Supraphysiological hyperinsulinemia acutely increases hypothalamic-pituitary-adrenal secretory activity in humans

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in associati on with hyperinsulinemia is frequently found in patients with type 1 and ty pe 2 diabetes mellitus and in subjects with abdominal adiposity. We questio ned whether insulin could cause HPA axis activation and, if so, whether thi s insulin action may arise at the adrenal level or at a central (i.e. hypot halamic-pituitary) level. Experiments lasting for 6 h each were done in 30 lean healthy men. In 15 men, insulin was infused at a rate of 1.5 mU min(-1 )kg(-1). Plasma glucose concentration was held constant during an euglycemi c clamp session and was decreased stepwise in a hypoglycemic clamp session. The sequence of the 2 clamp sessions was random, and a 4-weeks recovery pe riod was allowed between the two sessions. The protocol was essentially the same in another 15 men, with the exception that insulin was infused at a r ate of 15.0 mU min(-1)kg(-1). During the euglycemic clamp sessions, we foun d plasma ACTH levels to increase only in the high-, but not in the low-insu lin group (group by time interaction, P < 0.01); serum cortisol levels were greater in the high than in the low-insulin group (P < 0.02). In the hypog lycemic clamp sessions, plasma ACTH levels increased in the same pattern in the 2 groups; serum cortisol was greater in the high than in the low-insul in group at the beginning of the clamp (plasma glucose similar to 4.1 mmol/ L; P < 0.05). Our results demonstrate that insulin acutely stimulates the H PA secretory activity in humans. The pattern suggests an effect of insulin at both peripheral and central levels of the HPA axis.