Given the role of ER stress response in JNK caspase-12 activation, the high glucose-induced ROS generation-mediated increase in endothelial cell apoptosis due to the activation of JNK and caspase-3 activity and its reversal with blockade of JNK/caspases-3 or antioxidant treatment indicate that ER stress might play a significant role in endothelial cell dysfunction in diabetes. This evidence concerns the gene MAPK8 and diabetes mellitus.