The role of the amadori product in the complications of diabetes

Ann N Y Acad Sci. 2008 Apr;1126:81-8. doi: 10.1196/annals.1433.052.

Abstract

Strong evidence has emerged in recent years in support of an association between advanced glycation and the complications of diabetes, whereby both glycoxidation products and oxoaldehydes have been implicated. In contrast, except for the fact that skin collagen-linked fructosamine (Amadori product) is a strong predictor of the risk of progression of microvascular disease in humans, Amadori products have not been associated with complications in most animal experiments. Below we develop the hypothesis that glucose-derived advanced glycation end products (AGEs), such as glucosepane, may inflict sustained damage to the extracellular matrix in diabetes and contribute to tissue stiffening and accelerated sclerosis in arteries, kidneys, and other organs as supported by immunochemical studies using a glucosepane antibody. We also hypothesize that many more structures derived from Amadori products with nucleophiles, such as primary amines and thiols, are expected. The selective prevention of Amadori-derived AGEs using deglycating enzymes would be desirable. However, x-ray diffraction studies of Amadoriase I crystals show that the active site of the enzyme is deeply embedded, explaining why this approach is unlikely to succeed in vivo. Preliminary experiments with nucleophiles show that aminoguanidine and other compounds block glucosepane in vitro.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / metabolism
  • Diabetes Complications / enzymology
  • Diabetes Complications / pathology
  • Diabetes Complications / physiopathology*
  • Extracellular Matrix / pathology
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Isoenzymes / metabolism
  • Ketoses / metabolism
  • Kinetics
  • Maillard Reaction

Substances

  • Glycation End Products, Advanced
  • Isoenzymes
  • Ketoses
  • glucosone
  • Amino Acid Oxidoreductases
  • amadoriase