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Molecular Medicine

, Volume 21, Supplement 1, pp S32–S40 | Cite as

Advanced Glycation End Products: A Molecular Target for Vascular Complications in Diabetes

  • Sho-ichi Yamagishi
  • Nobutaka Nakamura
  • Mika Suematsu
  • Kuniyoshi Kaseda
  • Takanori Matsui
Invited Review Article

Abstract

A nonenzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and subsequently alters their structural integrity and function. This process has been known to progress at an accelerated rate under hyperglycemic and/or oxidative stress conditions. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent and senescent macroprotein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence indicating that interaction of AGEs with their receptor (RAGE) elicits oxidative stress generation and as a result evokes proliferative, inflammatory, thrombotic and fibrotic reactions in a variety of cells. This evidence supports AGEs’ involvement in diabetes- and aging-associated disorders such as diabetic vascular complications, cancer, Alzheimer’s disease and osteoporosis. Therefore, inhibition of AGE formation could be a novel molecular target for organ protection in diabetes. This report summarizes the pathophysiological role of AGEs in vascular complications in diabetes and discusses the potential clinical utility of measurement of serum levels of AGEs for evaluating organ damage in diabetes.

Notes

Acknowledgments

This study was supported in part by Grants-in-Aid for Scientific Research (B) (grant number 25293127) from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to S Yamagishi).

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Authors and Affiliations

  • Sho-ichi Yamagishi
    • 1
  • Nobutaka Nakamura
    • 1
  • Mika Suematsu
    • 1
    • 2
  • Kuniyoshi Kaseda
    • 2
  • Takanori Matsui
    • 1
  1. 1.Department of Pathophysiology and Therapeutics of Diabetic Vascular ComplicationsKurume University School of MedicineKurumeJapan
  2. 2.Saravio Central InstituteOitaJapan

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