| First Author | O'Neill HM | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 38 | Pages | 16092-7 |
| PubMed ID | 21896769 | Mgi Jnum | J:176578 |
| Mgi Id | MGI:5292266 | Doi | 10.1073/pnas.1105062108 |
| Citation | O'Neill HM, et al. (2011) 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. Proc Natl Acad Sci U S A 108(38):16092-7 |
| abstractText | AMP-activated protein kinase (AMPK) beta1 or beta2 subunits are required for assembling of AMPK heterotrimers and are important for regulating enzyme activity and cellular localization. In skeletal muscle, alpha2beta2gamma3-containing heterotrimers predominate. However, compensatory up-regulation and redundancy of AMPK subunits in whole-body AMPK alpha2, beta2, and gamma3 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 beta1 and beta2 isoforms in skeletal muscle (beta1beta2M-KO). beta1beta2M-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 beta1beta2M-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. |
