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研究生:嚴元鴻
研究生(外文):Yuan-Horng Yan
論文名稱:細懸浮微粒對肥胖與糖尿病大鼠之效應研究
論文名稱(外文):Effects of Fine Particulate Matters in Obese and Diabetic Rats
指導教授:鄭尊仁鄭尊仁引用關係
口試委員:李輝吳焜裕周崇光詹長權劉興華蘇大成
口試日期:2013-03-05
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2013
畢業學年度:101
語文別:英文
論文頁數:107
中文關鍵詞:懸浮微粒心血管毒性腎毒性胰島素阻抗糖尿病
外文關鍵詞:ambient particlescardiovascular toxicityinsulin resistancediabeteskidney
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流行病學研究顯示,細懸浮微粒與心肺疾病的死亡及罹病有相關,特別是易感族群更容易受到影響。研究也指出糖尿病患者是微粒空氣污染心血管疾病的易感族群。然而細懸浮微粒與糖尿病之發生與其併發症的因果關係並不清楚,也缺乏毒理學之效應研究。為了回答這個問題,我們進行一系列細懸浮微粒暴露的動物實驗,來探討細懸浮微粒對糖尿病大鼠引發之毒性效應。我們首先建立了以高脂食物導致之肥胖大鼠模式。並使用Sprague–Dawley(SD)大鼠,以高脂食物加上單次靜脈注射低劑量(35 mg/kg)的streptozotocin(STZ),以及高劑量(35 mg/kg)之STZ,分別建立第二型,與第一型糖尿病大鼠動物模式。我們也建立了細懸浮微粒動物暴露系統,進行糖尿病大鼠呼吸暴露。在急性暴露方面,我們以氣管灌注方式,將細懸浮微粒連續暴露肥胖大鼠,探討動物的胰島素阻抗與微粒暴露是否有關。在慢性暴露方面,我們進一步利用非濃縮大氣微粒,暴露健康SD大鼠與糖尿病大鼠3個月,探討細懸浮微粒是否造成心血管毒性與器官的損傷。以氣管灌注連續暴露細懸浮微粒後,我們發現肥胖大鼠的胰島素阻抗上升,而健康SD大鼠並沒有此效應。在亞慢性即時暴露方面,平均細微粒濃度大約13μg/m3,我們發現細懸浮微粒引發第二型糖尿病大鼠的Fibrinogen上升;第一型糖尿病大鼠的長期血糖值(HbA1c)上升;SD大鼠則有氧化壓力(8-OHdG),發炎反應(IL-6),與胰島素阻抗上升。組織病理學發現,細懸浮微粒造成在心肌發炎,腹主動脈血管壁增厚,以及腎臟之腎絲球、腎小管病變、以及腫瘤發生。糖尿病並未增強微粒效應,但可能加速腎病變與腫瘤發生。我們發現微粒暴露可造成胰島素阻抗的增加,此結果可以支持流行病學研究結果。我們也發現微粒可造成心血管毒性,與亞慢性病理組織變化,雖然沒有明顯的動脈粥狀硬化,但是有發現心肌發炎與主動脈變化,也支持流行病學對心臟血管疾病的發現。我們的研究也指出腎臟的病變與腫瘤發生,值得未來研究。另外,亞慢性暴露結果指出,在接近目前美國與世界衛生組織之細懸浮微粒法規濃度下,還可以觀察到微粒毒性與病理變化,跟流行病學顯示細懸浮微粒健康效應沒有閾值的觀察是一致的,未來值得進行慢性動物呼吸研究。

Epidemiological studies have shown associations between particulate air pollution and cardiovascular morbidity and mortality. Previous studies suggest that diabetes mellitus (DM) is a sub-population at risk for particulate matters (PM)-associated cardiovascular diseases (CVD). However, the biological plausibility for the relationship remains unclear. We conducted animal studies to determine if particle exposure altered glucose homeostasis and caused cardiovascular damage. First, we investigated the acute, and subacute effects of PM on insulin resistance (IR) in obese and healthy rats. Male Sprague-Dawley (SD) rats were fed with either a high fat diet (HFD) or normal chow diet (NCD). Both groups were then further assigned to receive PM10, PM2.5 or normal saline by intratracheal instillation (IT) once per week for 3 weeks. Homeostasis model assessment-insulin resistance (HOMA-IR) was used to assess IR. Second, to further understand the subchronic effects of ambient PM on IR and target organ damage, we constructed an inhalation system to expose animals to ambient submicron particles. Taipei Air Pollution Exposure System for Health Effects (TAPES), modified from individually ventilated caging (IVC) air handling system, was used for continuous, real-world, non-concentrated straight ambient PM2.5 (s-PM2.5) exposure study. DM rat model was developed after feeding with HFD, and