Effect of L-Arginine Infusion on Glucose Disposal during Exercise in Humans

LINDEN, K. C., G. D. WADLEY, A. P. GARNHAM, and G. K. MCCONELL. Effect of L-Arginine Infusion on Glucose Disposal during Exercise in Humans. Med. Sci. Sports Exerc., Vol. 43, No. 9, pp. 1626-1634, 2011. Purpose: We have previously shown that local infusion of a nitric oxide synthase (NOS) inhibitor attenuates increases in leg glucose uptake during exercise in humans. We have also shown that infusion of the NOS substrate, L-arginine (L-Arg), increases glucose clearance, although the mechanisms involved were not determined. A potential mechanism for NO-mediated glucose disposal is via interactions with NOS and the energy sensor AMP-activated protein kinase (AMPK). The aim of this study was to determine the mechanism(s) by which L-Arg infusion increases glucose disposal during exercise in humans by examining total NOS activity and AMPK signaling. Methods: Seven males cycled for 120 min at 64% +/- 1% (V) over dotO(2peak), during which the [6,6-H-2] glucose tracer was infused. During the final 60 min of exercise, either saline alone (Control, CON), or saline containing L-Arg HCl (L-Arg, 30 g at 0.5 g.min(-1)) was coinfused in a double-blind, randomized, counterbalanced order. Results: L-Arg increased the glucose rate of disappearance and glucose clearance rate during exercise; however, this was accompanied by a 150% increase in plasma insulin concentration from 65 to 75 min (P < 0.05) that remained significantly elevated until 90 min of exercise. Skeletal muscle AMPK signaling, nNOS mu phosphorylation by AMPK, and total NOS activity increased to a similar extent in the two trials. Conclusions: The increase in glucose disposal after L-Arg infusion during exercise is likely due to the significantly higher plasma insulin concentration.