The role of protein O-GlcNAcylation in diabetic cardiomyopathy.

It is well established that diabetes markedly increases the risk of multiple types of heart disease including heart failure. However, despite substantial improvements in the treatment of heart failure in recent decades the relative increased risk associated with diabetes remains unchanged. There is increasing appreciation of the importance of the post translational modification by O-linked-N-acetylglucosamine (O-GlcNAc) of serine and threonine residues on proteins in regulating cardiomyocyte function and mediating stress responses. In response to diabetes there is a sustained increase in cardiac O-GlcNAc levels, which has been attributed to many of the adverse effects of diabetes on the heart. Here we provide an overview of potential mechanisms by which increased cardiac O-GlcNAcylation contributes to the adverse effects on the heart and highlight some of the key gaps in our knowledge.