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 activit y and nerve-derived factors were eliminated (denervation) and in muscl es in which only muscle activity was eliminated but in which nerve-der ived factors were maintained [tetrodotoxin (TTX) treatment]. After 3 d ays of denervation, insulin-stimulated 3-O-methylglucose transport was markedly lowered in perfused fat hindlimb muscles (soleus, plantaris, and red and white gastrocnemius; less than or equal to 35%). GLUT-4 w as also decreased by 11-65% in denervated muscles. Blocking muscle act ivity with TTX superfusion of the sciatic nerve for 3 days reduced the insulin-stimulated glucose transport to the same extent as in the den ervated muscles (P > 0.05). However, in soleus, plantaris, and red gas trocnemius muscles, GLUT-4 expression was reduced much less by TTX tre atment than by denervation (P < 0.05). GLUT-4 mRNA abundance was decre ased in denervated muscles but not in TTX-treated muscles. These resul ts suggest that muscle activity largely regulates the insulin-signalin g mechanisms of glucose transport and that nerve-derived trophic facto rs affect pretranslational events to regulate GLUT-4 expression.