Myocardial glucotoxicity: Mechanisms and potential therapeutic targets

Abstract

Besides coronary artery disease, which remains the main cause of heart failure in patients with diabetes, factors independent of coronary artery disease are involved in the development of heart failure in the onset of what is called diabetic cardiomyopathy. Among them, hyperglycaemia - a hallmark of type 2 diabetes - has both acute and chronic deleterious effects on myocardial function, and clearly participates in the establishment of diabetic cardiomyopathy. In the present review, we summarize the cellular and tissular events that occur in a heart exposed to hyperglycaemia, and depict the complex molecular mechanisms proposed to be involved in glucotoxicity. Finally, from a more translational perspective, different therapeutic strategies targeting hyperglycaemia-mediated molecular mechanisms will be detailed.

Keywords: Adenosine monophosphate-activated protein kinase; Cardiomyopathie diabétique; Co-transporteurs aux sodium/glucose; Diabetes; Diabète; Glucotoxicity; Glucotoxicité; Heart failure; Insuffisance cardiaque; Protéine kinase activée par l’adénosine monophosphate; Sodium glucose cotransporter.