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It has been established that the liver, through the afferent pathway of the vagus nerve, can influence insulin secretion. The purpose of the present study was to determine if this influence can be altered by different nutritional status aimed at inducing metabolic changes in the liver. This was carried out by comparing the insulin response 30 min after sectioning of the hepatic vagus branch in five experimental conditions: a normal (NCD) and a medium-fat (MFD) for 3 weeks, both with and without an overnight fast, and after an overloading liver glycogen protocol (normal diet). All experiments were conducted using anesthetized, adrenodemedullated rats. Blood was collected before and after (30 min) the hepatic vagotomy (HV) or a sham operation (SHM). As expected, liver glycogen levels were significantly (p < 0.01) lower in the fasted than in the fed condition, and were approximately 50% higher (p < 0.01) in the overloaded than in the normally fed condition. Basal insulin concentrations were also lower (p < 0.01) in the fasted compared to the fed groups, but were significantly (p < 0.01) increased by the medium-fat diet. Plasma glucose levels were significantly (p < 0.01) decreased by the overnight fast, but were not affected by the hepatic vagotomy. Plasma catecholamine concentrations were similar in all experimental conditions. Insulin concentrations were significantly (p < 0.05) increased by the HV, compared to SHM rats, in all experimental conditions (from 50% to 75%). The extent of this response was altered by the diet manipulations as the HV-induced insulin increase was greater (p < 0.01) in the MFD than in the NCD groups, whether fed or fasted. Furthermore, and contrary to our expectations, high hepatic glycogen contents did not reduce the insulin response to an acute hepatic vagotomy. These results indicate that the insulin increase induced by an acute HV is influenced by the prevailing metabolic conditions, and suggest that the hepatic vagus nerve exerts a constant inhibition on insulin secretion, independently of the hepatic glycogen content.

The present investigation was designed to evaluate the effect of a selective hepatic vagotomy (HV) on the insulin response in rats fasted for 24 h when blood glucose levels were or were not maintained by a constant glucose infusion. Rats were divided into three dietary groups: one group of normally fed rats, one group of 24-h fasted rats, and one group of 24-h fasted rats infused with glucose throughout the fasting period. Each of these groups was subdivided into HV and sham-operated (SHM) rats. Fasting without glucose infusion resulted in a significant (p < 0.05) decrease in plasma glucose, liver glycogen, and insulin concentrations and in a significant (p < 0.01) increase in beta-hydroxybutyrate and FFA concentration. Despite the maintenance of plasma glucose concentrations in the glucose-infused groups, the concentrations of liver glycogen and insulin were still decreased (p < 0.01) and the concentrations of beta-hydroxybutyrate were still increased (p<0.05) at the end of the fasting period. However, no significant differences in insulin or in beta-hydroxybutyrate concentration were found between HV and SHM rats. It is concluded that the decline in plasma glucose concentration during fasting does not totally explain the insulinopenic response to fasting, and that the liver, through the mediation of the hepatic vagus nerve, does not seem to contribute to insulinopenia in 24-h fasted rats.

It is well known that several amino acids, such as arginine, are potent stimuli for insulin and glucagon secretion from the pancreas. Recently, vagal arginine sensors, which modulate arginine-induced pancreatic hormone secretion, have been reported to exist in the liver. The present investigation was designed to evaluate the role played by gluconeogenesis in this hepatic influence. To this end, we studied the effects of an intraperitoneal injection of 3-mercaptopicolinic acid (3-MPA), a gluconeogenic inhibitor, on the pancreatic hormonal response induced by intraperitoneal administration of arginine (1 g/kg body mass) to hepatic vagotomized and sham vagotomized rats. Fifteen min following the injection of arginine, the increases in glucose and insulin concentrations were significantly lower in rats with an inhibited gluconeogenesis than in rats with an intact capacity for gluconeogenesis. There were no effects of the hepatic vagotomy on the arginine-induced hormonal responses either with or without the 3-MPA injection. The results suggest that gluconeogenesis is implicated in the hepatic modulation of arginine-induced pancreatic hormone secretion.