Molecular susceptibility to glycation and its implication in diabetes mellitus and related diseases.

The modification of free amino groups on proteins, lipids, and nucleic acids by non-enzymatic glycosylation produce a variety of complex structures named advanced glycation end products (AGEs). Glycation of these molecules participate in the development of diabetic complications and related diseases. Diabetes mellitus is characterized by short-term metabolic changes in lipid and protein metabolism, and long-term irreversible changes in vascular and connective tissue. AGEs are directly implicated in the development of chronic complications in diabetes such as nephropathy, rethinopathy, neuropathy, and other related diseases such as atherosclerosis, heart disease, stroke, and peripheral vascular disease. In this review, we aim to explain how glycation occurs in different molecules and what the pathological consequence of AGE formation in diabetes mellitus and other diseases are.

Trends in advanced glycation end products research in diabetes mellitus and its complications.

Advanced glycation end-products (AGEs) are heterogeneous groups of compounds that result from the non-enzymatic reaction of reducing sugars with free amino groups of biological molecules such as proteins, lipids, and nucleic acids. A large number of studies have been focused on AGEs metabolism, analysis, treatments, and their implications in the pathogenesis of diseases, especially in diabetes mellitus. Here, we review recent advances in the understanding of pathological complications caused by the production of AGEs. We provide an overview of the most important issues published within this area in last years; we also present the number of scientific papers related to AGEs available since 1950 until 2008 in the most important fields including metabolism, physiology, and pharmacology, thus as analytical methods for AGE detection and quantification and studies carried out in human body fluids. Data were collected from ovidSP.

In vitro glycation of brain aminophospholipids by acetoacetate and its inhibition by urea.

Amino groups of amino acids, nucleic acids and lipids can react non-enzymatically with reducing sugars to form unstable Schiff bases that can then undergo the Amadori rearrangement to form irreversible advanced glycation end products (AGEs). Ketoacidosis is a life-threatening complication in patients with untreated diabetes mellitus and it is characterized by increased circulating ketone body concentrations. Recently, the in vitro glycation of hemoglobin by beta-hydroxybutyrate and acetone was described by our laboratory. This study was designed to evaluate the in vitro effect of acetoacetate on brain aminophospholipids at similar concentrations to that observed in ketoacidosis (16.13 mM total ketone bodies). The effect of acetoacetate was compared to that of glucose and the other ketone bodies; beta-hydroxybutyrate and acetone. The antiglycating activity of urea and glycylglycine was also investigated. The incubation of aminophospholipids with acetoacetate results in the formation of a new compound with an absorption peak at 280 nm. When this reaction product was analyzed by thin layer chromatography using an elusion system of methanol:chloroform:acetic acid:water (8:1:1:0.4), the R(f) value obtained (0.24-0.26) was similar to that of the compound formed by aminophospholipids with glucose. In contrast, this reaction product was not detected in those samples containing beta-hydroxybutyrate and acetone. The formation of this new compound was inhibited by urea more effectively than glycylglycine. In conclusion, this study provides the evidence that brain aminophospholipids react with acetoacetate forming AGEs and that this glycating effect of acetoacetate was remarkably decreased by urea, suggesting a protective physiological role for urea in the body as it was previously stated. Finally, this information adds knowledge about the contribution of ketoacidosis in the pathophysiology of diabetic complications, especially in type 1 diabetic patients.