Linden, Kelly C, Wadley, Glenn D, Garnham, Andrew and McConell, Glenn ORCID: 0000-0002-8572-9065 (2011) Effect of L-Arginine Infusion on Glucose Disposal during Exercise in Humans. Medicine and Science in Sports and Exercise, 43 (9). pp. 1626-1634. ISSN 0195-9131 (print) 1530-0315 (online)

Abstract

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·O2peak, during which the [6,6-2H]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, nNOSµ 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.

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