Protein kinase C and the vascular complications of diabetes mellitus
- Eli A Friedman, MD
Eli A Friedman, MD
- Distinguished Teaching Professor of Medicine
- Downstate Medical Center, Brooklyn, New York
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- David M Nathan, MD
David M Nathan, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Diabetes Mellitus
- Professor of Medicine
- Harvard Medical School
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".)
●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 .
●Increased activity of the hexosamine pathway, which may alter gene expression and protein function .
●Increased formation of advanced glycated end products (AGEs) , which may activate protein kinase C (PKC) isoforms . The mechanisms of oxidant-induced interaction between PKC isoforms and AGEs resulting in vascular disease are incompletely defined .
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