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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Pr A. Avignon, MGSD, Istambul 04/2007

The Unified Concept ofOxidative Stress

Pr A. AvignonService des Maladies MétaboliquesHôpital LapeyronieMontpellier

Pr A. Avignon, MGSD, Istambul 04/2007

The Unified Concept ofOxidative Stress

The Unified Concept ofOxidative Stress

OxidativeStress

OxidativeStress

Pr A. Avignon, MGSD, Istambul 04/2007

What is Oxidative Stress ?

What is Oxidative Stress ?

ANTIOXIDANTSANTIOXIDANTSOXIDANTSOXIDANTS

Oxygen Free RadicalsOxygen Free RadicalsNitrogen Free RadicalsNitrogen Free Radicals

Specific EnzymesSpecific EnzymesVitamin E, Vitamin C,Vitamin E, Vitamin C,Carotenoids, SeleniumCarotenoids, Selenium

Pr A. Avignon, MGSD, Istambul 04/2007

Free RadicalsFree Radicals

Any molecule containing one or more unpaired electrons

Reactive Oxygen Species (ROS) -

Reactive Nitrogen Species (RNS) - NO. Reactive Metabolites or Intermediates

- metabolic activation of drugs, toxins, pollutants, cigarette smokes, etc.

Pr A. Avignon, MGSD, Istambul 04/2007

Reactive Oxygen Species (ROS)

Reactive Oxygen Species (ROS) Superoxide (O2

.-)

Hydrogen Peroxide (H2O2) Hydroxyl Radical (OH.) - product of

Fenton reaction catalyzed by free Fe and Cu

Singlet Oxygen (1gO2) - oxygen at an excited state, requiring photosensitizers and photons

Pr A. Avignon, MGSD, Istambul 04/2007

Sources of oxygen free radicals

Sources of oxygen free radicals

Pr A. Avignon, MGSD, Istambul 04/2007

Free Radical Defense System

Free Radical Defense System

Pr A. Avignon, MGSD, Istambul 04/2007

Oxidative Stress: Consequences

Oxidative Stress: Consequences

Pr A. Avignon, MGSD, Istambul 04/2007

Obesity-induced oxidative stress

Obesity-induced oxidative stress

Pr A. Avignon, MGSD, Istambul 04/2007

Fatty Acids -Induced Oxidant Stress

Fatty Acids -Induced Oxidant Stress

J Clin Endocrinol Metab 81:4244-4248, 1996

Pr A. Avignon, MGSD, Istambul 04/2007

Obesity-Induced Oxidant Stress and Insulin Resistance

Obesity-Induced Oxidant Stress and Insulin Resistance

Muscle Cells

Pr A. Avignon, MGSD, Istambul 04/2007

ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes

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.

Pr A. Avignon, MGSD, Istambul 04/2007

ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes

ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes

Diabetes 53 (Suppl. 1):S119–S124, 2004

Pr A. Avignon, MGSD, Istambul 04/2007

Sensibility to oxidative stress Oxidative stress increased by

FFA FFA acids and oxidative stress

induce apoptosis of B-cells

ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes

ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes

Diabetes 53 (Suppl. 1):S119–S124, 2004

Pr A. Avignon, MGSD, Istambul 04/2007

Hyperglycemia / Oxidant Stress / Diabetic Complications

Hyperglycemia / Oxidant Stress / Diabetic Complications

Glucose-6-P

Hexokinase

Phosphohexoisomérase

Extra-cellular glucose

Fructose-6-P

Glyceraldéhyde-3-P

1,3-Diphosphoglycérate

GLUT-1

KidneyRetina

Neurones

pyruvate

Acetyl CoA

PDH

Cycle de

Krebs

Pyruvate

Pr A. Avignon, MGSD, Istambul 04/2007

Glucose-6-P

Hexokinase

Phosphohexoisomérase

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

Hyperglycemia Oxidative Stress Diabetic Complications

Pr A. Avignon, MGSD, Istambul 04/2007

International Journal of Obesity (2006) 30, 400–418.

Hyperglycemia / Oxidative Stress / Diabetic Complications

Hyperglycemia / Oxidative Stress / Diabetic Complications

Pr A. Avignon, MGSD, Istambul 04/2007Nature 404, 787 - 790 (2000)

Hyperglycemia / Oxidative Stress / Diabetic Complications

Hyperglycemia / Oxidative Stress / Diabetic Complications

Pr A. Avignon, MGSD, Istambul 04/2007

Conclusion

Conclusion

OxidativeStress

OxidativeStress

OxidativeStress

Pr A. Avignon, MGSD, Istambul 04/2007

Merci

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