EFFECT OF HYPERINSULINEMIA AN THE FUNCTION OF THE PITUITARY-ADRENAL AXIS IN HEALTHY MAN

OBJECTIVE 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 wa s examined during euglycaemia by stimulating the pituitary-adrenal axi s with human corticotrophin-releasing hormone (CRH). SUBJECTS Eight he althy males. DESIGN Following an overnight fast, insulin was infused a t 15 (low) and 60 (high) mU/kg/h from 0900 h for 180 minutes on separa te occasions in random order. On each occasion, blood glucose was clam ped at euglycaemia, and 1 mu g/kg (i.v. bolus) human CRH was administe red at 120 minutes. MEASUREMENTS Circulating hormone concentrations we re determined by radioimmunoassay. Peak cortisol and ACTH responses we re compared for the two study conditions. RESULTS Mean serum insulin l evels were threefold higher during the high compared with the low insu lin infusion (mean difference 320 pmol/l, 95% confidence interval (Cl) 150-490, P<0.001). Blood glucose levels during the clamps were compar able (mean difference 0.15 mmol/l, 95% Cl 0-0.63). Plasma cortisol lev els increased following CRH, although the peak concentration was signi ficantly lower during the high insulin infusion (mean difference 36 nm ol/l, Cl 0-110, P<O.02). However, peak ACTH levels were comparable for the two insulin levels (mean difference 8 ng/l (1.8 pmol/l), Cl 0-50) . CONCLUSIONS The peak cortisol response to CRH was diminished at the higher circulating insulin levels. This was not dependent upon concurr ent hypoglycaemia and did not appear to be mediated at the level of th e pituitary gland. CONCLUSIONS The peak cortisol response to CRH was d iminished at the higher circulating insulin levels. This was not depen dent upon concurrent hypoglycaemia and did not appear to be mediated a t the level of the pituitary gland.