Ozone exposure triggers insulin resistance through muscle c-Jun N-terminal kinase activation
| Autor: | Alain Géloën, Jennifer Rieusset, Sandra Pesenti, Bader Zarrouki, Roxane E. Vella, Marie-Agnès Chauvin, Nicolas J. Pillon, Marine L. Croze, Michel Guichardant, Christophe O. Soulage, Laetitia Koppe |
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| Přispěvatelé: | Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Multidisciplinaire de Biochimie des Lipides (IMBL), Covalab-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Ozone/*toxicity Endocrinology Diabetes and Metabolism medicine.medical_treatment [SDV]Life Sciences [q-bio] Type 2 diabetes Phenylbutyrates/pharmacology Biology medicine.disease_cause Acetylcysteine/pharmacology Cell Line Bronchoalveolar Lavage Fluid/chemistry Mice Ozone Insulin resistance Internal medicine 11. Sustainability Internal Medicine medicine Animals JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism Anthracenes Insulin c-jun JNK Mitogen-Activated Protein Kinases Skeletal muscle medicine.disease Phenylbutyrates Acetylcysteine 3. Good health Rats Enzyme Activation Anthracenes/pharmacology Insulin receptor Endocrinology medicine.anatomical_structure 13. Climate action Insulin Resistance/*physiology Unfolded protein response biology.protein Enzyme Activation/drug effects Insulin Resistance Bronchoalveolar Lavage Fluid Oxidative stress |
| Zdroj: | Diabetes Diabetes, American Diabetes Association, 2015, 64 (3), pp.1011-24. ⟨10.2337/db13-1181⟩ |
| ISSN: | 0012-1797 |
| DOI: | 10.2337/db13-1181⟩ |
| Popis: | International audience; A growing body of evidence suggests that exposure to traffic-related air pollution is a risk factor for type 2 diabetes. Ozone, a major photochemical pollutant in urban areas, is negatively associated with fasting glucose and insulin levels, but most aspects of this association remain to be elucidated. Using an environmentally realistic concentration (0.8 parts per million), we demonstrated that exposure of rats to ozone induced whole-body insulin resistance and oxidative stress, with associated endoplasmic reticulum (ER) stress, c-Jun N-terminal kinase (JNK) activation, and disruption of insulin signaling in skeletal muscle. Bronchoalveolar lavage fluids from ozone-treated rats reproduced this effect in C2C12 myotubes, suggesting that toxic lung mediators were responsible for the phenotype. Pretreatment with the chemical chaperone 4-phenylbutyric acid, the JNK inhibitor SP600125, or the antioxidant N-acetylcysteine alleviated insulin resistance, demonstrating that ozone sequentially triggered oxidative stress, ER stress, and JNK activation to impair insulin signaling in muscle. This study is the first to report that ozone plays a causative role in the development of insulin resistance, suggesting that it could boost the development of diabetes. We therefore provide a potential mechanism linking pollutant exposure and the increased incidence of metabolic diseases. |
| Databáze: | OpenAIRE |
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