2025 Volume 45 Issue 4 Pages 243-256
Abnormalities in intracellular calcium handling due to diabetic cardiomyopathy have been reported as a cause of sudden cardiac death in patients with diabetes. Meanwhile, selective sodium-glucose co-transporter 2（SGLT2）inhibitors, which were initially developed as antidiabetic drugs, have attracted attention for their cardioprotective effects and have become a standard treatment for heart failure. In addition, selective SGLT2 inhibitors have been reported to reduce the risk of sudden cardiac death. However, the mechanism has not fully examined. In this review, we introduce our findings from experiments using a diabetic mouse model which demonstrate a relationship between intracellular calcium handling abnormalities and the occurrence of ventricular arrhythmias as well as the inhibitory effects of selective SGLT2 inhibitors on ventricular arrhythmias through the improvement of intracellular calcium handling. Our research suggests that the selective SGLT2 inhibitor empagliflozin suppresses O-linked N-acetylglucosamine-mediated post-translational modifications of calcium handling regulatory proteins, thereby improving calcium handling abnormalities and ultimately suppressing ventricular arrhythmias.
