Feinstein D L, Spagnolo A, Akar C, Weinberg G, Murphy P, Gavrilyuk V, Dello Russo C
Department of Anesthesiology, University of Illinois, VA Chicago Health Care System, Research & Development, Chicago, IL 60612, USA.
Biochem Pharmacol. 2005 Jul 15;70(2):177-88. doi: 10.1016/j.bcp.2005.03.033.
Agonists of the peroxisome proliferator activated receptor gamma (PPAR(gamma)) are currently used for treatment of type 2 diabetes due to their insulin sensitizing and glucose metabolism stabilizing effects. More recently some of these same agonists were shown to exert anti-inflammatory and anti-proliferative effects as well. Although PPAR(gamma) agonists can operate via receptor-mediated events occurring at the genomic level, thereby causing long lasting changes in gene expression patterns, recent studies demonstrate non-genomic as well as genomic actions, and receptor-dependent as well as receptor-independent effects of the thiazolidinedione (TZD) class of PPAR(gamma) agonists. In this review we will summarize data describing some of these novel, receptor independent actions of TZDs, review evidence that TZDs directly influence mitochondrial function, and attempt to reconcile how changes in mitochondrial function could contribute to other receptor-independent actions of these drugs.
过氧化物酶体增殖物激活受体γ（PPARγ）激动剂目前用于治疗2型糖尿病，因为它们具有胰岛素增敏和稳定葡萄糖代谢的作用。最近，其中一些相同的激动剂还显示出抗炎和抗增殖作用。尽管PPARγ激动剂可以通过发生在基因组水平的受体介导事件发挥作用，从而导致基因表达模式的长期变化，但最近的研究表明，噻唑烷二酮（TZD）类PPARγ激动剂具有非基因组以及基因组作用，以及受体依赖性和受体非依赖性效应。在本综述中，我们将总结描述TZD这些新型受体非依赖性作用的一些数据，回顾TZD直接影响线粒体功能的证据，并试图阐明线粒体功能的变化如何导致这些药物的其他受体非依赖性作用。
