title: The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes.
abstract: To determine the role of the endoplasmic reticulum (ER) in diabetes, Akita mice, a mouse model of type 2 diabetes, were mated with either heterozygous knockout mice or two types of transgenic mice of 150-kDa oxygen-regulated protein (ORP150), a molecular chaperone located in the ER. Systemic expression of ORP150 in Akita mice improves insulin intolerance, whereas the exclusive overexpression of ORP150 in pancreatic beta-cells of Akita mice did not change their glucose tolerance. Both an insulin tolerance test and hyperinsulinemic-euglycemic clamp revealed that ORP150 enhanced glucose uptake, accompanied by suppression of oxidized protein. Furthermore, ORP150 enhanced the insulin sensitivity of myoblast cells treated with hydrogen peroxide. These data suggest that ORP150 plays an important role in insulin sensitivity and is a potential target for the treatment of diabetes.
authors.affiliation: Department of Neuroanatomy, Kanazawa University Medical School, 13-1, Takara-machi, Kanazawa City, Ishikawa, 920-8640, Japan. k.ozawa@mbi.nifty.com
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ozawa
authors.forename: Mayuki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Munehide
authors.initials: M
authors.lastname: Matsuhisa
authors.forename: Katsura
authors.initials: K
authors.lastname: Takano
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hatazaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Tamatani
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Miyagawa
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kitao
authors.forename: Osamu
authors.initials: O
authors.lastname: Hori
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005508:Food Deprivation; D015870:Gene Expression; D018149:Glucose Intolerance; D018840:HSP70 Heat-Shock Proteins; D006579:Heterozygote; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D018384:Oxidative Stress; D010179:Pancreas / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D011506:Proteins; C050087:oxygen-regulated proteins