate (K) and lower glucose half-life (T½; P Glucose area under the response curve (AUC) from 0 to 180 min after glucose infusion was decreased linearly (P glucose utilization and lipid oxidation of meat in fattening kid.

Associations of green tea and rock tea consumption with risk of impaired fasting glucose and impaired glucose tolerance in Chinese men and women.

Directory of Open Access Journals (Sweden)

Huibin Huang

Full Text Available OBJECTIVE: To explore the associations of green tea and rock tea consumption with risk of impaired fasting glucose (IFG and impaired glucose tolerance (IGT. METHODS: A multistage, stratified, cluster, random-sampling method was used to select a representative sample from Fujian Province in China. In total, 4808 subjects without cardiovascular disease, hypertension, cancer, or pancreatic, liver, kidney, or gastrointestinal diseases were enrolled in the study. A standard questionnaire was used to gather data on tea (green, rock, and black consumption and other relevant factors. The assessment of impaired glucose regulation (IGR was using 75-g oral glucose tolerance test (OGTT, the diagnostic criteria of normal glucose tolerance was according to American Diabetes Association. RESULTS: Green tea consumption was associated with a lower risk of IFG, while rock tea consumption was associated with a lower risk of IGT. The adjusted odds ratios for IFG for green tea consumption of 30 cups per week were 1.0 (reference, 0.42 (95% confidence intervals (CI 0.27-0.65, 0.23 (95% CI, 0.12-0.46, and 0.41 (95% CI, 0.17-0.93, respectively. The adjusted odds ratios for IGT for rock tea consumption of 30 cups per week were 1.0 (reference, 0.69 (95% CI, 0.48-0.98, 0.59 (95% CI, 0.39-0.90, and 0.64 (95% CI, 0.43-0.97, respectively. A U-shaped association was observed, subjects who consumed 16-30 cups of green or rock tea per week having the lowest odds ratios for IFG or IGT. CONCLUSIONS: Consumption of green or rock tea may protect against the development of type 2 diabetes mellitus in Chinese men and women, particularly in those who drink 16-30 cups per week.

Women With Gestational Diabetes Mellitus Randomized to a Higher-Complex Carbohydrate/Low-Fat Diet Manifest Lower Adipose Tissue Insulin Resistance, Inflammation, Glucose, and Free Fatty Acids: A Pilot Study.

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Hernandez, Teri L; Van Pelt, Rachael E; Anderson, Molly A; Reece, Melanie S; Reynolds, Regina M; de la Houssaye, Becky A; Heerwagen, Margaret; Donahoo, William T; Daniels, Linda J; Chartier-Logan, Catherine; Janssen, Rachel C; Friedman, Jacob E; Barbour, Linda A

2016-01-01

Diet therapy in gestational diabetes mellitus (GDM) has focused on carbohydrate restriction but is poorly substantiated. In this pilot randomized clinical trial, we challenged the conventional low-carbohydrate/higher-fat (LC/CONV) diet, hypothesizing that a higher-complex carbohydrate/lower-fat (CHOICE) diet would improve maternal insulin resistance (IR), adipose tissue (AT) lipolysis, and infant adiposity. At 31 weeks, 12 diet-controlled overweight/obese women with GDM were randomized to an isocaloric LC/CONV (40% carbohydrate/45% fat/15% protein; n = 6) or CHOICE (60%/25%/15%; n = 6) diet. All meals were provided. AT was biopsied at 37 weeks. After ∼7 weeks, fasting glucose (P = 0.03) and free fatty acids (P = 0.06) decreased on CHOICE, whereas fasting glucose increased on LC/CONV (P = 0.03). Insulin suppression of AT lipolysis was improved on CHOICE versus LC/CONV (56 vs. 31%, P = 0.005), consistent with improved IR. AT expression of multiple proinflammatory genes was lower on CHOICE (P vs. 12.6 ± 2%, respectively). A CHOICE diet may improve maternal IR and infant adiposity, challenging recommendations for a LC/CONV diet. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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

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

2012-06-01

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

Glucose oxidase-functionalized fluorescent gold nanoclusters as probes for glucose

International Nuclear Information System (INIS)

Xia, Xiaodong; Long, Yunfei; Wang, Jianxiu

2013-01-01

Highlights: ► A glucose oxidase/gold nanocluster conjugates formed by etching chemistry. ► Integration of the bioactivities and fluorescence properties within a single unit. ► These conjugates serve as novel fluorescent probe for glucose. -- Abstract: Creation and application of noble metal nanoclusters have received continuous attention. By integrating enzyme activity and fluorescence for potential applications, enzyme-capped metal clusters are more desirable. This work demonstrated a glucose oxidase (an enzyme for glucose)-functionalized gold cluster as probe for glucose. Under physiological conditions, such bioconjugate was successfully prepared by an etching reaction, where tetrakis (hydroxylmethyl) phosphonium-protected gold nanoparticle and thioctic acid-modified glucose oxidase were used as precursor and etchant, respectively. These bioconjugates showed unique fluorescence spectra (λ em max = 650 nm, λ ex max = 507 nm) with an acceptable quantum yield (ca. 7%). Moreover, the conjugated glucose oxidase remained active and catalyzed reaction of glucose and dissolved O 2 to produce H 2 O 2 , which quenched quantitatively the fluorescence of gold clusters and laid a foundation of glucose detection. A linear range of 2.0 × 10 −6 –140 × 10 −6 M and a detection limit of 0.7 × 10 −6 M (S/N = 3) were obtained. Also, another horseradish peroxidase/gold cluster bioconjugate was produced by such general synthesis method. Such enzyme/metal cluster bioconjugates represented a promising class of biosensors for biologically important targets in organelles or cells

Correlation of Salivary Glucose Level with Blood Glucose Level in Diabetes Mellitus

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Arati S. Panchbhai

2012-07-01

Full Text Available Objectives: There is alarming rise in number of people with diabetes mellitus over these years. If glucose in saliva is linked to glucose in blood it can be used to detect diabetes mellitus at an early stage. The present study is undertaken with the aim to assess the correlation of salivary glucose level with blood glucose level in people with diabetes mellitus. Material and Methods: For investigations, 2 sets of samples of people with diabetes and the age and sex matched non-diabetic subjects were recruited. The salivary glucose was analyzed in unstimulated whole saliva samples using glucose oxidase method. Pearson’s correlation coefficient test was applied to assess the correlation between salivary glucose level and blood glucose level. Results: The significant (P < 0.05 positive correlation of salivary glucose level and fasting blood glucose level was observed in people with uncontrolled diabetes in both the sets of samples.Conclusions: Although study suggests some potential for saliva as a marker in monitoring of diabetes mellitus, there are many aspects that need clarification before we reach to a conclusion.

Increased response to insulin of glucose metabolism in the 6-day unloaded rat soleus muscle

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Henriksen, Erik J.; Tischler, Marc E.; Johnson, David G.

1986-01-01

Hind leg muscles of female rats were unloaded by tail cast suspension for 6 days. In the fresh-frozen unloaded soleus, the significantly greater concentration of glycogen correlated with a lower activity ratio of glycogen phosphorylase (p less than 0.02). The activity ratio of glycogen synthase also was lower (p less than 0.001), possibly due to the higher concentration of glycogen. In isolated unloaded soleus, insulin (0.1 milliunit/ml) increased the oxidation of D(U-C-14) glucose, release of lactate and pyruvate, incorporation of D-(U-C-14) glucose into glycogen, and the concentration of glucose 6-phosphate more (p less than 0.05) than in the weight-bearing soleus. At physiological doses of insulin, the percent of maximal uptake of 2-deoxy-D-(1,2-H-3) glucose/muscle also was greater in the unloaded soleus. Unloading of the soleus increased, by 50 percent the concentration of insuling receptors, due to no decrease in total receptor number during muscle atrophy. This increase may account for the greater response of glucose metabolism to insulin in this muscle. The extensor digitorum longus, which generally shows little response to unloading, displayed no differential response of glucose metabolism to insulin.

First Clinical Experience with Retrospective Flash Glucose Monitoring (FGM) Analysis in South Africa

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

2016-01-01

Background: In 2014, an innovative blinded continuous glucose monitoring system was introduced with automated ambulatory glucose profile (AGP) reporting. The clinical use and interpretation of this new technology has not previously been described. Therefore we wanted to understand its use in characterizing key factors related to glycemic control: glucose exposure, variability, and stability, and risk of hypoglycemia in clinical practice. Methods: Clinicians representing affiliated diabetes centers throughout South Africa were trained and subsequently were given flash glucose monitoring readers and 2-week glucose sensors to use at their discretion. After patient use, sensor data were collected and uploaded for AGP reporting. Results: Complete data (sensor AGP with corresponding clinical information) were obtained for 50 patients with type 1 (70%) and type 2 diabetes (30%), irrespective of therapy. Aggregated analysis of AGP data comparing patients with type 1 versus type 2 diabetes, revealed that despite similar HbA1c values between both groups (8.4 ± 2 vs 8.6 ± 1.7%, respectively), those with type 2 diabetes had lower mean glucose levels (9.2 ± 3 vs 10.3 mmol/l [166 ± 54 vs 185 mg/dl]) and lower indices of glucose variability (3.0 ± 1.5 vs 5.0 ± 1.9 mmol/l [54 ± 27 vs 90 ± 34.2 mg/dl]). This highlights key areas for future focus. Conclusions: Using AGP, the characteristics of glucose exposure, variability, stability, and hypoglycemia risk and occurrence were obtained within a short time and with minimal provider and patient input. In a survey at the time of the follow-up visit, clinicians indicated that aggregated AGP data analysis provided important new clinical information and insights. PMID:27154973

DLK1 Regulates Whole-Body Glucose Metabolism

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Abdallah, Basem M; Ditzel, Nicholas; Laborda, Jorge

2015-01-01

due to impaired insulin signaling in OB and lowered Glu-OCN serum levels. Furthermore, Dlk1(-/-) mice treated with Glu-OC experienced significantly lower blood glucose levels than Glu-OCN-treated wild-type mice. The data suggest that Glu-OCN-controlled production of DLK1 by pancreatic β-cells acts...... metabolism. We show that Glu-OCN specifically stimulates Dlk1 expression by the pancreas. Conversely, Dlk1-deficient (Dlk1(-/-) ) mice exhibited increased circulating Glu-OCN levels and increased insulin sensitivity, whereas mice overexpressing Dlk1 in OB displayed reduced insulin secretion and sensitivity...

Glucose-Dependent Insulinotropic Polypeptide Augments Glucagon Responses to Hypoglycemia in Type 1 Diabetes

DEFF Research Database (Denmark)

Christensen, Mikkel; Calanna, Salvatore; Sparre-Ulrich, Alexander H

2015-01-01

constituted a "recovery phase." During the recovery phase, GIP infusions elicited larger glucagon responses (164 ± 50 [GIP] vs. 23 ± 25 [GLP-1] vs. 17 ± 46 [saline] min ⋅ pmol/L, P endogenous glucose production was higher with GIP and lower with GLP-1 compared with saline (P ... days, significantly less exogenous glucose was needed to keep plasma glucose above 2 mmol/L (155 ± 36 [GIP] vs. 232 ± 40 [GLP-1] vs. 212 ± 56 [saline] mg ⋅ kg(-1), P ... similar on all days. Our results suggest that during hypoglycemia in patients with T1DM, exogenous GIP increases glucagon responses during the recovery phase after hypoglycemia and reduces the need for glucose administration....

Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides

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Birsoy, Kıvanç; Possemato, Richard; Lorbeer, Franziska K.; Bayraktar, Erol C.; Thiru, Prathapan; Yucel, Burcu; Wang, Tim; Chen, Walter W.; Clish, Clary B.; Sabatini, David M.

2014-04-01

As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues, cancer cells must adapt their metabolism to the tumour microenvironment. A better understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function. Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.

Sodium-Glucose linked transporter 2 (SGLT2) inhibitors--fighting diabetes from a new perspective.

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Angelopoulos, Theodoros P; Doupis, John

2014-06-01

Sodium-Glucose linked transporter 2 (SGLT2) inhibitors are a new family of antidiabetic pharmaceutical agents whose action is based on the inhibition of the glucose reabsorption pathway, resulting in glucosuria and a consequent reduction of the blood glucose levels, in patients with type 2 diabetes mellitus. Apart from lowering both fasting and postprandial blood glucose levels, without causing hypoglycemia, SGLT2 inhibitors have also shown a reduction in body weight and the systolic blood pressure. This review paper explores the renal involvement in glucose homeostasis providing also the latest safety and efficacy data for the European Medicines Agency and U.S. Food and Drug Administration approved SGLT2 inhibitors, looking, finally, into the future of this novel antidiabetic category of pharmaceutical agents.

Sourcing and bioprocessing of brown seaweed for maximizing glucose release

DEFF Research Database (Denmark)

Manns, Dirk Martin

maximum levels of glucose. The first requirement was to develop a robust methodology, including acid hydrolysis and analytical composition analysis, to quantitatively estimate the carbohydrate composition of the brown seaweeds. The monosaccharide composition of four different samples of brown seaweeds...... with lower enzyme loading. Simple application of only the cellulase preparation enabled the release of only half of the present glucose after 8 h. Analysis after the enzymatic treatment indicated a potential extraction of proteins from the solid residue and the sulfated polysaccharide fucoidan solubilized...

Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test

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Rohit Babbar

2018-03-01

Full Text Available IntroductionImpaired glucose tolerance (IGT is diagnosed by a standardized oral glucose tolerance test (OGTT. However, the OGTT is laborious, and when not performed, glucose tolerance cannot be determined from fasting samples retrospectively. We tested if glucose tolerance status is reasonably predictable from a combination of demographic, anthropometric, and laboratory data assessed at one time point in a fasting state.MethodsGiven a set of 22 variables selected upon clinical feasibility such as sex, age, height, weight, waist circumference, blood pressure, fasting glucose, HbA1c, hemoglobin, mean corpuscular volume, serum potassium, fasting levels of insulin, C-peptide, triglyceride, non-esterified fatty acids (NEFA, proinsulin, prolactin, cholesterol, low-density lipoprotein, HDL, uric acid, liver transaminases, and ferritin, we used supervised machine learning to estimate glucose tolerance status in 2,337 participants of the TUEF study who were recruited before 2012. We tested the performance of 10 different machine learning classifiers on data from 929 participants in the test set who were recruited after 2012. In addition, reproducibility of IGT was analyzed in 78 participants who had 2 repeated OGTTs within 1 year.ResultsThe most accurate prediction of IGT was reached with the recursive partitioning method (accuracy = 0.78. For all classifiers, mean accuracy was 0.73 ± 0.04. The most important model variable was fasting glucose in all models. Using mean variable importance across all models, fasting glucose was followed by NEFA, triglycerides, HbA1c, and C-peptide. The accuracy of predicting IGT from a previous OGTT was 0.77.ConclusionMachine learning methods yield moderate accuracy in predicting glucose tolerance from a wide set of clinical and laboratory variables. A substitution of OGTT does not currently seem to be feasible. An important constraint could be the limited reproducibility of glucose tolerance status during a

Glucose metabolism disorder in obese children assessed by continuous glucose monitoring system.

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Zou, Chao-Chun; Liang, Li; Hong, Fang; Zhao, Zheng-Yan

2008-02-01

Continuous glucose monitoring system (CGMS) can measure glucose levels at 5-minute intervals over a few days, and may be used to detect hypoglycemia, guide insulin therapy, and control glucose levels. This study was undertaken to assess the glucose metabolism disorder by CGMS in obese children. Eighty-four obese children were studied. Interstitial fluid (ISF) glucose levels were measured by CGMS for 24 hours covering the time for oral glucose tolerance test (OGTT). Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), type 2 diabetic mellitus (T2DM) and hypoglycemia were assessed by CGMS. Five children failed to complete CGMS test. The glucose levels in ISF measured by CGMS were highly correlated with those in capillary samples (r=0.775, Pobese children who finished the CGMS, 2 children had IFG, 2 had IGT, 3 had IFG + IGT, and 2 had T2DM. Nocturnal hypoglycemia was noted during the overnight fasting in 11 children (13.92%). Our data suggest that glucose metabolism disorder including hyperglycemia and hypoglycemia is very common in obese children. Further studies are required to improve the precision of the CGMS in children.

