Involvement of the Cholinergic System in Insulin and Glucagon Oversecretion of Genetic Preobesity*

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Abstract
The etiology of the abnormal secretion of hormones from the endocrine pancreas of genetically obese (fa/fa) rats is unknown. The postulate that there is an early occurrence of increased efferent parasympathetic activity to the endocrine pancreas of these rodents were tested. Unweaned female 17 day old pups were anesthetized and tested by an i.v. 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 2 groups, as were the dynamics of arginine-induced hormone release. Arginine-induced insulin as well as glucagon output were higher in preobese than in lean pups. These 2 abnormalities were abolished by acute atropine pretreatment. The substrate-induced insulin and glucagon oversecretion of preobese pups apparently is an early defect that is mediated via the vagus nerve.