<scp>l</scp>-Arginine infusion increases glucose clearance during prolonged exercise in humans

<jats:p> Nitric oxide synthase (NOS) inhibition has been shown in humans to attenuate exercise-induced increases in muscle glucose uptake. We examined the effect of infusing the NO precursor l-arginine (l-Arg) on glucose kinetics during exercise in humans. Nine endurance-trained males cycled for 120 min at 72 ± 1% V̇o<jats:sub>2 peak</jats:sub> followed immediately by a 15-min “all-out” cycling performance bout. A [6,6-<jats:sup>2</jats:sup>H]glucose tracer was infused throughout exercise, and either saline alone (Control, CON) or saline containing l-Arg HCl (l-Arg, 30 g at 0.5 g/min) was coinfused in a double-blind, randomized order during the last 60 min of exercise. l-Arg augmented the increases in glucose rate of appearance, glucose rate of disappearance, and glucose clearance rate (l-Arg: 16.1 ± 1.8 ml·min<jats:sup>−1</jats:sup>·kg<jats:sup>−1</jats:sup>; CON: 11.9 ± 0.7 ml·min<jats:sup>−1</jats:sup>·kg<jats:sup>−1</jats:sup> at 120 min, P < 0.05) during exercise, with a net effect of reducing plasma glucose concentration during exercise. l-Arg infusion had no significant effect on plasma insulin concentration but attenuated the increase in nonesterified fatty acid and glycerol concentrations during exercise. l-Arg infusion had no effect on cycling exercise performance. In conclusion, l-Arg infusion during exercise significantly increases skeletal muscle glucose clearance in humans. Because plasma insulin concentration was unaffected by l-Arg infusion, greater NO production may have been responsible for this effect. </jats:p>