[Diabetes mellitus, oxidative stress and advanced glycation endproducts].
Chronic hyperglycemia in diabetes mellitus is an oxidative stress created by an imbalance of prooxidants over antioxidant defenses. The pathogenesis would involve several mechanisms including glucose autoxidation, protein glycation, the polyol pathway, and overproduction of superoxide radicals in mitochondria and via NAD(P)H oxidase. Glycemic equilibrium plays a very important role in the prooxidant/antioxidant balance. Macromolecules such as found in the extracellular matrix, lipoproteins, and deoxyribonucleic acid also constitute targets for free radicals in diabetes mellitus. This oxidative tress is involved in the pathophysiology of diabetes complications. The chronic hyperglycemic status also favors glycation reactions (irreversible glucose binding on protein amino groups), thereby leading to advanced glycation endproducts. Via their recognition by cell receptors, advanced glycation endproducts also participate in the development of oxidative stress and the inflammatory status. Involvement of oxidative stress and advanced glycation endproducts in diabetes complications is the basis of the development of adjunct therapies with antioxidant and/or anti)advanced glycation endproducts molecules.
Bonnefont-Rousselot
D
D
Laboratoire de Biochimie métabolique et clinique (EA 3617), Faculté de Pharmacie Paris 5, 4, avenue de l'Observatoire, F75270 Paris Cedex 06.
Beaudeux
J-L
JL
Thérond
P
P
Peynet
J
J
Legrand
A
A
Delattre
J
J
D000975:Antioxidants / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*
D000975:Antioxidants; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D008687:Metformin