NO-dependent and -independent elevation of plasma levels of insulin and glucose in rats by L-arginine

Br J Pharmacol. 1994 Oct;113(2):345-8. doi: 10.1111/j.1476-5381.1994.tb16993.x.


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 mumol 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology*
  • Blood Glucose / metabolism*
  • Blood Pressure / drug effects
  • Erythrocytes / metabolism
  • Glucose / pharmacology
  • Hemoglobins / metabolism
  • Insulin / blood*
  • Male
  • NG-Nitroarginine Methyl Ester
  • Nitrates / blood
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase
  • Rats
  • Rats, Wistar


  • Blood Glucose
  • Hemoglobins
  • Insulin
  • Nitrates
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Glucose
  • NG-Nitroarginine Methyl Ester