Glucose uptake patterns in exercised skeletal muscles of elite male long-distance and short-distance runners.

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Tai, Suh-Jun; Liu, Ren-Shyan; Kuo, Ya-Chen; Hsu, Chi-Yang; Chen, Chi-Hsien

2010-04-30

The aim of this study was to determine glucose uptake patterns in exercised skeletal muscles of elite male long-distance and short-distance runners. Positron emission tomography (PET) using 18F-fluoro-2-deoxyglucose (FDG) was performed to determine the patterns of glucose uptake in lower limbs of short-distance (SD group, n=8) and long-distance (LD group, n=8) male runners after a modified 20 min Bruce treadmill test. Magnetic resonance imaging (MRI) was used to delineate the muscle groups in lower limbs. Muscle groups from hip, knee, and ankle movers were measured. The total FDG uptake and the standard uptake value (SUV) for each muscle group were compared between the 2 groups. For the SD and LD runners, the 2 major muscle groups utilizing glucose during running were knee extensors and ankle plantarflexors, which accounted for 49.3 +/- 8.1% (25.1 +/- 4.7% and 24.2 +/- 6.0%) of overall lower extremity glucose uptake for SD group, and 51.3 +/- 8.0% (27.2 +/- 2.7% and 24.0 +/- 8.1%) for LD group. No difference in muscle glucose uptake was noted for other muscle groups. For SD runners, the SUVs for the muscle groups varied from 0.49 +/- 0.27 for the ankle plantarflexors, to 0.20 +/- 0.08 for the hip flexor. For the LD runners, the highest and lowest SUVs were 0.43 +/- 0.15 for the ankle dorsiflexors and 0.21 +/- 0.19 for the hip. For SD and LD groups, no difference in muscle SUV was noted for the muscle groups. However, the SUV ratio between the ankle dorsiflexors and plantarflexors in the LD group was significantly greater than that in the SD group. We thus conclude that the major propelling muscle groups account for approximately 50% of lower limb glucose utilization during running. Thus, the other muscle groups involving maintenance of balance, limb deceleration, and shock absorption utilize an equal amount. This result provides a new insight into glucose distribution in skeletal muscle, suggesting that propellers and supporters are both energetically important

[Blood glucose and insulin responses to two hypocaloric enteral formulas in patients with diabetes mellitus type 2].

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de Luis, D A; Izaola, O; de la Fuente, B; Araújo, K

2013-01-01

The aim of this study is to compare the glycaemic and insulinemic response of type 2 diabetic patients after oral administration of 250 ml of two enteral formulas: a specific formula (Novasource Diabet Smartflex) against a standard isocaloric formula. The design was a cross-over study, with the diabetic patients (n = 15) receiving one of the two formulas in random order. Glycaemia and insulinemia curves were performed at 0, 10, 20, 30,60, 90,120,150 and 180 minutes. The variables studied were the area under the curve (AUC(0)-t), maximum concentration (Cmax), the time to reach maximum concentration (Tmax) and the concentrations of biochemical parameters in each study period. We studied 11 males (73.3%) and 4 females (26.7%), the mean age was 56.9 ± 10.9 years. Patients receiving Novasource Diabet showed a lower mean AUC(0)-t of glucose, mean difference - 4,753.26 mg/min/dl (95% CI: -7,256.7 to -2,249.82), also showed a mean insulinemia significantly lower AUC(0)-t, mean difference: 930.27 uU/min/ml (95% CI -1,696.34 to -164.2). The Cmax showed a significantly lower mean blood glucose levels with the specific formula, mean difference -26.89 mg/dl (95% CI -42.11 to -11.67) and insulin, mean difference: -5.39 uU/ml (95% CI: -10.37 to -1.43). The analysis shows that the mean Tmax of glucose with the specific formula are significantly lower, mean difference -19.82 min (95% CI: -32.11 to -7.33), however there was no difference in Tmax of insulin. Finally the analysis of glucose concentrations in the total study shows that the group with the specific formula has a lower mean glucose 25.77 mg / dl (95% CI 18.29 to 33.25), the same fact was detected with insulinemia 4.39 mU/ml (95% CI: 0.927 to 7.87). Diabetic patients treated diabet Novasource had significantly lower mean AUC0-t, Cmax and Tmax in blood glucose curves, also had lower mean AUC(0)-t and Cmax in insulin curves. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Glucose oxidase-functionalized fluorescent gold nanoclusters as probes for glucose

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Xia, Xiaodong [College of Chemistry and Chemical Engineering, Central South University, Changsha 410083 (China); School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201 (China); Long, Yunfei, E-mail: l_yunfei927@163.com [School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201 (China); Wang, Jianxiu, E-mail: jxiuwang@csu.edu.cn [College of Chemistry and Chemical Engineering, Central South University, Changsha 410083 (China)

2013-04-15

Highlights: ► A glucose oxidase/gold nanocluster conjugates formed by etching chemistry. ► Integration of the bioactivities and fluorescence properties within a single unit. ► These conjugates serve as novel fluorescent probe for glucose. -- Abstract: Creation and application of noble metal nanoclusters have received continuous attention. By integrating enzyme activity and fluorescence for potential applications, enzyme-capped metal clusters are more desirable. This work demonstrated a glucose oxidase (an enzyme for glucose)-functionalized gold cluster as probe for glucose. Under physiological conditions, such bioconjugate was successfully prepared by an etching reaction, where tetrakis (hydroxylmethyl) phosphonium-protected gold nanoparticle and thioctic acid-modified glucose oxidase were used as precursor and etchant, respectively. These bioconjugates showed unique fluorescence spectra (λ{sub em} {sub max} = 650 nm, λ{sub ex} {sub max} = 507 nm) with an acceptable quantum yield (ca. 7%). Moreover, the conjugated glucose oxidase remained active and catalyzed reaction of glucose and dissolved O{sub 2} to produce H{sub 2}O{sub 2}, which quenched quantitatively the fluorescence of gold clusters and laid a foundation of glucose detection. A linear range of 2.0 × 10{sup −6}–140 × 10{sup −6} M and a detection limit of 0.7 × 10{sup −6} M (S/N = 3) were obtained. Also, another horseradish peroxidase/gold cluster bioconjugate was produced by such general synthesis method. Such enzyme/metal cluster bioconjugates represented a promising class of biosensors for biologically important targets in organelles or cells.

Effect of dietary fiber in lowering serum glucose and body weight in sprague dawley rats

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Muhammad Imran Chohan

2011-08-01

Full Text Available Introduction:The present study evaluated the hypoglycemic perspectives and weight loss significance of dietary fiber. Dietary fiber was supplemented in commercial wheat flour (atta for the preparation of chapaties, a staple diet of South Asia. Male Sprague Dawley rats (n = 100 were randomly divided into 4 diet groups (n = 25 per group. The control group was fed basal diet that included commercial wheat flour chapati, cornstarch, corn oil, salt and vitamin mixture in such a way that 10% of the protein was available from the final diet. To the basal diet of other 3 groups, chapaties supplemented with 2% guar gum (GG 2%, 3% guar gum (GG 3% and 5% chickpea + 1% guar gum (CP5%+GG1% were added, respectively. All diets were fed to the rats for a period of 8 weeks to perceive the impact of respective compositions. Rats fed on CP 5% + GG1%, showed maximum glucose reduction (14.57% followed by GG 3% (11.64% and GG 2% (9.60% as compared to control diet. Likewise, rats fed on 3% GG showed maximum decline (7.90% in body weight. It was concluded that chapaties prepared from selected treatments provide an additional dietary fiber that could be supportive for diabetic and obese individuals.Results:The results indicated that addition of dietary fiber influenced the physical characteristics of chapati non-significantly. Maximum glucose concentration was found to be 112.50 mg/dL in control group followed by 101.70 and 99.41 mg/dL in groups fed on guar gum 2% and guar gum 3%, respectively. Lowest glucose concentration (96.11 mg/dL was observed in rats fed on the combination of chickpea 5 %+ guar gum 1%. Maximum serum protein concentration was found to be 6.39 g/dL in rats fed on combination of chickpea 5 % + guar gum 1% whilst the remaining three groups showed non significant variations with respect to each other. Means for serum Functional Foods in Health and Disease 2011; 8:261-278 protein were 6.33, 6.30 and 6.32 g/dL for control, guar gum 3%, and guar gum 2

Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease.

Science.gov (United States)

Willette, Auriel A; Bendlin, Barbara B; Starks, Erika J; Birdsill, Alex C; Johnson, Sterling C; Christian, Bradley T; Okonkwo, Ozioma C; La Rue, Asenath; Hermann, Bruce P; Koscik, Rebecca L; Jonaitis, Erin M; Sager, Mark A; Asthana, Sanjay

2015-09-01

Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET). To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicted variation in regional glucose metabolism is associated with worse cognitive performance. This population-based, cross-sectional study included 150 cognitively normal, late middle-aged (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for Alzheimer's Prevention (WRAP) study, a general community sample enriched for AD parental history. Participants underwent cognitive testing, fasting blood draw, and FDG-PET at baseline. We used the homeostatic model assessment of peripheral insulin resistance (HOMA-IR). Regression analysis tested the statistical effect of HOMA-IR on global glucose metabolism. We used a voxelwise analysis to determine whether HOMA-IR predicted regional glucose metabolism. Finally, predicted variation in regional glucose metabolism was regressed against cognitive factors. Covariates included age, sex, body mass index, apolipoprotein E ε4 genotype, AD parental history status, and a reference region used to normalize regional uptake. Regional glucose uptake determined using FDG-PET and neuropsychological factors. Higher HOMA-IR was associated with lower global glucose metabolism (β = -0.29; P factor scores. Our results show that insulin resistance, a prevalent and increasingly common condition in developed countries, is associated with significantly lower regional cerebral glucose metabolism, which in turn may predict worse memory performance. Midlife may be a critical period for initiating treatments to lower peripheral insulin resistance to maintain neural metabolism

Acute effects of ethanol and acetate on glucose kinetics in normal subjects

International Nuclear Information System (INIS)

Yki-Jaervinen, H.; Koivisto, V.A.; Ylikahri, R.; Taskinen, M.R.

1988-01-01

The authors compared the effects of two ethanol doses on glucose kinetics and assessed the role of acetate as a mediator of ethanol-induced insulin resistance. Ten normal males were studied on four occasions, during which either a low or moderate ethanol, acetate, or saline dose was administered. Both ethanol doses similarly inhibited basal glucose production. The decrease in R a was matched by a comparable decrease in glucose utilization (R d ), resulting in maintenance of normoglycemia. During hyperinsulinemia glucose disposal was lower in the moderate than the low-dose ethanol or saline studies. During acetate infusion, the blood acetate level was comparable with those in the ethanol studies. Acetate had no effect on glucose kinetics. In conclusion, (1) in overnight fasted subjects, ethanol does not cause hypoglycemia because its inhibitory effect on R a is counterbalanced by equal inhibition of R d ; (2) basal R a and R d are maximally inhibited already by small ethanol doses, whereas inhibition of insulin-stimulated glucose disposal requires a moderate ethanol dose; and (3) acetate is not the mediator of ethanol-induced insulin resistance

Selective reductions in prefrontal glucose metabolism in murderers.

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Raine, A; Buchsbaum, M S; Stanley, J; Lottenberg, S; Abel, L; Stoddard, J

1994-09-15

This study tests the hypothesis that seriously violent offenders pleading not guilty by reason of insanity or incompetent to stand trial are characterized by prefrontal dysfunction. This hypothesis was tested in a group of 22 subjects accused of murder and 22 age-matched and gender-matched controls by measuring local cerebral uptake of glucose using positron emission tomography during the continuous performance task. Murderers had significantly lower glucose metabolism in both lateral and medial prefrontal cortex relative to controls. No group differences were observed for posterior frontal, temporal, and parietal glucose metabolism, indicating regional specificity for the prefrontal deficit. Group differences were not found to be a function of raised levels of left-handedness, schizophrenia, ethnic minority status, head injury, or motivation deficits in the murder group. These preliminary results suggest that deficits localized to the prefrontal cortex may be related to violence in a selected group of offenders, although further studies are needed to establish the generalizability of these findings to violent offenders in the community.

Transcriptional responses to glucose at different glycolytic rates in Saccharomyces cerevisiae.

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Elbing, Karin; Ståhlberg, Anders; Hohmann, Stefan; Gustafsson, Lena

2004-12-01

The addition of glucose to Saccharomyces cerevisiae cells causes reprogramming of gene expression. Glucose is sensed by membrane receptors as well as (so far elusive) intracellular sensing mechanisms. The availability of four yeast strains that display different hexose uptake capacities allowed us to study glucose-induced effects at different glycolytic rates. Rapid glucose responses were observed in all strains able to take up glucose, consistent with intracellular sensing. The degree of long-term responses, however, clearly correlated with the glycolytic rate: glucose-stimulated expression of genes encoding enzymes of the lower part of glycolysis showed an almost linear correlation with the glycolytic rate, while expression levels of genes encoding gluconeogenic enzymes and invertase (SUC2) showed an inverse correlation. Glucose control of SUC2 expression is mediated by the Snf1-Mig1 pathway. Mig1 dephosphorylation upon glucose addition is known to lead to repression of target genes. Mig1 was initially dephosphorylated upon glucose addition in all strains able to take up glucose, but remained dephosphorylated only at high glycolytic rates. Remarkably, transient Mig1-dephosphorylation was accompanied by the repression of SUC2 expression at high glycolytic rates, but stimulated SUC2 expression at low glycolytic rates. This suggests that Mig1-mediated repression can be overruled by factors mediating induction via a low glucose signal. At low and moderate glycolytic rates, Mig1 was partly dephosphorylated both in the presence of phosphorylated, active Snf1, and unphosphorylated, inactive Snf1, indicating that Mig1 was actively phosphorylated and dephosphorylated simultaneously, suggesting independent control of both processes. Taken together, it appears that glucose addition affects the expression of SUC2 as well as Mig1 activity by both Snf1-dependent and -independent mechanisms that can now be dissected and resolved as early and late/sustained responses.

Effect of glucose treatment on texture and colour of pidan white during storage.

Science.gov (United States)

Ganesan, Palanivel; Benjakul, Soottawat

2014-04-01

Changes in texture and colour of pidan white as influenced by glucose treatment at levels of 0, 2 and 5% were determined after pickling (week 3) and during the storage up to 12 weeks. Hardness and cohesiveness of pidan white without glucose treatment were more retained but showed a decrease in adhesiveness as storage time increased up to week 12 (P white treated with glucose at both levels as the storage time increased (P colour, mainly via the Maillard reaction with free amino groups of pidan white at alkaline pH, but it could impair the textural property. Pidan white without glucose treatment showed the higher color and appearance likeness score, but lower texture and odour likeness score than commercial counterpart (P < 0.05). Therefore, glucose was not a necessary aid for pidan production.

Glucagon-like peptide-1 (GLP-1) raises blood-brain glucose transfer capacity and hexokinase activity in human brain

OpenAIRE

Gejl, Michael; Lerche, Susanne; Egefjord, L?rke; Brock, Birgitte; M?ller, Niels; Vang, Kim; Rodell, Anders B.; Bibby, Bo M.; Holst, Jens J.; Rungby, J?rgen; Gjedde, Albert

2013-01-01

In hyperglycemia, glucagon-like peptide-1 (GLP-1) lowers brain glucose concentration together with increased net blood-brain clearance and brain metabolism, but it is not known whether this effect depends on the prevailing plasma glucose (PG) concentration. In hypoglycemia, glucose depletion potentially impairs brain function. Here, we test the hypothesis that GLP-1 exacerbates the effect of hypoglycemia. To test the hypothesis, we determined glucose transport and consumption rates in seven h...

