title: Emerging Targets for Therapeutic Development in Diabetes and Its Complications: The RAGE Signaling Pathway.
abstract: 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.
authors.affiliation: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors.forename: Ems
authors.initials: E
authors.lastname: Litwinoff
authors.affiliation: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hurtado Del Pozo
authors.affiliation: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ramasamy
authors.affiliation: Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Schmidt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D048909:Diabetes Complications / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D015195:Drug Design; D000080865:Formins; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D001786:Blood Glucose; C108962:DIAPH1 protein, human; D000080865:Formins; D007004:Hypoglycemic Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic