Effect of metformin on substrate utilization after exercise training in adults with impaired glucose tolerance

2013 ◽  
Vol 38 (4) ◽  
pp. 427-430 ◽  
Author(s):  
Steven K. Malin ◽  
Barry Braun
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Oxygen Uptake ◽  
Indirect Calorimetry ◽  
Substrate Utilization ◽  
Peak Oxygen Uptake ◽  
Whole Body ◽  
Glucose Kinetics

Metformin attenuates the higher insulin sensitivity that occurs with exercise training. Sixteen people with prediabetes trained for 10 weeks while taking metformin (n = 8) or placebo (n = 8). Substrate utilization was assessed using glucose kinetics and indirect calorimetry. After training, exercise whole-body fat oxidation was higher and glycogen use lower (p < 0.05), with no differences between groups. Blood glucose use was unchanged. Training-induced enhancement of insulin sensitivity (clamp) correlated with higher peak oxygen uptake (r = 0.70; p < 0.05), but was independent of glucose kinetic and substrate metabolism.

scholarly journals Chronic Prednisolone Treatment Reduces Hepatic Insulin Sensitivity while Perturbing the Fed-to-Fasting Transition in Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2171-2178 ◽  
Author(s):  
Anke J. Laskewitz ◽  
Theo H. van Dijk ◽  
Vincent W. Bloks ◽  
Dirk-Jan Reijngoud ◽  
Marie-José van Lierop ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Plasma Insulin ◽  
Fasting Blood Glucose ◽  
Whole Body ◽  
Fibroblast Growth Factor 21 ◽  
Glucose Kinetics ◽  
Prednisolone Treatment ◽  
Hepatic Glucose ◽  
Blood Glucose Concentrations

Chronic glucocorticoid use for treatment of inflammatory diseases is accompanied by severe side effects in humans (e.g. hyperglycemia and insulin resistance). The present studies were conducted to characterize consequences of chronic treatment with the synthetic glucocorticoid prednisolone on insulin sensitivity and blood glucose kinetics in mice. Prednisolone treatment increased fasting blood glucose and plasma insulin concentrations, but this apparently reduced insulin sensitivity could not be confirmed in hyperinsulinemic euglycemic clamp studies. Therefore, a novel method to study whole body glucose kinetics was used. This method revealed that prednisolone-treated mice show an increased hepatic glucose production (HGP). The increased HGP was accompanied by elevated plasma insulin concentrations, indicating reduced insulin sensitivity of hepatic glucose metabolism in prednisolone-treated mice. Compared with vehicle, prednisolone-treated mice had lower blood glucose concentrations, higher plasma free fatty acids, and higher plasma fibroblast growth factor-21 concentrations in the fed condition, i.e. mimicking a fasting situation. Next, the effects of 24-h fasting on energy metabolism were studied. Compared with controls, fasted prednisolone-treated mice had higher blood glucose concentrations and lower plasma β-hydroxybutyrate concentrations. In conclusion, these results indicate that chronic prednisolone treatment reduces insulin sensitivity of HGP, induces a fasting-like phenotype in fed mice, and perturbs the fed-to-fasting transition.

Effect of aging on response to exercise training in humans: skeletal muscle GLUT-4 and insulin sensitivity

1999 ◽  
Vol 86 (6) ◽  
pp. 2019-2025 ◽  
Author(s):  
Julie H. Cox ◽  
Ronald N. Cortright ◽  
G. Lynis Dohm ◽  
Joseph A. Houmard
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Oxygen Uptake ◽  
Maximal Oxygen Uptake ◽  
Insulin Action ◽  
Whole Body ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Glut 4

The purpose of this study was to compare the effects of short-term exercise training on insulin-responsive glucose transporter (GLUT-4) concentration and insulin sensitivity in young and older individuals. Young and older women [22.4 ± 0.8 (SE) yr, n = 9; and 60.9 ± 1.0 yr, n = 10] and men (20.9 ± 0.9, n = 9; 56.5 ± 1.9 yr, n = 8), respectively, were studied before and after 7 consecutive days of exercise training (1 h/day, ≈75% maximal oxygen uptake). The older groups had more adipose tissue, increased central adiposity, and a lower maximal oxygen uptake. Despite these differences, increases in whole body insulin action (insulin sensitivity index, determined with an intravenous glucose tolerance test and minimal-model analysis) with training were similar regardless of age, in both the women and men (mean increase of 2.2 ± 0.3-fold). This was accompanied by similar relative increases in muscle (vastus lateralis) GLUT-4 protein concentration, irrespective of age (mean increase of 3.1 ± 0.7-fold). Body mass did not change with training in any of the groups. These data suggest that older human skeletal muscle retains the ability to rapidly increase muscle GLUT-4 and improve insulin action with endurance training.

Effect of increased blood glucose availability on glucose kinetics during exercise

1998 ◽  
Vol 84 (4) ◽  
pp. 1413-1417 ◽  
Author(s):  
Kirsten Howlett ◽  
Damien Angus ◽  
Joseph Proietto ◽  
Mark Hargreaves
Keyword(s):  
Blood Glucose ◽  
Oxygen Uptake ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Peak Oxygen Uptake ◽  
Strenuous Exercise ◽  
Glucose Kinetics ◽  
Hepatic Glucose ◽  
Glucose Plasma ◽  
Glucose Availability

This study examined the effect of increased blood glucose availability on glucose kinetics during exercise. Five trained men cycled for 40 min at 77 ± 1% peak oxygen uptake on two occasions. During the second trial (Glu), glucose was infused at a rate equal to the average hepatic glucose production (HGP) measured during exercise in the control trial (Con). Glucose kinetics were measured by a primed continuous infusion ofd-[3-3H]glucose. Plasma glucose increased during exercise in both trials and was significantly higher in Glu. HGP was similar at rest (Con, 11.4 ± 1.2; Glu, 10.6 ± 0.6 μmol ⋅ kg−1 ⋅ min−1). After 40 min of exercise, HGP reached a peak of 40.2 ± 5.5 μmol ⋅ kg−1 ⋅ min−1in Con; however, in Glu, there was complete inhibition of the increase in HGP during exercise that never rose above the preexercise level. The rate of glucose disappearance was greater ( P < 0.05) during the last 15 min of exercise in Glu. These results indicate that an increase in glucose availability inhibits the rise in HGP during exercise, suggesting that metabolic feedback signals can override feed-forward activation of HGP during strenuous exercise.

Prolonged exercise after diuretic-induced hypohydration: effects on substrate turnover and oxidation

2000 ◽  
Vol 279 (6) ◽  
pp. E1383-E1390 ◽  
Author(s):  
B. D. Roy ◽  
H. J. Green ◽  
M. Burnett
Keyword(s):  
Oxygen Uptake ◽  
Specific Effect ◽  
Fat Oxidation ◽  
Peak Oxygen Uptake ◽  
Whole Body ◽  
Moderate Intensity ◽  
Glucose Kinetics ◽  
Total Carbohydrate ◽  
Serum Free Fatty Acid ◽  
Young Males

To determine the influence of a diuretic-induced reduction in plasma volume (PV) on substrate turnover and oxidation, 10 healthy young males were studied during 60 min of cycling exercise at 61% peak oxygen uptake on two separate occasions ≥1 wk apart. Exercise was performed under control conditions (CON; placebo), and after 4 days of diuretic administration (DIU; Novotriamazide; 100 mg triamterene and 50 mg hydrochlorothiazide). DIU resulted in a calculated reduction of PV by 14.6 ± 3.3% ( P < 0.05). Rates of glucose appearance (Ra) and disappearance (Rd) and glycerol Ra were determined by using primed constant infusions of [6,6-2H]glucose and [2H5]glycerol, respectively. No differences in oxygen uptake during exercise were observed between trials. Main effects for condition ( P < 0.05) were observed for plasma glucose and glycerol, such that the values observed for DIU were higher than for CON. No differences were observed in plasma lactate and serum free fatty acid concentrations either at rest or during exercise. Hypohydration led to lower ( P < 0.05) glucose Ra and Rd at rest and at 15 and 30 min of exercise, but by 60 min, the effects were reversed ( P < 0.05). Hypohydration had no effect on rates of whole body lipolysis or total carbohydrate or fat oxidation. A main effect for condition ( P < 0.05) was observed for plasma glucagon concentrations such that larger values were observed for DIU than for CON. A similar decline in plasma insulin occurred with exercise in both conditions. These results indicate that diuretic-induced reductions in PV decreases glucose kinetics during moderate-intensity dynamic exercise in the absence of changes in total carbohydrate and fat oxidation. The specific effect on glucose kinetics depends on the duration of the exercise.

