Insulin and Growth Hormone Secretion in Rats with Ventromedial Hypothalamic Lesions Maintained on Restricted Food Intake

Abstract

Adult female rats were trained for one week to consume a subnormal amount of food (12 gm.) in two one-hour feeding sessions per day: 4 gm. between 8 and 9 a.m. and 8 gm. between 6 and 7 p.m. At the end of the training period the animals were subjected to either bilateral electrolytic destruction of the ventromedial hypothalamus (VMH) or to a sham operation. The restricted feeding regime was continued for forty-eight hours postoperatively, when comparative studies were made. Plasma insulin response to intravenous Glibenclamide was greater in the rats with VMH lesions than in the pair-fed, sham-operated controls. The former rats also exhibited decreased initial plasma glucose levels, degranulation of the beta cells and reduced pancreatic insulin content. In addition to marked islet enlargement, similar though more severe signs of islet hyper-function were observed in rats with VMH lesions fed ad libitum, which became hyperphagic immediately after the operation. VMH lesions did not significantly affect the plasma and pituitary levels of growth hormone (GH). The restricted feeding regime, however, caused an increase in plasma GH, responsiveness to hypoglycemic stimulation and a tendency to decreased pituitary GH content both in injured and sham-operated rats. These findings indicate that VMH lesions per se enhance the responsiveness of the pancreatic islets to insulin secretory stimulation independent of changes in food intake, meal size and meal frequency. The resulting hyperinsulinism might play an essential role in the occurrence of hypothalamic hyperphagia and obesity following VMH injury. In hyperphagic rats with VMH damage, the islet stimulation is magnified, possibly due to the combination of a direct hypothalamic effect plus the secondary effect of increased food intake. Defective secretion of GH does not appear to be primarily involved in the induction of the hypothalamic syndrome.