Insulin action and secretion in endurance-trained and untrained humans

1987 ◽  
Vol 63 (6) ◽  
pp. 2247-2252 ◽  
Author(s):  
D. S. King ◽  
G. P. Dalsky ◽  
M. A. Staten ◽  
W. E. Clutter ◽  
D. R. Van Houten ◽  
...  
Keyword(s):  
Insulin Action ◽  
Plasma Insulin ◽  
Insulin Response ◽  
Fat Free Mass ◽  
Glucose Disposal ◽  
Trained Subjects ◽  
Hyperglycemic Clamp ◽  
Significant Difference ◽  
Increased Sensitivity ◽  
Glucose Disposal Rate

To evaluate insulin sensitivity and responsiveness, a two-stage hyperinsulinemic euglycemic clamp procedure (insulin infusions of 40 and 400 mU.m-2.min-1) was performed on 11 endurance-trained and 11 untrained volunteers. A 3-h hyperglycemic clamp procedure (plasma glucose approximately 180 mg/dl) was used to study the insulin response to a fixed glycemic stimulus in 15 trained and 12 untrained subjects. During the 40-mU.m-2.min-1 insulin infusion, the glucose disposal rate was 10.2 +/- 0.5 mg.kg fat-free mass (FFM)-1.min-1 in the trained group compared with 8.0 +/- 0.6 mg.kg FFM-1.min-1 in the untrained group (P less than 0.01). In contrast, there was no significant difference in maximally stimulated glucose disposal: 17.7 +/- 0.6 in the trained vs. 16.7 +/- 0.7 mg.kg FFM-1.min-1 in the untrained group. During the hyperglycemic clamp procedure, the incremental area for plasma insulin was lower in the trained subjects for both early (0–10 min: 140 +/- 18 vs. 223 +/- 23 microU.ml–1.min; P less than 0.005) and late (10–180 min: 4,582 +/- 689 vs. 8,895 +/- 1,316 microU.ml–1.min; P less than 0.005) insulin secretory phases. These data demonstrate that 1) the improved insulin action in healthy trained subjects is due to increased sensitivity to insulin, with no change in responsiveness to insulin, and 2) trained subjects have a smaller plasma insulin response to an identical glucose stimulus than untrained individuals.

Effects of exercise and lack of exercise on insulin sensitivity and responsiveness

1988 ◽  
Vol 64 (5) ◽  
pp. 1942-1946 ◽  
Author(s):  
D. S. King ◽  
G. P. Dalsky ◽  
W. E. Clutter ◽  
D. A. Young ◽  
M. A. Staten ◽  
...  
Keyword(s):  
Insulin Action ◽  
Plasma Insulin ◽  
Insulin Concentration ◽  
Glucose Disposal ◽  
Plasma Insulin Concentration ◽  
Cross Sectional ◽  
Increased Sensitivity ◽  
Lack Of Exercise ◽  
Insulin Responsiveness ◽  
Glucose Disposal Rate

Insulin action is enhanced in people who exercise regularly and vigorously. In the present study, the hyperinsulinemic, euglycemic clamp procedure was used to determine whether this enhanced insulin action is due to an increased sensitivity and/or an increased responsiveness to insulin. To avoid the variability that exists between individuals and complicates cross-sectional studies, the same subjects were studied in the trained exercising state and again after 10 days of physical inactivity. When the plasma insulin concentration was maintained at approximately 78 microU.ml-1 (a submaximal level), glucose disposal rate averaged 8.7 +/- 0.5 mg.kg-1.min-1 before and 6.7 +/- 0.6 mg.kg-1.min-1 after 10 days of activity (P less than 0.001). When the plasma insulin concentration was maintained at approximately 2,000 microU.ml-1 (a maximally effective concentration), the rate of glucose disposal was not significantly different before (15.3 +/- 0.5 mg.kg-1.min-1) compared with after (14.5 +/- 0.4 mg.kg-1.min-1) 10 days without exercise. These results provide evidence that the reversal of enhanced insulin action that occurs within a few days when exercise-trained individuals stop exercising is due to a decrease in sensitivity to insulin, not to a decrease in insulin responsiveness.

