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1 Departments of Reproductive Biology and Nutrition, Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio 44109; and 2 Noll Physiological Research Center and the General Clinical Research Center, Pennsylvania State University, University Park, Pennsylvania 16802
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 · min1)-euglycemic
(5.0 mM) clamps were performed on eight healthy exercise-trained [24 ± 1 yr, 71.8 ± 2.0 kg, maximal O2 uptake
(
O2 max) of 56.1 ± 2.5 ml · kg1 · min1]
and eight healthy sedentary men and women (24 ± 1 yr, 64.7 ± 4.4 kg,
O2 max of
44.4 ± 2.7 ml · kg1 · min1).
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
mass1 · min1).
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 (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.
glucose metabolism; exercise training; insulin action; muscle; enzymes; insulin receptor substrate-1; phosphatidylinositol 3-kinase
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