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Published on: January 12, 2024

[Possible participation of advanced glycation endproducts and their receptor system in the development of diabetic

Yasuhiko Yamamoto1, Shigeru Sakurai, Takuo Watanabe

  • 1Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. yasuyama@med.kanazawa-u.ac.jp

Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
|March 6, 2003
PubMed

Insights

Advanced glycation endproducts (AGE) and their receptor (RAGE) drive diabetic vascular complications. A soluble RAGE variant shows potential for preventing these conditions.

Area of Science:

  • Endocrinology
  • Vascular Biology
  • Diabetology

Background:

  • Diabetes mellitus leads to significant vascular complications like retinopathy and nephropathy.
  • The accumulation of advanced glycation endproducts (AGE) due to hyperglycemia is a key factor in these complications.
  • The interaction between AGE and the receptor for AGE (RAGE) is implicated in diabetic vasculopathy.

Purpose of the Study:

  • To investigate the role of the AGE-RAGE system in diabetic vascular complications.
  • To identify and characterize novel RAGE variants with potential therapeutic value.
  • To establish a relevant animal model for studying diabetic vascular disease.

Main Methods:

  • Utilized transgenic mice overexpressing human RAGE in vascular endothelial cells (EC).
  • Induced diabetes in these mice to study the development of nephropathy.
  • Identified and characterized RAGE variants, including soluble forms, from human sera.

Main Results:

  • Transgenic mice overexpressing RAGE developed advanced nephropathy when diabetic, serving as a model for diabetic vascular disease.
  • AGE-RAGE interaction induced EC changes, including angiogenic and thrombogenic responses.
  • A novel, soluble C-terminally truncated RAGE variant was identified in human sera with neutralizing activity against AGE-induced EC injury.

Conclusions:

  • The AGE-RAGE system plays a critical role in the pathogenesis of diabetic vasculopathy.
  • This system represents a promising therapeutic target for preventing and treating diabetic vascular complications.
  • Stimulating the secretion of soluble RAGE variants may offer a novel strategy for preventing chronic vascular disease in diabetes.

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