title: Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle.
abstract: -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.
authors.affiliation: College of Sport and Exercise Science and Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia;
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Trewin
authors.affiliation: Departments of Physiology and Pharmacology and.
authors.forename: Leonidas S
authors.initials: LS
authors.lastname: Lundell
authors.affiliation: College of Sport and Exercise Science and Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia;
authors.forename: Ben D
authors.initials: BD
authors.lastname: Perry
authors.affiliation: Departments of Physiology and Pharmacology and.
authors.forename: Kim Vikhe
authors.initials: KV
authors.lastname: Patil
authors.affiliation: Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; and.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Chibalin
authors.affiliation: College of Sport and Exercise Science and Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia;
authors.forename: Itamar
authors.initials: I
authors.lastname: Levinger
authors.affiliation: Australian Proteome Analysis Facility, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Leon R
authors.initials: LR
authors.lastname: McQuade
authors.affiliation: College of Sport and Exercise Science and Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia; Nigel.Stepto@vu.edu.au.
authors.forename: Nigel K
authors.initials: NK
authors.lastname: Stepto
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
chemical_list: D007328:Insulin; D017382:Reactive Oxygen Species; D000111:Acetylcysteine
keywords: exercise; insulin sensitivity; reactive oxygen species; signaling