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

Abstract

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.

The Endogenous Cannabinoid, Anandamide, Activates the Hypothalamo-Pituitary-Adrenal Axis in CB₁ Cannabinoid Receptor Knockout Mice

“…The interassay variation was 10% and intra-assay variation 5.5%, respectively. Concentrations of ACTH were measured in 50 µl of unextracted plasma as described earlier [33]. The assay was highly specific showing 0.2% cross-reaction with γ-MSH, CLIP, ACTH 11–24 , ACTH 1–14 and ACTH 1–19 .…”

Neurotoxic Lesions Induced by Monosodium Glutamate Result in Increased Adenopituitary Proopiomelanocortin Gene Expression and Decreased Corticosterone Clearance in Rats

“…ACTH in plasma and pituitary extracts was analyzed by a radioimmunoassay described previously [17]. The specific antibody was kindly donated by G.B.…”

Insulin-induced hypoglycemia stimulates corticotropin-releasing factor and arginine vasopressin secretion into hypophysial portal blood of conscious, unrestrained rams.

“…In another report it was suggested that during IIH the main factors triggering ACTH release were of central rather than peripheral origin, and that circulating catecholamines had no direct action at the pituitary level (3). Indeed, the participation of the hypothalamus in the stimulation of ACTH release during hypoglycemia was substantiated by Plotsky et al (4), who reported that IIH in rats resulted in no change in hypophysial portal venous corticotropin-releasing factor (CRF) levels, but caused significant increases in arginine vasopressin (AVP) levels.…”