Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes

被引：2028

作者：

Oezcan, Umut ^{[1
]}

Yilmaz, Erkan ^{[1
]}

Oezcan, Lale ^{[1
]}

Furuhashi, Masato ^{[1
]}

Vaillancourt, Eric ^{[1
]}

Smith, Ross O. ^{[1
]}

Goerguen, Cem Z. ^{[1
]}

Hotamisligil, Goekhan S. ^{[1
]}

机构：

[1] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA

来源：

SCIENCE | 2006年 / 313卷 / 5790期

关键词：

D O I：

10.1126/science.1128294

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Endoplasmic reticulum ( ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid and taurine-conjugated ursodeoxycholic acid alleviated ER stress in cells and whole animals. Treatment of obese and diabetic mice with these compounds resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease, and enhancement of insulin action in liver, muscle, and adipose tissues. Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes.

引用

页码：1137 / 1140

页数：4

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