Insulin resistance of glucose response produced by hepatic denervations

This study investigated the glucose response to insulin infused after hepatic denervation. Hepatic denervations were performed on 13 anesthetized cats at different levels: (i) surgical hepatic anterior plexus denervation, (ii) chemical total hepatic denervation by painting phenol on the tissues around the portal vein, bile duct, common hepatic artery, and hepatic ligaments, and (iii) bilateral vagotomy. Sham denervations were performed on 9 animals. Before denervation and after each performance of denervations, insulin (100 mU/kg, i.v.) was infused. Plasma glucose concentrations were analyzed at 15, 30, 45, and 60 min after insulin infusion. Hepatic anterior plexus denervation produced a significant reduction in insulin effectiveness. Phenol denervation and bilateral vagotomy failed to further significantly alter the level of insulin resistance developed by hepatic anterior plexus denervation. These observations demonstrate that the effect of insulin on glucose regulation is markedly reduced in the absence of hepatic anterior plexus innervation, suggesting that hepatic nerve function is necessary for the normal glucose response to insulin. Furthermore, the hepatic nerves of relevance appear to reach the liver primarily, if not exclusively, by the anterior hepatic plexus.