Adrenalectomy suppresses insulin secretion from pancreatic islets of ob/ob mice

The aim of this work was to examine effects of adrenalectomy and intracerebroventricular injection of dexamethasone on insulin secretion from pancreatic islets of ob/ob mice. Female ob/ob and lean mice fed a stock diet were adrenalectomized at 5 wk of age and studied at 8-9 wks of age. Removal of the adrenal glands from ob/ob mice fed a stock diet normalized their plasma insulin concentration, islet size, and essentially normalized insulin secretion from islets incubated in 10 mM glucose. Insulin secretion from islets was, however, not fully normalized when the incubation buffer contained higher concentrations of glucose (20 mM), or acetylcholine, a potentiator of glucose-induced insulin secretion. Within 90 min after intracerebroventricular administration of dexamethasone plasma insulin concentrations were elevated and glucose-induced (10 mM) insulin secretion from isolated islets of adrenalectomized ob/ob mice increased, but dexamethasone was ineffective in lean mice. Regulation of insulin secretion from pancreatic islets of adrenalectomized ob/ob mice remains abnormal even though adrenalectomy normalized plasma insulin concentrations in these mice. Alterations in glucocorticoid-mediated, central nervous system regulation of insulin secretion likely contribute to hyperinsulinemia in ob/ob mice.