Glucose Uptake In Human Muscle Research Articles

Short-term green tea extract supplementation attenuates the postprandial blood glucose and insulin response following exercise in overweight men.

Green tea extract (GTE) ingestion improves glucose homeostasis in healthy and diabetic humans, but the interactive effect of GTE and exercise is unknown. The present study examined the effect of short-term GTE supplementation on the glycemic response to an oral glucose load at rest and following an acute bout of exercise, as well as substrate oxidation during exercise. Eleven sedentary, overweight men with fasting plasma glucose (FPG) ≥5.6 mmol·L-1 (age, 34 ± 13 years; body mass index = 32 ± 5 kg·m-2; FPG = 6.8 ± 1.0; mean ± SD) ingested GTE (3× per day, 1050 mg·day-1 total) or placebo (PLA) for 7 days in a double-blind, crossover design. The effects of a 75-g glucose drink were assessed on 4 occasions during both GTE and PLA treatments: On days 1 and 5 at rest, and again following an acute bout of exercise on days 3 and 8. The glycemic response was assessed via an indwelling continuous glucose monitor (CGM) and venous blood draws. At rest, 1-h CGM glucose area under the curve was not different (P > 0.05), but the postexercise response was lower after GTE versus PLA (330 ± 53 and 393 ± 65 mmol·L-1·min-1, main effect of treatment, P < 0.05). The 1-h postprandial peaks in venous blood glucose (8.6 ± 1.6 and 9.8 ± 2.2 mmol·L-1) and insulin (96 ± 59 and 124 ± 68 μIU·ml-1) were also lower postexercise with GTE versus PLA (time × treatment interactions, P < 0.05). In conclusion, short-term GTE supplementation did not affect postprandial glucose at rest; however, GTE was associated with an attenuated glycemic response following a postexercise oral glucose load. These data suggest that GTE might alter skeletal muscle glucose uptake in humans.

5-Aminoimidazole-4-Carboxamide 1-β-d-Ribofuranoside Acutely Stimulates Skeletal Muscle 2-Deoxyglucose Uptake in Healthy Men

Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake. The aim of this study was to determine whether AICAR stimulates muscle glucose uptake in humans. We studied 29 healthy men (aged 26 +/- 8 years, BMI 25 +/- 4 kg/m(2) [mean +/- SD]). Rates of muscle 2-deoxyglucose (2DG) uptake were determined by measuring accumulation of total muscle 2DG (2DG and 2DG-6-phosphate) during a primed, continuous 2DG infusion. The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined. Whole-body glucose disposal was compared before and during AICAR with the euglycemic-hyperinsulinemic clamp. Muscle 2DG uptake was linear over 9 h (R(2) = 0.88 +/- 0.09). After 3 h, 2DG uptake increased 2.1 +/- 0.8- and 4.7 +/- 1.7-fold in response to AICAR or bicycle exercise, respectively. AMPK alpha(1) and alpha(2) activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise. AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of beta-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged. Mean whole-body glucose disposal increased by 7% with AICAR from 9.3 +/- 0.6 to 10 +/- 0.6 mg x kg(-1) x min(-1) (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole-body glucose disposal.

Effect of training on insulin-mediated glucose uptake in human muscle.

During insulin stimulation whole body glucose uptake is increased in trained compared with untrained humans. However, it is not known which tissue is responsible. Seven young male subjects bicycle trained one leg for 10 wk at 70% of maximal O2 consumption (VO2max). Sixteen hours after last exercise bout, a three-step euglycemic hyperinsulinemic clamp (clamp 1) was performed (insulin levels, means +/- SE: 9 +/- 1, 53 +/- 3, 174 +/- 5, and 2,323 +/- 80 was microU/ml), with measurement of arteriovenous differences and blood flow in both legs. After 6 days of detraining subjects were restudied, having exercised the untrained leg 16 h before. VO2max for trained (T) and untrained (UT) legs was 52 +/- 2 vs. 44 +/- 2 ml.min-1.kg-1 (P < 0.05). In clamp 1 glucose uptake in T and UT legs was 1.0 +/- 0.2 vs. 0.5 +/- 0.1 mg.min-1.kg-1 (basal), 9.7 +/- 2.3 vs. 6.7 +/- 1.7 (P < 0.05) (step I), 19.2 +/- 2.8 vs. 14.3 +/- 2.0 (P < 0.05) (step II), and 22.8 +/- 2.3 vs. 18.6 +/- 2.2 (P < 0.05) (step III). During insulin infusion lactate release (P < 0.05) [8.9 +/- 1.8 vs. 2.9 +/- 0.9 mumol.min-1.kg-1 (step I), 24.6 +/- 3.1 vs. 12.5 +/- 2.6 (step III)] and glycogen storage (P < 0.1) calculated by indirect calorimetry [6.7 +/- 2.3 vs. 5.0 +/- 1.7 mg.min-1.kg-1 (step I), 16.8 +/- 2.1 vs. 14.1 +/- 1.8 (step III)] were always higher in T than in UT legs. Release of glycerol, free fatty acids, and tyrosine and clearance of insulin were not influenced by training. Insulin-mediated glucose uptake was not increased after detraining or a single bout of exercise. In conclusion, training increases sensitivity and responsiveness of insulin-mediated glucose uptake in human muscle by local mechanisms. Glycolysis and glycogen storage are equally enhanced. The training effect represents a genuine adaptation to repeated exercise but is short lived. Insulin clearance in muscle is not influenced by training.

