Stimulation of Insulin Release by Corticotropin1

Corticotropin has been shown to exert numerous extra-adrenal metabolic effects on carbohydrate and lipid metabolism. Among the more prominent of these effects are the mobilization of free fatty acids, the depression of the blood sugar and the production of ketosis. The present study was an investigation of the mechanism of the hypoglycemic action and its relationship to the ketosis. Corticotropin- induced hypoglycemia did not occur in alloxan-diabetic mice maintained at normal blood sugar levels with insulin treatment. Thus, an intact pancreas appeared to be necessary for the hypoglycemic action. Utilizing a radioimmunoassay, it was possible to demonstrate that corticotropin administration results in a 5- to 10-fold rise in plasma insulin levels. This rise in plasma insulin was accompanied by a decrease in the blood sugar and a rise in the blood ketones. Simultaneous administration of D-mannoheptulose with the corticotropin partially blocked the rise in plasma insulin levels, suggesting that the rise was related to insulin secretion from the pancreas. Final documentation that the ACTHinduced rise in plasma insulin levels was the result of a direct stimulation of pancreatic insulin release was obtained by in vitro studies. Mouse pancreases incubated in medium with 10 μg/ml of corticotropin added secreted twice as much insulin into the medium as the controls. Thus, corticotropin has a direct stimulatory action on the release of pancreatic insulin and this accounts for the hypoglycemic action. The primary ketogenic action of corticotropin overrides the antiketogenic action of the released insulin and ketosis occurs at the same time as the hyperinsulinemia and the hypoglycemia. (Endocrinology76: 1093, 1965)