Effect of exercise training on whole-body insulin sensitivity and responsiveness

Exercise training causes a decline in basal and glucose-stimulated plasma insulin levels and improves glucose tolerance. Furthermore evidence has been presented for effects on both insulin receptors and postreceptor events. However, it is unclear how these changes affect the in vivo dose-response relationship between insulin levels and whole-body glucose utilization. The aim was to examine the effect of exercise training on this relationship and distinguish between changes in insulin sensitivity and responsiveness. Euglycemic clamps were performed in trained (ET, running 1 h/day for 7 wk), sedentary (CON), and sedentary food-restricted ( SFR ) rats. ET rats showed no increase in maximal net glucose utilization in response to insulin (ET 29.5 +/- 0.6 vs. CON 28.2 +/- 1.5 mg X kg-1 X min-1, NS), whereas insulin sensitivity was increased as indicated by the insulin concentration causing half-maximal stimulation (ED50) (49 +/- 20 for ET and 133 +/- 30 mU/l for CON). Thus 7 wk of moderate exercise training resulted in a significant shift of whole-body insulin sensitivity to place ED50 well within the physiological range of insulin concentrations. This would undoubtedly result in improved glucose disposal in the postprandial state and emphasizes the potential benefit of exercise in obesity and type II diabetes.     

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

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 microU/ml; ET, 17.6 +/- 1.9 vs. 13.9 +/- 2. 4 microU/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 microU/ml; P < 0.05) and ET (69 +/- 14 vs. 41 +/- 7 microU/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.     

Fatigue depresses maximal in vitro skeletal muscle Na(+)-K(+)-ATPase activity in untrained and trained individuals.

This study investigated whether fatiguing dynamic exercise depresses maximal in vitro Na(+)-K(+)-ATPase activity and whether any depression is attenuated with chronic training. Eight untrained (UT), eight resistance-trained (RT), and eight endurance-trained (ET) subjects performed a quadriceps fatigue test, comprising 50 maximal isokinetic contractions (180 degrees /s, 0.5 Hz). Muscle biopsies (vastus lateralis) were taken before and immediately after exercise and were analyzed for maximal in vitro Na(+)-K(+)-ATPase (K(+)-stimulated 3-O-methylfluoroscein phosphatase) activity. Resting samples were analyzed for [(3)H]ouabain binding site content, which was 16.6 and 18.3% higher (P < 0.05) in ET than RT and UT, respectively (UT 311 +/- 41, RT 302 +/- 52, ET 357 +/- 29 pmol/g wet wt). 3-O-methylfluoroscein phosphatase activity was depressed at fatigue by -13.8 +/- 4.1% (P < 0.05), with no differences between groups (UT -13 +/- 4, RT -9 +/- 6, ET -22 +/- 6%). During incremental exercise, ET had a lower ratio of rise in plasma K(+) concentration to work than UT (P < 0.05) and tended (P = 0.09) to be lower than RT (UT 18.5 +/- 2.3, RT 16.2 +/- 2.2, ET 11.8 +/- 0.4 nmol. l(-1). J(-1)). In conclusion, maximal in vitro Na(+)-K(+)-ATPase activity was depressed with fatigue, regardless of training state, suggesting that this may be an important determinant of fatigue.     

Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in human skeletal muscle.

Insulin action in skeletal muscle is enhanced by regular exercise. Whether insulin signaling in human skeletal muscle is affected by habitual exercise is not well understood. Phosphatidylinositol 3-kinase (PI3-kinase) activation is an important step in the insulin-signaling pathway and appears to regulate glucose metabolism via GLUT-4 translocation in skeletal muscle. To examine the effects of regular exercise on PI3-kinase activation, 2-h hyperinsulinemic (40 mU. m(-2). min(-1))-euglycemic (5.0 mM) clamps were performed on eight healthy exercise-trained [24 +/- 1 yr, 71.8 +/- 2.0 kg, maximal O(2) uptake (VO(2 max)) of 56.1 +/- 2.5 ml. kg(-1). min(-1)] and eight healthy sedentary men and women (24 +/- 1 yr, 64.7 +/- 4.4 kg, VO(2 max) of 44.4 +/- 2.7 ml. kg(-1). min(-1)). A [6, 6-(2)H]glucose tracer was used to measure hepatic glucose output. A muscle biopsy was obtained from the vastus lateralis muscle at basal and at 2 h of hyperinsulinemia to measure insulin receptor substrate-1(IRS-1)-associated PI3-kinase activation. Insulin concentrations during hyperinsulinemia were similar for both groups (293 +/- 22 and 311 +/- 22 pM for trained and sedentary, respectively). Insulin-mediated glucose disposal rates (GDR) were greater (P < 0.05) in the exercise-trained compared with the sedentary control group (9.22 +/- 0.95 vs. 6.36 +/- 0.57 mg. kg fat-free mass(-1). min(-1)). Insulin-stimulated PI3-kinase activation was also greater (P < 0.004) in the trained compared with the sedentary group (3.8 +/- 0.5- vs. 1.8 +/- 0.2-fold increase from basal). Endurance capacity (VO(2 max)) was positively correlated with PI3-kinase activation (r = 0.53, P < 0.04). There was no correlation between PI3-kinase and muscle morphology. However, increases in GDR were positively related to PI3-kinase activation (r = 0.60, P < 0.02). We conclude that regular exercise leads to greater insulin-stimulated IRS-1-associated PI3-kinase activation in human skeletal muscle, thus facilitating enhanced insulin-mediated glucose uptake.     