The effect of dynamic knee-extension exercise on patellar tendon and quadriceps femoris muscle glucose uptake in humans studied by positron emission tomography

Both tendon and peritendinous tissue show evidence of metabolic activity, but the effect of acute exercise on substrate turnover is unknown. We therefore examined the influence of acute exercise on glucose uptake in the patellar and quadriceps tendons during dynamic exercise in humans. Glucose uptake was measured in five healthy men in the patellar and quadriceps tendons and the quadriceps femoris muscle at rest and during dynamic knee-extension exercise (25 W) using positron emission tomography and [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG). Glucose uptake index was calculated by dividing the tissue activity with blood activity of [18F]FDG. Exercise increased glucose uptake index by 77% in the patellar tendon (from 0.30 +/- 0.09 to 0.51 +/- 0.16, P = 0.03), by 106% in the quadriceps tendon (from 0.37 +/- 0.15 to 0.75 +/- 0.36, P = 0.02), and by 15-fold in the quadriceps femoris muscle (from 0.31 +/- 0.11 to 4.5 +/- 1.7, P = 0.005). The exercise-induced increase in the glucose uptake in neither tendon correlated with the increase in glucose uptake in the quadriceps muscle (r = -0.10, P = 0.87 for the patellar tendon and r = -0.30, P = 0.62 for the quadriceps tendon). These results show that tendon glucose uptake is increased during exercise. However, the increase in tendon glucose uptake is less pronounced than in muscle and the increases are uncorrelated. Thus tendon glucose uptake is likely to be regulated by mechanisms independently of those regulating skeletal muscle glucose uptake.

BLOOD FLOW EFFECTS ON GLUCOSE UPTAKE FOLLOWING RESISTANCE EXERCISE

Although the effects of blood flow on insulin-stimulated glucose uptake have been extensively investigated, the relative importance of blood flow per se on glucose uptake remains unclear. The purpose of this study was to determine if elevated muscle blood flow following exercise affects muscle glucose uptake. Six subjects (three males, three females) were studied before and after a strenuous bout of lower-body resistance exercise. Following exercise, blood flow was selectively reduced in one leg to approximately the resting rate by inflation of an arterial balloon catheter. Femoral artery blood flow was determined using doppler ultrasound and femoral arterial and venous blood glucose concentrations were measured with a glucose analyzer. Post-exercise femoral artery blood flow was significantly reduced by balloon inflation (855 ± 93 ml/min in the control leg, 440 ± 106 ml/min in the decreased flow leg). Reduction of post-exercise blood flow resulted in a significant (p < 0.05) reduction in glucose uptake (0.196 ± 0.043 mmolòmin-1òleg-1 vs. 0.109 ± 0.038 mmolòmin-1òleg-1) when only femoral flow was considered. When collateral flow was considered, a trend toward a reduction in glucose uptake persisted (0.154 ± 0.045 mmolòmin-1òleg-1; P = 0.10). We conclude that the rate of blood flow is a determinant of muscle glucose uptake in humans following resistance exercise.

Differential regulation of intracellular glucose metabolism by glucose and insulin in human muscle.

Insulin and glucose stimulate glucose uptake in human muscle by different mechanisms. Insulin has well-known effects on glucose transport, glycogen synthesis, and glucose oxidation, but the effects of hyperglycemia on the intracellular routing of glucose are less well characterized. We used euglycemic and hyperglycemic clamps with leg balance measurements to determine how hyperglycemia affects skeletal muscle glucose storage, glycolysis, and glucose oxidation in normal human subjects. Glycogen synthase (GS) and pyruvate dehydrogenase complex (PDHC) activities were determined using muscle biopsies. During basal insulin replacement, hyperglycemia (11.6 +/- 0.31 mM) increased leg muscle glucose uptake (0.522 +/- 0.129 vs. 0.261 +/- 0.071 mumol.min-1 x 100 ml leg tissue-1, P < 0.05), storage (0.159 +/- 0.082 vs. -0.061 +/- 0.055, P < 0.05), and oxidation (0.409 +/- 0.080 vs. 0.243 +/- 0.085, P < 0.05) compared with euglycemia (6.63 +/- 0.33 mM). The increase in basal glucose oxidation due to hyperglycemia was associated with increased muscle PDHC activity (0.499 +/- 0.087 vs. 0.276 +/- 0.049, P < 0.05). However, the increase in leg glucose storage was not accompanied by an increase in muscle GS activity. During hyperinsulinemia, hyperglycemia (11.9 +/- 0.49 mM) also caused an additional increase in leg glucose uptake over euglycemia (6.14 +/- 0.42 mM) alone (5.75 +/- 1.25 vs. 3.75 +/- 0.58 mumol.min-1 x 100 ml leg-1, P < 0.05). In this case the major intracellular effect of hyperglycemia was to increase glucose storage (5.03 +/- 1.16 vs. 2.39 +/- 0.37, P < 0.05). At hyperinsulinemia, hyperglycemia had no effect on muscle GS or PDHC activity.(ABSTRACT TRUNCATED AT 250 WORDS)