Effect of training on insulin binding to rat skeletal muscle sarcolemmal vesicles

1986 ◽  
Vol 250 (5) ◽  
pp. E570-E575
Author(s):  
G. K. Grimditch ◽  
R. J. Barnard ◽  
S. A. Kaplan ◽  
E. Sternlicht
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Insulin Binding ◽  
Whole Body ◽  
Rat Skeletal Muscle ◽  
Binding Studies ◽  
Muscle Enzyme ◽  
Intravenous Glucose ◽  
High Affinity

We examined the hypothesis that the exercise training-induced increase in skeletal muscle insulin sensitivity is mediated by adaptations in insulin binding to sarcolemmal (SL) insulin receptors. Insulin binding studies were performed on rat skeletal muscle SL isolated from control and trained rats. No significant differences were noted between groups in body weight or fat. An intravenous glucose tolerance test showed an increase in whole-body insulin sensitivity with training, and specific D-glucose transport studies on isolated SL vesicles indicated that this was due in part to adaptations in skeletal muscle. Enzyme marker analyses revealed no differences in yield, purity, or contamination of SL membranes between the two groups. Scatchard analyses indicated no significant differences in the number of insulin binding sites per milligram SL protein on the high-affinity (15.0 +/- 4.1 vs. 18.1 +/- 6.4 X 10(9)) or on the low-affinity portions (925 +/- 80 vs. 884 +/- 106 X 10(9)) of the curves. The association constants of the high-affinity (0.764 +/- 0.154 vs. 0.685 +/- 0.264 X 10(9) M-1) and of the low affinity sites (0.0096 +/- 0.0012 vs. 0.0102 +/- 0.0012 X 10(9) M-1) also were similar. These results do not support the hypothesis that the increased sensitivity to insulin after exercise training is due to changes in SL insulin receptor binding.

scholarly journals Deletion of CaMKK2 from the Liver Lowers Blood Glucose and Improves Whole-Body Glucose Tolerance in the Mouse

2012 ◽  
Vol 26 (2) ◽  
pp. 281-291 ◽  
Author(s):  
Kristin A. Anderson ◽  
Fumin Lin ◽  
Thomas J. Ribar ◽  
Robert D. Stevens ◽  
Michael J. Muehlbauer ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Dependent Protein Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dependent Protein

Abstract Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca2+/CaM-dependent protein kinase family that is expressed abundantly in brain. Previous work has revealed that CaMKK2 knockout (CaMKK2 KO) mice eat less due to a central nervous system -signaling defect and are protected from diet-induced obesity, glucose intolerance, and insulin resistance. However, here we show that pair feeding of wild-type mice to match food consumption of CAMKK2 mice slows weight gain but fails to protect from diet-induced glucose intolerance, suggesting that other alterations in CaMKK2 KO mice are responsible for their improved glucose metabolism. CaMKK2 is shown to be expressed in liver and acute, specific reduction of the kinase in the liver of high-fat diet-fed CaMKK2floxed mice results in lowered blood glucose and improved glucose tolerance. Primary hepatocytes isolated from CaMKK2 KO mice produce less glucose and have decreased mRNA encoding peroxisome proliferator-activated receptor γ coactivator 1-α and the gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, and these mRNA fail to respond specifically to the stimulatory effect of catecholamine in a cell-autonomous manner. The mechanism responsible for suppressed gene induction in CaMKK2 KO hepatocytes may involve diminished phosphorylation of histone deacetylase 5, an event necessary in some contexts for derepression of the peroxisome proliferator-activated receptor γ coactivator 1-α promoter. Hepatocytes from CaMKK2 KO mice also show increased rates of de novo lipogenesis and fat oxidation. The changes in fat metabolism observed correlate with steatotic liver and altered acyl carnitine metabolomic profiles in CaMKK2 KO mice. Collectively, these results are consistent with suppressed catecholamine-induced induction of gluconeogenic gene expression in CaMKK2 KO mice that leads to improved whole-body glucose homeostasis despite the presence of increased hepatic fat content.

