title: Effect of l-arginine infusion on glucose disposal during exercise in humans.
abstract: OBJECTIVE
  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% VO(2)peak, during which the [6,6-H]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.
authors.affiliation: Exercise Physiology and Metabolism Laboratory, Department of Physiology, The University of Melbourne, Victoria, Australia.
authors.forename: Kelly C
authors.initials: KC
authors.lastname: Linden
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Wadley
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Garnham
authors.forename: Glenn K
authors.initials: GK
authors.lastname: McConell
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000328:Adult; D001120:Arginine / Q000008:administration & dosage*; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D055815:Young Adult
chemical_list: D007328:Insulin; D001120:Arginine; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I; D055372:AMP-Activated Protein Kinases; D005947:Glucose