Insulin signaling and insulin sensitivity after exercise in human skeletalmuscle

Muscle glucose uptake, glycogen synthase activity, and insulin signaling we re investigated in response to a physiological hyperinsulinemic (600 pmol/l )-euglycemic clamp in young healthy subjects. Four hours before the Clamp, the subjects performed one-legged exercise for 1 h, In the exercised leg, i nsulin more rapidly activated glucose uptake (half activation time [t(1/2)] = 11 vs. 34 min) and glycogen synthase activity (t(1/2) = 8 vs. 17 min), a nd the magnitude of increase was two- to fourfold higher compared with the rested leg. However, prior exercise did not result in a greater or more rap id increase in insulin-induced receptor tyrosine kinase (IRTK) activity (t( 1/2) = 50 min), serine phosphorylation of Akt (t(1/2) = 1-2 min), or serine phosphorylation of glycogen synthase kinase-3 (GSK-3) (t(1/2)= 1-2 min) or in a larger or more rapid decrease in GSK-3 activity (t(1/2) = 3-8 min). T hirty minutes after cessation of insulin infusion, glucose uptake, glycogen synthase activity, and signaling events were partially reversed in both th e rested and the exercised leg. We conclude the following: 1) physiological hyperinsulinemia induces sustained activation of insulin-signaling molecul es in human skeletal muscle; 2) the more distal insulin-signaling component s (Akt, GSK-3) are activated much more rapidly than the proximal signaling molecules (IRTK as well as insulin receptor substrate 1 and phosphatidylino sitol 3-kinase [Wojtaszewski et al., Diabetes 46:1775-1781, 1997]); and 3) prior exercise increases insulin stimulation of both glucose uptake and gly cogen synthase activity in the absence of an upregulation of signaling even ts in human skeletal muscle.