WORTMANNIN INHIBITS INSULIN-STIMULATED BUT NOT CONTRACTION-STIMULATEDGLUCOSE-TRANSPORT ACTIVITY IN SKELETAL-MUSCLE

In skeletal muscle, glucose transport is stimulated by insulin, contra ctions and hypoxia, In this study, we used the phosphatidylinositol 3- kinase (PI 3-kinase) inhibitor wortmannin to examine whether (i) PI 3- kinase activity is necessary for stimulation of glucose transport by i nsulin in muscle, and (ii) PI 3-kinase mediates a step in the pathway by which contractions/ hypoxia stimulate glucose transport. Wortmannin completely blocked insulin- and insulin-like growth factor-1-stimulat ed glucose transport in muscle. In contrast, wortmannin had no effect on the stimulation of glucose transport by contractions or hypoxia, pr oviding evidence that PI 3-kinase activity is not involved in the acti vation of glucose transport by these stimuli.