Amadori glycated proteins: role in production of autoantibodies in diabetes mellitus and effect of inhibitors on non-enzymatic glycation

Abstract

Nonenzymatic glycation of macromolecules, especially proteins leading to their oxidation is increased in diabetes mellitus due to hyperglycemia and play an important role in associated complications of the disease. The glycation primarily occurs at intrachain lysine residues of proteins and results in the formation of an early stage stable product as Amadori-lysine which undergo further irreversible chemical reactions to form advanced glycation endproducts. This review deals with the role of Amadori modified proteins in pathogenesis of diabetes. We aim to explain immunogenicity of Amadori-glycated proteins, which might be involve in production of serum autoantibodies in the diabetic patients, and effect of inhibitors on the glycation process.

Keywords: Amadori products; Antibodies; diabetes complications; lysine rich proteins.

Figure 1.

A scheme showing cyclic form of Amadori products during non-enzymatic glycation of proteins [Adapted from Bioorg Med Chem, 16, Adrover M, Vilanova B, Frau J, Munoz F, Donoso F, The pyridoxamine action on Amadori compounds: A reexamination of its scavenging capacity and chelating effect, 5557–5569, Copyright (2008), with permission from Elsevier (37)].

Figure 2.

Reactivity of autoantibodies to native and modified poly-L-lysine (PLL) in diabetes patients. Reactivity of serum antibodies from diabetes mellitus (DM) patients to native PLL (□), glycated PLL (▪) and NaBH4 reduced glycated PLL (▓). Serum samples from normal human subjects (NHS) served as control. The microtitre ELISA plates were coated with the respective antigens (10 μg/ml). *p < 0.001 vs. native poly-L-lysine (PLL) [Adapted from Human Immunol,70, Ansari NA, Moinuddin, Alam K, Ali A, Preferential recognition of Amadori-rich lysine residues by serum antibodies in diabetes mellitus: Role of protein glycation in the disease process, 417–424, Copyright (2009), with permission from Elsevier (26)].

Figure 3.

Inhibitors for the products of non-enzymatic glycation of proteins. Potential sites of intervention in the formation of Amadori-modified proteins (GLY-230) and AGEs (aminoguanidine, pyridoxamine and benfotiamine), AGE crosslink breaking (ALT 711) and AGE–RAGE-mediated damage (sRAGE) [Adapted from reference (40)].