选择性PPARγ调节剂治疗二型糖尿病的分子机制研究进展

摘要

The unique insulin sensitizer peroxisome proliferator activated receptor γ ( PPARγ ) agonists thiazolidinediones ( TZDs ), are once indispensible for the treatment of type 2 dia-betes( T2DM ). However, because TZDs are linked to safety issues such as weight gain, fluid retention, edema, congestive heart failure, the development of selective PPARγ modulators ( SPPARγM ) retaining insulin sensitizing effect and removing TZDs-like side effects now becomes tendency. To date, the preliminary studies about the molecular mechanism of SPPARγM candidates have mainly orientated several aspects such as the impact of SPPARγM on the conformation change of PPARγ, the PPARγ phosphorylation, the selective coregulators recruitment to PPARγ, and the transcriptional regulation of PPARγ target genes. This review mainly reports the molecular mechanism of SPPARγM for type 2 diabetes treatment.%第一类胰岛素增敏剂--过氧化物酶体增殖体激活受体γ(PPARγ)激动剂噻唑烷二酮类药物(TZDs)曾在二型糖尿病(T2DM)治疗中具有不可替代的作用.但由于TZDs类药物存在增重、水肿、骨折、充血性心力衰竭等严重副作用,保留TZDs类药物的胰岛素增敏效果而无其副作用的选择性PPARγ调节剂(SPPARγM)是新型胰岛素增敏剂的发展方向.现有实验主要对SPPARγM候选分子影响PPARγ受体构象改变、受体磷酸化、受体对共调节因子的选择性募集和PPARγ下游靶基因选择性开启等几个层次的分子作用机制作了初步探讨.该文综述了SPPARγM治疗二型糖尿病的分子机制研究进展.