Roles of PKC Isoforms in Development of Diabetes-Induced Cardiovascular Complications

Chapter
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 9)

Abstract

Diabetes-induced cardiovascular abnormalities are the major causes of mortality and morbidity in diabetic populations. Vascular complications of diabetes can be evaluated as microvascular anomalies leading to retinopathy, nephropathy, and neuropathy, and macrovascular anomalies causing atherosclerosis, coronary artery disease, and peripheral vascular disease. Independent of coronary artery disease and hypertension, cardiomyopathy is also an important abnormality that can occur in the diabetic heart. Hyperglycemia, hyperinsulinemia related to insulin resistance, and increased levels of free fatty acids and lipids seem to have prominent roles in the development of microvascular and macrovascular complications and diabetic cardiomyopathy. Several mechanisms can be implicated in these complications, including increased polyol pathway flux, enhanced nonenzymatic glycation, and intracellular formation of advanced glycation end products (AGEs), activation of protein kinase C (PKC) isoforms, and increased hexosamine pathway activity. The focus of this chapter is recent concepts regarding PKC isoform-specific activation mechanisms and actions that have implications for the development of PKC-targeted therapeutics in diabetic complications. The PKC family of serine/threonine kinases have been associated with a diverse array of biological responses in health and disease. In diabetes, activation of different isoforms of PKC is associated with many pathologies seen in the retina, kidneys, vasculature, and heart. Therefore, inhibition of PKC isoforms can be evaluated as a therapeutic target for preventing of diabetic complications. In this regard, clinical trials using ruboxistaurin, a PKC-β isoform inhibitor, have promising results for treatment of diabetic retinopathy, nephropathy, and endothelial dysfunction.

Keywords

PKC Diabetes Insulin resistance Diabetic complications PKC inhibitors 

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of PharmacologyAnkara UniversityAnkaraTurkey

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