title: L-arginine but not D-arginine stimulates insulin-mediated glucose uptake.
abstract: Our study aims at investigating a possible role for L-arginine and D-arginine in insulin-mediated glucose uptake. Twelve lean healthy subjects volunteered for the study and were submitted to three euglycemic-hyperinsulinemic glucose clamps to investigate the effect of L-arginine (0.5 g/min in the last 60 minutes of the clamp), D-arginine (0.5 g/min in the last 60 minutes of the clamp), and saline 0.9% NaCl on insulin-mediated glucose uptake. All tests were made in random order. In study 1, L-arginine versus saline infusion was associated with a significant increase in blood flow (131% +/- 7% v 87% +/- 5%, P < .001) and whole-body glucose disposal ([WBGD] 61.4 +/- 4.4 v 41.3 +/- 3.5 mumol/kg fat-free mss [FFM].min, P < .001). Analysis of substrate oxidation demonstrated that both oxidative and nonoxidative glucose metabolism was improved by L-arginine delivery. After adjustment for the change in blood flow, WBGD was still greater after L-arginine than after saline infusion. Along with L-arginine infusion and independently of the change in blood flow, the percent change in WBGD correlated with the percent change in plasma cGMP (r = .55, P < .05). D-Arginine infusion did not affect insulin-mediated glucose uptake. In particular, WBGD (42.1 +/- 3.4 v 41.3 +/- 3.5 mumol/kg FFM.min, P = NS) was similar in both experimental conditions. Basal levels (2.8 +/- 0.2 v 2.7 +/- 0.3 nmol/L, P = NS) and the insulin-mediated increase (43% +/- 5% v 39% +/- 4%, P = NS) in plasma cGMP were also superimposable along with insulin plus D-arginine and insulin alone, respectively. Finally, blood flow (224 +/- 29 v 230 +/- 35 mL/min, P = NS) was not different at baseline and was similarly stimulated (84% +/- 4% v 87% +/- 5%, P = NS) by insulin infusion. In conclusion, L-arginine but not D-arginine stimulates insulin-mediated glucose uptake. Nitric oxide (NO), the metabolic mediator for L-arginine, potentiates insulin-mediated glucose uptake through the increase in blood flow. Nevertheless, an independent effect of intracellular cGMP on WBGD cannot be ruled out.
authors.affiliation: Department of Geriatric Medicine and Metabolic Diseases, II University of Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Paolisso
authors.forename: M R
authors.initials: MR
authors.lastname: Tagliamonte
authors.forename: R
authors.initials: R
authors.lastname: Marfella
authors.forename: G
authors.initials: G
authors.lastname: Verrazzo
authors.forename: F
authors.initials: F
authors.lastname: D'Onofrio
authors.forename: D
authors.initials: D
authors.lastname: Giugliano
mesh_terms: D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000502:physiology*; D008297:Male; D012016:Reference Values; D013237:Stereoisomerism
chemical_list: D007328:Insulin; D001120:Arginine; D005947:Glucose