Sodium-glucose co-transporter 2 (SGLT2 inhibitors: a growing class of anti-diabetic agents

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Eva M Vivian

2014-12-01

Full Text Available Although several treatment options are available to reduce hyperglycemia, only about half of individuals with diagnosed diabetes mellitus (DM achieve recommended glycemic targets. New agents that reduce blood glucose concentrations by novel mechanisms and have acceptable safety profiles are needed to improve glycemic control and reduce the complications associated with type 2 diabetes mellitus (T2DM. The renal sodium-glucose co-transporter 2 (SGLT2 is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors of SGLT2 lower blood glucose independent of the secretion and action of insulin by inhibiting renal reabsorption of glucose, thereby promoting the increased urinary excretion of excess glucose. Canagliflozin, dapagliflozin, and empagliflozin are SGLT2 inhibitors approved as treatments for T2DM in the United States, Europe, and other countries. Canagliflozin, dapagliflozin, and empagliflozin increase renal excretion of glucose and improve glycemic parameters in patients with T2DM when used as monotherapy or in combination with other antihyperglycemic agents. Treatment with SGLT2 inhibitors is associated with weight reduction, lowered blood pressure, and a low intrinsic propensity to cause hypoglycemia. Overall, canagliflozin, dapagliflozin, and empagliflozin are well tolerated. Cases of genital infections and, in some studies, urinary tract infections have been more frequent in canagliflozin-, dapagliflozin-, and empagliflozin-treated patients compared with those receiving placebo. Evidence from clinical trials suggests that SGLT2 inhibitors are a promising new treatment option for T2DM.

In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue.

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Matsen, Miles E; Thaler, Joshua P; Wisse, Brent E; Guyenet, Stephan J; Meek, Thomas H; Ogimoto, Kayoko; Cubelo, Alex; Fischer, Jonathan D; Kaiyala, Karl J; Schwartz, Michael W; Morton, Gregory J

2013-04-01

Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls. We therefore sought to determine whether activation of thyroid hormone receptors is sufficient in and of itself to lower blood glucose levels in STZ-diabetes and whether this effect involves activation of BAT. We found that, although systemic administration of the thyroid hormone (TR)β-selective agonist GC-1 increases energy expenditure and induces further weight loss in STZ-diabetic rats, it neither increased BAT glucose uptake nor attenuated diabetic hyperglycemia. Even when GC-1 was administered in combination with a β(3)-adrenergic receptor agonist to mimic sympathetic nervous system activation, glucose uptake was not increased in STZ-diabetic rats, nor was blood glucose lowered, yet this intervention potently activated BAT. Similar results were observed in animals treated with active thyroid hormone (T3) instead of GC-1. Taken together, our data suggest that neither returning normal plasma thyroid hormone levels nor BAT activation has any impact on diabetic hyperglycemia, and that in BAT, increases of Ucp1 gene expression and glucose uptake are readily dissociated from one another in this setting.

Low Red Blood Cell Vitamin C Concentrations Induce Red Blood Cell Fragility: A Link to Diabetes Via Glucose, Glucose Transporters, and Dehydroascorbic Acid

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Hongbin Tu

2015-11-01

Full Text Available Strategies to prevent diabetic microvascular angiopathy focus on the vascular endothelium. Because red blood cells (RBCs are less deformable in diabetes, we explored an original concept linking decreased RBC deformability to RBC ascorbate and hyperglycemia. We characterized ascorbate concentrations from human and mouse RBCs and plasma, and showed an inverse relationship between RBC ascorbate concentrations and deformability, measured by osmotic fragility. RBCs from ascorbate deficient mice were osmotically sensitive, appeared as spherocytes, and had decreased β-spectrin. These aberrancies reversed with ascorbate repletion in vivo. Under physiologic conditions, only ascorbate's oxidation product dehydroascorbic acid (DHA, a substrate for facilitated glucose transporters, was transported into mouse and human RBCs, with immediate intracellular reduction to ascorbate. In vitro, glucose inhibited entry of physiologic concentrations of dehydroascorbic acid into mouse and human RBCs. In vivo, plasma glucose concentrations in normal and diabetic mice and humans were inversely related to respective RBC ascorbate concentrations, as was osmotic fragility. Human RBC β-spectrin declined as diabetes worsened. Taken together, hyperglycemia in diabetes produced lower RBC ascorbate with increased RBC rigidity, a candidate to drive microvascular angiopathy. Because glucose transporter expression, DHA transport, and its inhibition by glucose differed for mouse versus human RBCs, human experimentation is indicated.

Experience-dependent escalation of glucose drinking and the development of glucose preference over fructose - association with glucose entry into the brain.

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Wakabayashi, Ken T; Spekterman, Laurence; Kiyatkin, Eugene A

2016-06-01

Glucose, a primary metabolic substrate for cellular activity, must be delivered to the brain for normal neural functions. Glucose is also a unique reinforcer; in addition to its rewarding sensory properties and metabolic effects, which all natural sugars have, glucose crosses the blood-brain barrier and acts on glucoreceptors expressed on multiple brain cells. To clarify the role of this direct glucose action in the brain, we compared the neural and behavioural effects of glucose with those induced by fructose, a sweeter yet metabolically equivalent sugar. First, by using enzyme-based biosensors in freely moving rats, we confirmed that glucose rapidly increased in the nucleus accumbens in a dose-dependent manner after its intravenous delivery. In contrast, fructose induced a minimal response only after a large-dose injection. Second, we showed that naive rats during unrestricted access consumed larger volumes of glucose than fructose solution; the difference appeared with a definite latency during the initial exposure and strongly increased during subsequent tests. When rats with equal sugar experience were presented with either glucose or fructose in alternating order, the consumption of both substances was initially equal, but only the consumption of glucose increased during subsequent sessions. Finally, rats with equal glucose-fructose experience developed a strong preference for glucose over fructose during a two-bottle choice procedure; the effect appeared with a definite latency during the initial test and greatly amplified during subsequent tests. Our results suggest that direct entry of glucose in the brain and its subsequent effects on brain cells could be critical for the experience-dependent escalation of glucose consumption and the development of glucose preference over fructose. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

A glucose oxidase-coupled DNAzyme sensor for glucose detection in tears and saliva.

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Liu, Chengcheng; Sheng, Yongjie; Sun, Yanhong; Feng, Junkui; Wang, Shijin; Zhang, Jin; Xu, Jiacui; Jiang, Dazhi

2015-08-15

Biosensors have been widely investigated and utilized in a variety of fields ranging from environmental monitoring to clinical diagnostics. Glucose biosensors have triggered great interest and have been widely exploited since glucose determination is essential for diabetes diagnosis. In here, we designed a novel dual-enzyme biosensor composed of glucose oxidase (GOx) and pistol-like DNAzyme (PLDz) to detect glucose levels in tears and saliva. First, GOx, as a molecular recognition element, catalyzes the oxidation of glucose forming H2O2; then PLDz recognizes the produced H2O2 as a secondary signal and performs a self-cleavage reaction promoted by Mn(2+), Co(2+) and Cu(2+). Thus, detection of glucose could be realized by monitoring the cleavage rate of PLDz. The slope of the cleavage rate of PLDz versus glucose concentration curve was fitted with a Double Boltzmann equation, with a range of glucose from 100 nM to 10mM and a detection limit of 5 μM. We further applied the GOx-PLDz 1.0 biosensor for glucose detection in tears and saliva, glucose levels in which are 720±81 μM and 405±56 μM respectively. Therefore, the GOx-PLDz 1.0 biosensor is able to determine glucose levels in tears and saliva as a noninvasive glucose biosensor, which is important for diabetic patients with frequent/continuous glucose monitoring requirements. In addition, induction of DNAzyme provides a new approach in the development of glucose biosensors. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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

2017-08-01

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

Lactate overrides central nervous but not beta-cell glucose sensing in humans.

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Schmid, Sebastian M; Jauch-Chara, Kamila; Hallschmid, Manfred; Oltmanns, Kerstin M; Peters, Achim; Born, Jan; Schultes, Bernd

2008-12-01

Lactate has been shown to serve as an alternative energy substrate in the central nervous system and to interact with hypothalamic glucose sensors. On the background of marked similarities between central nervous and beta-cell glucose sensing, we examined whether lactate also interacts with pancreatic glucose-sensing mechanisms in vivo. The effects of intravenously infused lactate vs placebo (saline) on central nervous and pancreatic glucose sensing were assessed during euglycemic and hypoglycemic clamp experiments in 10 healthy men. The release of neuroendocrine counterregulatory hormones during hypoglycemia was considered to reflect central nervous glucose sensing, whereas endogenous insulin secretion as assessed by serum C-peptide levels served as an indicator of pancreatic beta-cell glucose sensing. Lactate infusion blunted the counterregulatory hormonal responses to hypoglycemia, in particular, the release of epinephrine (P = .007) and growth hormone (P = .004), so that higher glucose infusion rates (P = .012) were required to maintain the target blood glucose levels. In contrast, the decrease in C-peptide concentrations during the hypoglycemic clamp remained completely unaffected by lactate (P = .60). During euglycemic clamp conditions, lactate infusion did not affect the concentrations of C-peptide and of counterregulatory hormones, with the exception of norepinephrine levels that were lower during lactate than saline infusion (P = .049) independently of the glycemic condition. Data indicate that glucose sensing of beta-cells is specific to glucose, whereas glucose sensing at the central nervous level can be overridden by lactate, reflecting the brain's ability to rely on lactate as an alternative major energy source.

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

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Choi, Kevin; Weber, Jean-Michel

2016-03-15

This study examines how chronically hyperglycemic rainbow trout modulate glucose kinetics in response to graded exercise up to critical swimming speed (Ucrit), with or without exogenous glucose supply. Our goals were 1) to quantify the rates of hepatic glucose production (Ra glucose) and disposal (Rd glucose) during graded swimming, 2) to determine how exogenous glucose affects the changes in glucose fluxes caused by exercise, and 3) to establish whether exogenous glucose modifies Ucrit or the cost of transport. Results show that graded swimming causes no change in Ra and Rd glucose at speeds below 2.5 body lengths per second (BL/s), but that glucose fluxes may be stimulated at the highest speeds. Excellent glucoregulation is also achieved at all exercise intensities. When exogenous glucose is supplied during exercise, trout suppress hepatic production from 16.4 ± 1.6 to 4.1 ± 1.7 μmol·kg(-1)·min(-1) and boost glucose disposal to 40.1 ± 13 μmol·kg(-1)·min(-1). These responses limit the effects of exogenous glucose to a 2.5-fold increase in glycemia, whereas fish showing no modulation of fluxes would reach dangerous levels of 114 mM of blood glucose. Exogenous glucose reduces metabolic rate by 16% and, therefore, causes total cost of transport to decrease accordingly. High glucose availability does not improve Ucrit because the fish are unable to take advantage of this extra fuel during maximal exercise and rely on tissue glycogen instead. In conclusion, trout have a remarkable ability to adjust glucose fluxes that allows them to cope with the cumulative stresses of a glucose overload and graded exercise. Copyright © 2016 the American Physiological Society.

Correlation of reversely increased level of plasma glucose during pregnancy to the pregnancy outcome

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Xiao-ya SHEN

2017-02-01

Full Text Available Objective　To explore the correlation of the reversely increased results of 75g oral glucose tolerance test (OGTT during pregnancy to the pregnancy outcome, so as to provide a reliable theoretical basis of the early intervention for the pregnant women with high plasma glucose. Methods　The clinical data of 461 cases were retrospectively analyzed. Patients were chosen from the pregnant women undergoing routine antenatal examination in our hospital during 2014. According to the results of 75g OGTT, 226 patients were analyzed as the observation group, in whom the level of postprandial 2-hour plasma glucose was higher than that of postprandial 1-hour plasma glucose. Meanwhile 235 pregnant women with or without gestational diabetes mellitus (GDM were randomly selected as the control group. Results　The levels of fasting plasma glucose and 1-hour postprandial plasma glucose were lower, but those of 2-hour postprandial plasma glucose was higher in observation group than in control group (P0.05 in the incidences of polyhydramnios, oligohydramnios, fetal growth restriction (FGR, premature labor (PTL, pregnancy induced hypertension (PIH, complicated with premature rupture of membrane (PROM, intrauterine fetal death (IUFD and non scar uterus cesarean section rate (CSR. Compared with the observation group, the rates of neonatal dysplasia and neonatal asphyxia and the newborn transfer rate were lower in the control group, of which the newborn transfer rate was statistically different (P<0.01. Conclusions　There might be a delayed plasma glucose metabolism in the patients with reversely increased result of 75g OGTT during pregnancy, which may affect the long-term prognosis of the newborn. Therefore, more attention should be paid to such patients with reversely increased result of 75g OGTT. DOI: 10.11855/j.issn.0577-7402.2017.01.09

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...

Estimation of endogenous glucose production during hyperinsulinemic-euglycemic glucose clamps. Comparison of unlabeled and labeled exogenous glucose infusates

International Nuclear Information System (INIS)

Finegood, D.T.; Bergman, R.N.; Vranic, M.

1987-01-01

Tracer methodology has been applied extensively to the estimation of endogenous glucose production (Ra) during euglycemic glucose clamps. The accuracy of this approach has been questioned due to the observation of significantly negative estimates for Ra when insulin levels are high. We performed hyperinsulinemic (300 microU/ml)-euglycemic glucose clamps for 180 min in normal dogs and compared the standard approach, an unlabeled exogenous glucose infusate (cold GINF protocol, n = 12), to a new approach in which a tracer (D-[3- 3 H]glucose) was added to the exogenous glucose used for clamping (hot GINF protocol, n = 10). Plasma glucose, insulin and glucagon concentrations, and glucose infusion rates were similar for the two protocols. Plasma glucose specific activity was 20 +/- 1% of basal (at 120-180 min) in the cold GINF studies, and 44 +/- 3 to 187 +/- 5% of basal in the hot GINF studies. With the one-compartment, fixed pool volume model of Steele, Ra for the cold GINF studies was -2.4 +/- 0.7 mg X min-1 X kg-1 at 25 min and remained significantly negative until 110 min (P less than .05). For the hot GINF studies, Ra was never significantly less than zero (P greater than .05) and was greater than in the cold GINF studies at 20-90 min (P less than .05). There was substantially less between-(78%) and within- (40%) experiment variation for the hot GINF studies compared with the cold GINF studies. An alternate approach (regression method) to the application of the one-compartment model, which allows for a variable and estimable effective distribution volume, yielded Ra estimates that were suppressed 60-100% from basal

Genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

Science.gov (United States)

Scott, Robert A.; Freitag, Daniel F.; Li, Li; Chu, Audrey Y.; Surendran, Praveen; Young, Robin; Grarup, Niels; Stancáková, Alena; Chen, Yuning; V.Varga, Tibor; Yaghootkar, Hanieh; Luan, Jian'an; Zhao, Jing Hua; Willems, Sara M.; Wessel, Jennifer; Wang, Shuai; Maruthur, Nisa; Michailidou, Kyriaki; Pirie, Ailith; van der Lee, Sven J.; Gillson, Christopher; Olama, Ali Amin Al; Amouyel, Philippe; Arriola, Larraitz; Arveiler, Dominique; Aviles-Olmos, Iciar; Balkau, Beverley; Barricarte, Aurelio; Barroso, Inês; Garcia, Sara Benlloch; Bis, Joshua C.; Blankenberg, Stefan; Boehnke, Michael; Boeing, Heiner; Boerwinkle, Eric; Borecki, Ingrid B.; Bork-Jensen, Jette; Bowden, Sarah; Caldas, Carlos; Caslake, Muriel; Cupples, L. Adrienne; Cruchaga, Carlos; Czajkowski, Jacek; den Hoed, Marcel; Dunn, Janet A.; Earl, Helena M.; Ehret, Georg B.; Ferrannini, Ele; Ferrieres, Jean; Foltynie, Thomas; Ford, Ian; Forouhi, Nita G.; Gianfagna, Francesco; Gonzalez, Carlos; Grioni, Sara; Hiller, Louise; Jansson, Jan-Håkan; Jørgensen, Marit E.; Jukema, J. Wouter; Kaaks, Rudolf; Kee, Frank; Kerrison, Nicola D.; Key, Timothy J.; Kontto, Jukka; Kote-Jarai, Zsofia; Kraja, Aldi T.; Kuulasmaa, Kari; Kuusisto, Johanna; Linneberg, Allan; Liu, Chunyu; Marenne, Gaëlle; Mohlke, Karen L.; Morris, Andrew P.; Muir, Kenneth; Müller-Nurasyid, Martina; Munroe, Patricia B.; Navarro, Carmen; Nielsen, Sune F.; Nilsson, Peter M.; Nordestgaard, Børge G.; Packard, Chris J.; Palli, Domenico; Panico, Salvatore; Peloso, Gina M.; Perola, Markus; Peters, Annette; Poole, Christopher J.; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Salomaa, Veikko; Sánchez, María-José; Sattar, Naveed; Sharp, Stephen J.; Sims, Rebecca; Slimani, Nadia; Smith, Jennifer A.; Thompson, Deborah J.; Trompet, Stella; Tumino, Rosario; van der A, Daphne L.; van der Schouw, Yvonne T.; Virtamo, Jarmo; Walker, Mark; Walter, Klaudia; Abraham, Jean E.; Amundadottir, Laufey T.; Aponte, Jennifer L.; Butterworth, Adam S.; Dupuis, Josée; Easton, Douglas F.; Eeles, Rosalind A.; Erdmann, Jeanette; Franks, Paul W.; Frayling, Timothy M.; Hansen, Torben; Howson, Joanna M. M.; Jørgensen, Torben; Kooner, Jaspal; Laakso, Markku; Langenberg, Claudia; McCarthy, Mark I.; Pankow, James S.; Pedersen, Oluf; Riboli, Elio; Rotter, Jerome I.; Saleheen, Danish; Samani, Nilesh J.; Schunkert, Heribert; Vollenweider, Peter; O'Rahilly, Stephen; Deloukas, Panos; Danesh, John; Goodarzi, Mark O.; Kathiresan, Sekar; Meigs, James B.; Ehm, Margaret G.; Wareham, Nicholas J.; Waterworth, Dawn M.

