Prevention of diabetic cardiomyopathy through metabolic amendments of myocardium by melatonin: a role beyond antioxidative efficiency

Abstract

The alarming rise in diabetes throughout the world brings the scientist at the brink of finding a suitable compound that can impede glucotoxicity and insulin resistance involved development as well as progression of diabetes. Either devoid of insulin or resistance of cells to insulin brings forward the pancreatic tissue as the most vulnerably affected system. However, cardiac tissue, being the most exposed to circulation with high glucose content, is another target of hyperglycaemia. The remodelling of cardiac tissue in insulin resistant diabetic individuals includes cardiac hypertrophy along with misaligned diastolic and systolic functions. All these amendments cause declined cardiac contractility, the major indication of heart failure. The search for rationale behind such undesirable alterations put forward the involvement of altered cardiac metabolism in diabetes. Both carbohydrate and fatty acid metabolism have been found to be affected in diabetic individuals with declined glycolysis alongwith escalated lipolysis leading toward rise in fatty acid oxidation. Melatonin, with its antioxidative virtue prevents glucotoxicity induced excess reactive oxygen species (ROS) generation to afford protection to cellular systems. Nevertheless, the indole hinders ROS production by lowering both glucose and fatty acid accumulation through augmenting glycolysis along with diminishing lipolysis. Melatonin also expands its worth by keeping in  order gluconeogenesis and glycogenesis pathways of metabolism in diabetic myocardium. The regulation of important metabolic pathways by melatonin in hyperglycaemic cardiac tissue assists the myocardium to maintain energy balance, the primary need for contractile behaviour. Hence, this review focuses on metabolic modulatory actions of melatonin in diabetic myocardium, which may encourage its usage as a saviour for diabetic cardiomyopathy.