engleski

Advanced glycation and the pathogenesis of diabetic complications

Advanced glycation is a major pathway in the pathogenesis of late complications of diabetes. It is a process by which sugars irreversibly bind to protein aminogroups and nucleic acids causing post-translation modifications. Nonenzymatic glycation can in physiological conditions be detected in the ageing process; in pathophysiological conditions, the reactions are significantly faster and more intensive (diabetes mellitus) as body fluids frequently contain increased glucose concentrations Nonenzymatic glycation is a classical covalent reaction in which sugar-protein complex is formed by N-glycoside bonding through a series of complex chemical reactions described by a chemist Maillard. The intermediate and late products of this cascade of events can best be described as a class of heterogeneous sugar-amino acid adducts, which form through progressive dehydration, condensation, fragmentation, oxidation and cyclisation reactions, and are jointly called advanced glycated endproducts (AGE). Once formed AGE proteins are irreversibly modified and thus such structures accumulate during the lifespan of the protein on which they had been formed. The examples include all types of collagen, albumin, basic myelin protein, eye lens proteins, lipoproteins and nucleic acids. The organism contains no enzymes which would be capable of AGE structure hydrolisis. Specific AGE-receptors were identified on different tissues and cell types including macrophages and vascular endothelium. Binding of AGE to receptor triggers the atherogenic events in the homeostasis of blood vessel and their environment. The major biological effect of excessive glycation includes: inhibition of regulatory molecule binding, crosslinking of glycated proteins, trapping of soluble proteins by glycated extracellular matrix, decreased susceptibility to proteolysis, inactivation of enzymes, abnormalities of nucleic acid function, and increased immunogenicity in relation to immune complexes formation. It has been very well documented how advanced glycation endproducts progressively accumulate on those tissues and organs which manifest chronic complications of diabetes mellitus, i.e. retinopathy, neprhopathy, neuropathy and progressive atherosclerosis.

Diabetes; Complications; Advanced Glycation

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