Comparison of short-term diet and exercise on insulin action in individuals with abnormal glucose tolerance

1999 ◽  
Vol 86 (6) ◽  
pp. 1930-1935 ◽  
Author(s):  
Paul J. Arciero ◽  
Matthew D. Vukovich ◽  
John O. Holloszy ◽  
Susan B. Racette ◽  
Wendy M. Kohrt
Keyword(s):  
Glucose Tolerance ◽  
Insulin Action ◽  
Fat Free Mass ◽  
Glucose Disposal ◽  
Abnormal Glucose Tolerance ◽  
High Fat ◽  
Short Term ◽  
Arginine Infusion ◽  
Hyperglycemic Clamp ◽  
Calorie Diet

The effects of a 10-day low-calorie diet (LCD; n = 8) or exercise training (ET; n = 8) on insulin secretion and action were compared in obese men ( n = 9) and women ( n = 7), aged 53 ± 1 yr, with abnormal glucose tolerance by using a hyperglycemic clamp with superimposed arginine infusion and a high-fat drink. Body mass (LCD, 115 ± 5 vs. 110 ± 5 kg; ET, 111 ± 7 vs. 109 ± 7 kg; P < 0.01) and fasting plasma glucose (LCD, 115 ± 10 vs. 99 ± 4 mg/dl; ET, 112 ± 4 vs. 101 ± 5 mg/dl, P < 0.01) and insulin (LCD, 23.9 ± 5.6 vs. 15.2 ± 3.9 μU/ml; ET, 17.6 ± 1.9 vs. 13.9 ± 2.4 μU/ml; P < 0.05) decreased in both groups. There was a 40% reduction in plasma insulin during hyperglycemia (0–45 min) after LCD (peak: 118 ± 18 vs. 71 ± 14 μU/ml; P < 0.05) and ET (69 ± 14 vs. 41 ± 7 μU/ml; P < 0.05) and trends for reductions during arginine infusion and a high-fat drink. The 56% increase in glucose uptake after ET (4.95 ± 0.90 vs. 7.74 ± 0.82 mg ⋅ min−1 ⋅ kg fat-free mass−1; P < 0.01) was significantly ( P < 0.01) greater than the 19% increase (5.72 ± 1.12 vs. 6.80 ± 0.94 mg ⋅ min−1 ⋅ kg fat-free mass−1; P = not significant) that occurred after LCD. The marked increase in glucose disposal after ET, despite lower insulin levels, suggests that short-term exercise is more effective than diet in enhancing insulin action in individuals with abnormal glucose tolerance.

scholarly journals Beneficial Effect of Diazoxide in Obese Hyperinsulinemic Adults1

1998 ◽  
Vol 83 (6) ◽  
pp. 1911-1915 ◽  
Author(s):  
Ramin Alemzadeh ◽  
Gina Langley ◽  
Lori Upchurch ◽  
Pam Smith ◽  
Alfred E. Slonim
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Body Fat ◽  
Therapeutic Potential ◽  
Controlled Trial ◽  
Insulin Response ◽  
Tolerance Test ◽  
Fat Free Mass ◽  
Zucker Rats ◽  
Significant Difference

Hyperinsulinemia, insulin resistance, and increased adipose tissue are hallmarks of the obesity state in both humans and experimental animals. The role of hyperinsulinemia as a possible preceding event in the development of obesity has been proposed. We previously demonstrated that administration of diazoxide (DZ), an inhibitor of insulin secretion, to obese hyperinsulinemic Zucker rats resulted in less weight gain, enhanced insulin sensitivity, and improved glucose tolerance. Assuming that hyperinsulinemia plays a major role in the development of human obesity, then its reversal should have therapeutic potential. To test this hypothesis, we conducted a randomized placebo-controlled trial in 24 hyperinsulinemic adults [body mass index (BMI) &gt; 30 kg/m2]. All subjects were placed on a low-calorie (1260 for females and 1570 for males) Optifast (Sandoz, Minneapolis, MN) diet. After an initial 1-week lead-in period, 12 subjects (mean ± se for age and BMI, 31 ± 1 and 40 ± 2, respectively) received DZ (2 mg/kg BW·day; maximum, 200 mg/day, divided into 3 doses) for 8 weeks; and 12 subjects (mean± se for age and BMI, 28 ± 1 and 43 ± 1, respectively) received placebo. Compared with the placebo group, DZ subjects had greater weight loss (9.5 ± 0.69% vs. 4.6 ± 0.61%, P &lt; 0.001), greater decrease in body fat (P &lt; 0.01), greater increase in fat-free mass to body fat ratio (P &lt; 0.01), and greater attenuation of acute insulin response to glucose (P &lt; 0.01). However, there was no significant difference in insulin sensitivity and glucose effectiveness, as determined by the insulin-modified iv glucose tolerance test (Bergman’s minimal model) and no significant difference in glycohemoglobin values. Conclusion: 8 weeks treatment with DZ had a significant antiobesity effect in hyperinsulinemic obese adults without inducing hyperglycemia.

