title: Regulation of 5'AMP-activated protein kinase activity and substrate utilization in exercising human skeletal muscle.
abstract: The metabolic role of 5'AMP-activated protein kinase (AMPK) in regulation of skeletal muscle metabolism in humans is unresolved. We measured isoform-specific AMPK activity and beta-acetyl-CoA carboxylase (ACCbeta) Ser(221) phosphorylation and substrate balance in skeletal muscle of eight athletes at rest, during cycling exercise for 1 h at 70% peak oxygen consumption, and 1 h into recovery. The experiment was performed twice, once in a glycogen-loaded (glycogen concentration approximately 900 mmol/kg dry wt) and once in a glycogen-depleted (glycogen concentration approximately 160 mmol/kg dry wt) state. At rest, plasma long-chain fatty acids (FA) were twofold higher in the glycogen-depleted than in the loaded state, and muscle alpha1 AMPK (160%) and alpha2 AMPK (145%) activities and ACCbeta Ser(221) phosphorylation (137%) were also significantly higher in the glycogen-depleted state. During exercise, alpha2 AMPK activity, ACCbeta Ser(221) phosphorylation, plasma catecholamines, and leg glucose and net FA uptake were significantly higher in the glycogen-depleted than in the glycogen-loaded state without apparent differences in muscle high-energy phosphates. Thus exercise in the glycogen-depleted state elicits an enhanced uptake of circulating fuels that might be associated with elevated muscle AMPK activation. It is concluded that muscle AMPK activity and ACCbeta Ser(221) phosphorylation at rest and during exercise are sensitive to the fuel status of the muscle. During exercise, this dependence may in part be mediated by humoral factors.
authors.affiliation: Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. Jwojtaszewski@aki.ku.dk
authors.forename: Jorgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
authors.forename: Christopher
authors.initials: C
authors.lastname: MacDonald
authors.forename: Jakob N
authors.initials: JN
authors.lastname: Nielsen
authors.forename: Ylva
authors.initials: Y
authors.lastname: Hellsten
authors.forename: D Grahame
authors.initials: DG
authors.lastname: Hardie
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Kemp
authors.forename: Bente
authors.initials: B
authors.lastname: Kiens
authors.forename: Erik A
authors.initials: EA
authors.lastname: Richter
mesh_terms: D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005227:Fatty Acids / Q000097:blood; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007866:Leg / Q000098:blood supply; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012039:Regional Blood Flow / Q000502:physiology; D013379:Substrate Specificity
chemical_list: D001786:Blood Glucose; D002395:Catecholamines; D005227:Fatty Acids; D009097:Multienzyme Complexes; D006003:Glycogen; C526181:PRKAA2 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; D000103:Acetyl-CoA Carboxylase