NO-DEPENDENT AND NO-INDEPENDENT ELEVATION OF PLASMA-LEVELS OF INSULIN AND GLUCOSE IN RATS BY L-ARGININE

1 L-Arginine elevates plasma insulin in man. Recent in vitro data indicate that this is based on stimulation of endogenous nitric oxide (NO) with subsequent pancreatic release of insulin by L-arginine. L-Arginine also raises plasma glucose. 2 We studied plasma levels of insulin, glucose and NO metabolites, as well as systemic blood pressure, in anaesthetized rats during i.v. infusion of L-arginine (25-200 mg kg(-1) min(-1)) or glucose (55 mg kg(-1) min(-1)), before and after administration of the NO synthesis inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 50 mg kg(-1)). 3 Before L-NAME, L-arginine elevated plasma insulin from about 15 to 65 ul(-1) and glucose from 5.2 to 6.7 mmol l(-1). These effects of L-arginine were not dose-related. 4 L-NAME alone had no effect on plasma insulin and glucose levels, but diminished the effects of a low dose (25 mg kg(-1) min(-1)) of L-arginine on plasma insulin by about 40%, and that on plasma glucose by more than 90%. In contrast, the effects of a high dose (200 mg kg(-1) min(-1)) of L-arginine on plasma insulin and glucose levels were not affected by L-NAME. 5 L-NAME elevated systemic blood pressure by about 35 mmHg. L-Arginine (25-100 mg kg(-1) min(-1)) had no effect on systemic blood pressure, either before or after L-NAME. L-Arginine (200 mg kg(-1) min(-1)) lowered systemic blood pressure, both before and after L-NAME. 6 Glucose infusion elevated plasma glucose from about 5.5 to 6.8 mmol l(-1), and plasma insulin from about 18 to 26 ul(-1). 7 The basal plasma levels of the NO metabolite nitrate (18+4 mu mol l(-1)) were not affected by L-arginine (200 mg kg(-1) min(-1)). Plasma nitrosohaemoglobin was likewise unaffected by L-arginine (200 mg kg(-1) min(-1)). 8 We conclude that L-arginine separately elevates plasma insulin and glucose levels, both by NO-dependent and -independent mechanisms.