Angiotensin receptor blockers improve insulin resistance in type 2 diabetic rats by modulating adipose tissue
Angiotensin receptor blockers improve insulin resistance in type 2 diabetic rats by modulating adipose tissue
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DOI：
10.1038/ki.2008.313
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发表时间：
2008-10-01
影响因子：
19.6
通讯作者：
Cha, Dae R.
中科院分区：
文献类型：
--
作者：
Lee, Mi H.;Song, Hye K.;Cha, Dae R.
脂肪组织被认为是胰岛素抵抗发展的关键器官。本研究旨在确定血管紧张素受体阻断剂（ARB）对培养的脂肪细胞和2型糖尿病大鼠模型的胰岛素抵抗的影响。用ARB L158809给药大冢Long-Evans德岛肥胖大鼠6个月，显著降低空腹血糖、胆固醇和甘油三酯水平，但导致血浆脂联素水平升高。通过腹膜内葡萄糖耐量试验测量的经治疗大鼠的胰岛素抵抗显著改善，沿着小分化脂肪细胞数量的增加;然而，附睾脂肪量减少。治疗显着降低脂质过氧化和MCP-1的表达，同时增加脂联素的生产脂肪组织。AR B处理显著改善胰岛素敏感性，并显著抑制AT 2诱导的氧化应激、派-1和MCP-1水平以及培养的脂肪细胞的NF-κ B活化。处理增加脂联素和过氧化物酶体增殖物激活受体γ表达，沿着细胞内甘油三酯水平，反映培养的脂肪细胞的分化。我们的研究表明，ARB治疗通过改变脂肪组织来改善胰岛素抵抗，从而减缓糖尿病的发展。
Adipose tissue is recognized as a pivotal organ in the development of insulin resistance. This study seeks to determine the effect of angiotensin receptor blockade (ARB) on insulin resistance of adipocytes in culture and in a rat model of type 2 diabetes. Treatment of Otsuka Long-Evans Tokushima Fatty rats with the ARB L158809 for six months significantly lowered fasting plasma glucose, cholesterol and triglyceride levels but led to higher plasma adiponectin levels. Insulin resistance, measured by an intraperitoneal glucose tolerance test, of the treated rats was significantly improved along with an increase in the number of small differentiated adipocytes; however, epididymal fat mass decreased. Treatment significantly lowered lipid peroxidation and MCP-1 expression while increasing adiponectin production by the adipose tissue. ARB treatment significantly improved insulin sensitivity and markedly suppressed AT2-induced oxidative stress, PAI-1 and MCP-1 levels and NF-kappa B activation of adipocytes in culture. Treatment increased adiponectin and PPAR gamma expression along with intracellular triglyceride levels reflecting differentiation of the cultured adipocytes. Our study suggests that ARB treatment improves insulin resistance by modification of adipose tissue thereby blunting the development of diabetes.