糖脂毒性对胰腺β细胞的功能损伤作用及机制

Progresses of molecular mechanisms of glucolipotoxicity in the beta cell

现在关于高糖高脂对胰腺β细胞的毒性机制已经有了明显的进展,但还不完全清楚。实际上,β细胞响应过量营养物质的过程是一个连续的过程,包括β细胞补偿和β细胞功能失调。在早期,β细胞应对高糖高脂的反应是一个积极主动的过程;而到后期,过量的糖脂会导致胰岛素分泌下降,削弱胰岛素基因表达量,并促进胰岛β细胞凋亡。最终对2型糖尿病的发展有促进作用。综述了近年来细胞水平和分子水平,在葡萄糖存在的条件下,脂肪酸对胰腺β细胞的损伤作用及其机制的研究进展,重在说明葡萄糖和脂肪酸在2型糖尿病发展中的共同作用。

In recent years, major progress has been made towards a better understanding of the cellular and molecular mechanisms of glucolipotoxicity in the beta cell. However, the role of glucolipotoxicity is still debated. In fact, the beta cell＇s response to nutrient ex- cess likely represents a continuum encompassing all stages of beta-cell compensation and beta-cell failure. In that sense, some of the early manifestations of glucolipotoxicity should actually be considered as a positive response. The combination of excessive levels of fatty acids and glucose leads to decrease insulin secretion, impaire insulin gene expression and beta-cell death by apoptosis. Finally, glucolipotoxicity contributes to beta-cell failure in type 2 diabetes. The most recent progresses in the molecular mechanisms which glucolipotoxicity induces beta ceils mass expansion and function were summarized, and the reciprocity of glucose and fat in development of type 2 diabetes was chiefly explained.