Exercise ameliorates diabetic cardiomyopathy by inducing beta2‐adrenergic receptors and miR‐133a, and attenuating MMP‐9

Abstract

To test the hypothesis that exercise ameliorates diabetic cardiomyopathy by inducing beta2-adrenergic receptors (AR) and microRNA-133a (miR-133a), and attenuating matrix metalloproteinase-9 (MMP-9); ten weeks male db/db (a model for T2D)- DB (i) mice were treated with salbutamol (a beta2-AR agonist-200μg/kg/i.p)-DBS (ii), exercised (swimming-1hr/daily)-DBE (iii), and both treated with salbutamol and exercised (DBES) (iv) for ten days. The cardiac function was determined by echocardiography and contractile function of cardiomyocytes. The levels of beta2-adrenergic receptors (AR), miR-133a and MMP-9 were measured by Western blot, RT-PCR and qPCR. The results show decrease in percentage fractional shortening (%FS=~30) in db/db mice. The improvement in contractile function (±dL/dt) of cardiomyocytes was evident from significant decrease in the time (sec) to attain 90% peak height in DBE (0.175±0.004) and DBES (0.168±0.002) as compared to DB (0.178±0.002) cardiomyocytes, and corroborated by calcium consumption ratio during the same duration DBE (19.02±1.09), DBES (24.13±1.69), and DB (15.46±0.80). The beta2-AR and miR-133a were up regulated, and MMP-9 was down regulated in DBS, DBE and DBES heart as compared to DB group. Based on these findings, we conclude that exercise ameliorates cardiac dysfunction in db/db mice by improving beta2-AR response and miR-133a, and attenuating MMP-9.