MAMs and Diabetic Cardiomyopathy: Research Progress on Calcium Homeostasis Regulatory Mechanisms

Diabetic cardiomyopathy (DCM) is a highly specific cardiovascular complication of diabetes that occurs independently of hypertension and coronary atherosclerotic heart disease, and is primarily characterized by diffuse myocardial fibrosis and impaired diastolic and systolic function. In recent years, mitochondria-associated membranes (MAMs), as dynamic membrane contact points connecting the endoplasmic reticulum and mitochondria, have attracted much attention in maintaining calcium homeostasis in myocardial cells, regulating energy metabolism and cell survival fate. This article systematically reviews the structural composition of MAMs and their core roles in apoptosis, mitophagy, inflammatory response and calcium homeostasis regulation. It focuses on the molecular mechanisms by which FUNDC1/IP3R2, Bmal1/Bcl-2/IP3R and PPARα/Mfn2 MAM-related signaling pathways mediate calcium overload in DCM, and reviews the research progress of drugs such as dapagliflozin, ferulic acid, quercetin, and ginsenoside Rb1 in improving DCM by targeting the MAM–calcium homeostasis axis. Finally, this review discusses the key scientific issues and future translational research directions in this field, aiming to provide references for mechanism research and new drug development in DCM.