2016-01-01

Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to inform development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in 6 genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing, and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr;rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and lower T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomised controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process. PMID:27252175

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

Science.gov (United States)

Janukonyté, Jurgita; Parkner, Tina; Bruun, Niels Henrik; Lauritzen, Torsten; Christiansen, Jens Sandahl; Laursen, Torben

2015-05-01

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 insulin aspart (s-IAsp), and blood glucose levels in an experimental short-term crossover design. Eight T2DM patients (63.52 years old; range, 49-69 years; mean body mass index, 28.8±3.8 kg/m(2)) were randomized to treatment with individual fixed doses of insulin aspart (0.5-1.5 IU/h) as a continuous subcutaneous insulin infusion (CSII) during a 10-h period on two occasions with different duration of hyperglycemia: (1) transient hyperglycemia for 2 h (visit TH) and (2) continuous hyperglycemia for 12 h (visit CH). During steady state the variances of plasma glucose (p-glucose), s-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 100 min of both visits when s-IAsp was undetectable (adjusted R(2)=0.9). A complex but statistically significant interaction among s-IAsp, s-EI, p-glucose, and patients was observed during measurable s-IAsp levels (adjusted R(2)=0.70). Endogenous and exogenous insulin showed higher variation during continuous hyperglycemia. Significantly lower levels of exogenous insulin were observed following CSII during continuous hyperglycemia compared with transient hyperglycemia. Endogenous insulin levels could in a complex way be explained by an individual interaction among p-glucose and serum exogenous insulin, if present.

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

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Giray Bozkaya

2010-01-01

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

Repeated Plyometric Exercise Attenuates Blood Glucose in Healthy Adults.

Science.gov (United States)

Barillas, Saldiam R; Watkins, Casey M; Wong, Megan A; Dobbs, Ian J; Archer, David C; Munger, Cameron N; Galpin, Andrew J; Coburn, Jared W; Brown, Lee E

2017-01-01

Plyometric exercise is popular in commercial exercise programs aiming to maximize energy expenditure for weight loss. However, the effect of plyometric exercise on blood glucose is unknown. The purpose of this study was to investigate the effect of relatively high intensity plyometric exercise on blood glucose. Thirteen subjects (6 females age= 21.8 ± 1.0 yrs.; height= 163.7 ± 7.8 cm; mass= 60.8 ± 6.7 kg and 7 males age= 22.0 ± 2.6 yrs.; height= 182.3 ± 3.6 cm; mass= 87.4 ± 12.5 kg) volunteered to participate. Subjects completed two random conditions on two separate days, consisting of either five sets of 10 maximal effort countermovement squat jumps (SJ) with 50 seconds' rest between sets or quiet sitting (SIT) for the time equated to the SJ duration (~4min). Immediately after each condition, subjects drank 75g of anhydrous glucose (CHO) in 100ml of water. Blood glucose measurements were taken via finger prick pre and immediately post SJ or SIT, and 5, 15, 30, and 60 min post. A 2×6 (condition × time) ANOVA revealed a significant interaction where SJ blood glucose was lower at 15 (114.0 ± 14.6 mg/dl) and 30 (142.1 ± 22.5 mg/dl) min compared to SIT (15min 130.8 ± 14.0 mg/dl and 30min 159.3 ± 21.0 mg/dl). The current plyometric protocol attenuated CHO-induced blood glucose at 15 and 30 min. This may be due to increased physiological stress applied to the muscles, thus increasing muscular glucose uptake.

Zinc Status Affects Glucose Homeostasis and Insulin Secretion in Patients with Thalassemia

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Ellen B. Fung

2015-06-01

Full Text Available Up to 20% of adult patients with Thalassemia major (Thal live with diabetes, while 30% may be zinc deficient. The objective of this study was to explore the relationship between zinc status, impaired glucose tolerance and insulin sensitivity in Thal patients. Charts from thirty subjects (16 male, 27.8 ± 9.1 years with Thal were reviewed. Patients with low serum zinc had significantly lower fasting insulin, insulinogenic and oral disposition indexes (all p < 0.05 and elevated glucose response curve, following a standard 75 g oral load of glucose compared to those with normal serum zinc after controlling for baseline (group × time interaction p = 0.048. Longitudinal data in five patients with a decline in serum zinc over a two year follow up period (−19.0 ± 9.6 μg/dL, showed consistent increases in fasting glucose (3.6 ± 3.2 mg/dL and insulin to glucose ratios at 120 min post glucose dose (p = 0.05. Taken together, these data suggest that the frequently present zinc deficiency in Thal patients is associated with decreased insulin secretion and reduced glucose disposal. Future zinc trials will require modeling of oral glucose tolerance test data and not simply measurement of static indices in order to understand the complexities of pancreatic function in the Thal patient.

Opuntia ficus-indica ingestion stimulates peripheral disposal of oral glucose before and after exercise in healthy men.

Science.gov (United States)

Van Proeyen, Karen; Ramaekers, Monique; Pischel, Ivo; Hespel, Peter

2012-08-01

The purpose of this study was to investigate the effect of Opuntia ficus-indica (OFI) cladode and fruit-skin extract on blood glucose and plasma insulin increments due to high-dose carbohydrate ingestion, before and after exercise. Healthy, physically active men (n = 6; 21.0 ± 1.6 years, 78.1 ± 6.0 kg) participated in a double-blind placebo-controlled crossover study involving 2 experimental sessions. In each session, the subjects successively underwent an oral glucose tolerance test at rest (OGTT(R)), a 30-min cycling bout at ~75% VO(2max), and another OGTT after exercise (OGTT(EX)). They received capsules containing either 1,000 mg OFI or placebo (PL) 30 min before and immediately after the OGTT(R). Blood samples were collected before (t₀) and at 30-min intervals after ingestion of 75 g glucose for determination of blood glucose and serum insulin. In OGTT(EX) an additional 75-g oral glucose bolus was administered at t₆₀. In OGTT(R), OFI administration reduced the area under the glucose curve (AUC(GLUC)) by 26%, mainly due to lower blood glucose levels at t₃₀ and t₆₀ (p blood glucose at t₆₀ was ~10% lower in OFI than in PL, which resulted in a decreased AUC(GLUC) (-37%, p AUC(INS) were not different between OFI and PL. In conclusion, the current study shows that OFI extract can increase plasma insulin and thereby facilitate the clearance of an oral glucose load from the circulation at rest and after endurance exercise in healthy men.

Glucose oxidase probe as a surface-enhanced Raman scattering sensor for glucose.

Science.gov (United States)

Qi, Guohua; Wang, Yi; Zhang, Biying; Sun, Dan; Fu, Cuicui; Xu, Weiqing; Xu, Shuping

2016-10-01

Glucose oxidase (GOx) possessing a Raman-active chromophore (flavin adenine dinucleotide) is used as a signal reporter for constructing a highly specific "turn off" surface-enhanced Raman scattering (SERS) sensor for glucose. This sensing chip is made by the electrostatic assembly of GOx over silver nanoparticle (Ag NP)-functionalized SERS substrate through a positively charged polyelectrolyte linker under the pH of 6.86. To trace glucose in blood serum, owing to the reduced pH value caused by the production of gluconic acid in the GOx-catalyzed oxidation reaction, the bonding force between GOx and polyelectrolyte weakens, making GOx drop off from the sensing chip. As a result, the SERS intensity of GOx on the chip decreases along with the concentration of glucose. This glucose SERS sensor exhibits excellent selectivity based on the specific GOx/glucose catalysis reaction and high sensitivity to 1.0 μM. The linear sensing range is 2.0-14.0 mM, which also meets the requirement on the working range of the human blood glucose detection. Using GOx as a probe shows superiority over other organic probes because GOx almost has no toxicity to the biological system. This sensing mechanism can be applied for intracellular in vivo SERS monitoring of glucose in the future. Graphical abstract Glucose oxidase is used as a Raman signal reporter for constructing a highly specific glucose surface-enhanced Raman scattering (SERS) sensor.

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

Science.gov (United States)

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

2009-01-01

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

Review of human studies investigating the post-prandial blood-glucose lowering ability of oat and barley food products.

Science.gov (United States)

Tosh, S M

2013-04-01

Oat and barley foods have been shown to reduce human glycaemic response, compared to similar wheat foods or a glucose control. The strength of the evidence supporting the hypothesis that the soluble fibre, mixed linkage β-glucan, reduces glycaemic response was evaluated. A search of the literature was conducted to find clinical trials with acute glycaemic response as an end point using oat or barley products. Of the 76 human studies identified, 34 met the inclusion and exclusion criteria. Dose response and ratio of β-glucan to available carbohydrate as predictors of glycaemic response were assessed. Meals provided 0.3-12.1 g oat or barley β-glucan, and reduced glycaemic response by an average of 48 ± 33 mmol · min/l compared to a suitable control. Regression analysis on 119 treatments indicated that change in glycaemic response (expressed as incremental area under the post-prandial blood-glucose curve) was greater for intact grains than for processed foods. For processed foods, glycaemic response was more strongly related to the β-glucan dose alone (r(2)=0.48, Pfoods containing 4 g of β-glucan, the linear model predicted a decrease in glycaemic response of 27 ± 3 mmol · min/l, and 76% of treatments significantly reduced glycaemic response. Thus, intact grains as well as a variety of processed oat and barley foods containing at least 4 g of β-glucan and 30-80 g available carbohydrate can significantly reduce post-prandial blood glucose.

Lower urinary tract symptoms are associated with low levels of serum serotonin, high levels of adiponectin and fasting glucose, and benign prostatic enlargement.

Science.gov (United States)

Haghsheno, Mohammad-Ali; Mellström, Dan; Peeker, Ralph; Hammarsten, Jan; Lorentzon, Mattias; Sundh, Valter; Karlsson, Magnus; Ohlsson, Claes; Damber, Jan-Erik

2015-04-01

The aim of this study was to test whether lower urinary tract symptoms (LUTS) and urinary incontinence are associated with the metabolic syndrome (MetS). The association between LUTS and benign prostatic enlargement (BPE) was also investigated. A cross-sectional, representative risk factor analysis of LUTS, as measured by the International Prostate Symptom Score (IPSS), and urinary incontinence was conducted. Among 950 representative individuals, aged 69-81 years, the association between clinical, anthropometric, endocrine, metabolic and inflammatory factors on the one hand, as both major and minor aspects of MetS, and LUTS and urinary incontinence, on the other hand, was analysed. The prostate gland volume was measured in a subgroup of 155 randomly selected individuals and the association between LUTS and BPE was estimated. No significant association was found between LUTS or urinary incontinence and the major aspects of the MetS. However, in a multivariate analysis, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. Furthermore, in a subgroup of 155 individuals, the prostate gland volume correlated positively with LUTS. The study did not show an association between LUTS or urinary incontinence and the major components of the MetS. However, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. The data confirm the general knowledge that BPE may be one of the causative factors of LUTS.

Lupanine Improves Glucose Homeostasis by Influencing KATP Channels and Insulin Gene Expression

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Mats Wiedemann

2015-10-01

Full Text Available The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight. In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca2+ action potentials. Determination of the current through ATP-dependent K+ channels (KATP channels revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h, the KATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes.

Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging

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Nugent Scott

2016-01-01

Full Text Available Brain energy metabolism in Alzheimer’s disease (AD is characterized mainly by temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a consequence of the disease, i.e. deteriorating neuronal function leading to lower demand for glucose. This review will address deteriorating glucose metabolism as a problem specific to glucose and one that precedes AD. Hence, ketones and medium chain fatty acids (MCFA could be an alternative source of energy for the aging brain that could compensate for low brain glucose uptake. MCFA in the form of dietary medium chain triglycerides (MCT have a long history in clinical nutrition and are widely regarded as safe by government regulatory agencies. The importance of ketones in meeting the high energy and anabolic requirements of the infant brain suggest they may be able to contribute in the same way in the aging brain. Clinical studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive effects on cognition.

Parsing glucose entry into the brain: novel findings obtained with enzyme-based glucose biosensors.

Science.gov (United States)

Kiyatkin, Eugene A; Wakabayashi, Ken T

2015-01-21

Extracellular levels of glucose in brain tissue reflect dynamic balance between its gradient-dependent entry from arterial blood and its use for cellular metabolism. In this work, we present several sets of previously published and unpublished data obtained by using enzyme-based glucose biosensors coupled with constant-potential high-speed amperometry in freely moving rats. First, we consider basic methodological issues related to the reliability of electrochemical measurements of extracellular glucose levels in rats under physiologically relevant conditions. Second, we present data on glucose responses induced in the nucleus accumbens (NAc) by salient environmental stimuli and discuss the relationships between local neuronal activation and rapid glucose entry into brain tissue. Third, by presenting data on changes in NAc glucose induced by intravenous and intragastric glucose delivery, we discuss other mechanisms of glucose entry into the extracellular domain following changes in glucose blood concentrations. Lastly, by showing the pattern of NAc glucose fluctuations during glucose-drinking behavior, we discuss the relationships between "active" and "passive" glucose entry to the brain, its connection to behavior-related metabolic activation, and the possible functional significance of these changes in behavioral regulation. These data provide solid experimental support for the "neuronal" hypothesis of neurovascular coupling, which postulates the critical role of neuronal activity in rapid regulation of vascular tone, local blood flow, and entry of glucose and oxygen to brain tissue to maintain active cellular metabolism.

Effects of turtle oil on insulin sensitivity and glucose metabolism in insulin resistant cell model

International Nuclear Information System (INIS)

Bai Jing; Tian Yaping; Guo Duo

2007-01-01

To evaluate the effects of turtle oil on insulin sensitivity and glucose metabolism in an insulin-resistant (IR) cell model which was established by the way of high concentration of insulin induction with HepG 2 cell in vitro culture. The IR cells were treated by turtle oil, the glucose consumption and 3 H-D-glucose incorporation rate in IR cells were detected by the way of glucose oxidase and 3 H-D-glucose incorporation assay respectively. The state of cell proliferation was tested by MTT method. The results showed that the incorporation rate of 3 H-D-glucose in IR cells was significantly lower than that in the control cells(P 3 H-D-glucose incorporation rate in either IR cells or control cells was increased with the increase of insulin concentration. Moreover, the 3 H-D-glucose incorporation rate of IR cells increased slower than that of control cells. The MTT assay showed that turtle oil can promote the proliferation of IR cell and control cell. The glucose uptake and glucose consumption in IR cell which treated with turtle oil was significantly increase than that in the control cells (P<0.05). Turtle oil can improve the insulin sensitivity and glucose metabolism in the IR cell model. (authors)

Effect of blood glucose level on acute stress response of grass carp Ctenopharyngodon idella.

