Insulin-Induced Hypoglycemia Activates the Release of Adrenocorticotropin Predominantly via Central and Propranolol Insensitive Mechanisms

The dynamic patterns of pituitary-adrenocortical and sympatho-adrenal hormone responses to insulin hypoglycemia as well as the relative importance of central vs. peripheral control of hypoglycemia-induced ACTH secretion were evaluated. In conscious rats bearing indwelling cannulae, the changes in hormone concentrations after insulin injection were dependent on the changes in blood glucose levels with respect to both time course and magnitude. ACTH, corticosterone, epinephrine, and norepinephrine levels were found to be maximal at 60 min after 2.5 IU kg-1 insulin injected ip, whereas earlier (20 min) but smaller increases were obtained in response to 0.5 IU kg-1 insulin injected iv. In rats 6-7 days after lesions of the medial basal hypothalamus (MBH), the rise of ACTH during insulin hypoglycemia was markedly inhibited and corticosterone levels were significantly reduced. Simultaneously, the hypoglycemia-induced increase in plasma epinephrine was unchanged and that in plasma norepinephrine was significantly enhanced in rats with the MBH destroyed. The beta-adrenoreceptor blocker propranolol did not inhibit ACTH and corticosterone responses to hypoglycemia in either sham-operated or MBH-lesioned animals. We conclude that the main factors triggering ACTH release during insulin-induced hypoglycemia are of central rather than peripheral origin. The high concentrations of circulating catecholamines occurring during insulin hypoglycemia are not responsible for pituitary-adrenocortical activation by direct, beta-adrenoreceptor mediated action at the pituitary level.