AMP-activated protein kinase (AMPK) {beta}1{beta}2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Hayley M O'Neill
  • Stine Just Maarbjerg
  • Justin D Crane
  • Jacob Jeppesen
  • Sebastian B Jørgensen
  • Jonathan D Schertzer
  • Olga Shyroka
  • Kiens, Bente
  • Bryce J van Denderen
  • Mark A Tarnopolsky
  • Bruce E Kemp
  • Richter, Erik A.
  • Gregory R Steinberg
AMP-activated protein kinase (AMPK) ß1 or ß2 subunits are required for assembling of AMPK heterotrimers and are important for regulating enzyme activity and cellular localization. In skeletal muscle, a2ß2¿3-containing heterotrimers predominate. However, compensatory up-regulation and redundancy of AMPK subunits in whole-body AMPK a2, ß2, and ¿3 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 ß1 and ß2 isoforms in skeletal muscle (ß1ß2M-KO). ß1ß2M-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 ß1ß2M-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 a, ß, or ¿ subunits.
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Udgave nummer38
Sider (fra-til)16092-16097
Antal sider6
StatusUdgivet - 2011

Bibliografisk note

CURIS 2011 5200 093

ID: 34409495