The AMPK ß2 Subunit Is Required for Energy Homeostasis during Metabolic Stress

Biplab Dasgupta*, Jeong Sun Ju, Yo Sasaki, Xiaona Liu, Su Ryun Jung, Kazuhiko Higashida, Diana Lindquist, Jeffrey Milbrandt

*この研究の対応する著者

研究成果: Article査読

48 被引用数 (Scopus)

抄録

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 ß2 subunit of AMPK in systemic energy metabolism, we characterized ß2 subunit-deficient mice. Using these mutant mice, we demonstrated that the ß2 subunit plays an important role in regulating glucose, glycogen, and lipid metabolism during metabolic stress. The ß2 mutant animals failed to maintain euglycemia and muscle ATP levels during fasting. In addition, ß2-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 ß2 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 PGC1ß-mediated transcription in skeletal muscle. Our results highlight specific roles of AMPK complexes containing the ß2 subunit and suggest the potential utility of AMPK isoform-specific pharmacological modulators for treatment of metabolic, cardiac, and neurological disorders.

本文言語English
ページ(範囲)2837-2848
ページ数12
ジャーナルMolecular and Cellular Biology
32
14
DOI
出版ステータスPublished - 2012 7月

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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