Troglitazone prevents mitochondrial alterations, β cell destruction, and diabetes in obese prediabetic rats
Troglitazone prevents mitochondrial alterations, β cell destruction, and diabetes in obese prediabetic rats
复制标题
DOI：
10.1073/pnas.96.20.11513
复制
发表时间：
1999-09-28
影响因子：
11.1
通讯作者：
Unger, RH
中科院分区：
文献类型：
--
作者：
Higa, M;Zhou, YT;Unger, RH
为了确定曲格列酮（TGZ）的降糖作用是否也涉及保护β细胞免受脂肪凋亡，我们给糖尿病前期Zucker糖尿病脂肪大鼠每天200 mg/kg的TGZ。它们的血浆游离脂肪酸和三酰甘油分别降至1.3 mM和111 mg/dl，而未治疗的对照组分别为2.0 mM和560 mg/dl，它们的胰岛三酰甘油含量比对照组低34%，在对照组大鼠的胰岛中，β细胞减少82%，胰岛结构被破坏；β细胞葡萄糖转运蛋白-2缺失，85%的线粒体发生改变，对葡萄糖无反应。在接受治疗的大鼠中，β细胞的损失、β细胞葡萄糖转运体-2的损失、线粒体的改变和葡萄糖刺激的胰岛素分泌的损害都得到了预防。我们得出结论，TGZ对糖尿病前期Zucker糖尿病脂肪大鼠的降糖作用包括预防脂肪毒性和β细胞的脂肪凋亡，以及改善胰岛素敏感性。
To determine whether the antidiabetic action of troglitazone (TGZ), heretofore attributed to insulin sensitization, 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 1.3 mM and 111 mg/dl, respectively, compared with 2.0 mM and 560 mg/dl in untreated controls, Their islet triacylglycerol 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 glucose. In treated rats, the loss of beta cells,vas prevented, as were the loss of beta cell glucose transporter-2, the mitochondrial alterations, and the impairment of glucose-stimulated insulin secretion. We conclude that the antidiabetic effect of TGZ in prediabetic Zucker Diabetic Fatty rats involves prevention of lipotoxicity and lipoapoptosis of beta cells, as well as improvement in insulin sensitivity.