Chronic Diabetic Complications and Tissue Glycosylation: Relevant Concern for Diabetes-Prone Black Population

Author:

Vlassara Helen1

Affiliation:

1. Rockefeller University New York, New York

Abstract

A significant segment of the Black population is affected by chronic diabetes, and most of them are subjected to severe cardiovascular, renal, and neurological complications that shorten survival and diminish quality of life. One of the important pathogenetic mechanisms under intensive investigation is advanced tissue glycosylation. Tissue and cell surface proteins modified nonenzymatically by glucose are shown to be highly active in protein cross-linking and have been implicated in tissue damage. Such protein-glucose interactions, called advanced glycosylation end products (AGEs), are processed by macrophages through a high-affinity receptor. Coupling of AGE proteins to their AGE receptors results in their degradation and removal and, simultaneously, in synthesis and secretion of pluripotential cytokines such as tumor necrosis factor and interleukin 1. This suggests that AGE may act normally as a signal for growth-promoting factor secretion in a coordinated replacement process during tissue remodeling. In chronic diabetes, however, where accelerated accumulation of tissue AGE occurs, a disturbance of this balance may lead to several pathological, lytic, and/or proliferative responses like those in the vasculopathy of diabetes. Progress has been made with the discovery of aminoguanidine HCI, an AGE inhibitor, which has prevented significant pathology in short-term diabetic animal studies.

Publisher

American Diabetes Association

Subject

Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine

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