Effects of treadmill exercise to exhaustion on the insulin response to hyperglycemia in untrained men

1991 ◽  
Vol 70 (1) ◽  
pp. 246-250 ◽  
Author(s):  
J. P. Kirwan ◽  
R. E. Bourey ◽  
W. M. Kohrt ◽  
M. A. Staten ◽  
J. O. Holloszy
Keyword(s):  
Insulin Secretion ◽  
Early Phase ◽  
Pancreatic Beta Cell ◽  
Late Phase ◽  
Insulin Response ◽  
Creatine Kinase Activity ◽  
Whole Body ◽  
Glucose Disposal ◽  
C Peptide ◽  
Hyperglycemic Clamp

The effects of a single bout of exercise to exhaustion on pancreatic insulin secretion were determined in seven untrained men by use of a 3-h hyperglycemic clamp with plasma glucose maintained at 180 mg/100 ml. Clamps were performed either 12 h after an intermittent treadmill run at approximately 77% maximum O2 consumption or without prior exercise. Arterialized blood samples for glucose, insulin, and C-peptide determination were obtained from a heated hand vein. The peak insulin response during the early phase (0–10 min) of the postexercise clamp was higher (81 +/- 8 vs. 59 +/- 9 microU/ml; P less than 0.05) than in the nonexercise clamp. Incremental areas under the insulin (376 +/- 33 vs. 245 +/- 51 microU.ml-1.min) and C-peptide (17 +/- 2 vs. 12 +/- 1 ng.ml-1.min) curves were also greater (P less than 0.05) during the early phase of the postexercise clamp. No differences were observed in either insulin concentrations or whole body glucose disposal during the late phase (15–180 min). Area under the C-peptide curve was greater during the late phase of the postexercise clamp (650 +/- 53 vs. 536 +/- 76 ng.ml-1.min, P less than 0.05). The exercise bout induced muscle soreness and caused an elevation in plasma creatine kinase activity (142 +/- 32 vs. 305 +/- 31 IU/l; P less than 0.05) before the postexercise clamp. We conclude that in untrained men a bout of running to exhaustion increased pancreatic beta-cell insulin secretion during the early phase of the hyperglycemic clamp. Increased insulin secretion during the late phase of the clamp appeared to be compensated by increased insulin clearance.

Glucose tolerance and insulin action in healthy centenarians

1996 ◽  
Vol 270 (5) ◽  
pp. E890-E894 ◽  
Author(s):  
G. Paolisso ◽  
A. Gambardella ◽  
S. Ammendola ◽  
A. D'Amore ◽  
V. Balbi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Insulin Action ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Aged Subjects

Advancing age has been found to be associated with a decline in insulin action. Nevertheless, no study has been conducted in healthy centenarians. Our study investigates glucose tolerance and insulin action in centenarians. Fifty-two subjects were enrolled. The subjects were divided in three groups as follows: 1) adults (< 50 yr; n = 20);2) aged subjects (> 75 yr; n = 22); and 3) centenarians (> 100 yr; n = 14). Body composition was studied by bioimpedance analysis. In all subjects, an oral glucose tolerance test and euglycemic glucose clamp were performed. Centenarians have a lower fat-free mass (FFM) than aged subjects and adults, whereas fasting plasma glucose, triglycerides, free fatty acids, urea, and creatinine were not different in the groups studies. Centenarians had a 2-h plasma glucose concentration (6.0 +/- 0.2 mmol/l) that was lower than that in aged subjects (6.6 +/- 0.5 mmol/l, P < 0.05) but not different from adults [6.4 +/- 0.4 mmol/l, P = not significant (NS)]. During the clamp, plasma glucose and insulin concentrations were similar in the three groups. In these conditions, centenarians had a whole body glucose disposal (34.1 +/- 0.6 mumol.kg FFM-1.min 1) that was greater than that in aged subjects (23.3 +/- 0.5 mumol.kg FFM-1.min-1 P < 0.01) but not different from adults (34.6 +/- 0.5 mumol/kg x min, P = NS). In conclusion, our study demonstrates that centenarians compared with aged subjects had a preserved glucose tolerance and insulin action.

