Pioglitazone Reduces ER Stress in the Liver: Direct Monitoring of in vivo ER Stress Using ER Stress-activated Indicator Transgenic Mice
Pioglitazone Reduces ER Stress in the Liver: Direct Monitoring of in vivo ER Stress Using ER Stress-activated Indicator Transgenic Mice
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DOI：
10.1507/endocrj.k09e-140
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发表时间：
2009-12-01
影响因子：
2
通讯作者：
Matsuhisa, Munehide
中科院分区：
文献类型：
--
作者：
Yoshiuchi, Kazutomi;Kaneto, Hideaki;Matsuhisa, Munehide
众所周知，内质网（ER）应激是在糖尿病条件下引起的，并且可能与胰岛素抵抗的发展有关。在这项研究中，我们使用在内质网应激条件下表达绿色荧光蛋白的内质网应激激活指示剂（ERAI）转基因小鼠，直接评估了糖尿病药物吡格列酮对糖尿病条件下体内内质网应激的影响。在高脂肪和高蔗糖饮食诱导的糖尿病 ERAI 转基因果汁中，8 周的吡格列酮治疗减少了肝脏中脂肪滴的积累，并减弱了胰岛素抵抗的发展。在 ERAI 转基因小鼠的肝脏中，早在吡格列酮治疗 4 周后，ERAI 荧光活性就明显降低，随后胰岛素抵抗得到改善。此外，吡格列酮治疗后，血清游离脂肪酸和甘油三酯水平降低，血清脂联素水平升高。这些数据表明吡格列酮治疗抑制肝脏内质网应激，这可以至少部分解释吡格列酮降低胰岛素抵抗的药理作用。
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 juice, 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.