The hepatic vagus nerve and the neural regulation of insulin secretion

Despite considerable evidence that vagal neural efferent pathways between brainstem and pancreatic islets may alter the secretion of insulin, afferent pathways which might affect this system have received little attention. In the present work we have examined the effects on plasma insulin concentration of several treatments designed to alter the neural activity of the hepatic vagus nerve, a major afferent pathway between the liver and the medulla. The hepatic vagus nerve was acutely sectioned or stimulated electrically in separate experiments in rats. In a third experiment, glucose or 3-O-methylglucose was given ip to stimulate or inhibit, respectively, the hypothetical hepatic glucoreceptors. The effects of these treatments were assessed by measuring arterial or portal plasma insulin concentrations. Anesthesia and its possible secondary inhibitory effects on insulin secretion were avoided by a spinal sectioning of the rats in the cervical region, before experimentation. Acute section of the hepatic vagus nerve between the liver and the main anterior vagal trunk caused an increase in both arterial and portal plasma insulin concentrations. Stimulation of the central end of the nerve suppressed the concentration of the hormone in both the arterial and portal plasma relative to sham-stimulated controls. Section of the celiac vagal branches to the pancreas abolished these changes. Intraperitoneal glucose enhanced arterial insulin more in sham-vagotomized than in hepatic-vagotomized rats. After 3-O-methylglucose was given ip, the response was the opposite: insulin rose more in the arterial plasma of the hepatic-vagotomized animals than in those sham vagotomized. These results suggest that the hepatic vagus nerve plays a role in the regulation of insulin secretion. They are consistent with the hypothesis that afferent fibers in this nerve exert a tonic inhibition on the brainstem centers of an efferent vagal pancreatic neuroendocrine system.