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

Abstract

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 Endurance Exercise Training on Insulin Signaling in Human Skeletal Muscle

“…However, the existing data in human skeletal muscle are not equivocal. Previously, one cross-sectional study reported a greater fold increase in IRS-1-associated PI3-K activity in response to insulin stimulation in trained compared with untrained subjects (42). Furthermore, it has been shown that insulin-stimulated phosphotyrosine-associated PI3-K activity is greater after 7 days of endurance training in young (18) but not in middle-aged obese (19,43) or type 2 diabetic subjects (43).…”

Increased Skeletal Muscle Tumor Necrosis Factor-α and Impaired Insulin Signaling Persist in Obese Women With Gestational Diabetes Mellitus 1 Year Postpartum

“…Muscle biopsies were performed using the Bergstrom needle biopsy procedure as previously described (28). Approximately 100 mg of tissue was obtained from the vastus lateralis muscle during late pregnancy and again ϳ1 year postpartum.…”

Improved glucose tolerance and insulin sensitivity after electrical stimulation-assisted cycling in people with spinal cord injury

“…20 ± 23 Aerobic endurance exercise has traditionally been advocated as the most suitable exercise mode to prevent and treat DM. 24 ± 28 Exercise has been proven to be e ective in improving muscular, 21,26,27 adipose tissue 20,23,28 and whole body insulin sensitivity. 21,22,25 In one study, 10 subjects with Type 2 DM who had signi®cant insulin resistance and eight controls without insulin resistance were trained with 1 h of stair climbing for 6 weeks.…”

“…The underlying mechanisms responsible for the improvements in muscle glucose metabolism are not fully understood but they seem to involve increases in the glucose transporter protein (GLUT-4), 28 increased blood¯ow, 29 body composition 20,23 and enzyme activities. 26,27 Although, there is enough evidence to conclude that exercise improves insulin sensitivity in the general population, there is a lack of information with respect to the e ects of exercise on insulin sensitivity in people with SCI. Also, it is very di cult for people with SCI to exercise at an appropriate intensity for improvement in insulin sensitivity due to many limitations.…”