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

EMS Litwinoff, C Hurtado Del Pozo… - Clinical …, 2015 - Wiley Online Library
EMS Litwinoff, C Hurtado Del Pozo, R Ramasamy, AM Schmidt
Clinical Pharmacology & Therapeutics, 2015Wiley Online Library
Types 1 and 2 diabetes are on the rise worldwide. Although the treatment of hyperglycemia
has benefited from recent advances, aggressive efforts to maintain euglycemia may 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 both micro‐and …
Types 1 and 2 diabetes are on the rise worldwide. Although the treatment of hyperglycemia has benefited from recent advances, aggressive efforts to maintain euglycemia may 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 both micro‐ and macrovascular complications of diabetes, insights from the study of mouse models of obesity and diabetic complications, and from associative 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/mDia1 may identify a novel class of therapeutics preventing diabetes and its complications.
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