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.
authors.affiliation: From the Program in Genetics and Genome Biology.
authors.forename: Julie
authors.initials: J
authors.lastname: Turnbull
authors.forename: Erica
authors.initials: E
authors.lastname: Tiberia
authors.forename: Sandra
authors.initials: S
authors.lastname: Pereira
authors.forename: Xiaochu
authors.initials: X
authors.lastname: Zhao
authors.forename: Nela
authors.initials: N
authors.lastname: Pencea
authors.forename: Anne L
authors.initials: AL
authors.lastname: Wheeler
authors.forename: Wen Qin
authors.initials: WQ
authors.lastname: Yu
authors.forename: Alexander
authors.initials: A
authors.lastname: Ivovic
authors.forename: Taline
authors.initials: T
authors.lastname: Naranian
authors.forename: Nyrie
authors.initials: N
authors.lastname: Israelian
authors.forename: Arman
authors.initials: A
authors.lastname: Draginov
authors.forename: Mark
authors.initials: M
authors.lastname: Piliguian
authors.forename: Paul W
authors.initials: PW
authors.lastname: Frankland
authors.forename: Peixiang
authors.initials: P
authors.lastname: Wang
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Ackerley
authors.forename: Adria
authors.initials: A
authors.lastname: Giacca
authors.forename: Berge A
authors.initials: BA
authors.lastname: Minassian
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D054637:Dual-Specificity Phosphatases / Q000235:genetics* / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis* / Q000235:genetics; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D010766:Phosphorylation; D054558:Protein Tyrosine Phosphatases, Non-Receptor
chemical_list: D007328:Insulin; D019298:Glucose-6-Phosphate; D006003:Glycogen; D006006:Glycogen Synthase; D054637:Dual-Specificity Phosphatases; C491989:Epm2a protein, mouse; D054558:Protein Tyrosine Phosphatases, Non-Receptor
keywords: Carbohydrate Metabolism; Diabetes; Glycogen Metabolism; Glycogen Synthase; Lafora Disease; Mouse Genetics; Mouse Model; Obesity