title: The AMPK β2 subunit is required for energy homeostasis during metabolic stress.
abstract: 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 β2 subunit of AMPK in systemic energy metabolism, we characterized β2 subunit-deficient mice. Using these mutant mice, we demonstrated that the β2 subunit plays an important role in regulating glucose, glycogen, and lipid metabolism during metabolic stress. The β2 mutant animals failed to maintain euglycemia and muscle ATP levels during fasting. In addition, β2-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 β2 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 PGC1α-mediated transcription in skeletal muscle. Our results highlight specific roles of AMPK complexes containing the β2 subunit and suggest the potential utility of AMPK isoform-specific pharmacological modulators for treatment of metabolic, cardiac, and neurological disorders.
authors.affiliation: Department of Pediatrics, Division of Hematology and Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA. biplab.dasgupta@cchmc.org
authors.forename: Biplab
authors.initials: B
authors.lastname: Dasgupta
authors.forename: Jeong Sun
authors.initials: JS
authors.lastname: Ju
authors.forename: Yo
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Xiaona
authors.initials: X
authors.lastname: Liu
authors.forename: Su-Ryun
authors.initials: SR
authors.lastname: Jung
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Higashida
authors.forename: Diana
authors.initials: D
authors.lastname: Lindquist
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Milbrandt
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004734:Energy Metabolism; D005215:Fasting / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D053858:Metabolic Networks and Pathways; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D005082:Physical Exertion / Q000502:physiology; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D013312:Stress, Physiological; D014018:Tissue Distribution
chemical_list: D021122:Protein Subunits; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C569522:Prkab2 protein, mouse; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose