Schematic diagram demonstrating speculated roles of ER stress signaling pathways in diabetic cardiomyopathy. Firstly, under pathological condition of hyperglycemia in myocytes, ROS is generated by glucose oxidation in mitochondria. Then ROS is released to ER and sensed by three independent ER stress sensors- ATF6, IER1 and PERK to induce ER stress. Under excessive ER stress, apoptotic signals are transducted by ATF6, IRE1 and PERK signaling pathways to induce myocytes apoptosis. Meanwhile, as a component of MAMs proteins, PERK also receives signals from ROS affecting MAMs. Thus, as PERK signaling pathway received double stimulation of ROS in ER and MAMs, PERK is proposed the major signaling pathway transducting apoptotic signals in ROS- mediated ER stress- induced cell apoptosis in DCM. (Non-specific or cross- talk signaling transduction by ER stress sensors is not shown in this figure).