Effects of HRT and exercise training on insulin action, glucose tolerance, and body composition in older women.

The independent and combined effects of exercise training and hormone replacement therapy (HRT) on body composition, fat distribution, glucose tolerance, and insulin action were studied in postmenopausal women, aged 68 +/- 5 yr, assigned to control (n = 19), exercise (n = 18), HRT (n = 15), and exercise + HRT (n = 16) groups. The exercise consisted of 2 mo of flexibility exercises followed by 9 mo of endurance exercise. HRT was conjugated estrogens 0.625 mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days. Total and regional body composition were measured by dual-energy X-ray absorptiometry. Serum glucose and insulin responses were measured during a 2-h oral glucose tolerance test. There were significant main effects of exercise on reductions in total and regional (trunk, arms, legs) fat mass, increase in leg fat-free mass, and improvements in glucose tolerance and insulin action. There were significant main effects of HRT on the reduction of total fat mass (HRT, -3.0 +/- 4.0 kg; no HRT, -1.3 +/- 2.6 kg), with a strong trend for reductions in trunk and leg fat mass (both P = 0.07). There was also a significant improvement in insulin action in response to HRT. These results suggest that there are independent and additive effects of exercise training and HRT on the reduction in fat mass and improvement in insulin action in postmenopausal women; the effect of HRT on insulin action may be mediated, in part, through changes in central adiposity.     

Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats.

Exercise training improves skeletal muscle insulin sensitivity in the obese Zucker rat. The purpose of this study was to investigate whether the improvement in insulin action in response to exercise training is associated with enhanced insulin receptor signaling. Obese Zucker rats were trained for 7 wk and studied by using the hindlimb-perfusion technique 24 h, 96 h, or 7 days after their last exercise training bout. Insulin-stimulated glucose uptake (traced with 2-deoxyglucose) was significantly reduced in untrained obese Zucker rats compared with lean controls (2.2 +/- 0.17 vs. 5.4 +/- 0.46 micromol x g(-1) x h(-1)). Glucose uptake was normalized 24 h after the last exercise bout (4.9 +/- 0.41 micromol x g(-1) x h(-1)) and remained significantly elevated above the untrained obese Zucker rats for 7 days. However, exercise training did not increase insulin receptor or insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, phosphatidylinositol 3-kinase (PI3-kinase) activity associated with IRS-1 or tyrosine phosphorylated immunoprecipitates, or Akt serine phosphorylation. These results are consistent with the hypothesis that, in obese Zucker rats, adaptations occur during training that lead to improved insulin-stimulated muscle glucose uptake without affecting insulin receptor signaling through the PI3-kinase pathway.     

Effect of body weight gain on insulin sensitivity after retirement from exercise training

The objectives of this study were to determine how long increased insulin sensitivity, elicited by exercise training, persists after the end of training and what the effect of weight gain is on this retention. Exercise-trained (ET) rats ran voluntarily in freely rotating wheel cages, and insulin sensitivity was assessed by oral glucose tolerance tests (OGTT) and insulin suppression tests (IST). After training, ET rats were retired for 1, 3, or 7 days (R1, R3, or R7). Initial OGTT and IST studies indicated that sensitivity to insulin-induced glucose uptake was increased in ET rats compared with sedentary control (C) rats and was progressively lost with retirement: ET greater than R1 and R3 greater than R7 and C rats, and this reaction was generally associated with a rapid gain in body weight. Subsequent IST tests were performed on C and R7 rats fed laboratory chow or a hypocaloric diet consisting of equal parts of cellulose and chow for 7 days before the test. The results of these tests showed that steady-state serum glucose (SSSG) levels averaged 165 +/- 12 mg/dl for chow-fed C rats and 172 +/- 11 mg/dl for chow-fed R7 rats that gained body weight at rates twice those of C rats. Chow-fed R7 rats, gaining weight at rates comparable to C rats, had SSSG levels of 104 +/- 6 mg/dl. C and R7 rats fed the hypocaloric diet had SSSG values of 102 +/- 6 and 59 +/- 4 mg/dl, respectively. Muscle glycogen levels were comparable in all groups, and liver glycogen was lower in C and R7 rats fed the hypocaloric diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Voluntary exercise training enhances glucose transport but not insulin signaling capacity in muscle of hypertensive TG(mREN2)27 rats.

Male heterozygous TG(mREN2)27 rats (TGR) overexpress a murine renin transgene, display marked hypertension, and have insulin resistance of skeletal muscle glucose transport and insulin signaling. We have shown previously that voluntary exercise training by TGR improves insulin-mediated skeletal muscle glucose transport (Kinnick TR, Youngblood EB, O'Keefe MP, Saengsirisuwan V, Teachey MK, and Henriksen EJ. J Appl Physiol 93: 805-812, 2002). The present study evaluated whether this training-induced enhancement of muscle glucose transport is associated with upregulation of critical insulin signaling elements, including insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase, Akt, and glycogen synthase kinase-3. TGR remained sedentary or ran spontaneously in activity wheels for 6 wk, averaging 7.1 +/- 0.8 km/day by the end of week 3 and 4.3 +/- 0.5 km/day over the final week of training. Exercise training reduced total abdominal fat by 20% (P < 0.05) in TGR runners (2.64 +/- 0.01% of body weight) compared with sedentary TGR controls (3.28 +/- 0.01%). Insulin-stimulated (2 mU/ml) glucose transport activity in soleus muscle was 36% greater in TGR runners compared with sedentary TGR controls. However, the protein expression and functionality of tyrosine phosphorylation of insulin receptor and IRS-1, IRS-1 associated with the p85 regulatory subunit of phosphatidylinositol 3-kinase, and Ser473 phosphorylation of Akt were not altered by exercise training. Only insulin-stimulated glycogen synthase kinase-3beta Ser9 phosphorylation was increased (22%) by exercise training. These results indicate that voluntary exercise training in TGR can enhance insulin-mediated glucose transport in skeletal muscle, as well as reduce total abdominal fat mass. However, this adaptive response in muscle occurs independently of modifications in the proximal elements of the insulin signaling cascade.     

Muscle glucose uptake of obese Zucker rats trained at two different intensities

Exercise training reduces the muscle insulin resistance of the obese Zucker rat. The purpose of the present study was to determine whether the magnitude of this training response is exercise intensity specific. Obese Zucker rats were randomly divided into sedentary (SED), low-intensity (LI), and high-intensity (HI) exercise groups. For the LI rats, exercise training consisted of running on a rodent treadmill at 18 m/min up an 8% grade for 90 min. Rats in the HI group ran at 24 m/min up an 8% grade for four 17-min bouts with 3 min between bouts. Both exercise groups performed the same amount of work and trained 5 days/wk for 7 wk. To evaluate muscle insulin resistance, rat hindlimbs were perfused for 30 min with perfusate containing 6 mM glucose (0.15 mu Ci of D-[14C(U)] glucose/ml) and either a maximal (10.0 mU/ml) or a submaximal (0.50 mU/ml) insulin concentration. Perfusions were performed 48-56 h after the last exercise bout and a 12-h fast. In the presence of 0.5 mU/ml insulin, the rate of muscle glucose uptake was found to be significantly faster for the HI (9.56 +/- 0.66 mumol.h-1.g-1) than for the LI (7.72 +/- 0.65 mumol.h-1.g-1) and SED (6.64 +/- 0.44 mumol.h-1.g-1) rats. The difference in glucose uptake between the LI and SED rats was not significant. In the presence of 10.0 mU/ml insulin, the rate of glucose uptake was significantly faster for the HI (16.43 +/- 1.02 mumol.h-1.g-1) than for the LI rats (13.76 +/- 0.84 mumol.h-1.g-1) and significantly faster for the LI than for the SED rats (11.02 +/- 0.35 mumol.h-1.g-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of a two-month detraining on glucose tolerance and insulin sensitivity in athletes--link to adrenal steroid hormones

