Pioglitazone Reduces ER Stress in the Liver: Direct Monitoring of in vivo ER Stress Using ER Stress-activated Indicator Transgenic Mice

Endocrine Journal

Taka-aki MATSUOKA¹  Ryuichi KASAMI¹  Takao IWAWAKI²  Kenji KOHNO³  Munehide MATSUHISA¹  Hideaki KANETO¹  Iichiro SHIMOMURA¹  Yoshihisa NAKATANI¹  Kazutomi YOSHIUCHI¹  Yoshimitsu YAMASAKI¹ 

[1] Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan;Iwawaki Initiative Research Unit, Frontier Research System, RIKEN, Saitama, Japan;Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan

关键词: Type 2 diabetes;    Insulin resistance;    ER stress;    Pioglitazone;   

DOI  :  10.1507/endocrj.K09E-140

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(33)Cited-By(10)It is known that endoplasmic reticulum (ER) stress is provoked under diabetic conditions and is possibly involved in the development of insulin resistance. In this study, using ER stress-activated indicator (ERAI) transgenic mice which express green fluorescent protein under ER stress conditions, we directly evaluated the effects of a diabetic agent pioglitazone on in vivo ER stress under diabetic conditions. In high fat and high sucrose diet-induced diabetic ERAI transgenic mice, 8 weeks of pioglitazone treatment reduced the accumulation of fat droplets in the liver and attenuated the development of insulin resistance. In the liver of the ERAI transgenic mice, ERAI fluorescence activity was clearly reduced as early as after 4 weeks of pioglitazone treatment, preceding the improvement of insulin resistance. In addition, after the pioglitazone treatment, serum free fatty acid and triglyceride levels were decreased, and serum adiponectin levels were increased. These data indicate that pioglitazone treatment suppresses ER stress in the liver which may explain, at least in part, the pharmacological effects of pioglitazone to reduce insulin resistance.

【 授权许可】

Unknown