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

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)2837-2848
Number of pages12
JournalMolecular and Cellular Biology
Volume32
Issue number14
DOIs
Publication statusPublished - 2012 Jul

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Physiological Stress
AMP-Activated Protein Kinases
Homeostasis
High Fat Diet
Glycogen
Muscles
Skeletal Muscle
Adenosine Triphosphate
Glucose Intolerance
Facilitative Glucose Transport Proteins
Nervous System Diseases
Lipid Metabolism
Hyperglycemia
Energy Metabolism
Insulin Resistance
Fasting
Protein Isoforms
Pharmacology
Glucose
Food

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Dasgupta, B., Ju, J. S., Sasaki, Y., Liu, X., Jung, S. R., Higashida, K., ... Milbrandt, J. (2012). The AMPK ß2 Subunit Is Required for Energy Homeostasis during Metabolic Stress. Molecular and Cellular Biology, 32(14), 2837-2848. https://doi.org/10.1128/MCB.05853-11

The AMPK ß2 Subunit Is Required for Energy Homeostasis during Metabolic Stress. / Dasgupta, Biplab; Ju, Jeong Sun; Sasaki, Yo; Liu, Xiaona; Jung, Su Ryun; Higashida, Kazuhiko; Lindquist, Diana; Milbrandt, Jeffrey.

In: Molecular and Cellular Biology, Vol. 32, No. 14, 07.2012, p. 2837-2848.

Research output: Contribution to journalArticle

Dasgupta, B, Ju, JS, Sasaki, Y, Liu, X, Jung, SR, Higashida, K, Lindquist, D & Milbrandt, J 2012, 'The AMPK ß2 Subunit Is Required for Energy Homeostasis during Metabolic Stress', Molecular and Cellular Biology, vol. 32, no. 14, pp. 2837-2848. https://doi.org/10.1128/MCB.05853-11
Dasgupta, Biplab ; Ju, Jeong Sun ; Sasaki, Yo ; Liu, Xiaona ; Jung, Su Ryun ; Higashida, Kazuhiko ; Lindquist, Diana ; Milbrandt, Jeffrey. / The AMPK ß2 Subunit Is Required for Energy Homeostasis during Metabolic Stress. In: Molecular and Cellular Biology. 2012 ; Vol. 32, No. 14. pp. 2837-2848.
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