Reduction in physical activity has been demonstrated to associate with the increased risk in insulin resistance and type 2 diabetes. To determine whether alteration in insulinemia, due to abstention from regular exercise training, is associated with changes in serum dehydroepiandrosterone sulfate (DHEA-S) and cortisol, 18 highly trained badminton players (21.2 +/- 0.3 years) were enrolled into a 2-month detraining study. Fasting serum insulin, glucose, DHEA-S, and cortisol were determined at trained state and at day 60 of detraining. Glucose tolerance and insulin sensitivity were assessed by an oral glucose tolerance test (OGTT). The 2-month detraining increased fasting glucose and insulin concentrations and body weight slightly, but did not significantly affect glucose tolerance and insulin response curve, in which 10 subjects had increased and 8 subjects had slightly decreased in the area under curve for insulin (IAUC). In the subjects with increased IAUC, serum cortisol was also elevated (from 0.44 +/- 0.07 to 0.83 +/- 0.26 U/l, P < 0.05) in parallel, and serum creatine kinase (CK) was unaltered during detraining. Whereas in the subjects with decreased IAUC, serum cortisol (from 0.51 +/- 0.19 to 0.54 +/- 0.14 U/l, no significance) was not changed and serum creatine kinase (from 461 +/- 179 to 151 +/- 21 U/l) was decreased during detraining. Two groups of detrained subjects exhibited a similar reduction in serum DHEA-S levels and slight elevation in body weight. The novel finding of the study is that the changes in serum cortisol, but not DHEA-S, were associated with the change in insulin sensitivity during early phase of lifestyle change from physically active to sedentary, and this response appears to be varied individually among athletes.     

Improved insulin action following short-term exercise training: role of energy and carbohydrate balance.

Short-term exercise training improves insulin action, but the impact of replacing the energy expended during exercise to prevent energy deficit is unclear. The purpose of this study was to establish the role of an energy deficit in mediating improved insulin action after short-term exercise training. Two groups of previously sedentary, overweight/obese subjects performed 6 consecutive days of moderate-intensity walking to expend approximately 500 kcal/day. In one group, energy and carbohydrate expended during exercise was replaced [balance group (BAL), n = 8] and in the other group, energy was not replaced [deficit group (DEF), n = 8]. Insulin action (blood glucose uptake during glucose infusion) and selected lipids and adipokines were measured pre- and posttraining. Training increased estimated daily energy expenditure by approximately 500 kcal/day (DEF = 469 +/- 45, BAL = 521 +/- 48), generating an energy deficit in DEF (-481 +/- 24 kcal/day) but not BAL (+8 +/- 20 kcal/day). Insulin action increased 40% in DEF (P = 0.032) but not BAL (-8.4%, P = 0.107). Hepatic glucose production was suppressed during glucose infusion in DEF (30.2 +/- 9.5%, P = 0.037) but not BAL (-10.0 +/- 7.4%, P = 0.417). Fasting leptin concentrations declined in DEF but not BAL. Six days of exercise training without energy replacement significantly increased insulin action. Restoring energy balance by refeeding the energy and carbohydrate expended during exercise resulted in no change in insulin action. These findings suggest that changes in short-term energy and/or carbohydrate balance play a key role in mediating the beneficial effects of exercise on whole body and hepatic insulin action.     

Glucose uptake after resistance training of different intensities but of equal work volume

