Muscle glycogen content affects insulin-stimulated glucose transport and protein kinase B activity

We investigated the possible regulatory role of glycogen in insulin-stimula ted glucose transport and insulin signaling in skeletal muscle. Rats were p reconditioned to obtain low (LG), normal, or high (HG) muscle glycogen cont ent, and perfused isolated hindlimbs were exposed to 0, 100, or 10,000 muU/ ml insulin. In the fast-twitch white gastrocnemius, insulin-stimulated glu cose transport was significantly higher in LG compared with HG. This differ ence was less pronounced in the mixed-fiber red gastrocnemius and was absen t in the slow-twitch soleus. In the white gastrocnemius, insulin activation of insulin receptor tyrosine kinase and phosphoinositide 3-kinase was unaf fected by glycogen levels, whereas protein kinase B activity was significan tly higher in LG compared with HG. In additional incubation experiments on fast-twitch epitrochlearis muscles, insulin-stimulated cell surface GLUT-4 content was significantly higher in LG compared with HG. The data indicate that, in fast-twitch muscle, the effect of insulin on glucose transport and cell surface GLUT-4 content is modulated by glycogen content, which does n ot involve initial but possibly more downstream signaling events.