AJP - Regulatory, Integrative and Comparative Physiology, Vol 269, Issue 5 1148-R1153, Copyright © 1995 by American Physiological Society

ARTICLES

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

L. A. Megeney, R. N. Michel, C. S. Boudreau, P. K. Fernando, M. Prasad, M. H. Tan and A. Bonen
Department of Kinesiology, University of Waterloo, Ontario, Canada.

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.

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