Effect of denervation or unweighting on GLUT-4 protein in rat soleus muscle.

The purpose of this study was to test the hypothesis that the decreased capacity for glucose transport in the denervated rat soleus and the increased capacity for glucose transport in the unweighted rat soleus are related to changes in the expression of the regulatable glucose transporter protein in skeletal muscle (GLUT-4). One day after sciatic nerve sectioning, when decreases in the stimulation of soleus 2-deoxyglucose (2-DG) uptake by insulin (-51%, P less than 0.001), contractions (-29%, P less than 0.05), or insulin and contractions in combination (-40%, P less than 0.001) were observed, there was a slight (-18%, NS) decrease in GLUT-4 protein. By day 3 of denervation, stimulation of 2-DG uptake by insulin (-74%, P less than 0.001), contractions (-31%, P less than 0.001), or the two stimuli in combination (-59%, P less than 0.001), as well as GLUT-4 protein (-52%, P less than 0.001), was further reduced. Soleus muscle from hindlimb-suspended rats, which develops an enhanced capacity for insulin-stimulated glucose transport, showed muscle atrophy similar to denervated soleus but, in contrast, displayed substantial increases in GLUT-4 protein after 3 (+35%, P less than 0.05) and 7 days (+107%, P less than 0.001). These results indicate that altered GLUT-4 expression may be a major contributor to the changes in insulin-stimulated glucose transport that are observed with denervation and unweighting. We conclude that muscle activity is an important factor in the regulation of GLUT-4 expression in skeletal muscle.