High-intensity (HI) resistance exercise augments postexercise glucose uptake to a greater degree than low-intensity (LO) resistance exercise; however, few studies have equated the work volumes between intensity levels. The purpose of this study was to compare the effect of acute HI and LO resistance exercise of equal work volume on glucose uptake in resistant-trained men. Fifteen healthy male (22.9 +/- 3.8 years old), resistance-trained (6.7 +/- 3.9 years) subjects completed three treatment sessions: CON (no-exercise control), HI (3 x 8, 85% 10-RM), and LO (3 x 15, 45% 10-RM). HI and LO sessions consisted of eight exercises. Glucose uptake was measured the following morning by using the hyperinsulinemic euglycemic clamp technique. Glucose disposal was measured by analyzing the glucose infusion rate during the final 30 minutes of steady-state blood glucose concentrations. Insulin sensitivity was calculated by dividing the glucose infusion rate by the average insulin infusion. Results indicate that fasting blood glucose levels were not significantly different among treatment sessions (CON = 80.5 +/- 5.3 versus HI = 77.0 +/- 4.9 versus LO = 77.1 +/- 6.0 mg.dL). Glucose uptake was not significantly different among treatment sessions (CON = 11.3 +/- 3.0 versus HI = 11.7 +/- 2.7 versus LO = 11.4 +/- 2.8 mg.kg FFM.min). Insulin sensitivity did not change among treatment sessions (CON = 0.26 +/- 0.09 versus HI = 0.28 +/- 0.07 versus LO = 0.27 +/- 0.06 (mg.kg FFM.min)/(uU.mL)). The data indicate that the resistance training sessions did not modify acute insulin sensitivity. This may have been because of the high levels of fitness of the subjects, which allowed for the cellular adaptations for enhanced insulin sensitivity and glucose uptake that are unaffected by this volume of acute exercise.     

Interactions of exercise training and lipoic acid on skeletal muscle glucose transport in obese Zucker rats.

Exercise training (ET) or the antioxidant R(+)-alpha-lipoic acid (R-ALA) individually increases insulin action in the insulin-resistant obese Zucker rat. The purpose of the present study was to determine the interactions of ET and R-ALA on insulin action and oxidative stress in skeletal muscle of the obese Zucker rat. Animals either remained sedentary, received R-ALA (30 mg x kg body wt(-1) x day(-1)), performed ET (treadmill running), or underwent both R-ALA treatment and ET for 6 wk. During an oral glucose tolerance test, ET alone or in combination with R-ALA resulted in a significant lowering of the glucose (26-32%) and insulin (29-30%) responses compared with sedentary controls. R-ALA alone decreased (19%) the glucose-insulin index (indicative of increased insulin sensitivity), and this parameter was reduced (48-52%) to the greatest extent in the ET and combined treatment groups. ET or R-ALA individually increased insulin-mediated glucose transport activity in isolated epitrochlearis (44-48%) and soleus (37-57%) muscles. The greatest increases in insulin action in these muscles (80 and 99%, respectively) were observed in the combined treatment group. Whereas the improvement in insulin-mediated glucose transport in soleus due to R-ALA was associated with decreased protein carbonyl levels (an index of oxidative stress), improvement because of ET was associated with decreased protein carbonyls as well as enhanced GLUT-4 protein. However, there was no interactive effect of ET and R-ALA on GLUT-4 protein or protein carbonyl levels. These results indicate that ET and R-ALA interact in an additive fashion to improve insulin action in insulin-resistant skeletal muscle. Because the further improvement in muscle glucose transport in the combined group was not associated with additional upregulation of GLUT-4 protein or a further reduction in oxidative stress, the mechanism for this interaction must be due to additional, as yet unidentified, factors.     

Circulating plasma VEGF response to exercise in sedentary and endurance-trained men.

The skeletal muscle capillary supply is an important determinant of maximum exercise capacity, and it is well known that endurance exercise training increases the muscle capillary supply. The muscle capillary supply and exercise-induced angiogenesis are regulated in part by vascular endothelial growth factor (VEGF). VEGF is produced by skeletal muscle cells and can be secreted into the circulation. We investigated whether there are differences in circulating plasma VEGF between sedentary individuals (Sed) and well-trained endurance athletes (ET) at rest or in response to acute exercise. Eight ET men (maximal oxygen consumption: 63.8 +/- 2.3 ml x kg(-1) x min(-1); maximum power output: 409.4 +/- 13.3 W) and eight Sed men (maximal oxygen consumption: 36.3 +/- 2.1 ml x kg(-1) x min(-1); maximum power output: 234.4 +/- 13.3 W) exercised for 1 h at 50% of maximum power output. Antecubital vein plasma was collected at rest and at 0, 2, and 4 h postexercise. Plasma VEGF was measured by ELISA analysis. Acute exercise significantly increased VEGF at 0 and 2 h postexercise in ET subjects but did not increase VEGF at any time point in Sed individuals. There was no difference in VEGF between ET and Sed subjects at any time point. When individual peak postexercise VEGF was analyzed, exercise did increase VEGF independent of training status. In conclusion, exercise can increase plasma VEGF in both ET athletes and Sed men; however, there is considerable variation in the individual time of the peak VEGF response.     

