Increasing prevalence of
diabetes mellitus worldwide has pushed the complex disease state to the foreground of biomedical research, especially concerning its multifaceted impacts on the cardiovascular system. Current
therapies for
diabetic cardiomyopathy have had a positive impact, but with diabetic patients still suffering from a significantly greater burden of cardiac pathology compared to the general population, the need for novel therapeutic approaches is great. A new therapeutic target,
calcium/
calmodulin-dependent
kinase II (
CaMKII), has emerged as a potential treatment option for preventing cardiac dysfunction in the setting of diabetes. Within the last 10 years, new evidence has emerged describing the pathophysiological consequences of
CaMKII activation in the diabetic heart, the mechanisms that underlie persistent
CaMKII activation, and the protective effects of
CaMKII inhibition to prevent
diabetic cardiomyopathy. This review will examine recent evidence tying cardiac dysfunction in diabetes to
CaMKII activation. It will then discuss the current understanding of the mechanisms by which
CaMKII activity is enhanced during diabetes. Finally, it will examine the benefits of
CaMKII inhibition to treat
diabetic cardiomyopathy, including contractile dysfunction,
heart failure with preserved ejection fraction, and arrhythmogenesis. We intend this review to serve as a critical examination of
CaMKII inhibition as a therapeutic strategy, including potential drawbacks of this approach.