A low-calorie diet with or without interval exercise training improves adiposopathy in obese women

2019 ◽  
Vol 44 (10) ◽  
pp. 1057-1064 ◽  
Author(s):  
Nicole M. Gilbertson ◽  
Natalie Z.M. Eichner ◽  
Emily M. Heiston ◽  
Julian M. Gaitán ◽  
Monique E. Francois ◽  
...  
Keyword(s):  
Heart Rate ◽  
Body Composition ◽  
Insulin Sensitivity ◽  
Oxygen Uptake ◽  
Peak Oxygen Uptake ◽  
Energy Deficit ◽  
Obese Women ◽  
Interval Exercise ◽  
Low Calorie Diet ◽  
Calorie Diet

The objective of this study was to test if a low-calorie diet plus interval exercise (LCD+INT) improves adiposopathy, an endocrine dysfunction, when compared with an energy-deficit–matched LCD in obese women. Subjects (age: 48.2 ± 2.4 years, body mass index: 37.8 ± 1.3 kg/m2) were randomized to a 13-day LCD (n = 12; mixed meals of ∼1200 kcal/day) or LCD+INT (n = 12; 12 sessions of 60 min/day alternating 3 min at 50% and 90% peak heart rate). Exercise was estimated to expend 350 kcal per oxygen uptake–heart rate regression analysis and individuals were refed calories expended to match energy availability between groups. Absolute (post – pre caloric intake) and relative (total daily and exercise energy expenditure relative to calorie intake) energy deficits were calculated. Fitness (peak oxygen uptake) and body composition (BodPod; Cosmed USA Inc.) were measured and a 120-min, 75g oral glucose tolerance test was performed at pre- and post-intervention to assess adiposopathy (i.e., ratio of high molecular weight–adiponectin to leptin) and estimate insulin sensitivity. LCD and LCD+INT had similar absolute (P = 0.55) and relative (P = 0.76) energy deficits. LCD and LCD+INT had similar reductions in fat mass (both P < 0.001), despite LCD inducing greater weight loss (P = 0.02) than LCD+INT. Both treatments improved adiposopathy (P = 0.003) and peripheral insulin sensitivity (P = 0.02). Absolute energy deficit correlated to improved adiposopathy (r = –0.41, P = 0.05), and absolute and relative energy deficits were associated with increased insulin sensitivity (r = –0.47, P = 0.02; and r = –0.40, P = 0.05, respectively), independent of body composition changes and increased peak oxygen uptake. Taken together, LCD, with or without INT, improves adiposopathy in relation to insulin sensitivity in obese women, suggesting that a short-term energy deficit is key for reducing risk of type 2 diabetes.

scholarly journals Lipid Metabolism Links Nutrient-Exercise Timing to Insulin Sensitivity in Men Classified as Overweight or Obese

2019 ◽  
Vol 105 (3) ◽  
pp. 660-676 ◽  
Author(s):  
Robert M Edinburgh ◽  
Helen E Bradley ◽  
Nurul-Fadhilah Abdullah ◽  
Scott L Robinson ◽  
Oliver J Chrzanowski-Smith ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Whole Body ◽  
Moderate Intensity ◽  
Type I ◽  
Training Study ◽  
Exercise Timing ◽  
Lipid Utilization ◽  
Acute Study ◽  
Intramuscular Lipid

