Novel impact of metal ion-induced cell death on diabetic cardiomyopathy pathogenesis and therapy

Diabetes mellitus is a common chronic metabolic disease, with its prevalence escalating annually. Diabetic cardiomyopathy is a leading cause of mortality among diabetic patients, characterized by intricate metabolic disturbances and myocardial cell demise. Various forms of cellular death pathways including apoptosis, pyroptosis, autophagic cell death, necroptosis, ferroptosis, and entosis have been identified in diabetic cardiomyopathy. Inhibiting myocardial cell death pathways has shown promise in mitigating diabetic cardiomyopathy progression. However, there are still gaps in understanding the role of metal ions in diabetic cardiomyopathy pathogenesis. Recent research endeavors have found that iron, copper, zinc, calcium, manganese and other metal elements related to cell death play an intricate and critical role in the pathogenesis and progression of diabetic cardiomyopathy. Notably, many animal studies have shown that the development and progression of diabetic cardiomyopathy can be alleviated by inhibiting the cell death process induced by these metal ions. Therefore, we review the molecular mechanisms underlying the death of various metal ions and the potential pathophysiological roles they play in diabetic cardiomyopathy. In addition, the value of these metal ions in the treatment of diabetic cardiomyopathy is also described.

Graphic abstract