Glycation, oxidation, and lipoxidation in the development of the complications of diabetes: a carbonyl stress hypothesis

TJ Lyons*, AJ Jenkins

*Corresponding author for this work

Research output: Contribution to journalLiterature review

127 Citations (Scopus)

Abstract

Modifications of extant plasma proteins, structural proteins,and other macromolecules are enhanced in diabetes because of increased glycation (secondary to increased glucose concentrations) and perhaps because of increased oxidative stress, Increased glycation is present from the time of onset of diabetes, but the relation between diabetes and oxidative stress is less clear: increased oxidative stress may occur later in the course of disease, as vascular damage becomes established, or it may be a feature of uncomplicated diabetes, The combined effects of protein modification by glycation and oxidation may contribute to the development of accelerated atherosclerosis in diabetes and to the development of microvascular complications, Thus, even if not increased by diabetes, variations in oxidative stress may modulate the consequences of hyperglycemia in individual diabetic patients, In this review, the close interaction between glycation and oxidative processes is discussed, and the theme is developed that the most significant modifications of proteins are the result of interactions with reactive carbonyl groups, While glucose itself contains a carbonyl group that is involved in the initial glycation reaction, the most important and reactive carbonyls are formed by free radical-oxidation reactions damaging either carbohydrates (including glucose itself) or lipids, The resulting carbonyl-containing intermediate products then modify proteins, yielding "glycoxidation" and "lipoxidation" products, respectively, This common pathway for glucose and lipid-mediated stress, which may contribute to diabetic complications, is the basis for the carbonyl stress hypothesis for the development of diabetic complications.

Original languageEnglish
Pages (from-to)365-391
Number of pages27
JournalDIABETES-METABOLISM RESEARCH AND REVIEWS
Volume5
Issue number4
Publication statusPublished - 1997

Keywords

  • LOW-DENSITY-LIPOPROTEIN
  • GLYCOSYLATION END-PRODUCTS
  • NON-ENZYMATIC GLYCOSYLATION
  • MONOCYTE-DERIVED MACROPHAGES
  • AGE-DEPENDENT ACCUMULATION
  • HUMAN-ENDOTHELIAL-CELLS
  • HUMAN-SKIN COLLAGEN
  • HERITABLE HYPERLIPIDEMIC RABBIT
  • CHOLESTERYL ESTER SYNTHESIS
  • MAILLARD REACTION-PRODUCTS

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