4. A review of the formation and role of advanced glycated end products and their receptor in the progression of diabetic complications
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Abstract
In diabetic type 2, a persistent hyperglycemic state leads to the formation of covalent adducts via a non-enzymatic reaction between glucose and proteins. The reaction is called glycation reaction, results in the formation of a heterogeneous group of compounds called Advanced Glycated End Products (AGEs), which play a crucial role in the initiation and progression of diabetic complications. The glycation reaction disrupts the normal functions of molecular conformation and changes the activities of various enzymes by altering receptor functioning. The AGEs accumulate in different tissues and the circulating blood of a person. AGEs play a significant role in accelerating the receptor expression for AGEs that cause various diabetic complications via different mechanisms by disrupting molecular conformation, interfering with the functioning of receptors, and intra- and extracellular crosslinking. AGEs for crosslinking with other endogenous molecules, such as lipids and proteins, contribute to the development of diabetic complications. The chief receptor for the AGEs is the Receptor for Advanced Glycated End Products (RAGE). The RAGE/AGE signaling activates different pathways such as NF-Κb, MAPK/ERK, and TGF-β. This review aims to recapitulate the formation of AGEs and the role of AGE/RAGE receptors in the progression of diabetic complications. The pathophysiological cascade activated by AGEs has a dominant role in the onset of complications associated with diabetes. This review may help in offering therapeutic interventions to lower the formation of AGEs and slow down the progression of complications related to Diabetes Mellitus.
Keywords: AGEs; Diabetes; Diabetic complications; RAGE