From hyperglycemia to AGE-RAGE interaction on the cell surface: a dangerous metabolic route for diabetic patients.
BACKGROUND
Diabetes mellitus constitutes a serious public health problem. Recent advances in therapies are unable to control its vascular complications. New medications have been suggested but without comprehensive knowledge of the signaling pathways induced by hyperglycemia.


OBJECTIVE
To review the mechanisms of the inducer and effector phases of the metabolic cascade in diabetes, with emphasis on the steps that have been targeted to date The route from hyperglycemia to advanced glycation end products (AGE)-receptor of advanced glycation end products (RAGE) complex formation is suggested as a target for new therapies.


METHODS
A review of literature, including historical papers and recent manuscripts.


RESULTS
All the components of the suggested route are initially activated or indirectly formed due to hyperglycemia via a two-phase cascade that represents a dangerous metabolic route, especially for diabetics. Recent experiments with new drugs and clinical trials targeting this pathway are examined.


CONCLUSIONS
In order to control vascular injury in diabetes, several steps in the cascade need to be inhibited simultaneously together with aggressive glycemic control.
Hospital Santa Casa de Belo Horizonte, Núcleo de Pesquisa e Pós-Graduação, Avenue Francisco Sales, 1111, 30250-330, Belo Horizonte, MG, Brazil. nogueira.machado@pq.cnpq.br
José Augusto
JA
Nogueira-Machado
Miriam Martins
MM
Chaves
D000818:Animals; D002986:Clinical Trials as Topic; D048909:Diabetes Complications / Q000517:prevention & control; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology; D016503:Drug Delivery Systems; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic