Nϵ-(carboxymethyl)lysine, Nϵ-(carboxymethyl)hydroxylysine, and the fluorescent cross-link pentosidine are formed by sequential glycation and oxidation reactions between reducing sugars and proteins. These compounds, termed glycoxidation products, accumulate in tissue collagen with age and at an accelerated rate in diabetes. Although glycoxidation products are present in only trace concentrations, even in diabetic collagen, studies on glycation and oxidation of model proteins in vitro suggest that these products are biomarkers of more extensive underlying glycative and oxidative damage to the protein. Possible sources of oxidative stress and damage to proteins in diabetes include free radicals generated by autoxidation reactions of sugars and sugar adducts to protein and by autoxidation of unsaturated lipids in plasma and membrane proteins. The oxidative stress may be amplified by a continuing cycle of metabolic stress, tissue damage, and cell death, leading to increased free radical production and compromised free radical inhibitory and scavenger systems, which further exacerbate the oxidative stress. Structural characterization of the cross-links and other products accumulating in collagen in diabetes is needed to gain a better understanding of the relationship between oxidative stress and the development of complications in diabetes. Such studies may lead to therapeutic approaches for limiting the damage from glycation and oxidation reactions and for complementing existing therapy for treatment of the complications of diabetes.
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Perspectives in Diabetes|
April 01 1991
Role of Oxidative Stress in Development of Complications in Diabetes
John W Baynes
John W Baynes
Department of Chemistry and School of Medicine, University of South Carolina
Columbia, South Carolina
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Address correspondence to J.W. Baynes, Department of Chemistry, University of South Carolina, Columbia, SC 29208.
Diabetes 1991;40(4):405–412
Article history
Received:
December 06 1990
Revision Received:
December 11 1990
Accepted:
December 11 1990
PubMed:
2010041
Citation
John W Baynes; Role of Oxidative Stress in Development of Complications in Diabetes. Diabetes 1 April 1991; 40 (4): 405–412. https://doi.org/10.2337/diab.40.4.405
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