L-arginine but not D-arginine stimulates insulin-mediated glucose uptake

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.