Deficiency of a glycogen synthase-associated protein, Epm2aip1, causes decreased glycogen synthesis and hepatic insulin resistance

Julie Turnbull, Erica Tiberia, Sandra Pereira, Xiaochu Zhao, Nela Pencea, Anne L. Wheeler, Wen Qin Yu, Alexander Ivovic, Taline Naranian, Nyrie Israelian, Arman Draginov, Mark Piliguian, Paul W. Frankland, Peixiang Wang, Cameron A. Ackerley, Adria Giacca, Berge A. Minassian

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Glycogen synthesis is a major component of the insulin response, and defective glycogen synthesis is a major portion of insulin resistance. Insulin regulates glycogen synthase (GS) through incompletely defined pathways that activate the enzyme through dephosphorylation and, more potently, allosteric activation. We identify Epm2aip1 as a GS-associated protein. We show that the absence of Epm2aip1 in mice impairs allosteric activation of GS by glucose 6-phosphate, decreases hepatic glycogen synthesis, increases liver fat, causes hepatic insulin resistance, and protects against age-related obesity. Our work identifies a novel GS-associated GS activity-modulating component of insulin resistance.

Original languageEnglish (US)
Pages (from-to)34627-34637
Number of pages11
JournalJournal of Biological Chemistry
Volume288
Issue number48
DOIs
StatePublished - Nov 29 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Turnbull, J., Tiberia, E., Pereira, S., Zhao, X., Pencea, N., Wheeler, A. L., Yu, W. Q., Ivovic, A., Naranian, T., Israelian, N., Draginov, A., Piliguian, M., Frankland, P. W., Wang, P., Ackerley, C. A., Giacca, A., & Minassian, B. A. (2013). Deficiency of a glycogen synthase-associated protein, Epm2aip1, causes decreased glycogen synthesis and hepatic insulin resistance. Journal of Biological Chemistry, 288(48), 34627-34637. https://doi.org/10.1074/jbc.M113.483198