脂毒性导致胰岛β细胞衰竭的机制

Mechanisms of pancreatic β-cell failure induced by lipotoxicity

脂毒性可通过抑制β细胞胰一十二指肠同源盒因子-1（PDX—1）和肌腱膜纤维肉瘤癌基因同源核A（MafA）的表达，使胰岛素基因表达减少，并通过上调固醇调节元件结合蛋白-1c（SREBP—1c）激活其下游靶分子，导致β细胞胰岛素分泌功能受损。脂毒性还可通过激活氧化应激、导致各种凋亡因子失衡、内质网应激、microRNA途径引起β细胞凋亡。

Lipotoxicity can inhibit the expression of pancreatic duodenal homeobox-1 （ PDX-1 ） and mammalian homologue of avian （ MafA ） , so it can reduce the insulin gene expression. Lipotoxicity also can impair insulin secretion of β-cell by upregulating the expression of sterol regulatory element-binding protein- 1 c （SREBP-1c ） and activing the target gene. Moreover lipotoxieity can increase the β-cell apoptosis by inducing oxidative stress,imbalance of apoptotic factor, endoplasmic reticulum stress and mieroRNA pathway.