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Jiang, Danli; Wu, Yubo; Huang, Di; Ren, Xing; Wang, Yan

2017-10-01

Stress has a considerable impact on welfare and productivity of fish, and blood glucose level of fish may be a factor modulating stress response. This study evaluated the effect of blood glucose level and handling on acute stress response of grass carp Ctenopharyngodon idella. Fish were intraperitoneally injected with glucose at 0, 0.2, 0.5, and 1.0 mg g -1 body mass (BM) and then were exposed to handling for 5 min. Glucose injection resulted in increase of plasma glucose level and liver glycogen content and decrease of plasma lactate level. Handling resulted in increase of plasma levels of cortisol, glucose, and lactate and plasma lactic dehydrogenase (LDH) activity and decrease of liver glycogen content. At 1 h post-stress, the plasma cortisol level was lower in the stressed fish injected with glucose at 0.5 mg g -1 BM than the stressed fish injected with glucose at 0, 0.2, and 1.0 mg g -1 BM. No significant differences were found in the activities of phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate kinase (PK) in the liver between the stressed and unstressed fish, regardless of the dose of glucose injection. At 1 h post-stress, the liver glucose-6-phosphatase (G6Pase) activity was higher in the fish without glucose injection than in the fish injected with glucose. This study reveals that blood glucose level can affect stress response of grass carp by modulating cortisol release and glucose homeostasis through glycogen metabolism and gluconeogenesis in the liver.

Effect of consumption of micronutrient enriched wheat steamed bread on postprandial plasma glucose in healthy and type 2 diabetic subjects.

Science.gov (United States)

Su-Que, Lan; Ya-Ning, Meng; Xing-Pu, Li; Ye-Lun, Zhang; Guang-Yao, Song; Hui-Juan, Ma

2013-05-17

Steamed wheat bread have previously been shown to induce comparatively high postprandial plasma glucose responses, on the contrary, buckwheat products induced lower postprandial plasma glucose. The present study was to assess the effects of micronutrient enriched bread wheat variety Jizi439 and buckwheat on postprandial plasma glucose in healthy and diabetic subjects comparing with buckwheat and other bread wheat varieties. Two experiments were conducted to study the effects of bread wheat variety Jizi439 on the postprandial plasma glucose levels of the randomly selected subjects. The first experiment involved three types of steamed bread with equivalent of 50 g available carbohydrate fed to 10 normal weight young healthy subjects. Two types of steamed bread were made from two purple-grain bread wheat varieties, Jizi439 and Chu20, respectively, and the third type was made from the mixture of different white grain wheat varieties. Plasma glucose levels of each subject were measured at 15, 30, 45, 60, 120 min after eating. Glucose was used as a reference, the total area under curve (AUC) and glycemic index (GI) was calculated for test meal. The second experiment was performed among ten type 2 diabetics who were served equivalent of 50 g available carbohydrate of steamed bread made from Jizi 439, the mixture of white grain bread wheat and buckwheat, respectively. The plasma glucose increment was determined two hours thereafter. In the first experiment, consumption of the steamed bread made from Jizi439 resulted in the least increase in plasma glucose and the GI was significantly lower than that of Chu20 and the mixture. In the second experiment, the average of postprandial 2 h plasma glucose increment of Jizi439 was 2.46 mmol/L which was significantly lower than that of the mixture of white wheat but was not significantly different from buckwheat. The results indicated that consumption of Jizi439 steamed bread resulted in significantly lower plasma glucose in

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

OpenAIRE

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

2009-01-01

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

Glucose-dependent Insulinotropic Polypeptide

DEFF Research Database (Denmark)

Christensen, Mikkel B; Calanna, Salvatore; Holst, Jens Juul

2014-01-01

CONTEXT: Patients with type 2 diabetes mellitus (T2DM) have clinically relevant disturbances in the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP). OBJECTIVE: We aimed to evaluate the importance of the prevailing plasma glucose levels for the effect of GIP on responses......: During fasting glycemia (plasma glucose ∼8 mmol/L), GIP elicited significant increments in both insulin and glucagon levels, resulting in neutral effects on plasma glucose. During insulin-induced hypoglycemia (plasma glucose ∼3 mmol/L), GIP elicited a minor early-phase insulin response and increased...... 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 glucose ∼12 mmol/L), GIP augmented insulin secretion throughout the clamp, with slightly less glucagon...

Epithelial structure and function in the hen lower intestine

DEFF Research Database (Denmark)

Laverty, G.; Elbrønd, Vibeke Sødring; Árnason, Sigvatur S.

2006-01-01

In birds, transport processes in the lower intestine mediate absorption of ions, water and a variety of organic substrates, including significant amounts of glucose, amino acids derived from protein associated with urate spheres, and short-chain fatty acids derived from fermentation processes...

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

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Mie Tonoike

2016-01-01

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

Prevalence of Non-responders for Glucose Control Markers after 10 Weeks of High-Intensity Interval Training in Adult Women with Higher and Lower Insulin Resistance

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Cristian Álvarez

2017-07-01

Full Text Available Background: Exercise training improves performance and biochemical parameters on average, but wide interindividual variability exists, with individuals classified as responders (R or non-responders (NRs, especially between populations with higher or lower levels of insulin resistance. This study assessed the effects of high-intensity interval training (HIIT and the prevalence of NRs in adult women with higher and lower levels of insulin resistance.Methods: Forty adult women were assigned to a HIIT program, and after training were analyzed in two groups; a group with higher insulin resistance (H-IR, 40 ± 6 years; BMI: 29.5 ± 3.7 kg/m2; n = 20 and a group with lower insulin resistance (L-IR, 35 ± 9 years; 27.8 ± 2.8 kg/m2; n = 20. Anthropometric, cardiovascular, metabolic, and performance variables were measured at baseline and after 10 weeks of training.Results: There were significant training-induced changes [delta percent (Δ%] in fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR scores in the H-IR group (−8.8, −26.5, −32.1%, p < 0.0001, whereas no significant changes were observed in the L-IR. Both groups showed significant pre-post changes in other anthropometric variables [waist circumference (−5.2, p < 0.010, and −3.8%, p = 0.046 and tricipital (−13.3, p < 0.010, and −13.6%, p < 0.0001, supra-iliac (−19.4, p < 0.0001, and −13.6%, p < 0.0001, and abdominal (−18.2, p < 0.0001, and −15.6%, p < 0.010 skinfold measurements]. Systolic blood pressure decreased significantly only in the L-IR group (−3.2%, p < 0.010. Both groups showed significant increases in 1RMLE (+12.9, p < 0.010, and +14.7%, p = 0.045. There were significant differences in the prevalence of NRs between the H-IR and L-IR groups for fasting glucose (25 vs. 95%, p < 0.0001 and fasting insulin (p = 0.025 but not for HOMA-IR (25 vs. 45%, p = 0.185.Conclusion: Independent of the “magnitude” of the

Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice

International Nuclear Information System (INIS)

Kang, Seong-Il; Jin, Young-Jun; Ko, Hee-Chul; Choi, Soo-Youn; Hwang, Joon-Ho; Whang, Ilson; Kim, Moo-Han; Shin, Hye-Sun; Jeong, Hyung-Bok; Kim, Se-Jae

2008-01-01

The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor γ (PPARγ) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPARγ luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes

Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

International Nuclear Information System (INIS)

Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

2012-01-01

Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver. �

Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D., E-mail: cklaasse@kumc.edu

2012-11-01

Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver. �

Ratiometric glucose sensing based on fluorescent oxygen films and glucose oxidase

OpenAIRE

Fengyu Su; Liqiang Zhang; Xiangxing Kong; Fred Lee; Yanqing Tian; Deirdre R. Meldrum

2017-01-01

A new two-layer sensor film was constructed for sensing glucose based on glucose oxidase and oxygen sensing material. The first layer of film containing the oxygen sensor and intra-reference material was polymerized, then the second layer of glucose oxidase and glutaraldehyde was formed on the oxygen sensor layer. The two-layer sensor film has a resolution up to 0.05 mM and a detection range from 0 to 5 mM to glucose. The effects of pH and temperature on the sensing performance were systemati...

Sex steroids and glucose metabolism

Directory of Open Access Journals (Sweden)

Carolyn A Allan

2014-04-01

Full Text Available Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus (T2DM and also predict the onset of these adverse metabolic states. Body composition (body mass index, waist circumference is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter's syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.

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

International Nuclear Information System (INIS)

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

1982-01-01

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

Electrocatalytic glucose sensor

Energy Technology Data Exchange (ETDEWEB)

Gebhardt, U; Luft, G; Mund, K; Preidel, W; Richter, G J

1983-01-01

An artificial pancreas consists of an insulin depot, a dosage unit and a glucose sensor. The measurement of the actual glucose concentration in blood is still an unsolved problem. Two methods are described for an electrocatalytic glucose sensor. Under the interfering action of amino acids and urea in-vitro measurements show an error of between 10% and 20%.

Effects of MDMA on blood glucose levels and brain glucose metabolism

Energy Technology Data Exchange (ETDEWEB)

Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M. [Hospital General Universitario Gregorio Maranon, Laboratorio de Imagen, Medicina Experimental, Madrid (Spain); Arango, C. [Hospital General Gregorio Maranon, Departamento de Psiquiatria, Madrid (Spain); Ricaurte, G. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States)

2007-06-15

This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

Effects of MDMA on blood glucose levels and brain glucose metabolism

International Nuclear Information System (INIS)

Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M.; Arango, C.; Ricaurte, G.

2007-01-01

This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

A Paleolithic diet confers higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet in domestic pigs

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Ugander Martin

2006-11-01

Full Text Available Abstract Background A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2 diabetes, obesity and cardiovascular disease. The aim of this study was to experimentally study the long-term effect of a Paleolithic diet on risk factors for these diseases in domestic pigs. We examined glucose tolerance, post-challenge insulin response, plasma C-reactive protein and blood pressure after 15 months on Paleolithic diet in comparison with a cereal based swine feed. Methods Upon weaning twenty-four piglets were randomly allocated either to cereal based swine feed (Cereal group or cereal free Paleolithic diet consisting of vegetables, fruit, meat and a small amount of tubers (Paleolithic group. At 17 months of age an intravenous glucose tolerance test was performed and pancreas specimens were collected for immunohistochemistry. Group comparisons of continuous variables were made by use of the t-test. P Results At the end of the study the Paleolithic group weighed 22% less and had 43% lower subcutaneous fat thickness at mid sternum. No significant difference was seen in fasting glucose between groups. Dynamic insulin sensitivity was significantly higher (p = 0.004 and the insulin response was significantly lower in the Paleolithic group (p = 0.001. The geometric mean of C-reactive protein was 82% lower (p = 0.0007 and intra-arterial diastolic blood pressure was 13% lower in the Paleolithic group (p = 0.007. In evaluations of multivariate correlations, diet emerged as the strongest explanatory variable for the variations in dynamic insulin sensitivity, insulin response, C-reactive protein and diastolic blood pressure when compared to other relevant variables such as weight and subcutaneous fat thickness at mid sternum. There was no obvious immunohistochemical difference in pancreatic islets

Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): Crossover pilot study (J-VICTORIA study)

Science.gov (United States)

2012-01-01

Background No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters. Methods Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin. Conclusions CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and

Glucose-dependent insulinotropic polypeptide

DEFF Research Database (Denmark)

Christensen, Mikkel Bring

2016-01-01

was to investigate how the blood glucose level affects the glucagon and insulin responses to GIP in healthy subjects (Study 1) and patients with Type 2 diabetes (Study 2), and more specifically to investigate the effects of GIP and GLP-1 at low blood glucose in patients with Type 1 diabetes without endogenous...... as his own control. Interventions were intravenous administration of hormones GIP, GLP-1 and placebo (saline) during different blood glucose levels maintained (clamped) at a certain level. The end-points were plasma concentrations of glucagon and insulin as well as the amount of glucose used to clamp...... the blood glucose levels. In Study 3, we also used stable glucose isotopes to estimate the endogenous glucose production and assessed symptoms and cognitive function during hypoglycaemia. The results from the three studies indicate that GIP has effects on insulin and glucagon responses highly dependent upon...

Lifestyle, glucose regulation and the cognitive effects of glucose load in middle-aged adults.

Science.gov (United States)

Riby, Leigh M; McLaughlin, Jennifer; Riby, Deborah M; Graham, Cheryl

2008-11-01

Interventions aimed at improving glucose regulatory mechanisms have been suggested as a possible source of cognitive enhancement in the elderly. In particular, previous research has identified episodic memory as a target for facilitation after either moderate increases in glycaemia (after a glucose drink) or after improvements in glucose regulation. The present study aimed to extend this research by examining the joint effects of glucose ingestion and glucose regulation on cognition. In addition, risk factors associated with the development of poor glucose regulation in middle-aged adults were considered. In a repeated measures design, thirty-three middle-aged adults (aged 35-55 years) performed a battery of memory and non-memory tasks after either 25 g or 50 g glucose or a sweetness matched placebo drink. To assess the impact of individual differences in glucose regulation, blood glucose measurements were taken on four occasions during testing. A lifestyle and diet questionnaire was also administered. Consistent with previous research, episodic memory ability benefited from glucose ingestion when task demands were high. Blood glucose concentration was also found to predict performance across a number of cognitive domains. Interestingly, the risk factors associated with poor glucose regulation were linked to dietary impacts traditionally associated with poor health, e.g. the consumption of high-sugar sweets and drinks. The research replicates earlier work suggesting that task demands are critical to the glucose facilitation effect. Importantly, the data demonstrate clear associations between elevated glycaemia and relatively poor cognitive performance, which may be partly due to the effect of dietary and lifestyle factors.

Application of the Oral Minimal Model to Korean Subjects with Normal Glucose Tolerance and Type 2 Diabetes Mellitus

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Min Hyuk Lim

2016-06-01

Full Text Available BackgroundThe oral minimal model is a simple, useful tool for the assessment of β-cell function and insulin sensitivity across the spectrum of glucose tolerance, including normal glucose tolerance (NGT, prediabetes, and type 2 diabetes mellitus (T2DM in humans.MethodsPlasma glucose, insulin, and C-peptide levels were measured during a 180-minute, 75-g oral glucose tolerance test in 24 Korean subjects with NGT (n=10 and T2DM (n=14. The parameters in the computational model were estimated, and the indexes for insulin sensitivity and β-cell function were compared between the NGT and T2DM groups.ResultsThe insulin sensitivity index was lower in the T2DM group than the NGT group. The basal index of β-cell responsivity, basal hepatic insulin extraction ratio, and post-glucose challenge hepatic insulin extraction ratio were not different between the NGT and T2DM groups. The dynamic, static, and total β-cell responsivity indexes were significantly lower in the T2DM group than the NGT group. The dynamic, static, and total disposition indexes were also significantly lower in the T2DM group than the NGT group.ConclusionThe oral minimal model can be reproducibly applied to evaluate β-cell function and insulin sensitivity in Koreans.

CMOS image sensor-based implantable glucose sensor using glucose-responsive fluorescent hydrogel.

Science.gov (United States)

Tokuda, Takashi; Takahashi, Masayuki; Uejima, Kazuhiro; Masuda, Keita; Kawamura, Toshikazu; Ohta, Yasumi; Motoyama, Mayumi; Noda, Toshihiko; Sasagawa, Kiyotaka; Okitsu, Teru; Takeuchi, Shoji; Ohta, Jun

2014-11-01

A CMOS image sensor-based implantable glucose sensor based on an optical-sensing scheme is proposed and experimentally verified. A glucose-responsive fluorescent hydrogel is used as the mediator in the measurement scheme. The wired implantable glucose sensor was realized by integrating a CMOS image sensor, hydrogel, UV light emitting diodes, and an optical filter on a flexible polyimide substrate. Feasibility of the glucose sensor was verified by both in vitro and in vivo experiments.

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

OpenAIRE

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

2014-01-01

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

The performance of flash glucose monitoring in critically ill patients with diabetes.

