The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes.
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.
Ozawa
Kentaro
K
Department of Neuroanatomy, Kanazawa University Medical School, 13-1, Takara-machi, Kanazawa City, Ishikawa, 920-8640, Japan. k.ozawa@mbi.nifty.com
Miyazaki
Mayuki
M
Matsuhisa
Munehide
M
Takano
Katsura
K
Nakatani
Yoshihisa
Y
Hatazaki
Masahiro
M
Tamatani
Takashi
T
Yamagata
Kazuya
K
Miyagawa
Jun-Ichiro
J
Kitao
Yasuko
Y
Hori
Osamu
O
Yamasaki
Yoshimitsu
Y
Ogawa
Satoshi
S
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*
D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D011506:Proteins; C050087:oxygen-regulated proteins