L-ARGININE BUT NOT D-ARGININE STIMULATES INSULIN-MEDIATED GLUCOSE-UPTAKE

Our study aims at investigating a possible role for L-arginine and D-a rginine in insulin-mediated glucose uptake. Twelve lean healthy subjec ts volunteered for the study and were submitted to three euglycemic-hy perinsulinemic 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 ?, L-arginine versus saline infusion was associated with a significan t Increase in blood flow (131% +/- 7% v87% +/- 5%, P<.007) and whole-b ody glucose disposal ([WBGD] 61,4 +/- 4.4 v41.3 +/- 3,5 mu mol/kg fat- free mass [FFM].min, P<.001). Analysis of substrate oxidation demonstr ated that both oxidative and nonoxidative glucose metabolism was impro ved by L-arginine delivery. After adjustment for the change in brood f low, WBGD was sti II greater after L-arginine than after saline infusi on. Along with L-arginine infusion and independently of the change in blood flow, the percent change in WBGD correlated with the percent cha nge in plasma cGMP (r=.56, P<.05). D-Arginine infusion did not affect insulin-mediated glucose uptake. In particular, WBGD (42.1 +/- 3.4 v 4 1.3 +/- 3,5 mu mol/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 plasm a 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 sti mulated (84% +/- 4% v 87% +/- 5%, P=NS) by insulin infusion, In conclu sion, L-arginine but not D-arginine stimulates insulin-mediated glucos e uptake. Nitric oxide (NO), the metabolic mediator for L-arginine, po tentiates insulin-mediated glucose uptake through the increase in bloo d flow. Nevertheless, an independent effect of intracellular cGMP on W BGD cannot be ruled out. Copyright (C) 1997 by W.B. Saunders Company.