Figure 1
Metabolic disturbance in the diabetic heart and prospective therapeutic targets. Thickened lines denote activated pathways, and dotted lines denote reduced pathway. (1) The therapeutic reduction of FAT/CD36 activity may attenuate myocardial steatosis, inflammation and oxidative stress, and further improve the energetic yield by shifting metabolism to glucose utilization. (2) Induction of specific PPAR isoforms such as PPARβ/δ may provide cardioprotection by down-regulating FA transporters and TAG synthesis and up-regulating GLUT4, β-oxidation enzymes, and anti-inflammatory transcripts. (3) The elevation of incretin signaling by GLP-1 agonists (or DPP-4 inhibitors) may also control insulin resistance and hyperlipidemia. GLP-1R-dependent actions may include the regulation of glucose and FA receptors trafficking to the sarcolemma, and the amelioration of apoptosis and fibrosis. IR, insulin receptor; FA-CoA, fatty acid-coenzyme A.