Science.gov (United States)

Ancona, Paolo; Eastwood, Glenn M; Lucchetta, Luca; Ekinci, Elif I; Bellomo, Rinaldo; Mårtensson, Johan

2017-06-01

Frequent glucose monitoring may improve glycaemic control in critically ill patients with diabetes. We aimed to assess the accuracy of a novel subcutaneous flash glucose monitor (FreeStyle Libre [Abbott Diabetes Care]) in these patients. We applied the FreeStyle Libre sensor to the upper arm of eight patients with diabetes in the intensive care unit and obtained hourly flash glucose measurements. Duplicate recordings were obtained to assess test-retest reliability. The reference glucose level was measured in arterial or capillary blood. We determined numerical accuracy using Bland- Altman methods, the mean absolute relative difference (MARD) and whether the International Organization for Standardization (ISO) and Clinical and Laboratory Standards Institute Point of Care Testing (CLSI POCT) criteria were met. Clarke error grid (CEG) and surveillance error grid (SEG) analyses were used to determine clinical accuracy. We compared 484 duplicate flash glucose measurements and observed a Pearson correlation coefficient of 0.97 and a coefficient of repeatability of 1.6 mmol/L. We studied 185 flash readings paired with arterial glucose levels, and 89 paired with capillary glucose levels. Using the arterial glucose level as the reference, we found a mean bias of 1.4 mmol/L (limits of agreement, -1.7 to 4.5 mmol/L). The MARD was 14% (95% CI, 12%-16%) and the proportion of measurements meeting ISO and CLSI POCT criteria was 64.3% and 56.8%, respectively. The proportions of values within a low-risk zone on CEG and SEG analyses were 97.8% and 99.5%, respectively. Using capillary glucose levels as the reference, we found that numerical and clinical accuracy were lower. The subcutaneous FreeStyle Libre blood glucose measurement system showed high test-retest reliability and acceptable accuracy when compared with arterial blood glucose measurement in critically ill patients with diabetes.

Correlation between blood glucose levels and salivary glucose levels with oral ulcer in diabetic patients

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Fildzah Rahman

2016-06-01

Full Text Available Diabetes Mellitus (DM is a syndrome in metabolism of carbohydrates which indicated by the increased level of blood glucose and also may increase salivary glucose levels. Oral ulcer has been frequently recognized in diabetic patients, which can be due to increased glucose in oral fluids and immune dysfunction. This study aimed to determine the correlation of blood glucose levels and salivary glucose levels with oral ulcer in diabetic patients. Analytic observational study was carried out through the determination of blood glucose levels just by way of strip using a glucometer and salivary glucose levels with the method "GOD-PAP test enzymatic colorimetric". Oral ulcer was determined in presenting ulcer on 30 patients with DM. The results showed r = 0.228, which is higher salivary glucose levels followed by high levels of blood glucose, and intraoral examination of oral ulcer found in the whole sample and the most location commonly found in buccal mucosa and lingual. It was concluded that there is a correlation between blood glucose levels and salivary glucose levels, and glucose levels affect the occurrence of oral ulcer in patients with DM

The Glucose-Insulin Control System

DEFF Research Database (Denmark)

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

2008-01-01

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

Underestimation of glucose turnover corrected with high-performance liquid chromatography purification of [6-3H]glucose

International Nuclear Information System (INIS)

Schwenk, W.F.; Butler, P.C.; Haymond, M.W.; Rizza, R.A.

1990-01-01

We have recently reported that during infusion of commercially available [6-3H]glucose, a radioactive nonglucose contaminant may accumulate in plasma causing errors in the measurement of glucose turnover. To determine whether purification of this tracer by HPLC (high-performance liquid chromatography) before infusion would eliminate the contaminant in plasma and remove the underestimation of glucose turnover reported during hyperinsulinemia, four normal subjects each underwent two 5-h euglycemic clamps during infusion of insulin (1 mU.kg-1.min-1). Glucose turnover was measured with either commercially available [6-3H]glucose or with HPLC-purified [6-3H]glucose. HPLC analysis of samples from the clamps done with commercially available [6-3H]glucose showed that 9.7% of the infused tracer and 26% of the plasma glucose 3H radioactivity were contaminants. In contrast, no contaminant was observed in the plasma during infusion of HPLC-purified [6-3H]glucose. During the last hour of the clamp, mean glucose turnover using commercially available [6-3H]glucose was less (P less than 0.01) than the mean glucose infusion rate (7.6 +/- 0.3 vs. 10.5 +/- 0.3 mg.kg-1.min-1) yielding apparent negative (P less than 0.001) hepatic glucose release. In contrast, when HPLC-purified [6-3H]glucose was employed, glucose turnover equaled the glucose infusion rate (10.4 +/- 0.9 vs. 10.2 +/- 0.9 mg.kg-1.min-1) and hepatic glucose release was no longer negative. We conclude that removal of a tritiated nonglucose contaminant in [6-3H]glucose by HPLC yields correct estimations of glucose turnover at steady state

Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk

DEFF Research Database (Denmark)

Hulman, Adam; Simmons, Rebecca Kate; Vistisen, Dorte

2017-01-01

patterns of plasma glucose change during the oral glucose tolerance test. Cardiometabolic risk factor profiles were compared between the identified groups. Using latent class trajectory analysis, five glucose response curves were identified. Despite similar fasting and 2-h values, glucose peaks and peak......We aimed to examine heterogeneity in glucose response curves during an oral glucose tolerance test with multiple measurements and to compare cardiometabolic risk profiles between identified glucose response curve groups. We analyzed data from 1,267 individuals without diabetes from five studies...... in Denmark, the Netherlands and the USA. Each study included between 5 and 11 measurements at different time points during a 2-h oral glucose tolerance test, resulting in 9,602 plasma glucose measurements. Latent class trajectories with a cubic specification for time were fitted to identify different...

Coupling of glucose deprivation with impaired histone H2B monoubiquitination in tumors.

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Yasuyo Urasaki

Full Text Available Metabolic reprogramming is associated with tumorigenesis. However, glucose metabolism in tumors is poorly understood. Here, we report that glucose levels are significantly lower in bulk tumor specimens than those in normal tissues of the same tissue origins. We show that mono-ubiquitinated histone H2B (uH2B is a semi-quantitative histone marker for glucose. We further show that loss of uH2B occurs specifically in cancer cells from a wide array of tumor specimens of breast, colon, lung and additional 23 anatomic sites. In contrast, uH2B levels remain high in stromal tissues or non-cancerous cells in the tumor specimens. Taken together, our data suggest that glucose deficiency and loss of uH2B are novel properties of cancer cells in vivo, which may represent important regulatory mechanisms of tumorigenesis.

Continuous glucose monitoring microsensor with a nanoscale conducting matrix and redox mediator

Science.gov (United States)

Pesantez, Daniel

vitro testing for glucose shows increasing current with increasing analyte concentration. Testing the glucose microsensor with known concentrations of glucose over a period of 48 hours demonstrated both the potential durability and sensitivity of the device. Unknown/blind in vitro glucose experiments showed the reproducibility and accuracy of the microsensor to detect various glucose levels. Thinner polymer matrix films lead to better sensing performance during in vitro tests (0.6nA/mM lower limit sensitivity and 0.2nA/mM upper limit sensitivity). In vitro experiments using electroactive ascorbic acid (AA) and uric acid (UA) showed the selectivity of the sensor for glucose. In an effort to reduce the sensor's oxidation potential (0.7V) and noise, a second generation electron transfer approach was developed by incorporating into a modified Platinum WE with a nanoscale PPy and GOx matrix, a redox mediator. Ferrocene (Fc) was selected as the artificial electron carrier, substituting molecular oxygen in the enzymatic reaction. The incorporation of Fc into the polymer matrix is done by a simple electrochemical synthesis. Modifications in the microsensor design, materials and fabrication process are presented. Experiments with the new sensor generation resulted in higher sensitivity values (22.8nA/mM lower limit sensitivity and 12.5nA/mM upper limit sensitivity) for glucose and noise was further eliminated by operating the sensor at a lower oxidation potential (0.3V). The final experimental work consisted of preliminary ex vivo tests with the MetaSense microdevice on bovine kidney samples, which showed a qualitatively correlation between glucose consumption trend profile during preservation and viability histology outcome.

Sleep/wake dependent changes in cortical glucose concentrations.

Science.gov (United States)

Dash, Michael B; Bellesi, Michele; Tononi, Giulio; Cirelli, Chiara

2013-01-01

Most of the energy in the brain comes from glucose and supports glutamatergic activity. The firing rate of cortical glutamatergic neurons, as well as cortical extracellular glutamate levels, increase with time spent awake and decline throughout non rapid eye movement sleep, raising the question whether glucose levels reflect behavioral state and sleep/wake history. Here chronic (2-3 days) electroencephalographic recordings in the rat cerebral cortex were coupled with fixed-potential amperometry to monitor the extracellular concentration of glucose ([gluc]) on a second-by-second basis across the spontaneous sleep-wake cycle and in response to 3 h of sleep deprivation. [Gluc] progressively increased during non rapid eye movement sleep and declined during rapid eye movement sleep, while during wake an early decline in [gluc] was followed by an increase 8-15 min after awakening. There was a significant time of day effect during the dark phase, when rats are mostly awake, with [gluc] being significantly lower during the last 3-4 h of the night relative to the first 3-4 h. Moreover, the duration of the early phase of [gluc] decline during wake was longer after prolonged wake than after consolidated sleep. Thus, the sleep/wake history may affect the levels of glucose available to the brain upon awakening. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

[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.

Rational use of blood glucose test strips for self-monitoring in patients with diabetes mellitus: Economic impact in the Portuguese healthcare system.

Science.gov (United States)

Risso, Teresa; Furtado, Cláudia

2017-12-01

Self-monitoring of blood glucose is important for diabetes management in insulin-treated patients, but its effectiveness in patients treated with oral glucose lowering drugs only is not fully supported by current evidence. This paper aims to characterise the prescription patterns of blood glucose test strips (BGTS) in Portugal and estimate the potential cost-savings from the rational use of BGTS. A retrospective analysis of the Portuguese database of electronic medical prescriptions to assess the patterns of BGTS prescription. The database was searched for prescription, from 01 January 2016 to 31 December 2016, of insulin and other antidiabetics, as well as the associated prescriptions of BGTS. 894,637 patients were prescribed antidiabetic medicines during 2016, 82.7% of which were prescribed oral glucose lowering drugs only. BGTS were prescribed to 456,179 patients, being more frequently prescribed in insulin-treated patients. Still, 42.8% of patients treated with oral glucose lowering drugs only were also prescribed BGTS, with large proportion of those being prescribed antidiabetic drugs with lower risk of causing hypoglycaemia and, even so, >200 BGTS/year. Several scenarios for a more rational use of BGTS were estimated to result in cost-savings of up to €9.5 million per year. BGTS were prescribed to more than a third of patients treated with oral glucose lowering drugs only, despite accumulating evidence of their limited effectiveness in this population, resulting in substantial economic burden to the healthcare system. Given the estimated potential cost-savings, rational use of BGTS should be encouraged in Portugal. Copyright © 2017 Elsevier B.V. All rights reserved.

Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance.

Science.gov (United States)

Yang, Sae Jeong; Kim, Tae Nyun; Baik, Sei Hyun; Kim, Tae Sun; Lee, Kwan Woo; Nam, Moonsuk; Park, Yong Soo; Woo, Jeong-Teak; Kim, Young Seol; Kim, Sung-Hoon

2013-05-01

The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose ≥ 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index β-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p ≤ 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p insulin secretion status than the 3-hour abnormal levels group. Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both β-cell dysfunction and insulin resistance.

Аbоut a theoretical yield of glucose from starch

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V. V. Ananskikh

2016-01-01

Full Text Available Starch is the raw materials for production of crystal food glucose. With at enzyme conversion of the high purity starch, it is possible to receive glucosic syrups of a glucose equivalent (GE 98%, where there is about 95% glucose and maltose and maltotriose – of about 5%. Starch hydrolysis is carried out with a gain of solids. Thus, 100 kg of amylum is possible to give up to 109.81 kg of glucose syrup on dry basis. Taking in account the losses at manufacture steps a yield can decrease to 105.61 kg. The purified glucose syrup is concentrated up to 73–75% of dry matters and goes to a crystallization step. Crystallization of glucose is carried out in a supersaturated solution within 56–70 hours at reduced temperature from 46–48 °C to 24–26 °C, resulting a mixture of glucose crystals and an intercrystal run-off syrup called a massecuite. The crystallization process is stopped when a 50% of crystals content in massecuite is reached. At the same time glucose yield will be 105.61/2 = 52.8%. Crystallization is carried out according to the single-stage scheme, with partial return of the end product – hydrol into the hydrolised syrup. Then the massecuite is sent to a centrifugation step for dividing glucose crystals and a run-off syrup, which is partially returned to the initial syrup to reduce in GE. The second part of the run-off syrup goes to realization. It must be kept in mind: the higher GE of the glucose syrup sent to a crystallization step, the more quantity of a hydrol is possible to be returned to hydrolysed syrup. Therefore, it is in a resulted a higher yield of glucose crystals. On the basis of the carried-out calculations the computer program was made with which it is possible to define a theoretical glucose and a hydrol yield, while changing values of a hydrolysed syrup. The higher GE values of a hydrolysed syrup are the higher yield of crystal glucose and the lower one of hydrol are. So, at 98% GE of a hydrolysed syrup it is

The effects of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes

DEFF Research Database (Denmark)

Storgaard, Heidi; Gluud, Lise Lotte; Christensen, Mikkel

2014-01-01

INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) increase urinary glucose excretion through a reduced renal glucose reabsorption. We plan to perform a systematic review of SGLT-2i for treatment of type 2 diabetes. METHODS AND ANALYSIS: A systematic review with meta-analyses of r......INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) increase urinary glucose excretion through a reduced renal glucose reabsorption. We plan to perform a systematic review of SGLT-2i for treatment of type 2 diabetes. METHODS AND ANALYSIS: A systematic review with meta......-analyses of randomised clinical trials on SGLT-2i versus placebo, other oral glucose lowering drugs or insulin for patients with type 2 diabetes will be performed. The primary end point will be the glycated haemoglobin. Secondary end points will include changes in body weight, body mass index, fasting plasma glucose......, plasma cholesterol, kidney and liver blood tests, blood pressure and adverse events. Electronic (the Cochrane Library, MEDLINE, EMBASE and the Science Citation Index) and manual searches will be performed. Meta-analyses will be performed and the results presented as mean differences for continuous...

Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition.

Science.gov (United States)

Vallon, Volker; Thomson, Scott C

2017-02-01

Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule. In the absence or with inhibition of SGLT2, the renal reabsorptive capacity for glucose declines to ∼80 g/day (the residual capacity of SGLT1), i.e. the safety valve opens at a lower threshold, which makes it relevant to glucose homeostasis from day-to-day. Several SGLT2 inhibitors are now approved glucose lowering agents for individuals with type 2 diabetes and preserved kidney function. By inducing glucosuria, these drugs improve glycaemic control in all stages of type 2 diabetes, while their risk of causing hypoglycaemia is low because they naturally stop working when the filtered glucose load falls below ∼80 g/day and they do not otherwise interfere with metabolic counterregulation. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. Because SGLT2 reabsorbs sodium along with glucose, SGLT2 blockers are natriuretic and antihypertensive. Also, because they work in the proximal tubule, SGLT2 inhibitors increase delivery of fluid and electrolytes to the macula densa, thereby activating tubuloglomerular feedback and increasing tubular back pressure. This mitigates glomerular hyperfiltration, reduces the kidney's demand for oxygen and lessens albuminuria. For reasons that are less well understood, SGLT2 inhibitors are

A systematic literature review on the efficacy–effectiveness gap: comparison of randomized controlled trials and observational studies of glucose-lowering drugs

Directory of Open Access Journals (Sweden)

Ankarfeldt MZ

2017-01-01

Full Text Available Mikkel Z Ankarfeldt,1,2 Erpur Adalsteinsson,1 Rolf HH Groenwold,2,3 M Sanni Ali,2,3,4 Olaf H Klungel,2,3 On behalf of GetReal Work Package 2 1Novo Nordisk A/S, 2Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, the Netherlands; 4Nuffield Department of Orthopaedics, Rheumatology, Musculoskeletal Sciences, University of Oxford, Oxford, UK Aim: To identify a potential efficacy–effectiveness gap and possible explanations (drivers of effectiveness for differences between results of randomized controlled trials (RCTs and observational studies investigating glucose-lowering drugs. Methods: A systematic literature review was conducted in English language articles published between 1 January, 2000 and 31 January, 2015 describing either RCTs or observational studies comparing glucagon-like peptide-1 analogs (GLP-1 with insulin or comparing dipeptidyl peptidase-4 inhibitors (DPP-4i with sulfonylurea, all with change in glycated hemoglobin (HbA1c as outcome. Medline, Embase, Current Content, and Biosis were searched. Information on effect estimates, baseline characteristics of the study population, publication year, study duration, and number of patients, and for observational studies, characteristics related to confounding adjustment and selection- and information bias were extracted. Results: From 312 hits, 11 RCTs and 7 observational studies comparing GLP-1 with insulin, and from 474 hits, 16 RCTs and 4 observational studies comparing DPP-4i with sulfonylurea were finally included. No differences were observed in baseline characteristics of the study populations (age, sex, body mass index, time since diagnosis of type 2 diabetes mellitus, and HbA1c or effect sizes across study designs. Mean effect sizes ranged from −0.43 to 0.91 and from −0.80 to 1.13 in RCTs and

Reference intervals for glucose, beta-cell polypeptides and counterregulatory factors during prolonged fasting

DEFF Research Database (Denmark)

Højlund, Kurt; Wildner-Christensen, M; Eshøj, O

2001-01-01

To establish reference intervals for the pancreatic beta-cell response and the counterregulatory hormone response to prolonged fasting, we studied 33 healthy subjects (16 males, 17 females) during a 72-h fast. Glucose, insulin, C-peptide, and proinsulin levels decreased (P ... of counterregulatory factors increased during the fast [P fasting (P ... decreased from the second to third day of fasting (P = 0.03). Males had higher glucose and glucagon levels and lower FFA levels during the fast (P

EFFECTS OF GLUCOSE-INFUSION ON HORMONE-SECRETION AND HEPATIC GLUCOSE-PRODUCTION DURING HEAVY EXERCISE

NARCIS (Netherlands)

WIERSMA, MML; VISSING, J; STEFFENS, AB; GALBO, H

1993-01-01

Blood-borne metabolic feedback vs. neural feedforward regulation of glucose homeostasis during exercise was investigated by infusing glucose and [H-3]glucose for glucose appearance determination intravenously in rats running for 20 min at 28 m/min [almost-equal-to 85% of maximal 02 consumption

Effects of glucose on the formation of PhIP in a model system.

Science.gov (United States)

Skog, K; Jägerstad, M

1991-12-01

The effect of glucose on the formation of the food mutagen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) was studied in a model system. When a mixture of creatine (0.9 mmol), phenylalanine (0.9 mmol) and glucose (0.45 mmol) was heated in diethylene glycol and water (3 ml, 5:1) for 10 min at 180 or 225 degrees C several mutagens were produced. Identification by HPLC, UV absorption spectroscopy and mass spectrometry revealed the presence of PhIP as well as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and minor amounts of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline. Heating the system without glucose produced PhIP as a single mutagen, but in considerably lower amount. An inhibiting effect of glucose in high concentrations was demonstrated. When glucose was added in more than or equimolar amounts of the other two reactants, the formation of mutagens was markedly reduced. Tyrosine heated under the same conditions, with creatine and glucose, showed mutagenic activity. However, no PhIP nor any other known food mutagen was identified from the tyrosine mixture.

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

Science.gov (United States)

Li, Weiping; Li, Qifu

2012-01-01

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

Engineering glucose oxidase to minimize the influence of oxygen on sensor response

International Nuclear Information System (INIS)

Horaguchi, Yohei; Saito, Shoko; Kojima, Katsuhiro; Tsugawa, Wakako; Ferri, Stefano; Sode, Koji

2014-01-01

Glucose oxidase (GOx) is an important industrial enzyme and is recognized as the gold standard for monitoring blood glucose. However, due to its inherent oxidase property, the presence of oxygen affects electrochemical measurements of venous blood glucose employing artificial electron mediators. We therefore attempted to engineer Penicillium amagasakiense-derived GOx into a dehydrogenase by focusing on the amino acid residues predicted to interact with oxygen. Our rational amino acid substitution approach resulted in the construction of the Ser114Ala/Phe355Leu mutant, which has an 11-fold decrease in oxidase activity and 2.8-fold increase in dehydrogenase activity compared with wild-type GOx. As a result, the dehydrogenase/oxidase activity ratio of the engineered enzyme was 32-fold greater than that of the wild-type enzyme. The enzyme sensor constructed with Ser114Ala/Phe355Leu was considerably less affected by oxygen than the wild-type GOx-based sensor at lower glucose concentrations

Design of Cyclic Peptide Based Glucose Receptors and Their Application in Glucose Sensing.

Science.gov (United States)

Li, Chao; Chen, Xin; Zhang, Fuyuan; He, Xingxing; Fang, Guozhen; Liu, Jifeng; Wang, Shuo

2017-10-03

Glucose assay is of great scientific significance in clinical diagnostics and bioprocess monitoring, and to design a new glucose receptor is necessary for the development of more sensitive, selective, and robust glucose detection techniques. Herein, a series of cyclic peptide (CP) glucose receptors were designed to mimic the binding sites of glucose binding protein (GBP), and CPs' sequence contained amino acid sites Asp, Asn, His, Asp, and Arg, which constituted the first layer interactions of GBP. The properties of these CPs used as a glucose receptor or substitute for the GBP were studied by using a quartz crystal microbalance (QCM) technique. It was found that CPs can form a self-assembled monolayer at the Au quartz electrode surface, and the monolayer's properties were characterized by using cyclic voltammetry, electrochemical impedance spectroscopy, and atomic force microscopy. The CPs' binding affinity to saccharide (i.e., galactose, fructose, lactose, sucrose, and maltose) was investigated, and the CPs' sensitivity and selectivity toward glucose were found to be dependent upon the configuration,i.e., the amino acids sequence of the CPs. The cyclic unit with a cyclo[-CNDNHCRDNDC-] sequence gave the highest selectivity and sensitivity for glucose sensing. This work suggests that a synthetic peptide bearing a particular functional sequence could be applied for developing a new generation of glucose receptors and would find huge application in biological, life science, and clinical diagnostics fields.

Lifestyle, glucose regulation and the cognitive effects of glucose load in middle-aged adults

OpenAIRE

Riby, Leigh; McLaughlin, Jennifer; Riby, Deborah

2008-01-01

Interventions aimed at improving glucose regulatory mechanisms have been suggested as a possible source of cognitive enhancement in the elderly. In particular, previous research has identified episodic memory as a target for facilitation after either moderate increases in glycaemia (after a glucose drink) or after improvements in glucose regulation. The present study aimed to extend this research by examining the joint effects of glucose ingestion and glucose regulation on cognition. In addit...

Elucidation of the glucose transport pathway in glucose transporter 4 via steered molecular dynamics simulations.

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Aswathy Sheena

Full Text Available BACKGROUND: GLUT4 is a predominant insulin regulated glucose transporter expressed in major glucose disposal tissues such as adipocytes and muscles. Under the unstimulated state, GLUT4 resides within intracellular vesicles. Various stimuli such as insulin translocate this protein to the plasma membrane for glucose transport. In the absence of a crystal structure for GLUT4, very little is known about the mechanism of glucose transport by this protein. Earlier we proposed a homology model for GLUT4 and performed a conventional molecular dynamics study revealing the conformational rearrangements during glucose and ATP binding. However, this study could not explain the transport of glucose through the permeation tunnel. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the molecular mechanism of glucose transport and its energetic, a steered molecular dynamics study (SMD was used. Glucose was pulled from the extracellular end of GLUT4 to the cytoplasm along the pathway using constant velocity pulling method. We identified several key residues within the tunnel that interact directly with either the backbone ring or the hydroxyl groups of glucose. A rotation of glucose molecule was seen near the sugar binding site facilitating the sugar recognition process at the QLS binding site. CONCLUSIONS/SIGNIFICANCE: This study proposes a possible glucose transport pathway and aids the identification of several residues that make direct interactions with glucose during glucose transport. Mutational studies are required to further validate the observation made in this study.

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

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

2012-12-12

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

Glucose Binding Protein as a Novel Optical Glucose Nanobiosensor

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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.

Electrochemical non-enzymatic glucose sensors

International Nuclear Information System (INIS)

Park, Sejin; Boo, Hankil; Chung, Taek Dong

2006-01-01

The electrochemical determination of glucose concentration without using enzyme is one of the dreams that many researchers have been trying to make come true. As new materials have been reported and more knowledge on detailed mechanism of glucose oxidation has been unveiled, the non-enzymatic glucose sensor keeps coming closer to practical applications. Recent reports strongly imply that this progress will be accelerated in 'nanoera'. This article reviews the history of unraveling the mechanism of direct electrochemical oxidation of glucose and making attempts to develop successful electrochemical glucose sensors. The electrochemical oxidation of glucose molecules involves complex processes of adsorption, electron transfer, and subsequent chemical rearrangement, which are combined with the surface reactions on the metal surfaces. The information about the direct oxidation of glucose on solid-state surfaces as well as new electrode materials will lead us to possible breakthroughs in designing the enzymeless glucose sensing devices that realize innovative and powerful detection. An example of those is to introduce nanoporous platinum as an electrode, on which glucose is oxidized electrochemically with remarkable sensitivity and selectivity. Better model of such glucose sensors is sought by summarizing and revisiting the previous reports on the electrochemistry of glucose itself and new electrode materials

Diabetic Ketoacidosis in a Patient with Type 2 Diabetes After Initiation of Sodium-Glucose Cotransporter 2 Inhibitor Treatment

DEFF Research Database (Denmark)

Storgaard, Heidi; Bagger, Jonatan I; Knop, Filip K

2016-01-01

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were recently introduced for the treatment of type 2 diabetes (T2D). SGLT2i lower plasma glucose by inhibiting the renal reuptake of glucose leading to glucosuria. Generally, these drugs are considered safe to use. However, recently, SGLT2i have...... been suggested to predispose to ketoacidosis. Here, we present a case of diabetic ketoacidosis (DKA) developed in an obese, poorly controlled male patient with T2D treated with the SGLT2i dapagliflozin. He was admitted with DKA 5 days after the initiation of treatment with the SGLT2i dapagliflozin...... 72 hr with insulin as the only glucose-lowering therapy. After 1 month, dapagliflozin was reintroduced as add-on to insulin with no recurrent signs of ketoacidosis. During acute illness or other conditions with increased insulin demands in diabetes, SGLT2i may predispose to the formation of ketone...

Correlation of Salivary Glucose Level with Blood Glucose Level in Diabetes Mellitus

OpenAIRE

Arati S. Panchbhai

2012-01-01

ABSTRACT Objectives There is alarming rise in number of people with diabetes mellitus over these years. If glucose in saliva is linked to glucose in blood it can be used to detect diabetes mellitus at an early stage. The present study is undertaken with the aim to assess the correlation of salivary glucose level with blood glucose level in people with diabetes mellitus. Material and Methods For investigations, 2 sets of samples of people with diabetes and the age and sex matched non-diabetic ...

Clinical assessment of blood glucose homeostasis in horses: comparison of a continuous glucose monitoring system with a combined intravenous glucose and insulin test protocol.

Science.gov (United States)

Johnson, P J; Wiedmeyer, C E; LaCarrubba, A; Messer, N T; Dingfelder, H A; Cogswell, A M; Amorim, J R R; Ganjam, V K

2011-01-01

The combined glucose-insulin test (CGIT) is helpful for evaluating insulin sensitivity. A continuous glucose monitoring system (CGMS) reports changes in interstitial glucose concentrations as they occur in the blood. Use of the CGMS minimizes animal contact and may be useful when performing a CGIT. Results obtained using a CGMS are useful for the evaluation of glucose responses during the evaluation of insulin sensitivity in equids. Seven mature, obese ponies. Ponies were equipped with CGMS for determination of interstitial glucose concentrations. Glucose (150 mg/kg, i.v.) and insulin (0.1 U/kg, i.v.) were administered and blood glucose concentrations determined at (minutes after time zero) 1, 5, 15, 25, 35, 45, 60, 75, 90, 105, and 120 with a hand-held glucometer. Blood chemistry results were compared with simultaneously obtained results using CGMS. Concordance coefficients determined for comparison of blood glucose concentrations determined by a hand-held glucometer and those determined by CGMS after the zero time point were 0.623, 0.764, 0.834, 0.854, and 0.818 (for delays of 0, 5, 10, 15, and 20 minutes, respectively). Interstitial glucose concentrations obtained by the CGMS compared favorably to blood glucose concentrations. CGMS may be useful for assessment of glucose dynamics in the CGIT. Copyright © 2010 by the American College of Veterinary Internal Medicine.

ZnO nano-array-based EGFET biosensor for glucose detection

Science.gov (United States)

Qi, Junjie; Zhang, Huihui; Ji, Zhaoxia; Xu, Minxuan; Zhang, Yue

2015-06-01

Electrochemical biosensors are normally based on enzymatic catalysis of a reaction that produces or consumes electrons and the sensing membranes dominate the performance. In this work, ZnO nano-array-based EGFETs were fabricated for pH and glucose detection. The ZnO nano-arrays prepared via low-temperature hydrothermal method were well-aligned, with an average length of 2 μm and diameter of 100-150 nm, and have a typical hexagonal wurtzite structure. The sensor performed with a sensitivity of 45 mV/pH and response time of about 6-7 s from pH = 4-12. UV irradiation can improve the Vref response as a result of the formation of a depletion region at the surface of ZnO nanomaterials. Due to its high specific surface area, the ZnO nano-array EGFET sensor showed a sensitivity of -0.395 mV/μM to the glucose detection in a concentration range between 20 and 100 μM. These EGFET glucose biosensors demonstrate a low detectable concentration (20 μM) with good linearity, therefore may be used to detect glucose in saliva and tears at much lower concentrations than that in blood.

Studies on the production of glucose isomerase by Bacillus licheniformis

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Nwokoro Ogbonnaya

2015-09-01

Full Text Available This work reports the effects of some culture conditions on the production of glucose isomerase by Bacillus licheniformis. The bacterium was selected based on the release of 3.62 mg/mL fructose from the fermentation of glucose. Enzyme was produced using a variety of carbon substrates but the highest enzyme activity was detected in a medium containing 0.5% xylose and 1% glycerol (specific activity = 6.88 U/mg protein. Media containing only xylose or glucose gave lower enzyme productivies (specific activities= 4.60 and 2.35 U/mg protein respectively. The effects of nitrogen substrates on glucose isomerase production showed that yeast extract supported maximum enzyme activity (specific activity = 5.24 U/mg protein. Lowest enzyme activity was observed with sodium trioxonitrate (specific activity = 2.44 U/mg protein. In general, organic nitrogen substrates supported higher enzyme productivity than inorganic nitrogen substrates. Best enzyme activity was observed in the presence of Mg2+ (specific activity = 6.85 U/mg protein while Hg2+ was inhibitory (specific activity = 1.02 U/mg protein. The optimum pH for best enzyme activity was 6.0 while optimum temperature for enzyme production was 50ºC.

Optimizing insulin injection technique and its effect on blood glucose control

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Giorgio Grassi, MD

2014-12-01

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

ZnO nanowire-based glucose biosensors with different coupling agents

Energy Technology Data Exchange (ETDEWEB)

Jung, Juneui [Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lim, Sangwoo, E-mail: swlim@yonsei.ac.kr [Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of)

2013-01-15

Highlights: Black-Right-Pointing-Pointer Fabrication of ZnO nanowire-based glucose biosensors using different coupling agents. Black-Right-Pointing-Pointer Highest sensitivity for (3-aminopropyl)methyldiethoxysilane-treated biosensor. Black-Right-Pointing-Pointer Larger amount of glucose oxidase and lower electron transfer resistance for (3-aminopropyl)methyldiethoxysilane-treated biosensor. - Abstract: ZnO-nanowire-based glucose biosensors were fabricated by immobilizing glucose oxidase (GOx) onto a linker attached to ZnO nanowires. Different coupling agents were used, namely (3-aminopropyl)trimethoxysilane (APTMS), (3-aminopropyl)triethoxysilane (APTES), and (3-aminopropyl)methyldiethoxysilane (APS), to increase the affinity of GOx binding to ZnO nanowires. The amount of GOx immobilized on the ZnO nanowires, the performance, sensitivity, and Michaelis-Menten constant of each biosensor, and the electron transfer resistance through the biosensor were all measured in order to investigate the effect of the coupling agent on the ZnO nanowire-based biosensor. Among the different biosensors, the APS-treated biosensor had the highest sensitivity (17.72 {mu}A cm{sup -2} mM{sup -1}) and the lowest Michaelis-Menten constant (1.37 mM). Since APS-treated ZnO nanowires showed the largest number of C-N groups and the lowest electron transfer resistance through the biosensor, we concluded that these properties were the key factors in the performance of APS-treated glucose biosensors.

