The Role of the Amadori Product in the Complications of Diabetes

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.

Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus

“…AGEs are formed spontaneously by non-enzymatic glycation or oxidation. However, there are numerous sources of AGEs and unknown pathways leading to AGEs formation in vivo [83]. AGEs cross-links such as Pen are likely to be formed between helical Lys and Arg without involvement of the telopeptides.…”

“…1). The Amadori adduct can undergo further reaction with amino acids such as Lys or arginine (Arg) in adjacent collagen molecules to form AGEs cross-links between collagen molecules [83]. AGEs are formed spontaneously by non-enzymatic glycation or oxidation.…”

Influence of pyridoxylidene aminoguanidine on biomarkers of the oxidative stress and selected metabolic parameters of rats with diabetes mellitus

“…The Amadori products are changed over time and they provide another reactive compounds which can react with proteins and form cross-links as well as brown coloured and fluorescent molecules called Maillard products (advanced glycation end products − AGEs) (Wolff 1996;Kalousová et al 2005;Monnier et al 2008). AGEs are represented by a heterogeneous group of compounds, e.g.…”

Glycated Lysine Residues: A Marker for Non-Enzymatic Protein Glycation in Age-Related Diseases

“…Glycated immunoglobulins (IgG, IgA, IgM) and glycated hemoglobin have been found in increased level in both type 1 and 2 diabetic patients with nephropathy as compared to the patients without any complications [31]. The investigations resulted in a detailed study for Amadori product in diabetes complications [47]. Previous reports on poly-L-lysine, a homopolymer of lysine residues with a large number of free ε-amino groups, were restricted to characterization of their browning products or AGEs [37,38].…”