| First Author | Dasgupta B | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 14 | Pages | 2837-48 |
| PubMed ID | 22586267 | Mgi Jnum | J:186658 |
| Mgi Id | MGI:5432850 | Doi | 10.1128/MCB.05853-11 |
| Citation | Dasgupta B, et al. (2012) The AMPK beta2 subunit is required for energy homeostasis during metabolic stress. Mol Cell Biol 32(14):2837-48 |
| abstractText | AMP activated protein kinase (AMPK) plays a key role in the regulatory network responsible for maintaining systemic energy homeostasis during exercise or nutrient deprivation. To understand the function of the regulatory beta2 subunit of AMPK in systemic energy metabolism, we characterized beta2 subunit-deficient mice. Using these mutant mice, we demonstrated that the beta2 subunit plays an important role in regulating glucose, glycogen, and lipid metabolism during metabolic stress. The beta2 mutant animals failed to maintain euglycemia and muscle ATP levels during fasting. In addition, beta2-deficient animals showed classic symptoms of metabolic syndrome, including hyperglycemia, glucose intolerance, and insulin resistance when maintained on a high-fat diet (HFD), and were unable to maintain muscle ATP levels during exercise. Cell surface-associated glucose transporter levels were reduced in skeletal muscle from beta2 mutant animals on an HFD. In addition, they displayed poor exercise performance and impaired muscle glycogen metabolism. These mutant mice had decreased activation of AMPK and deficits in PGC1alpha-mediated transcription in skeletal muscle. Our results highlight specific roles of AMPK complexes containing the beta2 subunit and suggest the potential utility of AMPK isoform-specific pharmacological modulators for treatment of metabolic, cardiac, and neurological disorders. |
