Defective insulin signaling and mitochondrial dynamics in diabetic cardiomyopathy

• Insulin stimulates mitochondrial fusion in rat neonatal cardiomyocytes.
• Myocardial insulin resistance contributes to the development of diabetic cardiomyopathy.
• Human diabetic hearts are associated with the fragmentation of the mitochondrial network.
• Insulin regulates myocardial autophagy.
• Drp1 is essential for normal cardiac function regulating autophagy/mitophagy.

Diabetic cardiomyopathy (DCM) is a common consequence of longstanding type 2 diabetes mellitus (T2DM) and encompasses structural, morphological, functional, and metabolic abnormalities in the heart. Myocardial energy metabolism depends on mitochondria, which must generate sufficient ATP to meet the high energy demands of the myocardium. Dysfunctional mitochondria are involved in the pathophysiology of diabetic heart disease. A large body of evidence implicates myocardial insulin resistance in the pathogenesis of DCM. Recent studies show that insulin signaling influences myocardial energy metabolism by impacting cardiomyocyte mitochondrial dynamics and function under physiological conditions. However, comprehensive understanding of molecular mechanisms linking insulin signaling and changes in the architecture of the mitochondrial network in diabetic cardiomyopathy is lacking. This review summarizes our current understanding of how defective insulin signaling impacts cardiac function in diabetic cardiomyopathy and discusses the potential role of mitochondrial dynamics.