Inhibition of insulin-stimulated xylose uptake in denervated rat soleus muscle: a post-receptor effect.

Insulin (100 U/l) stimulated xylose uptake in rat soleus muscle from a basal value of 2.3 +/- 0.5 to 11.6 +/- 2.1 mumol . g-1 . h-1. Denervation (section of the sciatic nerve) markedly reduced the stimulatory action of insulin (basal 1.3 +/- 0.4 mumol . g-1 . h-1; insulin-stimulated 4.5 +/- 0.6 mumol . g-1 . h-1). This effect appeared 3 days after denervation and was maximal after 5 days. Denervation also affected the insulin dose response curve; there was no effect of insulin in denervated muscle until the concentration exceeded 1 U/l. Denervation inhibited insulin-stimulated alpha-aminoisobutyrate uptake by 77% but did not affect 125I-insulin binding or glucose-independent activation of glycogen synthase by insulin. There was no effect of denervation on the insulinomimetic effects of concanavalin A, hydrogen peroxide, vitamin K5, anoxia, 2:4-dinitrophenol, cooling, hyperosmolarity or EDTA, but the effect of diamide was inhibited. It is concluded [1] that denervation inhibits insulin-stimulated sugar transport at some early post-receptor step, and [2] that the mechanism whereby insulin activates glycogen synthase is different from the activation of the membrane transport of sugars and amino acids.