ангиотензин 1 型受体阻塞剂诱导过氧体增殖器激活的受体-马活性
Michael Schupp1, Jürgen Janke, Ronald Clasen
1Center for Cardiovascular Research, Institut für Pharmakologie und Toxikologie, Campus Charité-Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Circulation
|May 1, 2004
概括
一些安吉奥素1型受体抑制剂 (ARB) 增强过酶增殖器激活受体马 (PPARgamma) 活性,促进脂肪细胞的分化. 这为ARBs的胰岛素敏感和抗糖尿病作用提供了潜在的机制.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 已知1型 ангиотензин受体抑制剂 (ARBs) 通过未知的机制减少2型糖尿病的发生率.
- 过氧体增殖器激活受体- (PPARgamma) 是胰岛素敏感性和葡萄糖代谢的关键调节者.
研究的目的:
- 为了研究ARBs如何调节PPARgamma功能.
- 探索ARBs抗糖尿病作用背后的分子机制.
主要方法:
- 定量实时PCR测量基因标记基因脂肪蛋白2 (aP2) 的mRNA表达.
- 转录报告员测试以评估PPARgamma转录活动.
- 使用AT1R缺乏细胞模型 (PC12W) 的实验.
主要成果:
- 伊尔贝沙坦和特尔米沙坦 (10微摩尔/升) 显著增强了PPARgamma依赖的3T3-L1脂肪细胞分化和aP2mRNA表达.
- 泰尔米沙坦在药理上相关的度下显示出更强大的aP2诱导作用.
- 伊尔贝沙坦和特尔米沙坦诱导了PPARgamma活性,独立于AT(1) R阻断,正如AT1R缺乏细胞模型所示.
结论:
- 特定的ARB激活PPARgamma,促进脂肪细胞的分化.
- 这种PPARgamma激活代表了某些ARBs的一种新类作用.
- 这种机制可能解释了一些ARB观察到的胰岛素敏感化和抗糖尿病作用.
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