A novel approach to assess insulin sensitivity reveals no increased insulin sensitivity in mice with a dominant-negative mutant hepatocyte nuclear factor-1alpha

In phenotype experiments in mice, determination of dynamic insulin sensitivity often uses the insulin tolerance test. However, the interpretation of this test is complicated by the counterregulation occurring at low glucose. To overcome this problem, we determined the dynamic insulin sensitivity after inhibition of endogenous insulin secretion by diazoxide (25 mg/kg) in association with intravenous administration of glucose plus insulin (the DSGIT technique). Estimation of insulin sensitivity index (SI) by this technique showed good correlation to SI from a regular intravenous glucose tolerance test (r = 0.87; P < 0.001; n = 15). With DSGIT, we evaluated dynamic insulin sensitivity in mice with a rat insulin promoter (beta-cell-targeted) dominant-negative mutation of hepatic nuclear factor (HNF)-1alpha [RIP-DN HNF-1alpha (Tg) mice]. When insulin was administered exogenously at the same dose in Tg and wild-type (WT) mice, plasma insulin levels were higher in WT, indicating an increased insulin clearance in Tg mice. When the diazoxide test was used, different doses of insulin were therefore administered (0.1 and 0.15 U/kg in WT and 0.2 and 0.25 U/kg in Tg) to achieve similar insulin levels in the groups. Minimal model analysis showed that SI was the same in the two groups (0.78 +/- 0.21 x 10(-4) min.pmol(-1).l(-1) in WT vs. 0.60 +/- 0.11 in Tg; P = 0.45) as was the glucose elimination rate (P = 0.27). We conclude that 1) the DSGIT technique determines the in vivo dynamic insulin action in mice, 2) insulin clearance is increased in Tg mice, and 3) chronic islet dysfunction in RIP-DN HNF-1alpha mice is not compensated with increased insulin sensitivity.     

Glucose uptake by adipocytes of obese rats: effect of one bout of acute exercise.

The effect of one bout of acute exercise on impaired glucose metabolism was studied in obese (480 +/- 20 g), untrained rats, at rest (n = 10) and after 60 min of swimming (n = 5). Using the euglycemic, hyperinsulinemic (10 mU.kg-1 x min-1) clamp, glucose clearance rate increased from 7.6 +/- 0.9 at rest to 9.7 +/- 0.5 mL.kg-1 x min-1 after exercise (p < 0.05). Glucose (3-O-[14C]methylglucose) transport (GT) into epididymal adipocytes were incubated with or without insulin. In the absence of insulin, GT was 0.13 +/- 0.02 and 0.26 +/- 0.07 fmol.cell-1 x min-1 at rest and after exercise, respectively. In the presence of insulin (25-1000 microU.mL-1) GT increased at rest from 0.97 +/- 0.08 to 1.13 +/- 0.07 fmol.cell-1 x min-1, and after exercise from 1.35 +/- 0.05 to 1.87 +/- 0.11 fmol.cell-1 x min-1. GT was significantly higher after exercise compared with rest (p < 0.004). At rest, maximal insulin effect was achieved at 100 microU.mL-1, whereas with exercise, GT increased gradually with the insulin dosage. The following may be concluded: (i) the biological effect of insulin is amplified in obese rats by one bout of exercise and (ii) exercise affects GT into enlarged adipocytes by enhancing tissue responsiveness to insulin and by a cellular mechanism unrelated to the insulin action.     

Time course of insulin sensitivity and skeletal muscle glycogen synthase activity after a single bout of exercise in horses.

The time course of insulin sensitivity, skeletal muscle glycogen and GLUT4 content, and glycogen synthase (GS) activity after a single bout of intense exercise was examined in eight horses. On separate days, a euglycemic-hyperinsulinemic clamp (EHC) was undertaken at 0.5, 4, or 24 h after exercise or after 48 h of rest [control (Con)]. There was no increase in mean glucose infusion rate (GIR) with exercise (0.5-, 4-, and 24-h trials), and GIR was significantly decreased at 0.5 h postexercise (GIR: 8.6 +/- 2.7, 6.7 +/- 2.0, 9.0 +/- 2.0, and 10.6 +/- 2.2 mg.kg(-1).min(-1) for Con and at 0.5, 4, and 24 h, respectively). Before each EHC, muscle glycogen content (mmol glucosyl units/kg dry muscle) was higher (P < 0.05) for Con (565 +/- 102) than for other treatments (317 +/- 84, 362 +/- 79, and 382 +/- 74 for 0.5, 4, and 24 h, respectively) and muscle GLUT4 content was unchanged. Pre-EHC active-to-total GS activity ratio was higher (P < 0.05) at 0.5, 4, and 24 h after exercise than in Con. Post-EHC active GS and GS activity ratio were higher (P < 0.05) in Con and at 24 h. There was a significant inverse correlation (r = -0.43, P = 0.02) between glycogen content and GS activity ratio but no relationship between GS activity and GIR. The lack of increase in insulin sensitivity, determined by EHC, after exercise that resulted in a significant reduction in muscle glycogen content is consistent with the slow rate of muscle glycogen resynthesis observed in equine studies.     

