Des études épidémiologiques récentes suggèrent que certains polluants atmosphériques jouent un rôle dans le développement et la progression de l'insulino-résistance, associée au diabète de type 2. L'ozone, un polluant photochimique majeur des zones urbaines, est associé t à des concentrations augmentées de glucose et d'insuline plasmatiques à jeun, cependant de nombreux aspects de cette association restent à élucider. En utilisant une concentration réaliste, représentative des pics de pollution (0,8 ppm), nous avons démontré que l'exposition de rats à de l'ozone induit une insulino-résistance systémique et un stress oxydant, associé à un stress du réticulum endoplasmique (RE), une activation de JNK et donc, une perturbation du signal insulinique dans le muscle. Les lavages broncho-alvéolaires réalisés chez des rats exposés à l'ozone, reproduisent ces effets sur des myotubes C2C12, suggérant que des médiateurs pulmonaires toxiques sont responsables de ce phénotype. Des prétraitements avec le chaperon chimique acide 4-phénylbutyrique, l'inhibiteur de JNK SP600125, ou l'antioxydant N-acétylcystéine préviennent l'insulino-résistance, démontrant que l'ozone induit séquentiellement un stress oxydant, un stress du RE et une activation de JNK, entraînant une perte de la sensibilité à l'insuline dans le muscle. Notre étude est la première à montrer que la pollution à l'ozone provoque le développement de l'insulino-résistance, suggérant qu'elle pourrait accélérer la progression du diabète. Nous proposons ainsi un mécanisme liant exposition à des polluants et augmentation de l'incidence des maladies métaboliques / 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 concentrations but most aspects of this association remain to be elucidated. Using an environmentally realistic concentration (0.8 ppm), we demonstrated that exposition of rats to ozone induced whole body insulin resistance and oxidative stress, with associated endoplasmic reticulum (ER) stress, 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. Pre-treatments with the chemical chaperone 4-phenyl butyric 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

There are two parts in this study. The first part is to test the validity of the assumption of thermodynamic equilibrium between fine particulate (PM2.5) nitrate and ammonium and gas-phase nitric acid (HNO3(g)) and ammonia (NH3(g)). A rough estimation of the characteristic time to achieve thermodynamic equilibrium is first carried out, which suggests that PM2.5 and gas-phase species are in thermodynamic equilibrium. Then equilibrium is tested by calculating the equilibrium concentrations of HNO3(g) and NH3(g) implied by the PM2.5 inorganic composition, temperature and relative humidity observed at the Atlanta Supersite 1999 using ISORROPIA model. The second part of this study is to analyze the ground-level ozone pollution precursor relationships in Hong Kong area. Characteristics of O3 precursors are explored. Trace gases NO and CO, VOCs, absorption coefficient, temperature and solar radiation are associated with the O3 formation. Specific VOC and VOC-sources that contribute most to the formation of photochemical smog are identified. The accuracy of pollutant emission inventories for Hong Kong and PRD region is also assessed. Combined with back trajectory information, dCO/dNOy is used to define whether O3 is locally or regionally occurred. An OBM is used to investigate the relative benefits of various emission-control strategies. Generally the formation of O3 throughout much of Hong Kong area is limited by VOC, in which reactive aromatics are dominant.