Figure 1.

Overview of the molecular derangements linked to the pathogenesis of DCM. As a result of the metabolic inflexibility imposed by impaired insulin signaling, glucose is not oxidized by cardiomyocytes but instead is diverted into other metabolic pathways that lead to the synthesis of AGEsor to the O-GlyNacylation of proteins. The increased intracellular accumulation of glucose also activates the RAS pathway and alters calcium homeostasis. In addition, hyperlipidemia facilitates fatty acid uptake and leads to lipotoxicity and cardiac steatosis. Furthermore, enhanced but inefficient oxidation of fatty acids leads to the production of reactive oxygen species (ROS) and further promotes mitochondrial dysfunction. All these factors have been shown to contribute to some extent to the functional alterations that characterize DCM.