Hormonal responses to insulin-induced hypoglycemia in man

Insulin-induced hypoglycemia is a potent stress stimulating ACTH release, but the factors responsible for this ACTH secretion are not known. In this study, several ACTH-stimulating factors, such as CRH, arginine vasopressin (AVP), epinephrine (E), norepinephrine (NE), and dopamine, in addition to ACTH, cortisol, and glucose, were simultaneously measured in plasma before and 15, 30, 60, 90, and 120 min after iv administration of 0.1 U/kg BW regular insulin to seven normal subjects. Insulin administration resulted in significant rises in the mean plasma ACTH level from 4.6 +/- 1.1 (+/- SEM) to 21.6 +/- 4.8 pmol/L at 30 min (P less than 0.01) and in plasma cortisol from 330 +/- 60 to 720 +/- 50 nmol/L at 60 min (P less than 0.01). These increases were preceded by a 41.0 +/- 1.9% (P less than 0.001) fall in blood glucose levels. The mean plasma CRH level rose significantly from 1.0 +/- 0.1 to 1.2 +/- 0.1 pmol/L (P less than 0.01) at 30 min and remained elevated until 120 min. In addition, concomitant and significant rises in plasma AVP levels (basal, 1.5 +/- 0.01; peak, 4.5 +/- 1.1 pmol/L at 30 min; P less than 0.01), E (basal, less than 50; peak, 640 +/- 130 pmol/L at 30 min; P less than 0.01), and NE (basal, 0.07 +/- 0.01; peak, 0.17 +/- 0.03 nmol/L at 60 min; P less than 0.05), but not dopamine, also occurred. These results suggest that multiple ACTH-releasing factors, such as CRH, AVP, E, and NE, are involved in ACTH secretion induced by insulin-induced hypoglycemia in man.