Hyperinsulinemia causes activation of the hypothalamus-pituitary-adrenal axis in humans

OBJECTIVE: Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis i s frequently found in hyperinsulinemic subjects, such as patients with diab etes or abdominal obesity. Here, the question has been posed as to whether hyperinsulinemia increases HPA secretory activity. METHODS: We performed paired-euglycemic and stepwise hypoglycemic (76 - 66 - 56 - 46 mg/dl)- clamp experiments in two groups (each of 15 healthy men) at different insulin infusions rates, ie, 1.5 mU/min/kg (low-insulin condit ion) and 15.0 mU/min/kg (high-insulin condition). RESULTS: During the euglycemic clamp, the high rate insulin infusion increa sed plasma ACTH levels, whereas plasma ACTH levels remained essentially unc hanged during the low-insulin condition (condition by time interaction, P=0 .008). Likewise, serum cortisol levels were higher during the high- vs low- insulin condition (condition by time interaction, P=0.004). During the hypo glycemic clamp, plasma ACTH levels did not differ between the low- vs high- insulin condition, while serum cortisol levels were higher during the high- vs low-insulin condition at the beginning of the clamp (plasma glucose - 7 6 mg/dl; P=0.032). CONCLUSION: Data indicate that hyperinsulinemia acutely increases HPA secre tory activity in healthy men. This finding appears to be relevant to the pa thogenesis of many clinical abnormalities associated which diabetes and abd ominal adiposity, often referred to as the metabolic syndrome.