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

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Michael S. Scully ◽  
Tatiana A. Ort ◽  
Ian E. James ◽  
Peter J. Bugelski ◽  
Dorie A. Makropoulos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Receptor Agonist ◽  
Glucose Tolerance Test ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Class Effect ◽  
Epo Receptor ◽  
Insulin Resistant

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

scholarly journals No difference in exogenous carbohydrate oxidation during exercise in children with and without impaired glucose tolerance

2016 ◽  
Vol 121 (3) ◽  
pp. 724-729 ◽  
Author(s):  
Lisa Chu ◽  
Katherine M. Morrison ◽  
Michael C. Riddell ◽  
Sandeep Raha ◽  
Brian W. Timmons
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Normal Glucose Tolerance ◽  
Whole Body ◽  
Oral Glucose ◽  
Insulin Resistant ◽  
Glucose Levels

The capacity to match carbohydrate (CHO) utilization with availability is impaired in insulin-resistant, obese adults at rest. Understanding exogenous carbohydrate (CHOexo) oxidation during exercise and its association to insulin resistance (IR) is important, especially in children at risk for type 2 diabetes. Our objective was to examine the oxidative efficiency of CHOexo during exercise in obese children with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). Children attended two visits and were identified as NGT ( n = 22) or IGT ( n = 12) based on 2-h oral glucose tolerance test (OGTT) glucose levels of <7.8 mmol/l or ≥7.8 mmol/l, respectively. Anthropometry, body composition, and aerobic fitness (V̇o2max) were assessed. Insulin and glucose at baseline, 30, 60, 90, and 120 min during the OGTT were used to calculate measures of insulin sensitivity. On a separate day, a 13C-enriched CHO drink was ingested before exercise (3 × 20 min bouts) at 45% V̇o2max. Breath measurements were collected to calculate CHOexo oxidative efficiency. CHOexo oxidative efficiency during exercise was similar in IGT (17.0 ± 3.6%) compared with NGT (17.1 ± 4.4%) ( P = 0.90) despite lower whole body insulin sensitivity in IGT at rest ( P = 0.02). Area under the curve for insulin (AUCins) measured at rest during the OGTT was greater in IGT compared with NGT ( P = 0.04). The ability of skeletal muscle to utilize CHOexo was not impaired during exercise in children with IGT.

scholarly journals Direct Measurements of the Permeability Surface Area for Insulin and Glucose in Human Skeletal Muscle

2003 ◽  
Vol 88 (10) ◽  
pp. 4559-4564 ◽  
Author(s):  
Soffia Gudbjörnsdóttir ◽  
Mikaela Sjöstrand ◽  
Lena Strindberg ◽  
John Wahren ◽  
Peter Lönnroth
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Tolerance ◽  
Plasma Insulin ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Permeability Surface ◽  
One Step

Abstract To elucidate mechanisms regulating capillary transport of insulin and glucose, we directly calculated the permeability surface (PS) area product for glucose and insulin in muscle. Intramuscular microdialysis in combination with the forearm model and blood flow measurements was performed in healthy males, studied during an oral glucose tolerance test or during a one-step or two-step euglycemic hyperinsulinemic clamp. PS for glucose increased significantly from 0.29 ± 0.1 to 0.64 ± 0.2 ml/min·100 g after oral glucose tolerance test, and glucose uptake increased from 1.2 ± 0.4 to 2.6 ± 0.6 μmol/min·100 g (P &lt; 0.05). During one-step hyperinsulinemic clamp (plasma insulin, 1.962 pmol/liter), PS for glucose increased from 0.2 ± 0.1 to 2.3 ± 0.9 ml/min·100 g (P &lt; 0.05), and glucose uptake increased from 0.6 ± 0.2 to 5.0 ± 1.4 μmol/min·100 g (P &lt; 0.05). During the two-step clamp (plasma insulin, 1380 ± 408 and 3846 ± 348 pmol/liter), the arterial-interstitial difference and PS for insulin were constant. The PS for glucose tended to increase (P = not significant), whereas skeletal muscle blood flow increased from 4.4 ± 0.7 to 6.2 ± 0.8 ml/min·100 ml (P &lt; 0.05). The present data show that PS for glucose is markedly increased by oral glucose, whereas a further vasodilation exerted by high insulin concentrations may not be physiologically relevant for capillary delivery of either glucose or insulin in resting muscle.

scholarly journals Glucose area under the curve during oral glucose tolerance test as an index of glucose intolerance

