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

• DOI: 10.1152/jappl.2000.88.2.797
• Publication Date: 2017-12-22T16:34:12Z
• Authors: John P. Kirwan; Luis F. del Aguila; Jazmir M. Hernandez; David L. Williamson; Donal J. O'Gorman; Rebecca Lewis; Raj K. Krishnan
• Keywords: Adult; Blood Glucose; Male; 0301 basic medicine; Phosphoproteins; Enzyme Activation; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Glucose; Insulin Receptor Substrate Proteins; Humans; Insulin; Female; Infusions, Intravenous; Muscle, Skeletal; Exercise

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 O2uptake (V˙o2 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,V˙o2 maxof 44.4 ± 2.7 ml ⋅ kg−1⋅ min−1). A [6,6-2H]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 (V˙o2 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.