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Protein kinase C and the vascular complications of diabetes mellitus

Author
Eli A Friedman, MD
Section Editors
Richard J Glassock, MD, MACP
David M Nathan, MD
Deputy Editor
John P Forman, MD, MSc

INTRODUCTION

Among patients who have had diabetes mellitus for five or more years, vascular dysfunction results in nephropathy, retinopathy and at least some forms of neuropathy. The most likely cause of vascular dysfunction is chronic hyperglycemia, although hyperglycemia alone may not be sufficient to cause microvascular disease [1,2]. (See "Glycemic control and vascular complications in type 1 diabetes mellitus" and "Glycemic control and vascular complications in type 2 diabetes mellitus".)

Numerous mechanisms have been proposed to explain the association between hyperglycemia and vascular complications (algorithm 1) [3,4]. These include:

Increased activation of the polyol (or aldose reductase) pathway. Increased aldose reductase activity results in the depletion of NADPH, a decrease in cellular reduced glutathione levels, and increased oxidative stress [4].

Increased activity of the hexosamine pathway, which may alter gene expression and protein function [4].

Increased formation of advanced glycated end products (AGEs) [5], which may activate protein kinase C (PKC) isoforms [6]. The mechanisms of oxidant-induced interaction between PKC isoforms and AGEs resulting in vascular disease are incompletely defined [7].

          

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Literature review current through: Nov 2016. | This topic last updated: Wed May 06 00:00:00 GMT+00:00 2015.
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