title: Role of AMPKalpha2 in basal, training-, and AICAR-induced GLUT4, hexokinase II, and mitochondrial protein expression in mouse muscle.
abstract: We investigated the role of AMPKalpha2in basal, exercise training-, and AICAR-induced protein expression of GLUT4, hexokinase II (HKII), mitochondrial markers, and AMPK subunits. This was conducted in red (RG) and white gastrocnemius (WG) muscle from wild-type (WT) and alpha2-knockout (KO) mice after 28 days of activity wheel running or daily AICAR injection. Additional experiments were conducted to measure acute activation of AMPK by exercise and AICAR. At basal, mitochondrial markers were reduced by approximately 20% in alpha2-KO muscles compared with WT. In both muscle types, AMPKalpha2 activity was increased in response to both stimuli, whereas AMPKalpha1 activity was increased only in response to exercise. Furthermore, AMPK signaling was estimated to be 60-70% lower in alpha2-KO compared with WT muscles. In WG, AICAR treatment increased HKII, GLUT4, cytochrome c, COX-1, and CS, and the alpha2-KO abolished the AICAR-induced increases, whereas no AICAR responses were observed in RG. Exercise training increased GLUT4, HKII, COX-1, CS, and HAD protein in WG, but the alpha2-KO did not affect training-induced increases. Furthermore, AMPKalpha1, -alpha2, -beta1, -beta2, and -gamma3 subunits were reduced in RG, but not in WG, by 30-60% in response to exercise training. In conclusion, the alpha2-KO was associated with an approximately 20% reduction in mitochondrial markers in both muscle types and abolished AICAR-induced increases in protein expression in WG. However, the alpha2-KO did not reduce training-induced increases in HKII, GLUT4, COX-1, HAD, or CS protein in WG, suggesting that AMPKalpha2 may not be essential for metabolic adaptations of skeletal muscles to exercise training.
authors.affiliation: Dept. of Human Physiology, Copenhagen Muscle Research Centre, Inst. of Exercise and Sport Sciences, 13-Universitetsparken, Univ. of Copenhagen, DK-2100 Copenhagen, Denmark. SBJorgensen@ifi.ku.dk
authors.forename: Sebastian B
authors.initials: SB
authors.lastname: Jørgensen
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Treebak
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.forename: Sophie
authors.initials: S
authors.lastname: Vaulont
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
authors.forename: Erik A
authors.initials: EA
authors.lastname: Richter
mesh_terms: D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000235:genetics / Q000502:physiology*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D021122:Protein Subunits / Q000378:metabolism; D012265:Ribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D012420:Running
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D024101:Mitochondrial Proteins; D009097:Multienzyme Complexes; D021122:Protein Subunits; D012265:Ribonucleotides; C495693:Slc2a4 protein, mouse; D000620:Aminoimidazole Carboxamide; D006593:Hexokinase; C526221:Prkag3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide