title: AMP-activated protein kinase (AMPK) beta1beta2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise.
abstract: AMP-activated protein kinase (AMPK) β1 or β2 subunits are required for assembling of AMPK heterotrimers and are important for regulating enzyme activity and cellular localization. In skeletal muscle, α2β2γ3-containing heterotrimers predominate. However, compensatory up-regulation and redundancy of AMPK subunits in whole-body AMPK α2, β2, and γ3 null mice has made it difficult to determine the physiological importance of AMPK in regulating muscle metabolism, because these models have normal mitochondrial content, contraction-stimulated glucose uptake, and insulin sensitivity. In the current study, we generated mice lacking both AMPK β1 and β2 isoforms in skeletal muscle (β1β2M-KO). β1β2M-KO mice are physically inactive and have a drastically impaired capacity for treadmill running that is associated with reductions in skeletal muscle mitochondrial content but not a fiber-type switch. Interestingly, young β1β2M-KO mice fed a control chow diet are not obese or insulin resistant but do have impaired contraction-stimulated glucose uptake. These data demonstrate an obligatory role for skeletal muscle AMPK in maintaining mitochondrial capacity and contraction-stimulated glucose uptake, findings that were not apparent in mice with single mutations or deletions in muscle α, β, or γ subunits.
authors: Department of Medicine, McMaster University, Hamilton, ON, Canada L8N 3Z5.
authors: Hayley M
authors: HM
authors: O'Neill
authors: Stine J
authors: SJ
authors: Maarbjerg
authors: Justin D
authors: JD
authors: Crane
authors: Jacob
authors: J
authors: Jeppesen
authors: Sebastian B
authors: SB
authors: Jørgensen
authors: Jonathan D
authors: JD
authors: Schertzer
authors: Olga
authors: O
authors: Shyroka
authors: Bente
authors: B
authors: Kiens
authors: Bryce J
authors: BJ
authors: van Denderen
authors: Mark A
authors: MA
authors: Tarnopolsky
authors: Bruce E
authors: BE
authors: Kemp
authors: Erik A
authors: EA
authors: Richter
authors: Gregory R
authors: GR
authors: Steinberg
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008931:Mitochondria, Muscle / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004272:DNA, Mitochondrial; D007004:Hypoglycemic Agents; D007328:Insulin; D024101:Mitochondrial Proteins; C554549:Prkab1 protein, mouse; D055372:AMP-Activated Protein Kinases; D005947:Glucose