DR5 but not miRNA-181 or miRNA-211 is involved in ER stress-mediated apoptosis induced by palmitate in islet β cells.

Free fatty acid (FFA)-induced apoptosis and endoplasmic reticulum (ER) stress of pancreatic β-cells contribute to the development of type 2 diabetes; however, the molecular mechanisms involved are not explicated clearly. In this study we have investigated the role of miRNA-181 and miRNA-211 and DR5 in saturated FFA-induced apoptosis of the rat pancreatic β-cells INS-1. Rat pancreatic β-cells INS-1 were treated with or without palmitate for 24 h. CCK-8 was used for cell viability detection. The miRNA-181 and -211 and mRNA expression of GRP78, ATF4, CHOP and DR5 were explored by quantitative real-time PCR. We found that palmitate at apoptosis-inducing concentration activated ER stress signaling pathways and the expressions of GRP78, ATF4 and CHOP were significantly increased after stimulation in INS-1 cells. In addition, mRNA level of DR5 was also upregulated in palmitate treated group. But the expressions of miRNA-181 and -211 did not significantly changed during lipoapoptosis by palmitate in INS-1 cells. We have demonstrated that miRNA-181 and miRNA-211 are not key players in ER stress-related apoptosis induced by saturated FFA in rat pancreatic β cells INS-1. However, DR5 appears to be involved in the modulation of saturated FFA-induced apoptosis of INS-1 cells, probably by a mechanism dependent on ER stress signaling.