trewin-effectofnacetylcysteine-2015.pdf (925.66 kB)
Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle
journal contribution
posted on 2015-08-01, 00:00 authored by Adam Trewin, Leonidas S Lundell, Ben D Perry, Kim Vikhe Patil, Alexander V Chibalin, Itamar Levinger, Leon R McQuade, Nigel K Stepto-Reactive oxygen species (ROS) produced in skeletal muscle may play a role in potentiating the beneficial responses to exercise; however, the effects of exercise-induced ROS on insulin action and protein signaling in humans has not been fully elucidated. Seven healthy, recreationally active participants volunteered for this double-blind, randomized, repeated-measures crossover study. Exercise was undertaken with infusion of saline (CON) or the antioxidant N-acetylcysteine (NAC) to attenuate ROS. Participants performed two 1-h cycling exercise sessions 7-14 days apart, 55 min at 65% V̇o2peak plus 5 min at 85%V̇o2peak, followed 3 h later by a 2-h hyperinsulinemic euglycemic clamp (40 mIU·min(-1)·m(2)) to determine insulin sensitivity. Four muscle biopsies were taken on each trial day, at baseline before NAC infusion (BASE), after exercise (EX), after 3-h recovery (REC), and post-insulin clamp (PI). Exercise, ROS, and insulin action on protein phosphorylation were evaluated with immunoblotting. NAC tended to decrease postexercise markers of the ROS/protein carbonylation ratio by -13.5% (P = 0.08) and increase the GSH/GSSG ratio twofold vs. CON (P < 0.05). Insulin sensitivity was reduced (-5.9%, P < 0.05) by NAC compared with CON without decreased phosphorylation of Akt or AS160. Whereas p-mTOR was not significantly decreased by NAC after EX or REC, phosphorylation of the downstream protein synthesis target kinase p70S6K was blunted by 48% at PI with NAC compared with CON (P < 0.05). We conclude that NAC infusion attenuated muscle ROS and postexercise insulin sensitivity independent of Akt signaling. ROS also played a role in normal p70S6K phosphorylation in response to insulin stimulation in human skeletal muscle.
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Journal
American journal of physiology: endocrinology and metabolismVolume
309Issue
4Pagination
E388 - E397Publisher
American Physiological SocietyLocation
Bethesda, Md.Publisher DOI
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1522-1555Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2015, the American Physiological SocietyUsage metrics
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