Involvement of the cholinergic system in insulin and glucagon oversecretion of genetic preobesity.

The etiology of the abnormal secretion of hormones from the endocrine pancreas of genetically obese (fa/fa) rats is unknown. In this study, we tested the postulate that there is an early occurrence of increased efferent parasympathetic activity to the endocrine pancreas of these rodents. Unweaned female 17-day-old pups were anesthetized and tested by an iv bolus of arginine to stimulate insulin and glucagon output. At the time of the tests, pups were indistinguishable from each other. They were, therefore, kept to adulthood to allow for their separation into an obese (25% of total animals) and a lean (75%) group. Those animals that became obese were retrospectively referred to as preobese. Basal insulinemia and glucagonemia were identical in the two groups, as were the dynamics of arginine-induced hormone release. However, arginine-induced insulin as well as glucagon output were higher in preobese than in lean pups. These two abnormalities were abolished by acute atropine pretreatment. It is concluded that the substrate-induced insulin and glucagon oversecretion of preobese pups is an early defect that is mediated via the vagus nerve.