Alteration in the expression of GLUT-1 and GLUT-4 protein and messenger RNA levels in denervated rat muscles.

Abstract

Denervation induces insulin resistance of the glucose transport process in skeletal muscle. To determine whether this is due to alterations in the expression of muscle glucose transporters (GLUT) in different fiber types, we evaluated the amount of GLUT-1 and GLUT-4 protein and messenger RNA (mRNA) in extensor digitorum longus (EDL) and soleus at 1, 2, and 3 days after sciatotomy. Denervation elevated the basal rate of 2-[1,2-3H]deoxy-D-glucose (2-DOG) uptake in the EDL and decreased the insulin-stimulated DOG uptake in both muscles. Denervation after 1 day did not modify the GLUT-1 or the GLUT-4 protein level in either muscle. However, it increased GLUT-1 mRNA by 66% and decreased GLUT-4 mRNA by 70% in the EDL, but not in the soleus (P < 0.05). After 2 days of denervation, by which time GLUT-1 mRNA was increased 2-fold and GLUT-4 mRNA was reduced by 70%, we observed a 2-fold increase in GLUT-1 protein (P < 0.01) in the EDL and a 40-45% decrease in GLUT-4 protein in both muscles (P < 0.01). These results indicate that modifications in the expression of GLUT-1 and GLUT-4 protein cannot explain the insulin resistance of the glucose transport process in the EDL or soleus 1 day after denervation. After 2 days of denervation, however, alterations in GLUT-1 and GLUT-4 protein levels may contribute to the change in basal and insulin-stimulated DOG uptake in both the EDL and the soleus muscles.