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.

The temporal pattern for changes in rates of protein synthesis and glucose uptake after resistance exercise, especially relative to each other, is not known. Male Sprague-Dawley rats performed acute resistance exercise (n = 7) or remained sedentary (n = 7 per group), and the following were assessed in vivo 1, 3, 6, 12 and 24 h later: rates of protein synthesis, rates of glucose uptake, phosphatidylinositol 3-kinase (PI3-kinase) activity, and p70(S6k) activity. Rates of protein synthesis in mixed gastrocnemius muscle did not increase until 12 h after exercise (e.g., at 12 h, sedentary = 138 +/- 4 vs. exercised = 178 +/- 6 nmol phenylalanine incorporated x g muscle(-1) x h(-1), mean +/- SE, P < 0.05), whereas at 6 h after exercise rates of glucose uptake were significantly elevated (sedentary = 0.18 +/- 0.020 vs. exercised = 0.38 +/- 0.024 micromol glucose 6-phosphate incorporated x kg muscle(-1) x min(-1), P < 0.05). At 24 h after exercise, rates of protein synthesis were still elevated, whereas glucose uptake had returned to basal levels. Arterial insulin concentrations were not different between groups at any time. Non-insulin-stimulated activities of PI3-kinase and p70(S6k) were higher at 6, 12, and 24 h after exercise (P < 0.05), and, generally, these occurred when rates of protein synthesis (12 and 24 h) and glucose uptake were elevated (6 and 12 but not 24 h) by exercise. These data suggest that regulators of protein synthesis and glucose uptake may respond to the same contraction-generated signals with different kinetics or that they respond to different intra- or extracellular signals that are generated by exercise.

This study had the following objectives: 1) to determine whether diabetic rats could increase muscle mass due to a physiological manipulation (chronic resistance exercise), 2) to determine whether exercise training status modifies the effect of the last bout of exercise on elevations in rates of protein synthesis, and 3) to determine whether chronic resistance exercise alters basal glycemia. Groups consisted of diabetic or nondiabetic rats that performed progressive resistance exercise for 8 wk, performed acute resistance exercise, or remained sedentary. Arterial plasma insulin in diabetic groups was reduced by about one-half (P < 0.05) compared with nondiabetic groups. Soleus and gastrocnemius-plantaris complex muscle wet weights were lower because of diabetes, but in response to chronic exercise these muscles hypertrophied in diabetic (0.028 +/- 0.003 vs. 0.032 +/- 0.0015 g/cm for sedentary vs. exercised soleus and 0.42 +/- 0.068 vs. 0.53 +/- 0.041 g/cm for sedentary vs. exercised gastrocnemius-plantaris, both P < 0.05) but not in nondiabetic (0.041 +/- 0.0026 vs. 0.042 +/- 0.003 g/cm for sedentary vs. exercised soleus and 0.72 +/- 0.015 vs. 0.69 +/- 0.013 g/cm for sedentary vs. exercised gastrocnemius-plantaris) rats when muscle weight was expressed relative to tibial length or body weight (data not shown). Another group of diabetic rats that lifted heavier weights showed muscle hypertrophy. Rates of protein synthesis were higher in red gastrocnemius in chronically exercised than in sedentary rats: 155 +/- 11 and 170 +/- 7 nmol phenylalanine incorporated x g muscle(-1) x h(-1) in exercised diabetic and nondiabetic rats vs. 110 +/- 14 and 143 +/- 7 nmol phenylalanine incorporated x g muscle(-1) x h(-1) in sedentary diabetic and nondiabetic rats. These elevations, however, were lower than in acutely exercised (but untrained) rats: 176 +/- 15 and 193 +/- 8 nmol phenylalanine incorporated x g muscle(-1) x h(-1) in diabetic and nondiabetic rats. Finally, chronic exercise training in diabetic rats was associated with reductions in basal glycemia, and such reductions did not occur in sedentary diabetic groups. These data demonstrate that, despite lower circulating insulin concentrations, diabetic rats can increase muscle mass in response to a physiological stimulus.

These data show that whole milk and sports drinks that are designed for both quick (sport drink A) and long lasting (sport drink B) nutrient replenishment can be used by persons with type 1 diabetes in an effort to avoid LOPEH.

Eccentric exercise (ECC) causes muscle damage, insulin resistance, and increased pancreatic β-cell secretion in young individuals. However, the effects of age on the pancreatic β-cell response to glucose after ECC are unknown. Hyperglycemic clamps (180 min, 10.0 mM) were performed on eight young (age 22 ± 1 yr) and eight older (age 66 ± 2 yr) healthy sedentary males without exercise (CONT) and 48 h after ECC. ECC increased ( P < 0.02) muscle soreness ratings and plasma creatine kinase concentrations in both groups. Insulin and C-peptide secretions were similar between young and older subjects during CONT clamps. ECC increased ( P < 0.05) first-phase (0–10 min) C-peptide area under the curve in young (4.2 ± 0.4 vs. 3.7 ± 0.6 nM ⋅ min; ECC vs. CONT, respectively) but not in older subjects (3.2 ± 0.7 vs. 3.5 ± 0.7 nM ⋅ min; ECC vs. CONT), with significant group differences ( P < 0.02). Indeed, ECC repressed ( P < 0.05) first-phase peak C-peptide concentrations in older subjects (0.93 ± 0.16 vs. 1.12 ± 0.11 nM; ECC vs. CONT). Moreover, first-phase C-peptide-to-insulin molar ratios suggest age-related differences ( P < 0.05) in insulin/C-peptide clearance after ECC. Furthermore, the observed C-peptide response after ECC was related to abdominal adiposity [ r = −0.62, P < 0.02, and r = −0.66, P < 0.006, for first and second (10–180 min) phases, respectively]. In conclusion, older individuals did not exhibit the compensatory increase in β-cell secretion observed among young individuals after ECC. Thus, with increasing age, the pancreatic β-cell may be less responsive to the physiological stress associated with ECC.