Fig. 6

Summary of our understanding of the pathways accounting to improved cardiac function in diabetes in response to DAPA. The glucose lowering kidney targeted agent, DAPA, demonstrates direct cardiac effects by lowering myocardial [Na⁺]c through inhibition of NHE-1 and NCX and as well as Ca²⁺c through LTCC. The reduction in Ca²⁺ by DAPA appears to be directly correlated to the lowering of [Na⁺]c. The reduction in Ca²⁺ current by DAPA may partly explain the negative inotropic effects of DAPA in diabetic heart as seen by decreased hypertrophy better diastolic diameter following ATII treatment in one hand but augmented cell viability better mitochondrial function resulting less ROS production, reduced fibrosis and inflammation; all leading to better myocardial function on one hand and less cardiomyopathy markers on the other hand