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

6 Citations (Scopus)

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

Fingerprint

Glycogen Synthase
Liver Glycogen
Glycogen
Insulin Resistance
Insulin
Proteins
Chemical activation
Glucose-6-Phosphate
Liver
Obesity
Fats
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Deficiency of a glycogen synthase-associated protein, Epm2aip1, causes decreased glycogen synthesis and hepatic insulin resistance. / Turnbull, Julie; Tiberia, Erica; Pereira, Sandra; Zhao, Xiaochu; Pencea, Nela; Wheeler, Anne L.; Yu, Wen Qin; Ivovic, Alexander; Naranian, Taline; Israelian, Nyrie; Draginov, Arman; Piliguian, Mark; Frankland, Paul W.; Wang, Peixiang; Ackerley, Cameron A.; Giacca, Adria; Minassian, Berge A.

In: Journal of Biological Chemistry, Vol. 288, No. 48, 29.11.2013, p. 34627-34637.

Research output: Contribution to journalArticle

Turnbull, J, Tiberia, E, Pereira, S, Zhao, X, Pencea, N, Wheeler, AL, Yu, WQ, Ivovic, A, Naranian, T, Israelian, N, Draginov, A, Piliguian, M, Frankland, PW, Wang, P, Ackerley, CA, Giacca, A & Minassian, BA 2013, 'Deficiency of a glycogen synthase-associated protein, Epm2aip1, causes decreased glycogen synthesis and hepatic insulin resistance', Journal of Biological Chemistry, vol. 288, no. 48, pp. 34627-34637. https://doi.org/10.1074/jbc.M113.483198
Turnbull, Julie ; Tiberia, Erica ; Pereira, Sandra ; Zhao, Xiaochu ; Pencea, Nela ; Wheeler, Anne L. ; Yu, Wen Qin ; Ivovic, Alexander ; Naranian, Taline ; Israelian, Nyrie ; Draginov, Arman ; Piliguian, Mark ; Frankland, Paul W. ; Wang, Peixiang ; Ackerley, Cameron A. ; Giacca, Adria ; Minassian, Berge A. / Deficiency of a glycogen synthase-associated protein, Epm2aip1, causes decreased glycogen synthesis and hepatic insulin resistance. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 48. pp. 34627-34637.
@article{f5e2cb70a614408f83847cbdeb969f47,
title = "Deficiency of a glycogen synthase-associated protein, Epm2aip1, causes decreased glycogen synthesis and hepatic insulin resistance",
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.",
author = "Julie Turnbull and Erica Tiberia and Sandra Pereira and Xiaochu Zhao and Nela Pencea and Wheeler, {Anne L.} and Yu, {Wen Qin} and Alexander Ivovic and Taline Naranian and Nyrie Israelian and Arman Draginov and Mark Piliguian and Frankland, {Paul W.} and Peixiang Wang and Ackerley, {Cameron A.} and Adria Giacca and Minassian, {Berge A.}",
year = "2013",
month = "11",
day = "29",
doi = "10.1074/jbc.M113.483198",
language = "English (US)",
volume = "288",
pages = "34627--34637",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "48",

}

TY - JOUR

T1 - Deficiency of a glycogen synthase-associated protein, Epm2aip1, causes decreased glycogen synthesis and hepatic insulin resistance

AU - Turnbull, Julie

AU - Tiberia, Erica

AU - Pereira, Sandra

AU - Zhao, Xiaochu

AU - Pencea, Nela

AU - Wheeler, Anne L.

AU - Yu, Wen Qin

AU - Ivovic, Alexander

AU - Naranian, Taline

AU - Israelian, Nyrie

AU - Draginov, Arman

AU - Piliguian, Mark

AU - Frankland, Paul W.

AU - Wang, Peixiang

AU - Ackerley, Cameron A.

AU - Giacca, Adria

AU - Minassian, Berge A.

PY - 2013/11/29

Y1 - 2013/11/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84889053626&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84889053626&partnerID=8YFLogxK

U2 - 10.1074/jbc.M113.483198

DO - 10.1074/jbc.M113.483198

M3 - Article

C2 - 24142699

AN - SCOPUS:84889053626

VL - 288

SP - 34627

EP - 34637

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 48

ER -