Effect of human atrial natriuretic peptide on blood glucose concentrations and hormone stimulation during insulin-induced hypoglycaemia in healthy man

Abstract

A double-blind placebo-controlled study using the double-dummy technique has been done to examine whether the responses of pituitary and adrenal hormones to insulin-induced hypoglycaemia were impaired by a pharmacological dose of human atrial natriuretic peptide (human ANF-(99-126),hANP). After an overnight fast eight male healthy volunteers (aged 23-40 years) received in random order i.v. bolus injections of insulin 0.125 U.kg-1 + placebo,hANP 100 micrograms + placebo,insulin + hANP, or both placebo preparations. In the insulin-only experiment, human growth hormone, adrenocorticotrophic hormone, cortisol, aldosterone, plasma renin activity, adrenaline, and noradrenaline were all stimulated by hypoglycaemia. In the hANP-only experiment there were no hormonal changes other than decreases in plasma renin activity and aldosterone concentration. In the insulin + hANP experiment the nadir of blood glucose was decreased to 1.3 from the 2.0 mmol.1-1 found in the insulin-only experiment. The exaggerated hypoglycaemia resulted in increased stimulation of human growth hormone, adrenocorticotrophic hormone and adrenaline when compared to the insulin-only experiment. The rise in the cortisol and aldosterone concentrations was only slightly increased, and the stimulation of plasma renin activity was blunted. Unexpectedly, hANP was found to enhance the hypoglycaemic action of insulin, most probably by inhibiting insulin degradation within the liver. There was no evidence of an inhibitory effect of hANP on the stimulation of pituitary or adrenal hormones during insulin-induced hypoglycaemia. The reduction in renin may indicate an inhibitory action of hANP on catecholaminergic effects within the kidney.