Liraglutide ameliorates diabetic cardiomyopathy via activating Cav3/eNOS/NO signaling and enhancing interaction of Cav3 with RyR2

Abstract Purpose Liraglutide (LIRA), a Glucagon-like peptide-1 receptor agonist (GLP-1RA), showed potent cardioprotective effects of diabetic cardiomyopathy (DCM) with the mechanism remained incompletely understood. Methods T2DM rats were used as study subjects and randomly divided into four groups: 1) CON group, 2) CON + L group, 3) DM group and 4) DM + L group. All rats received either saline or LIRA 0.2 mg/kg (by i.p injection) per day for 4 weeks. After the model was successfully established, cardiac function was determined by invasive hemodynamic evaluation methods. Immunohistochemistry and western blot were performed to understand the molecular mechanism between cardiac function and LIRA. Cultured H9C2 cells with small interfering RNA (siRNA) of Cav3 under high glucose (HG), western blot was performed to understand the molecular mechanism between Cav3 and RyR2 with LIRA. Results Based on our results, LIRA treatment showed a trend to enhance LVSP (110.76 ± 5.61 mmHg) and ± dp/dtmax (5860.41 ± 200.32 mmHg and 3996.8 ± 179.3 mmHg), decreased LVEDP (7.23 ± 0.58 mmHg). The expression of Cav3, eNOS and RyR2 was significantly decreased in the myocardium in DM group, which increased in DM + L group after LIRA administrated. LIRA improved cardiac systolic and diastolic function, attenuate diabetic cardiomyopathy injury by improving Cav3/eNOS/NO signaling and increasing interaction of Cav3 and ryanodine receptor 2 (RyR2) in diabetic cardiac tissues. Conclusion In summary, we found that Liraglutide ameliorates cardiac dysfunction in rats with type 2 diabetes mellitus via improving Cav3/eNOS/NO signaling and increasing interaction of Cav3 and RyR2.