Advanced Glycation End Products and Diabetic Complications

Abstract

During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts with the plasma proteins through a non-enzymatic process known as glycation. Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with some other diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interferes with their normal functions by disrupting molecular conformation, altering enzymatic activity, and interfering with receptor functioning. AGEs form intra- and extracellular cross linking not only with proteins, but with some other endogenous key molecules including lipids and nucleic acids to contribute in the development of diabetic complications. Recent studies suggest that AGEs interact with plasma membrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, release of pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasma proteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore, the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract, neuropathy, nephropathy and cardiomyopathy is also discussed.

Protein carbamylation is a hallmark of aging

“…These chemical reactions interfere with normal functions by disrupting molecular conformations, altering enzymatic activities, reducing degradation capacities, or interfering with receptor recognitions (4,36). Among them, glycoxidation has been well-described, and its major contribution to the development of pathophysiological complications of various diseases, such as diabetes mellitus, has been established (37)(38)(39)(40). This reaction had also been shown to participate in the physiological aging process with an accumulation of AGEs in tissues with age.…”

“…CML is one of the most prevalent AGEs in vivo (51), but it seems that HCit is a better marker of skin aging and that carbamylation is a major modification of tissue proteins. Nevertheless, intercurrent diseases, such as chronic renal failure or diabetes mellitus, may cause an imbalance in favor of either HCit or CML formation (15,25,37,52). Because these diseases are commonly intertwined, carbamylation and glycation could induce synergistic deleterious effects on tissue proteins, which could accelerate agerelated complications.…”

The Mechanisms of Inhibition of Advanced Glycation End Products Formation through Polyphenols in Hyperglycemic Condition

“…AGEs contribute to the development and progression of diabetes complications, including micro-or macroangiopathy. AGEs exert their damaging effects on cell functions through several mechanisms such as production of free radicals, fragmentation of protein or lipid, altering enzyme activity, modifying immunogenicity, oxidation of nucleic acids or lipids, carbonyl stress or interaction with AGEs receptors on the cell surface [10]. The AGEs are capable of forming an AGE-receptor complex by binding to specific or non-specific receptors such as AGE-R1 (P60/OST-48 protein), AGE-R2 (80 K-H phosphoprotein), AGE-R3 (galectin), and AGE-RAGE [11][12][13].…”

Evaluation of aging, diabetes mellitus, and skin wounds by scanning acoustic microscopy with protease digestion

“…Protein glycation and formation of AGEs play an important role in the pathogenesis of diabetic complications such as retinopathy, nephropathy, neuropathy, and cardiomyopathy. AGEs form intra- and extracellular cross-linkages not only with proteins, but also with some other endogenous molecules, including lipids and nucleic acids, to contribute to the development of diabetic complications [30]. As wound healing and its dysregulation via fibrosis occur in all tissues, early detection of this process may help prevent disease progression.…”