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

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

来源：Proceedings of the National Academy of Sciences, 2011, 108(38): 16092-16097.

DOI：10.1073/pnas.1105062108

• TBC1D1
• PGC1-alpha
• AS160
• type 2 diabetes
• obesity

AMP-activated protein kinase (AMPK) beta 1 or beta 2 subunits are required for assembling of AMPK heterotrimers and are important for regulating enzyme activity and cellular localization. In skeletal muscle, alpha 2 beta 2 gamma 3-containing heterotrimers predominate. However, compensatory up-regulation and redundancy of AMPK subunits in whole-body AMPK alpha 2, beta 2, and gamma 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 beta 1 and beta 2 isoforms in skeletal muscle (beta 1 beta 2M-KO). beta 1 beta 2M-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 beta 1 beta 2M-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 alpha, beta, or gamma subunits.

• 出版日期2011-9-20
• 单位河北医科大学