title: Diabetes, oxidative stress and therapeutic strategies.
abstract: BACKGROUND
  Diabetes has emerged as a major threat to health worldwide.
  
  
  METHODS
  The exact mechanisms underlying the disease are unknown; however, there is growing evidence that excess generation of reactive oxygen species (ROS), largely due to hyperglycemia, causes oxidative stress in a variety of tissues. Oxidative stress results from either an increase in free radical production, or a decrease in endogenous antioxidant defenses, or both. ROS and reactive nitrogen species (RNS) are products of cellular metabolism and are well recognized for their dual role as both deleterious and beneficial species. In type 2 diabetic patients, oxidative stress is closely associated with chronic inflammation. Multiple signaling pathways contribute to the adverse effects of glucotoxicity on cellular functions. There are many endogenous factors (antioxidants, vitamins, antioxidant enzymes, metal ion chelators) that can serve as endogenous modulators of the production and action of ROS. Clinical trials that investigated the effect of antioxidant vitamins on the progression of diabetic complications gave negative or inconclusive results. This lack of efficacy might also result from the fact that they were administered at a time when irreversible alterations in the redox status are already under way. Another strategy to modulate oxidative stress is to exploit the pleiotropic properties of drugs directed primarily at other targets and thus acting as indirect antioxidants.
  
  
  CONCLUSIONS
  It appears important to develop new compounds that target key vascular ROS producing enzymes and mimic endogenous antioxidants.
  
  
  CONCLUSIONS
  This strategy might prove clinically relevant in preventing the development and/or retarding the progression of diabetes associated with vascular diseases.
authors.affiliation: Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques, INSERM UMR866, Université de Bourgogne, Facultés de Médecine et Pharmacie, 7 Boulevard Jeanne d'Arc, 21079 Dijon, France. Electronic address: luc.rochette@u-bourgogne.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Rochette
authors.affiliation: Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques, INSERM UMR866, Université de Bourgogne, Facultés de Médecine et Pharmacie, 7 Boulevard Jeanne d'Arc, 21079 Dijon, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Zeller
authors.affiliation: Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques, INSERM UMR866, Université de Bourgogne, Facultés de Médecine et Pharmacie, 7 Boulevard Jeanne d'Arc, 21079 Dijon, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Cottin
authors.affiliation: Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques, INSERM UMR866, Université de Bourgogne, Facultés de Médecine et Pharmacie, 7 Boulevard Jeanne d'Arc, 21079 Dijon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vergely
mesh_terms: D000975:Antioxidants / Q000378:metabolism* / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D010088:Oxidoreductases
keywords: Diabetes; Oxidative stress; Reactive oxygen specie; Signaling pathway; Therapeutics