The role of protein kinase C activation incardiovascular dysfunctions of diabetesand insulin resistance

摘要

A high rate of cardiovascular morbidity and mortality in diabetic patients is caused by metabolic abnormalities due to insulin deficiency or resistance, including hyperglycemi,hyper-lipidemi,hyperinsulinemi,and insulin resistance.These metabolic abnormalities have been shown to activate protein kinase C (PKC), enhance the formation of advanced glycation end products, and increase oxidative stress, which are suggested to play a crucial role in the development of cell dysfunctions.Dysfunction of vascular endothelium changes the balance of expression and actions of vasoactive substances in the vascular wall Imbalance of vasoactive substances toward vasocontraction decreases endothelium-dependent vasodilation and anti-atherogenic function, which promote vasospasm, thrombosis, and occlusion and lead to cardiovascular disease. Recently, the effects of activated PKC have been reported to inhibit insulin-induced production of nitric oxide in endothelial cells.Moreover, activation of PKC in the myocardium has been shown to reduce ventricular performance and promote myocyte hypertrophy and fibrosis, which may lead to cardiac disorder such as congestive heart failure.We have proposed that activation of PKC is a common downstream point of convergence for oxidants, glycation products, and other glycotoxins or lipotoxins to initiate cardiovascular disease in diabetes.