AMP-activated protein kinase (AMPK) β1β2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise

Hayley M O'Neill, Stine J Maarbjerg, Justin D Crane, Jacob Jeppesen, Sebastian B Jørgensen, Jonathan D Schertzer, Olga Shyroka, Bente Kiens, Bryce J van Denderen, Mark A Tarnopolsky, Bruce E Kemp, Erik A Richter, Gregory R Steinberg

Research output: Contribution to journalArticleResearchpeer-review

350 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)16092-7
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number38
DOIs
Publication statusPublished - 20 Sept 2011
Externally publishedYes

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