Regional effects of diabetes mellitus on the heart: Shortening and calcium transport in epicardial and endocardial ventricular myocytes

Diabetes mellitus (DM) is a major global disorder currently affecting over 450 million people and this number is rising rapidly. The disorder is due to elevated blood glucose beyond the physiological level or hyperglycemia (HG), leading to a number of long-term complications, including diabetic cardiomyopathy (DC) over time. Over 80% of all diabetics will eventually die from DC. The heart is both a complex and a versatile muscular organ. It is made of two parts, the atria and the ventricles, each of which consists of right and left chambers. The muscles of the heart comprise three main regions, the outer epicardium, the middle myocardium and the inner endocardium. Several studies have investigated the mechanism(s) of DC and concentrated their effort mainly on the whole heart, the left ventricle as a whole, or isolated myocytes from the ventricles. Few studies have investigated the possibility that the HG per se may affect different regions of the heart, for example the ventricular epicardium, the myocardium, and the endocardium. This review is devoted to the regional effects of DM on the heart, particularly the endocardium (ENDO) and the epicardium (EPI), investigating the process of excitation-contraction coupling (ECC). Either the HG itself or derived endogenous compounds, as a result of HG (for example, methylglyoxal and other aldehydes), may initiate localized dysfunction of the heart.