GLUT 4 and insulin receptor binding and kinase activity in trained human muscle.

1. Physical training enhances sensitivity and responsiveness of insulin-mediated glucose uptake in human muscle. This study examines if this effect of physical training is due to increased insulin receptor function or increased total concentration of insulin-recruitable glucose transporter protein (GLUT 4). 2. Seven healthy young subjects carried out single leg bicycle training for 10 weeks at 70% of one leg maximal oxygen uptake (VO2,max). Subsequently biopsies were taken from the vastus lateralis muscle of both legs. 3. Single leg VO2,max increased for the trained leg (46 +/- 3 to 52 +/- 2 ml min-1 kg-1 (means +/- S.E.M., P < 0.05), and cytochrome c oxidase activity was higher in this compared to the untrained leg (2.0 +/- 0.1 vs. 1.4 +/- 0.1 nmol s-1 (mg muscle)-1, P < 0.05). Insulin binding as well as basal- and insulin-stimulated receptor kinase activity did not differ between trained and untrained muscle. The concentration of GLUT 4 protein was higher in the former (14.9 +/- 1.9 vs. 11.6 +/- 1.0 arbitrary units (micrograms protein)-1 in crude membranes, P < 0.05). The training-induced increase in GLUT 4 (26 +/- 11%) matched a previously reported increase in maximum insulin-stimulated leg glucose uptake (25 +/- 7%) in the same subjects, and individual values of the two variables correlated (correlation coefficient (r) = 0.84, P < 0.05). 4. In conclusion, in human muscle training induces a local contraction-dependent increase in GLUT 4 protein, which enhances the effect of insulin on glucose uptake. On the other hand, insulin receptor function in muscle is unlikely to be affected by training.

Effect of training on insulin-mediated glucose uptake in human muscle

During insulin stimulation whole body glucose uptake is increased in trained compared with untrained humans. However, it is not known which tissue is responsible. Seven young male subjects bicycle trained one leg for 10 wk at 70% of maximal O2 consumption (VO2max). Sixteen hours after last exercise bout, a three-step euglycemic hyperinsulinemic clamp (clamp 1) was performed (insulin levels, means +/- SE: 9 +/- 1, 53 +/- 3, 174 +/- 5, and 2,323 +/- 80 was microU/ml), with measurement of arteriovenous differences and blood flow in both legs. After 6 days of detraining subjects were restudied, having exercised the untrained leg 16 h before. VO2max for trained (T) and untrained (UT) legs was 52 +/- 2 vs. 44 +/- 2 ml.min-1.kg-1 (P &lt; 0.05). In clamp 1 glucose uptake in T and UT legs was 1.0 +/- 0.2 vs. 0.5 +/- 0.1 mg.min-1.kg-1 (basal), 9.7 +/- 2.3 vs. 6.7 +/- 1.7 (P &lt; 0.05) (step I), 19.2 +/- 2.8 vs. 14.3 +/- 2.0 (P &lt; 0.05) (step II), and 22.8 +/- 2.3 vs. 18.6 +/- 2.2 (P &lt; 0.05) (step III). During insulin infusion lactate release (P &lt; 0.05) [8.9 +/- 1.8 vs. 2.9 +/- 0.9 mumol.min-1.kg-1 (step I), 24.6 +/- 3.1 vs. 12.5 +/- 2.6 (step III)] and glycogen storage (P &lt; 0.1) calculated by indirect calorimetry [6.7 +/- 2.3 vs. 5.0 +/- 1.7 mg.min-1.kg-1 (step I), 16.8 +/- 2.1 vs. 14.1 +/- 1.8 (step III)] were always higher in T than in UT legs. Release of glycerol, free fatty acids, and tyrosine and clearance of insulin were not influenced by training. Insulin-mediated glucose uptake was not increased after detraining or a single bout of exercise. In conclusion, training increases sensitivity and responsiveness of insulin-mediated glucose uptake in human muscle by local mechanisms. Glycolysis and glycogen storage are equally enhanced. The training effect represents a genuine adaptation to repeated exercise but is short lived. Insulin clearance in muscle is not influenced by training.