ZnO nanowire-based glucose biosensors with different coupling agents

International Nuclear Information System (INIS)

Jung, Juneui; Lim, Sangwoo

2013-01-01

Highlights: ► Fabrication of ZnO nanowire-based glucose biosensors using different coupling agents. ► Highest sensitivity for (3-aminopropyl)methyldiethoxysilane-treated biosensor. ► Larger amount of glucose oxidase and lower electron transfer resistance for (3-aminopropyl)methyldiethoxysilane-treated biosensor. - Abstract: ZnO-nanowire-based glucose biosensors were fabricated by immobilizing glucose oxidase (GOx) onto a linker attached to ZnO nanowires. Different coupling agents were used, namely (3-aminopropyl)trimethoxysilane (APTMS), (3-aminopropyl)triethoxysilane (APTES), and (3-aminopropyl)methyldiethoxysilane (APS), to increase the affinity of GOx binding to ZnO nanowires. The amount of GOx immobilized on the ZnO nanowires, the performance, sensitivity, and Michaelis–Menten constant of each biosensor, and the electron transfer resistance through the biosensor were all measured in order to investigate the effect of the coupling agent on the ZnO nanowire-based biosensor. Among the different biosensors, the APS-treated biosensor had the highest sensitivity (17.72 μA cm −2 mM −1 ) and the lowest Michaelis–Menten constant (1.37 mM). Since APS-treated ZnO nanowires showed the largest number of C-N groups and the lowest electron transfer resistance through the biosensor, we concluded that these properties were the key factors in the performance of APS-treated glucose biosensors.

Dehydration of Glucose to 5-Hydroxymethylfurfural Using Nb-doped Tungstite

KAUST Repository

Yue, Chaochao

2016-08-05

Dehydration of glucose to 5-hydroxymethylfurfural (HMF) remains a significant problem in the context of the valorization of lignocellulosic biomass. Hydrolysis of WCl6 and NbCl5 leads to precipitation of Nb-containing tungstite (WO3H2O) at low Nb content and mixtures of tungstite and niobic acid at higher Nb content. Tungstite is a promising catalyst for the dehydration of glucose to HMF. Compared with Nb2O5, fewer by-products are formed because of the low BrOnsted acidity of the (mixed) oxides. In water, an optimum yield of HMF was obtained for Nb-W oxides with low Nb content owing to balanced Lewis and BrOnsted acidity. In THF/water, the strong Lewis acidity and weak BrOnsted acidity caused the reaction to proceed through isomerization to fructose and dehydration of fructose to a partially dehydrated intermediate, which was identified by LC-ESI-MS. The addition of HCl to the reaction mixture resulted in rapid dehydration of this intermediate to HMF. The HMF yield obtained in this way was approximately 56% for all tungstite catalysts. Density functional theory calculations show that the Lewis acid centers on the tungstite surface can isomerize glucose into fructose. Substitution of W by Nb lowers the overall activation barrier for glucose isomerization by stabilizing the deprotonated glucose adsorbate.

Quantitative kinetics of renal glucose metabolism by the isotope dilution method in the unanesthetized sheep

International Nuclear Information System (INIS)

Sasaki, Shin-ichi; Watanabe, Yasukuni; Ambo, Kaichi; Tsuda, Tsuneyuki.

1982-01-01

Renal glucose production and utilization rates in normal fed and fasted sheep were determined by the measurements of renal blood flow and arteriovenous 14 C-glucose and glucose concentration differences using the method of primed continuous infusion of u- 14 C-glucose. At the same time total body glucose turnover rate was measured, and the contribution of renal glucose production to glucose requirement in the whole animal was quantitatively estimated. The renal blood flow for fed and fasted sheep were 20 +- 1 and 20 +- 3 ml/min/kg, respectively. No significant difference in the renal blood flow existed between the groups. The total body glucose turnover rate in fasted sheep (1.68 +- 0.20 mg/min/kg) was significantly lowered (P < 0.01) than that of fed sheep (2.20 +- 0.13 mg/min/kg). The renal glucose production rate in fed sheep was 0.47 +- 0.05 mg/min/kg and this rate accounted for about 21.4% of the glucose turnover rate. The renal glucose production rate in fasted sheep decreased to about 45% of that in fed sheep. However, the renal glucose utilization rate was similar in fed (0.26 +- 0.04 mg/min/kg) and fasted sheep (0.27 +- 0.04 mg/min/kg). Net renal glucose production rate in fed sheep, which was measured by the method of arteriovenous glucose concentration differences, was 0.22 +- 0.05 mg/min/kg, but that in fasted sheep was a negative value. These results suggest that the kidney of ruminant seems to produce a significant amount of glucose and to utilize it simultaneously with production. (author)

Effect of lycium barbarum polysaccharides on high glucose-induced retinal ganglion cell apoptosis, gene expression and delayed rectifier potassium current

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Xiao-Fei Ma

2017-05-01

Full Text Available Objective: To study the effect of lycium barbarum polysaccharides (LBP on high glucoseinduced retinal ganglion cell apoptosis, gene expression and delayed rectifier potassium current. Methods: RGC-5 retinal ganglion cell lines were cultured and divided into control group, high glucose group and LBP group that were treated with normal DMEM, highglucose DMEM as well as high-glucose DMEM containing 500 ng/mL LBP respectively. After treatment, the Annexin V-FITC/PI kits were used to measure the number of apoptotic cells, fluorescence quantitative PCR kits were used to determine the expression of apoptosis genes and antioxidant genes, and patch clamp was used to test delayed rectifier potassium current. Results: 12, 24, 36 and 48 h after intervention, the number of apoptotic cells of high glucose group was significantly higher than that of control group, and the number of apoptotic cells of LBP group was significantly lower than that of high glucose group (P<0.05; 24 and 48 h after intervention, c-fos, c-jun, caspase-3, caspase-9, Nrf-2, NQO1 and HO-1 mRNA expression as well as potassium current amplitude (IK and maximum conductance (Gmax of high glucose group were significantly higher than those of control group while half maximum activation voltage (V1/2 was significantly lower than that of control group (P<0.05; c-fos, c-jun, caspase-3 and caspase-9 mRNA expression as well as IK and Gmax of LBP group were significantly lower than those of high glucose group, while Nrf-2, NQO1 and HO-1 mRNA expression as well as V1/2 of LBP group were significantly higher than those of high glucose group (P<0.05. Conclusions: LBP can reduce the high glucose-induced retinal ganglion cell apoptosis and inhibit the delayed rectifier potassium current amplitude.

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

Hyperglycemia (High Blood Glucose)

Medline Plus

Full Text Available ... Carbohydrate Counting Make Your Carbs Count Glycemic Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type ... Checking Your Blood Glucose A1C and eAG Hypoglycemia (Low blood glucose) Hyperglycemia (High blood glucose) Dawn Phenomenon ...

Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity.

Science.gov (United States)

Ozcan, Lale; Wong, Catherine C L; Li, Gang; Xu, Tao; Pajvani, Utpal; Park, Sung Kyu Robin; Wronska, Anetta; Chen, Bi-Xing; Marks, Andrew R; Fukamizu, Akiyoshi; Backs, Johannes; Singer, Harold A; Yates, John R; Accili, Domenico; Tabas, Ira

2012-05-02

Hepatic glucose production (HGP) is crucial for glucose homeostasis, but the underlying mechanisms have not been fully elucidated. Here, we show that a calcium-sensing enzyme, CaMKII, is activated in a calcium- and IP3R-dependent manner by cAMP and glucagon in primary hepatocytes and by glucagon and fasting in vivo. Genetic deficiency or inhibition of CaMKII blocks nuclear translocation of FoxO1 by affecting its phosphorylation, impairs fasting- and glucagon/cAMP-induced glycogenolysis and gluconeogenesis, and lowers blood glucose levels, while constitutively active CaMKII has the opposite effects. Importantly, the suppressive effect of CaMKII deficiency on glucose metabolism is abrogated by transduction with constitutively nuclear FoxO1, indicating that the effect of CaMKII deficiency requires nuclear exclusion of FoxO1. This same pathway is also involved in excessive HGP in the setting of obesity. These results reveal a calcium-mediated signaling pathway involved in FoxO1 nuclear localization and hepatic glucose homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

Glucose Homeostasis, Pancreatic Endocrine Function, and Outcomes in Advanced Heart Failure.

Science.gov (United States)

Melenovsky, Vojtech; Benes, Jan; Franekova, Janka; Kovar, Jan; Borlaug, Barry A; Segetova, Marketa; Tura, Andrea; Pelikanova, Tereza

2017-08-07

The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucose-regulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome ( P =0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L -1 , 68-101 mg·dL -1 ) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L -1 , 108-142 mg·dL -1 ; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P =0.002). Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia. © 2017 The Authors. Published on behalf of the American Heart Association, Inc

The interaction of insulin, glucose, and insulin-glucose mixtures with a phospholipid monolayer.

Science.gov (United States)

Shigenobu, Hayato; McNamee, Cathy E

2012-12-15

We determined how glucose or insulin interacts with a phospholipid monolayer at the air/water interface and explained these mechanisms from a physico-chemical point of view. The 1,2-dipalmitoyl-2-sn-glycero-3-phosphatidylcholine (DPPC) monolayer at an air/water interface acted as a model membrane, which allowed the effect of the molecular packing density in the monolayer on the interactions to be determined. The interaction of glucose, insulin, and a mixture of glucose and insulin to the DPPC monolayer were investigated via surface pressure-area per molecule Langmuir isotherms and fluorescence microscopy. Glucose adsorbed to the underside of the DPPC monolayer, while insulin was able to penetrate through the monolayer when the phospholipid molecules were not densely packed. The presence of a mixture of insulin and glucose affected the molecular packing in the DPPC monolayer differently than the pure insulin or glucose solutions, and the glucose-insulin mixture was seen to be able to penetrate through the monolayer. These results indicated that glucose and insulin interact with one another, giving a material that may then transported through a pore in the monolayer or through the spaces between the molecules of the monolayer. Copyright © 2012 Elsevier Inc. All rights reserved.

Glucose biosensor based on glucose oxidase immobilized on unhybridized titanium dioxide nanotube arrays

International Nuclear Information System (INIS)

Wang, Wei; Xie, Yibing; Du, Hongxiu; Xia, Chi; Wang, Yong; Tian, Fang

2014-01-01

A glucose biosensor has been fabricated by immobilizing glucose oxidase (GOx) on unhybridized titanium dioxide nanotube arrays using an optimized cross-linking technique. The TiO 2 nanotube arrays were synthesized directly on a titanium substrate by anodic oxidation. The structure and morphology of electrode material were characterized by X-ray diffraction and scanning electron microscopy. The electrochemical performances of the glucose biosensor were conducted by cyclic voltammetry and chronoamperometry measurements. It gives a linear response to glucose in the 0.05 to 0.65 mM concentration range, with a correlation coefficient of 0.9981, a sensitivity of 199.6 μA mM −1 cm −2 , and a detection limit as low as 3.8 µM. This glucose biosensor exhibited high selectivity for glucose determination in the presence of ascorbic acid, sucrose and other common interfering substances. This glucose biosensor also performed good reproducibility and long-time storage stability. This optimized cross-linking technique could open a new avenue for other enzyme biosensors fabrication. (author)

[A comparison of post-surgical plasma glucose levels in patients on fluids with different glucose concentrations].

Science.gov (United States)

Martínez Carapeto, Isabel; López Castilla, José Domingo; Fresneda Gutiérrez, Reyes

2017-11-11

To compare plasma glucose levels and incidence of hyperglycaemia in the post-operative period after general surgery using fluids with different glucose. A randomised, open-label, non-blind, clinical trial was conducted on patients admitted to Paediatric Intensive Care Unit after elective surgery. The inclusion criteria were from 6 months to 14 years of age, with a weight greater than 6kg, onset glucose level >60mg/dL, and a signed informed consent, with no oral intake and maintenance intravenous fluid therapy using fluids with 3.3% or 5% glucose. Plasma glucose levels were measured before surgery, on admission, and 8, 24, and 48h, with the mean glucose levels and incidence of hyperglycaemia (glucose level >150mg/dL) in both groups being compared. A total of 60 patients received glucose/saline 1/3 (51mEq/L sodium and 33g/L glucose), and 70 glucose/saline 5/0.9% (154mEq/L sodium and 50g/L glucose). Mean glucose levels were higher in the group receiving glucose 5%, with no statistical difference. There was no significant difference in the incidence of hyperglycaemia; 8h: 26% in the 3.3% group vs. 21.3% in the 5% group (P=.63); 24h: 20% vs. 22.7% (P=.8); and 48h: 19% vs. 23.1% (P=.78). The use of fluids with 3.3% glucose in the post-operative period of general surgery maintains mean glucose levels in a similar range to that of patients receiving fluids with 5% glucose, with no difference in the incidence of hyperglycaemia. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Short communication: Associations between blood glucose concentration, onset of hyperketonemia, and milk production in early lactation dairy cows.

Science.gov (United States)

Ruoff, J; Borchardt, S; Heuwieser, W

2017-07-01

The objectives of this study were to describe the associations between hypoglycemia and the onset of hyperketonemia (HYK) within the first 6 wk of lactation, to evaluate the effects of body condition score at calving on glucose concentration, and to study the effects of hypoglycemia on milk production. A total of 621 dairy cows from 6 commercial dairy farms in Germany were enrolled between 1 and 4 d in milk (DIM). Cows were tested twice weekly using an electronic handheld meter for glucose and β-hydroxybutyrate (BHB), respectively, for a period of 42 d. Hypoglycemia was defined as glucose concentration ≤2.2 mmol/L. Hyperketonemia was defined as a BHB concentration ≥1.2 mmol/L. The onset of HYK was described as early onset (first HYK event within the first 2 wk postpartum) and late onset (first HYK event in wk 3 to 6 postpartum). The effect of ketosis status on blood glucose within 42 DIM was evaluated using a generalized linear mixed model. No effect was observed of HYK on glucose concentration in primiparous cows. Multiparous cows with early-onset HYK had a lower glucose concentration (-0.21 mmol/L) compared with nonketotic cows. Overall, primiparous cows had a lower prevalence and incidence of hypoglycemia than multiparous cows. Hypoglycemia in multiparous cows was associated with higher first test-day milk production and 100 DIM milk production. In conclusion, hypoglycemia mainly occurred in multiparous cows with early-onset HYK, whereas primiparous cows were at a lower risk for hypoglycemia. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The effects of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes

DEFF Research Database (Denmark)

Storgaard, Heidi; Gluud, Lise Lotte; Christensen, Mikkel

2014-01-01

INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) increase urinary glucose excretion through a reduced renal glucose reabsorption. We plan to perform a systematic review of SGLT-2i for treatment of type 2 diabetes. METHODS AND ANALYSIS: A systematic review with meta......-analyses of randomised clinical trials on SGLT-2i versus placebo, other oral glucose lowering drugs or insulin for patients with type 2 diabetes will be performed. The primary end point will be the glycated haemoglobin. Secondary end points will include changes in body weight, body mass index, fasting plasma glucose...... to the knowledge regarding the beneficial and harmful effects of SGLT-2i in patients with type 2 diabetes. We plan to publish the study irrespective of the results. RESULTS: The study will be disseminated by peer-review publication and conference presentation. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014008960...