title: Direct monitoring of in vivo ER stress during the development of insulin resistance with ER stress-activated indicator transgenic mice.
abstract: Type 2 diabetes is one of the most prevalent and serious metabolic diseases in the world, and insulin resistance and pancreatic beta-cell dysfunction are the hallmarks of the disease. It has been suggested 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 (GFP) under ER stress conditions, we directly monitored in vivo ER stress in various insulin target tissues such as liver, fat, and muscle in diabetic mice with insulin resistance induced by high fat and high sucrose (HF/HS) diet treatment. In the liver of the ERAI transgenic mice, ERAI fluorescence activity was clearly observed as early as after 4 weeks of HF/HS diet treatment, whereas it was not detected at all in the fat and muscle even after 12 weeks of HF/HS diet treatment. These results suggest that induction of ER stress is associated with the development of insulin resistance and that ER stress in the liver may facilitate the development of insulin resistance in the whole body. This is the first report to directly monitor in vivo ER stress in various insulin target tissues during the development of insulin resistance. In addition, our present results suggest that ERAI transgenic mice are very useful for evaluating in vivo ER stress, especially in the liver, during the development of insulin resistance.
authors: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Kazutomi
authors: K
authors: Yoshiuchi
authors: Hideaki
authors: H
authors: Kaneto
authors: Taka-Aki
authors: TA
authors: Matsuoka
authors: Kenji
authors: K
authors: Kohno
authors: Takao
authors: T
authors: Iwawaki
authors: Yoshihisa
authors: Y
authors: Nakatani
authors: Yoshimitsu
authors: Y
authors: Yamasaki
authors: Masatsugu
authors: M
authors: Hori
authors: Munehide
authors: M
authors: Matsuhisa
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology*; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism*; D008856:Microscopy, Fluorescence / Q000379:methods*; D009687:Nuclear Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors