Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA.
Nat Med. 2013 May;19(5):557-66. doi: 10.1038/nm.3159. Epub 2013 May 7.
Thiazolidinediones (TZDs) are potent insulin sensitizers that act through the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) and are highly effective oral medications for type 2 diabetes. However, their unique benefits are shadowed by the risk for fluid retention, weight gain, bone loss and congestive heart failure. This raises the question as to whether it is possible to build a safer generation of PPARγ-specific drugs that evoke fewer side effects while preserving insulin-sensitizing potential. Recent studies that have supported the continuing physiologic and therapeutic relevance of the PPARγ pathway also provide opportunities to develop newer classes of molecules that reduce or eliminate adverse effects. This review highlights key advances in understanding PPARγ signaling in energy homeostasis and metabolic disease and also provides new explanations for adverse events linked to TZD-based therapy.
噻唑烷二酮类（TZDs）是一种通过核受体过氧化物酶体增殖物激活受体-γ（PPARγ）发挥作用的强效胰岛素增敏剂，是治疗 2 型糖尿病的高效口服药物。然而，它们会导致液体潴留、体重增加、骨丢失和充血性心力衰竭，这些独特的益处被风险所掩盖。这就提出了一个问题，即是否有可能制造出更安全的新一代 PPARγ 特异性药物，在保留胰岛素增敏作用的同时减少副作用。最近的研究支持了 PPARγ 通路的持续生理和治疗相关性，也为开发减少或消除不良反应的新型分子提供了机会。这篇综述强调了在能量稳态和代谢疾病中理解 PPARγ 信号的关键进展，并为与 TZD 治疗相关的不良反应提供了新的解释。