Effects of intraduodenal glucose and fructose on antropyloric motility and appetite in healthy humans

2000 ◽  
Vol 278 (2) ◽  
pp. R360-R366 ◽  
Author(s):  
C. K. Rayner ◽  
H. S. Park ◽  
J. M. Wishart ◽  
M.-F. Kong ◽  
S. M. Doran ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Food Intake ◽  
Plasma Insulin ◽  
Insulin Response ◽  
Oral Glucose ◽  
Inhibitory Peptide ◽  
Healthy Humans ◽  
Significant Difference ◽  
Glucagon Like Peptide 1 ◽  
Gip Release

Oral fructose empties from the stomach more rapidly and may suppress food intake more than oral glucose. The purpose of the study was to evaluate the effects of intraduodenal infusions of fructose and glucose on antropyloric motility and appetite. Ten healthy volunteers were given intraduodenal infusions of 25% fructose, 25% glucose, or 0.9% saline (2 ml/min for 90 min). Antropyloric pressures, blood glucose, and plasma insulin, gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) were measured concurrently; a buffet meal was offered at the end of the infusion. Intraduodenal fructose and glucose suppressed antral waves ( P < 0.0005 for both), stimulated isolated pyloric pressure waves ( P < 0.05 for both), and increased basal pyloric pressure ( P = 0.10 and P < 0.05, respectively) compared with saline, without any significant difference between them. Intraduodenal glucose increased blood glucose ( P < 0.0005), as well as plasma insulin ( P < 0.0005) and GIP ( P < 0.005) more than intraduodenal fructose, whereas there was no difference in the GLP-1 response. Intraduodenal fructose suppressed food intake compared with saline ( P < 0.05) and glucose ( P = 0.07). We conclude that, when infused intraduodenally at 2 kcal/min for 90 min 1) fructose and glucose have comparable effects on antropyloric pressures, 2) fructose tends to suppress food intake more than glucose, despite similar GLP-1 and less GIP release, and 3) GIP, rather than GLP-1, probably accounts for the greater insulin response to glucose than fructose.

Effects of eccentric exercise on insulin secretion and action in humans

1993 ◽  
Vol 75 (5) ◽  
pp. 2151-2156 ◽  
Author(s):  
D. S. King ◽  
T. L. Feltmeyer ◽  
P. J. Baldus ◽  
R. L. Sharp ◽  
J. Nespor
Keyword(s):  
Insulin Secretion ◽  
Eccentric Exercise ◽  
Plasma Glucose ◽  
Early Phase ◽  
Pancreatic Beta Cell ◽  
Late Phase ◽  
Insulin Response ◽  
Whole Body ◽  
Glucose Disposal ◽  
Hyperglycemic Clamp

The effects of an exhaustive bout of eccentric exercise on insulin secretion and action were determined using the hyperglycemic clamp technique. Clamps were performed on eight healthy men after 7 days of inactivity and approximately 36 h after a bout of eccentric exercise. Eccentric exercise consisted of 10 sets of 10 repetitions of combined knee extensions and flexions for each leg at a mean torque 84 +/- 5% of peak concentric torque. During the hyperglycemic clamp procedure, plasma glucose concentration was acutely raised to 10 mmol/l and was maintained near this level for 120 min. Arterialized blood samples were obtained from a heated hand vein to determine plasma glucose and insulin concentrations. Eccentric exercise appeared to produce marked muscle damage, as indicated by a 50-fold increase in plasma creatine phosphokinase (100 +/- 17 vs. 5,209 +/- 3,811 U/l, P < 0.001) and subjective reports of muscle soreness. Peak insulin response during the early phase (0–10 min) of the hyperglycemic clamp was higher after eccentric exercise (183 +/- 38 microU/ml) than after the control clamp (100 +/- 23 microU/ml, P < 0.005). Late-phase (10- to 120-min) insulin response was not altered after eccentric exercise. Peak plasma C-peptide concentrations were higher during the early phase (5.0 +/- 0.7 vs. 4.3 +/- 0.8 ng/ml, P < 0.05) and the late phase (7.5 +/- 0.9 vs. 5.4 +/- 0.6 ng/ml, P < 0.05). Prior eccentric exercise had no significant effect on whole body glucose disposal or glucose disposal rate adjusted for prevailing plasma insulin concentration. These data provide evidence that a single bout of eccentric exercise causes an increase in pancreatic beta-cell insulin secretion in response to hyperglycemia.

