The sensory nitrergic nature of the hepatic insulin sensitizing substance mechanism in conscious rabbits.

Functional deterioration of sensory fibres in the anterior hepatic plexus or intraportal administration of 7-nitro indazole (1 mg/kg), a selective inhibitor of neural nitric oxide (NO) synthase, caused insulin resistance as determined by hyperinsulinaemic (100 micro U/ml) euglycaemic (5.5 mmol/l) glucose clamping in chronically instrumented conscious rabbits. Intraportal nitroglycerin restored insulin sensitivity in either case. We conclude that NO of sensory neural origin plays a major role in endogenous neurogenic insulin sensitizing mechanisms.