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Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier.

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Presentation on theme: "Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier."— Presentation transcript:

1 Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

2 Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Oxidative Stress

3 Pr A. Avignon, MGSD, Istambul 04/2007 What is Oxidative Stress ? ANTIOXIDANTS OXIDANTS Oxygen Free Radicals Nitrogen Free Radicals Specific Enzymes Vitamin E, Vitamin C, Carotenoids, Selenium

4 Pr A. Avignon, MGSD, Istambul 04/2007 Free Radicals l Any molecule containing one or more unpaired electrons l Reactive Oxygen Species (ROS) - l Reactive Nitrogen Species (RNS) - NO. l Reactive Metabolites or Intermediates - metabolic activation of drugs, toxins, pollutants, cigarette smokes, etc.

5 Pr A. Avignon, MGSD, Istambul 04/2007 Reactive Oxygen Species (ROS) l Superoxide (O 2. -) l Hydrogen Peroxide (H 2 O 2 ) l Hydroxyl Radical (OH. ) - product of Fenton reaction catalyzed by free Fe and Cu Singlet Oxygen ( 1 g O 2 ) - oxygen at an excited state, requiring photosensitizers and photons

6 Pr A. Avignon, MGSD, Istambul 04/2007 Sources of oxygen free radicals

7 Pr A. Avignon, MGSD, Istambul 04/2007 Free Radical Defense System

8 Pr A. Avignon, MGSD, Istambul 04/2007 Oxidative Stress: Consequences

9 Pr A. Avignon, MGSD, Istambul 04/2007 Obesity- induced oxidative stress

10 Pr A. Avignon, MGSD, Istambul 04/2007 Fatty Acids - Induced Oxidant Stress J Clin Endocrinol Metab 81: , 1996

11 Pr A. Avignon, MGSD, Istambul 04/2007 Obesity- Induced Oxidant Stress and Insulin Resistance Muscle Cells

12 Pr A. Avignon, MGSD, Istambul 04/2007 ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes Green K et al, Diabetes 53 (Suppl. 1):S110, 2004 Role of ß-cell mitochondria in sensing increases in plasma glucose and inducing insulin secretion.

13 Pr A. Avignon, MGSD, Istambul 04/2007 ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes Diabetes 53 (Suppl. 1):S119–S124, 2004

14 Pr A. Avignon, MGSD, Istambul 04/2007 l Sensibility to oxidative stress l Oxidative stress increased by FFA l FFA acids and oxidative stress induce apoptosis of B-cells ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes Diabetes 53 (Suppl. 1):S119–S124, 2004

15 Pr A. Avignon, MGSD, Istambul 04/2007 Hyperglycemia / Oxidant Stress / Diabetic Complications Glucose-6-P Hexokinase Phosphohexo isomérase Extra-cellular glucose Fructose-6-P Glyceraldéhyde-3-P 1,3-Diphosphoglycérate GLUT-1 Kidney Retina Neurones pyruvate Acetyl CoA PDH Cycle de Krebs Pyruvate

16 Pr A. Avignon, MGSD, Istambul 04/2007 Glucose-6-P Hexokinase Phosphohexo isomérase Glucose extra cellulaire Fructose-6-P Glyceraldéhyde-3-P 1,3-Diphosphoglycérate Voie des Polyols Voie des Hexosamines Voie de la Protéine Kinase C (PKC) Voie des Produits Terminaux de la Glycation Hyperglycemia Oxidative Stress Diabetic Complications

17 Pr A. Avignon, MGSD, Istambul 04/2007 International Journal of Obesity (2006) 30, 400–418. Hyperglycemia / Oxidative Stress / Diabetic Complications

18 Pr A. Avignon, MGSD, Istambul 04/2007 Nature 404, (2000) Hyperglycemia / Oxidative Stress / Diabetic Complications

19 Pr A. Avignon, MGSD, Istambul 04/2007 Conclusion Oxidative Stress Oxidative Stress

20 Pr A. Avignon, MGSD, Istambul 04/2007 Merci


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