Regulation of muscle glucose transport and GLUT-4 by nerve-derived factors and activity-related processes

Glucose transport and GLUT-4 were examined in muscles in which activity and nerve-derived factors were eliminated (denervation) and in muscles in which only muscle activity was eliminated but in which nerve-derived factors were maintained [tetrodotoxin (TTX) treatment]. After 3 days of denervation, insulin-stimulated 3-O-methylglucose transport was markedly lowered in perfused rat hindlimb muscles (soleus, plantaris, and red and white gastrocnemius; < or = 35%). GLUT-4 was also decreased by 11-65% in denervated muscles. Blocking muscle activity with TTX superfusion of the sciatic nerve for 3 days reduced the insulin-stimulated glucose transport to the same extent as in the denervated muscles (P > 0.05). However, in soleus, plantaris, and red gastrocnemius muscles, GLUT-4 expression was reduced much less by TTX treatment than by denervation (P < 0.05). GLUT-4 mRNA abundance was decreased in denervated muscles but not in TTX-treated muscles. These results suggest that muscle activity largely regulates the insulin-signaling mechanisms of glucose transport and that nerve-derived trophic factors affect pretranslational events to regulate GLUT-4 expression.