Role of protein kinase C in diabetic complications

Abstract

Hyperglycemia is an important factor in the development of macrovascular and microvascular complications in all diabetic patients. Several hypotheses have been postulated to explain the adverse effect of hyperglycemia on the vasculature; and one of these hypotheses is the activation of specific isoforms of protein kinase C (PKC) by diabetes. In this review, we summarize the molecular mechanisms of PKC activation and its relationship to diabetic complications. PKC activity regulates vascular permeability, contractility, extracellular matrix synthesis, hormone receptor turnover and proliferation, cell growth, angiogenesis, cytokine activation and leukocyte adhesion. All of these properties are abnormal in diabetes and are correlated with increased diacylglycerol–PKC pathway and PKCα, β1/2 and δ isoforms activation in the retina, aorta, heart and renal glomeruli.

Keywords::

• diabetes mellitus
• diabetic complications
• LY333531
• PKC isoforms
• protein kinase C
• ruboxistaurin

Financial & competing interests disclosure

This review used data supported by grants from the ADA (1-08-RA-93), NIH (R01 EY016150, R01 DK071359), DERC (5 P30 DK36836-23), and JDRF (1-2008-330, 8-2008-363, 25-2008-383) awarded to George King. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.