INSULIN-RESISTANCE OF SKELETAL-MUSCLE PRODUCED BY HEPATIC PARASYMPATHETIC INTERRUPTION

The objective was to determine the site of insulin resistance produced by intraportal atropine or surgical hepatic denervation. A modified e uglycemic clamp was used in fasted cats to test the acute effect of in sulin (100 mU/kg) on arteriovenous glucose gradients across the hindli mbs (mainly reflecting skeletal muscle), the guts (all organs draining into the portal vein), and the liver. Responses to insulin were deter mined before and after hepatic denervation and after 3 mg/kg intraport al atropine. The interventions were done in random order. Responses af ter either intervention were similar and were not potentiated by the c ombined treatment. Regional insulin resistance was assessed by compari ng the change in glucose gradients in response to insulin before and a fter treatments. Hepatic and gut responses to insulin were unaltered, but hindlimb responses were significantly impaired after denervation o r atropine. We speculate that the hepatic parasympathetic nerves regul ate release of a liver-generated factor that selectively controls insu lin effectiveness in skeletal muscle. This mechanism may be involved w ith insulin resistance in non-insulin-dependent diabetes and chronic l iver disease.