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. 2005 Mar;54(3):657-63.
doi: 10.2337/diabetes.54.3.657.

The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes

Kentaro Ozawa  1 , Mayuki Miyazaki, Munehide Matsuhisa, Katsura Takano, Yoshihisa Nakatani, Masahiro Hatazaki, Takashi Tamatani, Kazuya Yamagata, Jun-Ichiro Miyagawa, Yasuko Kitao, Osamu Hori, Yoshimitsu Yamasaki, Satoshi Ogawa
Affiliations

The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes

Kentaro Ozawa et al. Diabetes. 2005 Mar.

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.

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