From hyperglycemia to AGE-RAGE interaction on the cell surface: A dangerous metabolic route for diabetic patients

Abstract

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.

Keywords::

• advanced glycation end products
• advanced glycation end products receptor
• diabetes
• reactive oxygen species
• signaling pathways
• toll-like receptors

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