JunD Regulates Pancreatic β-Cells Function by Altering Lipid Accumulation

The impairment of pancreatic beta-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 beta-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 beta-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 beta-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 beta-cells. These results suggested that JunD regulated the function of pancreatic beta-cells by altering lipid accumulation.

Automated summary

JunD plays a significant role in regulating the function of pancreatic beta-cells by altering lipid accumulation, affecting insulin secretion and cell apoptosis. Gene silencing of JunD can reverse the lipotoxic effects on beta-cells.