scholarly journals Insulin action and glucose metabolism in sheep fed on dried-grass or ground, maize-based diets

1985 ◽  
Vol 54 (2) ◽  
pp. 459-471 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong
Keyword(s):  
Glucose Metabolism ◽  
Insulin Action ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Metabolic Clearance ◽  
Endogenous Glucose

1. The effect of an exogenous supply of glucose, provided by the digestion of maize starch in the small intestine, on endogenous glucose metabolism and insulin action was studied in sheep using the euglycaemic insulin clamp procedure.2. Insulin was infused intravenously at rates of 0.2, 0.5, 1.0 and 6.0 mU/min per kg live weight for four consecutive periods in each of four sheep fed on dried-grass and maize-based diets. Glucose was also infused intravenously at a variable rate, sufficient to maintain the plasma glucose concentration at basal levels. Whole-body rates of glucose metabolism were determined using a continuous infusion of [6-3H]glucose.3. From the resultinginsulin dose-response curves, it was observed that, when the sheep were fed on the dried-grass diet, the responsiveness of glucose metabolism to insulin was less than that reported for non-ruminants.4. When fed the maize-based diet, the glucose metabolic clearance rates (MCR) observed during insulin infusions were significantly greater (P < 0.05) than those observed for the dried-grass diet. However, after correcting for the non-insulin-mediated glucose disposal, differences between diets were not significant.5. The sensitivity of glucose utilization to insulin was not affected by diet. The plasma insulin concentrations causing half-maximal insulin-mediated glucose MCR were 103 (SE 21) and 85 (SE 11) mU/l for the dried-grass and maize-based diets respectively.6. The sensitivity of endogenous glucose production to insulin was also unaffected by diet. The plasma insulin concentrations resulting in the suppression of endogenous glucose production to half the basal level were 80 (SE 26) and 89 (SE 29) mU/l for the dried-grass and maize-based diets respectively.7. It is concluded that the observed increase in glucose utilization on the maize-based diet was due partly to a slight change in responsiveness to insulin and also partly to a change in the rate of non-insulin-mediated glucose disposal.

Alterations in liver, muscle, and adipose tissue insulin sensitivity in men with HIV infection and dyslipidemia

2006 ◽  
Vol 290 (1) ◽  
pp. E47-E53 ◽  
Author(s):  
D. N. Reeds ◽  
K. E. Yarasheski ◽  
L. Fontana ◽  
W. T. Cade ◽  
E. Laciny ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hiv Infection ◽  
Insulin Action ◽  
Plasma Insulin ◽  
Insulin Infusion ◽  
Glucose Production ◽  
Glucose Disposal ◽  
High Dose ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Stimulation Of

Dyslipidemia is common in patients with HIV infection. In this study, a two-stage euglycemic hyperinsulinemic clamp, with infusion of stable isotopically labeled tracers, was used to evaluate insulin action in skeletal muscle, liver, and adipose tissue in HIV-infected men with dyslipidemia (HIV-DL; plasma triglyceride >250 mg/dl and HDL <45mg/dl; n = 12), HIV-infected men without dyslipidemia (HIV w/o DL; n = 12), and healthy men ( n = 6). Basal rates of glucose production (glucose Ra), glucose disposal (glucose Rd), and lipolysis (palmitate Ra) were similar between groups. The relative suppression of glucose Ra(63 ± 4, 77 ± 2, and 78 ± 3%, P = 0.008) and palmitate Ra(49 ± 4, 63 ± 3, and 68 ± 3%, P = 0.005) during low-dose insulin infusion (plasma insulin ∼30 μU/ml), and the relative stimulation of glucose Rd(214 ± 21, 390 ± 25, and 393 ± 46%, P = 0.001) during high-dose insulin infusion (plasma insulin ∼75 μU/ml) were lower in HIV-DL than in HIV w/o DL and healthy volunteers, respectively. Suppression of basal glucose Racorrelated with plasma adiponectin ( r = 0.44, P = 0.02) and inversely with plasma IL-6 ( r = −0.49, P < 0.001). Stimulation of glucose Rdcorrelated directly with adiponectin ( r = 0.48, P < 0.01) and inversely with IL-6 ( r = −0.49, P = 0.02). We conclude that dyslipidemia in HIV-infected men is indicative of multiorgan insulin resistance, and circulating adipokines may be important in the pathogenesis of impaired insulin action.

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