Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle

Adam J. Trewin, Leonidas S. Lundell, Ben D. Perry, Kim Vikhe Patil, Alexander V. Chibalin, Itamar Levinger, Leon R. McQuade, Nigel K. Stepto

    Research output: Contribution to journalArticlepeer-review

    35 Citations (Scopus)


    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% VO₂peak plus 5 min at 85%VO₂peak, followed 3 h later by a 2-h hyperinsulinemic euglycemic clamp (40 mIU·min⁻¹·m²) 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.
    Original languageEnglish
    Pages (from-to)E388-E397
    Number of pages10
    JournalAmerican journal of physiology : endocrinology and metabolism
    Issue number4
    Publication statusPublished - Aug 2015


    • exercise
    • insulin sensitivity
    • signaling
    • reactive oxygen species
    • Signaling
    • Reactive oxygen species
    • Exercise
    • Insulin sensitivity


    Dive into the research topics of 'Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle'. Together they form a unique fingerprint.

    Cite this