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 studies in humans concerning a possible role of nitric oxide (NO) in the regulation of pancreatic endocrine secretions, whereas studies in the rat provided discrepant results, The aim of this study was to clarify whether NO is involved in the control of insulin and/or glucagon secretion in basal conditions and/or in response to arginine or glucose administration in normal male subjects. DESIGN We investigated whether an intravenous infusion of the NO synthase (NOS) inhibitor L-NAME, at a dose previously demonstrated not to produce blood pressure alterations or untoward side-effects, modifies insulin and/or glucagon secretory patterns, SUBJECTS Fourteen healthy male volunteers aged 24-35 years, within 10-13% of their ideal body weight and without family history of diabetes mellitus or other endocrine diseases, METHODS Seven normal men were treated intravenously with L-arginine (30 g in 50 ml of normal saline over 30 minutes) or glucose (0.33 g/kg body weight in a bolus) with 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 glucose injection. Another group of 7 men was infused over 60 minutes with 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 and basal and glucose stimulated insulin secretions were not altered by L-NAME administration, In contrast, the drug produced a partial but significant decrease in the insulin response to L-arginine, In fact, the 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 suggest that NO at least partially mediates the stimulatory action of L-arginine on insulin secretion in normal human subjects.