Updating Experimental Models of Diabetic Cardiomyopathy

Figure 1

The diabetic milieu at the myocardium. Thickened lines represent activated pathways, and dotted lines denote reduced pathways. The absence of insulin response by defect in its secretion (T1DM) or sensibility (T2DM) promotes a lack of glucose assimilation for energy demand in the cardiomyocytes and extracellular glucose accumulation. Thus, FA may be the unique energetic substrate but β-oxidation may saturate and lipid can accumulate and cause steatosis and lipotoxicity by DAG, ceramide, and ROS formation. These metabolites together with glucose derivatives (i.e., polyols, AGEs) damage the mitochondria and endoplasmic reticulum (ER) and regulate the expression of proinflammatory, hypertrophy, fibrotic, and apoptotic genes. RAGE, receptor for advanced glycation end products; UR, unspecific receptors; IR, insulin receptor; FAR, fatty acid receptors. Ch: cholesterol; Cyt. C: cytochrome-C.