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

LINDEN, KELLY C.1,2; WADLEY, GLENN D.1,3; GARNHAM, ANDREW P.3; MCCONELL, GLENN K.1,4

Medicine & Science in Sports & Exercise: September 2011 - Volume 43 - Issue 9 - pp 1626-1634
doi: 10.1249/MSS.0b013e318212a317
Basic Sciences

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.

1Exercise Physiology and Metabolism Laboratory, Department of Physiology, The University of Melbourne, Victoria, AUSTRALIA; 2School of Community Health, Charles Sturt University, Albury, New South Wales, AUSTRALIA; 3School of Exercise and Nutrition Sciences, Centre for Physical Activity and Nutrition Research, Deakin University, Burwood Victoria, AUSTRALIA; and 4Institute of Sport, Exercise and Active Living and School of Biomedical and Health Sciences, Victoria University, Victoria, AUSTRALIA

Address for correspondence: Glenn K. McConell, Ph.D., Institute of Sport, Exercise and Active Living and Biomedical and Health Sciences, Victoria University, Victoria 8001, Australia; E-mail: glenn.mcconell@vu.edu.au.

Submitted for publication July 2010.

Accepted for publication January 2011.

©2011The American College of Sports Medicine