表观遗传修饰在糖尿病代谢记忆中的作用

The role of epigenetic modification in diabetic metabolic memory

糖尿病患者在血糖得到控制后，糖尿病并发症仍然持续发展的现象提示了以前暴露于高血糖导致的“代谢记忆”。近来的研究提示“代谢记忆”可能归因于靶细胞的表观遗传改变。许多实验证据显示：组蛋白乙酰基转移酶（HATs）、组蛋白去乙酰化酶（HDACs）、组蛋白甲基转移酶（HMTs）、组蛋白赖氨酸去甲基化酶（KDMs）以及microRNA在调节几种与糖尿病并发症相关的关键基因表观遗传修饰中发挥了重要作用。进一步阐明表观遗传修饰在糖尿病“代谢记忆”中的作用机制以及明确相应的细胞信号通路，对于糖尿病及其并发症的防治有重要意义。

It is evident that metabolic memory, whereby diabetic complications continue to develop and progress in individuals who returned to normal glycemic control after a period of transient hyperglycemia, has long lasting effects. Recent studies suggest that ＂metabolic memory＂ may be due to epigenetic changes in target cells. Understanding the molecular changes in chromatin structure and the functional relationship with altered signaling pathways is now considered to represent an important conceptual challenge to explain diabetes and the phenomenon of metabolic memory. Emerging evidences indicate that critical gene-activating epigenetic changes may confer future cell memories. Many experimental evidences show that histone acetyltransferases （HATs）, histone deacetylases （ HDACs）, histone methyltransferases （ HMTs ）, histone lysine demethylases （ KDMs ）, and microRNAs play important roles in the epigenetic changes of several key genes related to diabetic complications. Transient hyperglycemia promotes gene-activating epigenetic changes and signaling events critical in the development and progression of diabetic vascular complications. Further characterisation of these glucose-induced epigenetic events and the identification of key enzymes involved will help us to develop new therapeutic strategies for diabetes and its complications.