THE INSULIN SECRETORY RESPONSE TO INTRAVENOUS GLUCOSE IN THE RAT IS INDEPENDENT OF NO FORMATION

In isolated pancreative beta cells from rats the insulin secretory response to glucose is amplified by L-arginine. Since this effect is inhibited by NO synthesis inhibitors, and since L-arginine is precursor of NO, the observation indicates a role for NO in insulin secretion from beta cells. We recently reported that i.v. L-arginine elicited insulin secretion in anaesthetized rats by a mechanism that was partly NO dependent. The aim of the present study was to assess if the insulin secretory response to an intravenous infusion of glucose also requires an intact NO formation. Anaesthetized rats were given D-glucose (100 mg kg(-1) min(-1) i.v. for 30 min). Plasma insulin (PI), blood glucose (BG) levels and mean arterial blood pressure (MAP) were assessed from before and until 15 min after the end of the infusion. One group of rats were untreated and served as controls. The two other groups were pretreated with either of the NO synthase inhibitors N-W-nitro-L-arginine methyl ester (L-NAME, 50 mg kg(-1) i.v.), or N-G-monomethyl-L-arginine (L-NMMA, 100 mg kg(-1) i.v.). In controls infusion of glucose elevated PI by up to 25 +/- 3 U L(-1), and BG by up to 27 +/- mmol L(-1). Pretreatment with L-NAME elevated MAP from 74 +/- 6 to 132 +/- 4 mmHg, indicating that NO synthase was inhibited. Infusion of glucose in rats pretreated with L-NAME increased PI by up to 28 +/- 2 U L(-1) and elevated BG by up to 30 +/- 1 mmol L(-1). Pretreatment with L-NMMA elevated MAP from 80 +/- 5 to 132 +/- 1 mmHg. Infusion of glucose in these rats increased PI by up to 23 +/- 3 U L(-1), and elevated BG by up to 29 +/- 2 mmol L(-1). The PI and BG responses to glucose infusion were not significantly affected by either of the NO synthase inhibitors studied. We conclude that the insulin secretory response to i.v. glucose infusion in the rat does not require an intact formation of NO.