Tanaka Toshiya
Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo.
Nihon Rinsho. 2010 Feb;68(2):249-55.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a ligand-activated transcription factor regulating gene expression involved in the fatty acids, lipoprotein and carbohydrate metabolism and inflammation. Its wide range of potential therapeutic actions make it attractive targets for the development of drugs treating metabolic disorders such as metabolic syndrome, type 2 diabetes and dyslipidemia. The thiazolidinediones (TZDs) insulin-sensitizer of PPARgamma agonist have been clinically used for insulin resistant and diabetes patients in a decade. Despite the proven benefits of TZDs, safety concerns have led to drop out of the various newly developed PPARgamma targeting drugs. Here, I summarize the therapeutic potential and adverse events of TZDs and non-TZDs class of PPARgamma modulators, and will discuss the future strategy of the PPARgamma modulator development.
过氧化物酶体增殖物激活受体γ（PPARγ）是一种配体激活的转录因子，可调节参与脂肪酸、脂蛋白和碳水化合物代谢及炎症的基因表达。其广泛的潜在治疗作用使其成为开发治疗代谢紊乱（如代谢综合征、2型糖尿病和血脂异常）药物的有吸引力的靶点。噻唑烷二酮类（TZDs）作为PPARγ激动剂的胰岛素增敏剂，已在临床上用于治疗胰岛素抵抗和糖尿病患者达十年之久。尽管TZDs已被证实具有益处，但安全问题导致各种新开发的靶向PPARγ的药物退出市场。在此，我总结了TZDs和非TZDs类PPARγ调节剂的治疗潜力和不良事件，并将讨论PPARγ调节剂开发的未来策略。
