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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Troglitazone prevents mitochondrial alterations, #beta# cell destruction, and diabetes in obese prediabetic rats
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Troglitazone prevents mitochondrial alterations, #beta# cell destruction, and diabetes in obese prediabetic rats

机译:曲格列酮可预防肥胖的糖尿病前期大鼠的线粒体改变,#beta#细胞破坏和糖尿病

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摘要

To determine whether the antidiabetic action of troglitazone (TGZ), heretofore attributed to insulin sensiti- zation, also involves protection of #beta# cells from lipoapoptosis, we treated prediabetic Zucker Diabetic Fatty rats with 200 mg/kg per day of TGZ. Their plasma-free fatty acids and triacylglycerol fell to l.3 mM and lll mg/dl, respectively, compared with 2.0 mM and 560 mg/dl in untreated controls. Their islet triacyl- glycerol content was 34 below controls. In islets of control rats, #beta# cells were reduced by 82 and the islet architecture was disrupted, #beta#-cell glucose transporter-2 was absent, 85 of their mitochondria were altered, and they were unresponsive to glu- cose. In treated rats, the loss of #beta# cells was prevented, as were the loss of #beta# cell glucose transporter-2, the mitochondrial alter- ations, and the impairment of glucose-stimulated insulin secre- tion. We conclude that the antidiabetic effect of TGZ in predi- abetic Zucker Diabetic Fatty rats involves prevention of lipotox- icity and lipoapoptosis of #beta# cells, as well as improvement in insulin sensitivity.
机译:为了确定以前归因于胰岛素敏感性的曲格列酮(TGZ)的抗糖尿病作用是否还涉及保护#beta#细胞免于脂质凋亡,我们以每天200 mg / kg TGZ的糖尿病前期Zucker糖尿病大鼠进行治疗。他们的血浆游离脂肪酸和三酰基甘油分别降至1.3 mM和111 mg / dl,而未经处理的对照组为2.0 mM和560 mg / dl。他们的胰岛三酰基甘油含量比对照低34。在对照组大鼠的胰岛中,#beta#细胞减少了82个,胰岛结构被破坏,#beta#细胞葡萄糖转运蛋白2缺失,线粒体中的85个被改变,并且它们对葡萄糖无反应。在接受治疗的大鼠中,防止了#beta#细胞的丢失,也防止了#beta#细胞葡萄糖转运蛋白2的丢失,线粒体改变和葡萄糖刺激的胰岛素分泌受损。我们得出的结论是,TGZ在糖尿病前期Zucker糖尿病肥胖大鼠中的抗糖尿病作用涉及预防#β#细胞的脂毒性和脂质凋亡,以及改善胰岛素敏感性。

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