Effects of exercise and insulin on insulin signaling proteins in human skeletal muscle

Insulin and exercise independently increase glucose metabolism in muscle. M oreover, exercise training or a prior bout of exercise increases insulin-st imulated glucose uptake in resting skeletal muscle. The present study was u ndertaken to compare how physiological hyperinsulinemia and moderate intens ity aerobic exercise affect the tyrosine phosphorylation state and activity of insulin signaling molecules in healthy, physically inactive volunteers. Subjects had biopsies of the vastus lateralis muscle before and immediatel y after 30 min of either hyperinsulinemia (euglycemic insulin clamp) or mod erate-intensity exercise on a cycle ergometer (similar to 60% of (V) over d ot O-2max). Insulin receptor and IRS-1 tyrosine phosphorylation, associatio n of the p85 regulatory subunit of PI 3-kinase with IRS-1, IRS-1 associated PIS-kinase activity, and glycogen synthase activity were determined in mus cle biopsy specimens taken from healthy subjects before and after insulin o r exercise. Physiological hyperinsulinemia increased the rare of glucose di sposal from 11.4 +/- 1.5 to 25.6 +/- 6.7 mu mol . kg(-1) . min(-1) (P < 0.0 1), insulin receptor and IRS-I tyrosine phosphorylation (173 +/- 19% and 15 9 +/- 35% of basal values, respectively, P < 0.05), association of the p85 regulatory subunit of PI 3-kinase with IRS-1 (159 +/- 10%, P < 0.05), and g lycogen synthase fractional velocity (136 +/- 11%, P < 0.01). Exercise also increased glucose disposal, from 10.4 +/- 0.5 to 15.6 +/- 1.7 mu mol . kg( -1) . min(-1) (P < 0.01) and glycogen synthase fractional velocity (253 +/- 35% of basil, P < 0.01. The exercise-induced increase in glycogen synthase was greater than that due to insulin (P < 0.05). In contrast to insulin, e xercise decreased tyrosine phosphorylation of the insulin receptor to 72 +/ - 10% of basal values (P < 0.05 vs basal and P < 0.05 vs insulin) and had n o effect on IRS-1 tyrosine phosphorylation, or association of p85 with IRS- 1. The exercise-induced decreased insulin receptor tyrosine phosphorylation could explain the well-known effect of exercise to enhance the sensitivity of muscle to insulin.