Endurance exercise training increases insulin responsiveness in isolated adipocytes through IRS/PI3-kinase/Akt pathway.

Endurance exercise training promotes important metabolic adaptations, and the adipose tissue is particularly affected. The aim of this study was to investigate how endurance exercise training modulates some aspects of insulin action in isolated adipocytes and in intact adipose tissue. Male Wistar rats were submitted to daily treadmill running (1 h/day) for 7 wk. Sedentary age-matched rats were used as controls. Final body weight, body weight gain, and epididymal fat pad weight did not show any statistical differences between groups. Adipocytes from trained rats were smaller than those from sedentary rats (205 +/- 16.8 vs. 286 +/- 26.4 pl; P < 0.05). Trained rats showed decreased plasma glucose (4.9 +/- 0.13 vs. 5.3 +/- 0.07 mM; P < 0.05) and insulin levels (0.24 +/- 0.012 vs. 0.41 +/- 0.049 mM; P < 0.05) and increased insulin-stimulated glucose uptake (23.1 +/- 3.1 vs. 12.1 +/- 2.9 pmol/cm(2); P < 0.05) compared with sedentary rats. The number of insulin receptors and the insulin-induced tyrosine phosphorylation of insulin receptor-beta subunit did not change between groups. Insulin-induced tyrosine phosphorylation insulin receptor substrates (IRS)-1 and -2 increased significantly (1.57- and 2.38-fold, respectively) in trained rats. Insulin-induced IRS-1/phosphatidylinositol 3 (PI3)-kinase (but not IRS-2/PI3-kinase) association and serine Akt phosphorylation also increased (2.06- and 3.15-fold, respectively) after training. The protein content of insulin receptor-beta subunit, IRS-1 and -2, did not differ between groups. Taken together, these data support the hypothesis that the increased adipocyte responsiveness to insulin observed after endurance exercise training is modulated by IRS/PI3-kinase/Akt pathway.     

Changes in insulin response to glucose after exercise training in partially pancreatectomized rats

The effects of exercise training on glucose-stimulated insulin secretion (GSIS) were studied in male Sprague-Dawley rats made mildly to severely diabetic by partial pancreatectomy. Exercise trained (10 wk treadmill; T) and untrained (Unt) rats were grouped according to posttraining fed-state hyperglycemia as follows: T less than 200 and Unt less than 200 (glucose concn less than 200 mg/dl), T 200-300 and Unt 200-300 (glucose concn 200-300 mg/dl), and T greater than 300 and Unt greater than 300 (glucose concn greater than 300 mg/dl). After exercise training, hyperglycemic glucose clamps were performed in awake rats by elevation of arterial blood glucose concentration 126 mg/dl above fasting basal levels for 90 min. Exercise training significantly increased muscle citrate synthase activity. Prevailing hyperglycemia was reduced during the 10-wk exercise training period in all T rats with fed-state glucose concentrations less than 300, and only 53% of Unt rats in these groups had reduced glycemia. GSIS was significantly higher in T less than 200 [2.4 +/- 0.7 (SD) ng/ml at 90 min] than in Unt less than 200 (1.5 +/- 0.3). A similar response was found for T 200-300 (1.1 +/- 0.3 ng/dl) vs. Unt 200-300 (0.7 +/- 0.1) but not T greater than 300 (0.36 +/- 0.2) vs Unt greater than 300 (0.44 +/- 0.05). Sham-operated control rats had insulin concentrations of 6.6 +/- 1.6 ng/ml at the 90th min of the clamp. Acute exercise reduced fed-state glycemia in rats with mild-to-moderate (less than 300 mg/dl) diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)