2015 ◽  
Vol 7 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Kazuhiko Sakaguchi ◽  
Kazuo Takeda ◽  
Mitsuo Maeda ◽  
Wataru Ogawa ◽  
Toshiyuki Sato ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Intolerance ◽  
Glucose Tolerance Test ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance

scholarly journals Insulin sensitivity obtained from the oral glucose tolerance test and its relationship with birthweight

2007 ◽  
Vol 27 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Yıldız Dallar ◽  
Dilek Dilli ◽  
Ilknur Bostancı ◽  
Elmas Öğüş ◽  
Şeyda Doğankoç ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance

scholarly journals Leptin/Adiponectin Ratios Using Either Total Or High-Molecular-Weight Adiponectin as Biomarkers of Systemic Insulin Sensitivity in Normoglycemic Women

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Carolina Bravo ◽  
Luis Rodrigo Cataldo ◽  
José Galgani ◽  
Javier Parada ◽  
José Luis Santos
Keyword(s):  
Molecular Weight ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
High Molecular Weight ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Sensitivity Index ◽  
High Molecular Weight Adiponectin ◽  
Intravenous Glucose ◽  
Negatively Associated

Plasma leptin/adiponectin ratio (LAR) is negatively associated with insulin sensitivity indexes. High-molecular-weight adiponectin (HMWA) was proposed as the most biologically active form of this insulin-sensitizing adipokine. There are no studies assessing the relative merits of leptin/HMWA ratio over LAR as a biomarker of systemic insulin sensitivity. A standard 2-hour oral glucose tolerance test (OGTT; 75 g of glucose) and a short minimal-model intravenous glucose tolerance test (IVGTT; 0.3 g/kg body weight) were performed in 58 Chilean normoglycemic women (age: 27 ± 6.3 years, BMI 23.6 ± 3.2 kg/m2). LAR was negatively associated with HOMA-S (r=−0.49; p<0.0001), Matsuda-ISICOMP (r=−0.54; p<0.0001), and the calculated sensitivity index (CSi) derived from IVGTT (r=−0.38; p=0.007). In comparison to LAR, leptin/HMWA ratio did not increase neither the linear fit (r2) nor the magnitude of association with insulin sensitivity indexes (slope of multiple linear regression). The discriminatory capacity of both ratios to classify insulin-resistant versus insulin-sensitive subjects was similar for HOMA-S (p=0.84), Matsuda-ISICOMP (p=0.43), or CSi (p=0.50). In conclusion, LAR showed consistent negative associations with different systemic insulin sensitivity indexes. The use of HMWA to generate leptin/HMWA ratio did not show any advantage over LAR as a biomarker of systemic insulin sensitivity in normoglycemic women.

scholarly journals Modelling the effects of glucagon during glucose tolerance testing

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Ross A. Kelly ◽  
Molly J. Fitches ◽  
Steven D. Webb ◽  
S. R. Pop ◽  
Stewart J. Chidlow
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Mathematical Models ◽  
Linear Relationship ◽  
Insulin Infusion ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Glucose Kinetics ◽  
Glucose Effectiveness ◽  
Tolerance Testing

Abstract Background Glucose tolerance testing is a tool used to estimate glucose effectiveness and insulin sensitivity in diabetic patients. The importance of such tests has prompted the development and utilisation of mathematical models that describe glucose kinetics as a function of insulin activity. The hormone glucagon, also plays a fundamental role in systemic plasma glucose regulation and is secreted reciprocally to insulin, stimulating catabolic glucose utilisation. However, regulation of glucagon secretion by α-cells is impaired in type-1 and type-2 diabetes through pancreatic islet dysfunction. Despite this, inclusion of glucagon activity when modelling the glucose kinetics during glucose tolerance testing is often overlooked. This study presents two mathematical models of a glucose tolerance test that incorporate glucose-insulin-glucagon dynamics. The first model describes a non-linear relationship between glucagon and glucose, whereas the second model assumes a linear relationship. Results Both models are validated against insulin-modified and glucose infusion intravenous glucose tolerance test (IVGTT) data, as well as insulin infusion data, and are capable of estimating patient glucose effectiveness (sG) and insulin sensitivity (sI). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness (sE) and glucagon sensitivity (δ). Conclusions The models are used to investigate how different degrees of pax‘tient glucagon sensitivity and effectiveness affect the concentration of blood glucose and plasma glucagon during IVGTT and insulin infusion tests, providing a platform from which the role of glucagon dynamics during a glucose tolerance test may be investigated and predicted.

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