Emerging targets for therapeutic development in diabetes and its complications: the RAGE signaling pathway

• Litwinoff Evelyn M.S.
• Hurtado del Pozo Carmen
• Ramasamy Ravichandran
• Schmidt Ann Marie

Abstract

Types 1 and 2 diabetes are on the rise worldwide. Although the treatment of hyperglycemia has benefited from recent advances, aggressive efforts tomaintain euglycemiamay be fraught with risk, especially in older subjects or in subjects vulnerable to hypoglycemic unawareness. Hence, strategies to prevent and treat the complications of hyperglycemia are essential. In this review we summarize recent updates on the biology of the receptor for advanced glycation endproducts (RAGE) in the pathogenesis of bothmicro- and macrovascular complications of diabetes, insights fromthe study ofmouse models of obesity and diabetic complications, and fromassociative studies in human subjects. The study of the mechanisms and consequences of the interaction of the RAGE cytoplasmic domain with the formin, mDia1, in RAGE signal transduction, will be discussed. Lastly, we review the «state-of-the-art» on RAGE-directed therapeutics. Tackling RAGE/mDia1may identify a novel class of therapeutics preventing diabetes and its complications.

Keywords:diabetes mellitus type 2, sulfonylurea, gliclazide