The Receptor for Advanced Glycation End Products: Mechanisms and Therapeutic Opportunities in Obesity and Diabetes

The Receptor for Advanced Glycation Endproducts (RAGE) plays important roles in the pathogenesis of metabolic disorders, including obesity, types 1 and 2 diabetes and diabetic complications. RAGE is recruited through the increased production and decreased removal of its ligand families in obese and diabetic tissues, which are driven by such metabolic stresses as high fat feeding, hyperglycemia, inflammation and oxidative stress. In this review, we summarized the state of knowledge regarding RAGE ligand binding to the extracellular domains of RAGE; the mechanism of RAGE signal transduction through DIAPH1 and its consequences in obesity and diabetic complications; and the implications for human subjects, from biomarkers to therapeutic interventions. This body of work supports targeting the RAGE/DIAPH1 signaling axis in metabolic disorders.