Alogliptin Reduces Oxidative Stress in Cardiomyocytes and Ameliorates Diabetic Cardiomyopathy via the <scp>AURKB</scp> / <scp>NLGN2</scp> Signaling

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus. This study investigated the effects of alogliptin on DCM and its underlying mechanisms. A DCM model was constructed and treated with alogliptin. Downstream targets of alogliptin were screened using bioinformatics analysis. An in vitro DCM model was constructed using mouse cardiomyocytes with a high concentration of glucose. Echocardiography was performed to measure the heart function parameters. Myocardial damage, collagenous fibrosis, and apoptosis of cardiomyocytes in mouse heart tissues were assessed using cardiac histological staining. AURKB and NLGN2 levels, ROS levels, MDA levels, SOD activity, and cardiomyocyte viability were determined. Alogliptin ameliorated DCM in mice. Bioinformatics analysis revealed that the target of alogliptin was AURKB, and the downstream target of AURKB was NLGN2. AURKB and NLGN2 levels were reduced in the heart tissues of streptozotocin-induced mice. Combined knockdown of AURKB and NLGN2 inhibited the therapeutic effect of alogliptin in DCM mice. Alogliptin attenuated oxidative stress, increased viability, and decreased apoptosis in cardiomyocytes treated with high glucose, which were reversed by combined knockdown of AURKB and NLGN2. Overall, alogliptin ameliorated oxidative stress in cardiomyocytes and DCM in mice by promoting AURKB expression to transcriptionally activate NLGN2.