Denervation provokes greater reductions in insulin-stimulated glucose transport in muscle than severe diabetes

We have examined the independent and combined effects of insulin insufficie ncy (streptozotocin (STZ)-induced diabetes, 85 mg/kg i.p.) and reduced musc le activity (denervation) (7 days) on basal, insulin-stimulated and contrac tion-stimulated glucose transport in rat muscles (soleus, red and white gas trocnemius). There were four treatments: control, denervated, diabetic, and denervated + diabetic muscles. Contraction-stimulated glucose transport wa s lowered (similar to 50%) (p < 0.05) to the same extent in all experimenta l groups. In contrast, there was a much smaller reduction insulin-stimulate d glucose transport in muscles from diabetic animals (18-24% reduction, p < 0.05) than in denervated muscles (40-60% reduction, p < 0.05) and in dener vated + diabetic muscles (40-60% reduction, p < 0.05). GLUT-4 mRNA reductio n was greatest in denervated + diabetic muscles ( similar to -75%, p < 0.05 ). GLUT-4 protein was decreased (p < 0.05) to a similar extent in all three experimental conditions ( similar to -30-40%). In conclusion, (1) muscle i nactivity (denervation) and STZ-induced diabetes had similar effects on red ucing contraction-stimulated glucose transport, but (2) muscle inactivity ( denervation), rather than severe diabetes, produced a 2-fold greater impair ment in skeletal muscle insulin-stimulated glucose transport.