Advanced Glycation End Products (AGEs) in Diabetic Complications

Hyperglycemic condition in diabetes accelerates formation of advanced glycation end products (AGEs) that are formed as a result of series of reaction between reducing sugars and proteins. Accumulation of AGEs has been implicated in development of insulin resistance as well as in the pathogenesis of diabetic complications. The principal mechanism by which AGEs render harmful effects is through interaction with cell bound receptors. Certain receptors like AGE-R1 are involved in degradation of AGEs, while certain other receptors like receptor for AGE (RAGE) bring about counter effects exacerbating the situation. Accumulation of diverse AGEs, synergistically down regulate AGE-R1 while up regulate RAGE causing vicious cycle leading to enhanced formation and further accumulation of AGEs. In this article we discuss the formation of heterogeneous AGEs, importance of detection and quantification of AGEs, biological degradation of AGEs via different receptors, AGE-RAGE and its role in proinflammatory signaling, AGE mediated diabetic vascular complications such as nephropathy, retinopathy, neuropathy, cardiovascular and cerebrovascular diseases and finally the biological inhibition of AGEs is discussed along with chemical inhibitors for AGEs and natural products in AGE inhibition as a measure for the prevention of diabetic complications.