The effects of glucocorticoids on the insulin secretory response to an intravenous glucose load have been studied in lean (Fa/?) and obese fa/fa Zucker rats. The role of parasympathetic drive to the pancreatic B-cells was assessed as that component of the insulin secretory response that was blocked by pretreatment of the rats with intravenous atropine. The insulin secretory response to the glucose load was greater in obese than in lean rats. Atropine significantly reduced basal and stimulated levels of insulin in obese but not in lean rats. Adrenalectomy reduced basal insulin levels and the secretory response in obese but not lean rats and also abolished the atropine-blockable component of the response. Peripheral corticosterone replacement of adrenalectomized fa/fa rats restored the hyperinsulinemia. Chronic infusion of dexamethasone intracerebroventricularly to adrenalectomized fa/fa rats increased basal insulin and the secretory response to glucose and this effect was blocked by atropine. In contrast, intracerebroventricular infusion of obese rats with corticotropin releasing factor reduced basal and stimulated insulin levels. It is concluded that the hypersecretion of insulin in obese fa/fa rats results, at least in part, from a central glucocorticoid-mediated stimulation of vagal drive to the pancreatic B-cells.
Adrenalectomy Animals