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

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Abstract
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 μmol · g-1 · h-1. Denervation (section of the sciatic nerve) markedly reduced the stimulatory action of insulin (basal 1.3 ±0.4 μmol · g-1 · h-1; insulin-stimulated 4.5±0.6 μmol · 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 α-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.

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