Abstract Context Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness. Objective To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism. Design (1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study). Setting General community. Participants Men with overweight/obesity (mean ± standard deviation, body mass index: 30.2 ± 3.5 kg⋅m-2 for Acute Study, 30.9 ± 4.5 kg⋅m-2 for Training Study). Interventions Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast (Acute Study) or carbohydrate (Training Study) ingestion. Results Acute Study—exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I (net change: –3.44 ± 2.63% versus 1.44 ± 4.18% area lipid staining, P &lt; 0.01) and type II fibers (–1.89 ± 2.48% versus 1.83 ± 1.92% area lipid staining, P &lt; 0.05). Training Study—postprandial glycemia was not differentially affected by 6 weeks of exercise training performed before versus after carbohydrate intake (P &gt; 0.05). However, postprandial insulinemia was reduced with exercise training performed before but not after carbohydrate ingestion (P = 0.03). This resulted in increased oral glucose insulin sensitivity (25 ± 38 vs –21 ± 32 mL⋅min-1⋅m-2; P = 0.01), associated with increased lipid utilization during exercise (r = 0.50, P = 0.02). Regular exercise before nutrient provision also augmented remodeling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (P &lt; 0.05). Conclusions Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (ie, in the fasted state) may exert beneficial effects on lipid utilization and reduce postprandial insulinemia.

Effect of heat stress on glucose kinetics during exercise

1996 ◽  
Vol 81 (4) ◽  
pp. 1594-1597 ◽  
Author(s):  
Mark Hargreaves ◽  
Damien Angus ◽  
Kirsten Howlett ◽  
Nelly Marmy Conus ◽  
Mark Febbraio
Keyword(s):  
Heat Stress ◽  
Oxygen Uptake ◽  
Plasma Catecholamines ◽  
Whole Body ◽  
Exercise Heart Rate ◽  
Metabolic Clearance ◽  
Glucose Kinetics ◽  
Pulmonary Oxygen Uptake ◽  
Glucose Levels ◽  
Glucose Output

Hargreaves, Mark, Damien Angus, Kirsten Howlett, Nelly Marmy Conus, and Mark Febbraio. Effect of heat stress on glucose kinetics during exercise. J. Appl. Physiol. 81(4): 1594–1597, 1996.—To identify the mechanism underlying the exaggerated hyperglycemia during exercise in the heat, six trained men were studied during 40 min of cycling exercise at a workload requiring 65% peak pulmonary oxygen uptake (V˙o 2 peak) on two occasions at least 1 wk apart. On one occasion, the ambient temperature was 20°C [control (Con)], whereas on the other, it was 40°C [high temperature (HT)]. Rates of glucose appearance and disappearance were measured by using a primed continuous infusion of [6,6-2H]glucose. No differences in oxygen uptake during exercise were observed between trials. After 40 min of exercise, heart rate, rectal temperature, respiratory exchange ratio, and plasma lactate were all higher in HT compared with Con ( P < 0.05). Plasma glucose levels were similar at rest (Con, 4.54 ± 0.19 mmol/l; HT, 4.81 ± 0.19 mmol/l) but increased to a greater extent during exercise in HT (6.96 ± 0.16) compared with Con (5.45 ± 0.18; P < 0.05). This was the result of a higher glucose rate of appearance in HT during the last 30 min of exercise. In contrast, the glucose rate of disappearance and metabolic clearance rate were not different at any time point during exercise. Plasma catecholamines were higher after 10 and 40 min of exercise in HT compared with Con ( P < 0.05), whereas plasma glucagon, cortisol, and growth hormone were higher in HT after 40 min. These results indicate that the hyperglycemia observed during exercise in the heat is caused by an increase in liver glucose output without any change in whole body glucose utilization.

scholarly journals Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance

2014 ◽  
Vol 307 (3) ◽  
pp. R332-R339 ◽  
Author(s):  
Jieyun Yin ◽  
Jian Kuang ◽  
Manisha Chandalia ◽  
Demidmaa Tuvdendorj ◽  
Batbayar Tumurbaatar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
High Fat

The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level ( P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA ( P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid.

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