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Abstract Diabetes Mellitus is a chronic disease without proper treatment can cause many complications , either chronic like diabetic retinopathy ,diabetic nephropathy , diabrtic neuropathy , diabetic cardiomyopathy or acute like diabetic ketoacedosis , non ketotic hyperosmolar coma . It produce its deleterious effects by the formation of sugar derived substances called advanced glycated end products (AGEs). AGEs formation is either endogenous or exogenous . The endogenous formation is through the maillard reaction which occur in three phases ,its exogenous source is from the diet high in protein and fat as meat, cheese, egg yolk, or due to increased cooking temperature through boiling and freezing or increase cooking times . AGEs have a range of pathological effect including increase vascular permeability, inhibition of vascular dilatation by interfere with nitric oxide , oxidizing LDL , binding cells including macrophage, endothelial and mesangial cells to induce the secretion of a variety of cytokines and enhancing oxidative stress. AGEs produce its damaging effect on body cells by binding to receptor called Receptor Advanced Glycated End products (RAGE). There are different types of this receptor like full-length , membrane bound forms (FL-RAGE or m RAGE), other lacking the transmembrane domain called soluble RAGE(s RAGE)., and endogenous secretory RAGE(es RAGE ). RAGE is highly expressed and assosciated with many inflammatory related pathological state such as vascular disease , cancer , neurodegenerative and diabetes . AGEs is the main activating ligand but there are many other ligands of RAGE including damage- assosciated molocular patterns (DAMPs), Amphoterin , S100b, Amyloid- β-protein. |