Effect of hyperinsulinaemia on the function of the pituitary-adrenal axis in healthy man

Circulating insulin levels in themselves have been reported to influence the counter-regulatory hormone response to hypoglycaemia in man. The effect of insulin on a specific aspect of this response was examined during euglycaemia by stimulating the pituitary-adrenal axis with human corticotrophin-releasing hormone (CRH).

Eight healthy males.

Following an overnight fast, insulin was infused at 15 (low) and 60 (high) mU/kg/h from 0900 h for 180 minutes on separate occasions in random order. On each occasion, blood glucose was clamped at euglycaemia, and 1 microgram/kg (i.v. bolus) human CRH was administered at 120 minutes.

Circulating hormone concentrations were determined by radioimmunoassay. Peak cortisol and ACTH responses were compared for the two study conditions.

Mean serum insulin levels were threefold higher during the high compared with the low insulin infusion (mean difference 320 pmol/l, 95% confidence interval (CI) 150-490, P < 0.001). Blood glucose levels during the clamps were comparable (mean difference 0.15 mmol/l, 95% CI 0-0.63). Plasma cortisol levels increased following CRH, although the peak concentration was significantly lower during the high insulin infusion (mean difference 36 nmol/l, CI 0-110, P < 0.02). However, peak ACTH levels were comparable for the two insulin levels (mean difference 8 ng/l (1.8 pmol/l), CI 0-50).

The peak cortisol response to CRH was diminished at the higher circulating insulin levels. This was not dependent upon concurrent hypoglycaemia and did not appear to be mediated at the level of the pituitary gland.