The role of CaMKII in diabetic heart dysfunction

Diabetes mellitus (DM) is an increasing epidemic that places a significant burden on health services worldwide. The incidence of heart failure (HF) is significantly higher in diabetic patients compared to non-diabetic patients. One underlying mechanism proposed for the link between DM and HF is activation of calmodulin-dependent protein kinase (CaMKII delta). CaMKII delta mediates ion channel function and Ca2+ handling during excitation-contraction and excitation-transcription coupling in the myocardium. CaMKII delta activity is up-regulated in the myocardium of diabetic patients and mouse models of diabetes, where it promotes pathological signaling that includes hypertrophy, fibrosis and apoptosis. Pharmacological inhibition and knockout models of CaMKII delta have shown some promise of a potential therapeutic benefit of CaMKII delta inhibition, with protection against cardiac hypertrophy and apoptosis reported. This review will highlight the pathological role of CaMKII delta in diabetes and discuss CaMKII delta as a therapeutic target in DM, and also the effects of exercise on CaMKII delta.