Mechanism of Action of Insulin Hypoglycemia on Adrenal Cortical Secretion

Insulin hypoglycemia elicited a prompt increase in 17-hydroxycorticosteroid (17-OHCS) secretion in the dog. It is of limited duration in spite of continued hypoglycemia. When insulin hypoglycemia was prevented by simultaneously administered 50% glucose, no increase in 17-OHCS secretion followed. The administration of insulin during a dexamethasone suppression test failed to give a significant 17OHCS response. Neither pituitary nor adrenal unresponsiveness is a factor in limiting this 17OHCS secretory response. (Endocrinology 78: 1264, 1966) T EXPERIMENTS of Goldnen and associates (1) and previous studies from our laboratory (2) have demonstrated that insulin hypoglycemia is a potent stimulus to a prompt increase in adrenal secretion of 17-hydroxycorticosteroids (17-OHCS). The present experiments were designed to elucidate the mode of action of insulin hypoglycemia on adrenal cortical function. Materials and Methods Adult mongrel dogs of either sex weighing 10-15 kg were anesthetized with pentobarbital. An indwelling lumbo-adrenal cannula was inserted to collect intermittent adrenal venous blood samples (3). In some animals, a complete supradiaphragmatic vagotomy was performed through a right thoracotomy at the time of adrenal vein cannulation. Beginning the day after operation, the effect of varying dosages of intravenous insulin (0.1-4.0 U/kg) on jig/min 17-OHCS secretion and peripheral venous blood glucose was determined in pentobarbital-anesthetized and unanesthetized dogs. Simultaneous adrenal and peripheral venous samples for 17-OHCS and blood glucose, respectively, were collected every 10 to 20 min for 2 hr and at£ hr intervals thereafter for 4 hr. The 17-OHCS response to a peripheral 10-min scald in water 98-100 C in anesthetized animals at varying time intervals after the induction of insulin hypoglycemia was studied in some of these experimental animals. In steroid suppression studies, 2.5-5.0 mg dexamethasone-21 phosphate (9 alpha-fluoro, 16 alphamethyl-prednisolone) was administered subcutaneously to pentobarbital-anesthetized dogs. A 2-hr Received December 27, 1965. Supported in part by USPHS Research Grant AM-05629, from the National Institute of Arthritis and Metabolic Diseases. intravenous infusion of 5-10 mg dexamethasone in 100 ml of isotonic saline was then given. At the completion of the infusion, intravenous insulin (0.5-1.0 U/kg) was administered. Samples for 17OHCS and blood glucose levels were collected every 20 min for 2 hr. At the conclusion of each experiment 10 U of aqueous adrenocorticotropin (ACTH) was given intravenously and adrenal venous samples were obtained for 17-OHCS levels 5 and 10 min later. All adrenal venous samples were collected for 1-min time intervals, and the plasma concentration was determined by the method of Peterson and associates (4). Secretion rate was expressed as ng per min. The blood glucose concentrations were determined by an AutoAnalyzer technique as mg/100 ml. All dogs used in these experiments had low resting 17-OHCS levels and were responsive to ACTH. Results The marked lowering of peripheral blood glucose by 0.5 U crystalline regular insulin/kg administered intravenously to 7 pentobarbitalanesthetized and 2 unanesthetized dogs resulted