INVOLVEMENT OF NITRIC-OXIDE IN ARGININE, BUT NOT GLUCOSE, INDUCED INSULIN-SECRETION IN NORMAL MEN

OBJECTIVE At present, there are no reports in the literature of studie s in humans concerning a possible role of nitric oxide (NO) in the reg ulation of pancreatic endocrine secretions, whereas studies in the rat provided discrepant results, The aim of this study was to clarify whe ther NO is involved in the control of insulin and/or glucagon secretio n in basal conditions and/or in response to arginine or glucose admini stration in normal male subjects. DESIGN We investigated whether an in travenous infusion of the NO synthase (NOS) inhibitor L-NAME, at a dos e previously demonstrated not to produce blood pressure alterations or untoward side-effects, modifies insulin and/or glucagon secretory pat terns, SUBJECTS Fourteen healthy male volunteers aged 24-35 years, wit hin 10-13% of their ideal body weight and without family history of di abetes mellitus or other endocrine diseases, METHODS Seven normal men were treated intravenously with L-arginine (30 g in 50 ml of normal sa line over 30 minutes) or glucose (0.33 g/kg body weight in a bolus) wi th or without the concomitant infusion of L-NAME (90 mu g/kg in 50 ml of normal saline), L-NAME was infused for 30 minutes before and during arginine infusion and over 30 minutes before and 30 minutes after glu cose injection. Another group of 7 men was infused over 60 minutes wit h L-NAME (90 mu g/kg in 50 ml of normal saline) alone or saline alone. RESULTS Basal and L-arginine or glucose induced glucagon secretions a nd basal and glucose stimulated insulin secretions were not altered by L-NAME administration, In contrast, the drug produced a partial but s ignificant decrease in the insulin response to L-arginine, In fact, th e mean peak insulin response to L-arginine was 5.3 times (53 +/- 5 mU/ I (mean +/- SE)) higher than basal value (10 +/- 2) in the absence of L-NAME, but only 3.33 times (40 +/- 4) higher than baseline (12 +/- 3) during the infusion of the NOS-inhibitor, CONCLUSION These data sugge st that NO at least partially mediates the stimulatory action of L-arg inine on insulin secretion in normal human subjects.