DataSheet_1_JunD Regulates Pancreatic β-Cells Function by Altering Lipid Accumulation.docx

The impairment of pancreatic β-cells function is partly caused by lipotoxicity, which aggravates the development of type 2 diabetes mellitus. Activator Protein 1 member JunD modulates apoptosis and oxidative stress. Recently, it has been found that JunD regulates lipid metabolism in hepatocytes and cardiomyocytes. Here, we studied the role of JunD in pancreatic β-cells. The lipotoxic effects of palmitic acid on INS-1 cells were measured, and JunD small-interfering RNA was used to assess the effect of JunD in regulating lipid metabolism and insulin secretion. The results showed that palmitic acid stimulation induced the overexpression of JunD, impaired glucose-stimulated insulin secretion, and increased intracellular lipid accumulation of β-cells. Moreover, the gene expression involved in lipid metabolism (Scd1, Fabp4, Fas, Cd36, Lpl, and Plin5) was upregulated, while gene expression involved in the pancreatic β-cells function (such as Pdx1, Nkx6.1, Glut2, and Irs-2) was decreased. Gene silencing of JunD reversed the lipotoxic effects induced by PA on β-cells. These results suggested that JunD regulated the function of pancreatic β-cells by altering lipid accumulation.

胰腺β细胞功能损伤部分由脂毒性（lipotoxicity）引发，而脂毒性会加剧2型糖尿病（type 2 diabetes mellitus）的病情进展。激活蛋白1（Activator Protein 1）成员JunD可调控细胞凋亡与氧化应激。近期研究发现，JunD能够调控肝细胞与心肌细胞内的脂质代谢。本研究旨在探究JunD在胰腺β细胞中的作用：我们检测了棕榈酸（palmitic acid, PA）对INS-1细胞的脂毒性效应，并通过JunD小干扰RNA（small-interfering RNA）评估JunD对脂质代谢与胰岛素分泌的调控功能。结果显示，棕榈酸刺激可诱导JunD过表达，损伤葡萄糖刺激的胰岛素分泌功能，并增加β细胞内的脂质蓄积；与此同时，与脂质代谢相关的基因（Scd1、Fabp4、Fas、Cd36、Lpl及Plin5）的表达均出现上调，而与胰腺β细胞功能相关的基因（如Pdx1、Nkx6.1、Glut2及Irs-2）的表达则显著下调。敲低JunD的表达可逆转PA诱导的β细胞脂毒性损伤。上述研究结果表明，JunD可通过改变细胞内脂质蓄积状态调控胰腺β细胞的功能。