streptozotocin injection. DM and SD rats were randomly assigned to s-PM2.5 or filtered air (FA) for 13-16 weeks in two consecutive winters in Taipei city. Glucose homeostasis was assessed by Hemoglobin A1c (HbA1c) and IR. Biomarkers of oxidative stress, systemic inflammation, endothelium dysfunction, and coagulation were measured. Organ damage was observed by histopathology. PM2.5 increased HOMA-IR after first IT and further increased HOMA-IR at the end of exposure. However, this increase was not observed in NCD rats and after PM10 IT exposure. Increased fibrinogen was also noted after repeated PM2.5 IT exposure in both HFD and NCD rats. The average concentration of s-PM2.5 in the exposure chamber of TAPES during the inhalation study period was 13.3μg/m3. HbA1c was significantly elevated after exposed to s-PM2.5 compared with exposure to FA (mean [SD], 7.4% [3.1%] vs. 5.7% [2.4%], p<.05, respectively) in DM rats. IR was significantly enhanced after exposed to s-PM2.5 compared with exposure to FA in SD rats (mean [SD], 8.1 [4.6] vs 3.9 [1.4] mmol/L*μU/ml, p<.05). Interleukin-6 (IL-6) and urinary 8-hydroxy-2''-deoxyguanosine (8-OHdG) were increased in SD rats and fibrinogen was increased in DM rats. S-PM2.5 caused focal myocarditis in the myocardium and increased aortic medial thickness. Morphometric analysis of the kidneys showed a significantly increased proportion of rats with advanced glomerulosclerosis, accentuation of tubular damage, and development of kidney tumors. We conclude that particulate air pollution, even at low concentrations close to current standard, may affect glucose homeostasis and lead to organ damage in susceptible population. Systematic inflammation, coagulation activation and IR may mediate these effects. This may potentially have implications for the policy of air pollution control and management.

中文摘要 1
Abstract 2
Chapter I. Introduction, Objectives, and Experimental Plan 4
1.1 Introduction 4
1.1.1 Particulate air pollution and diabetes 4
1.1.2 Effect of PM on glucose homeostasis and insulin resistance 4
1.1.3 Effect of PM on cardiovascular complications in diabetes 5
1.1.4 Animal models of obesity (with insulin resistance), and type 1 and 2 diabetes mellitus 5
1.1.5 Non-concentrated, real-world, inhalation exposure system 5
1.2 Objectives 7
1.3 Overall experimental approaches 8
Chapter II. Enhanced insulin resistance in diet-induced obese rats exposed to fine particles by instillation 9
1.1 Abstract 10
1.2 Introduction 11
1.3 Methods 22
1.4 Results 25
1.5 Discussion 17
1.6 Conclusions 20
1.7 Figures 21
Chapter III. Effects of Subchronic Straight Ambient PM2.5 Exposure on Blood Coagulation, Hemodynamics, and Histopathology in High-fat Diet-induced and Streptozotocin-treated Diabetic Rats (Type 2 diabetes rat model) 28
1.1 Abstract 29
1.2 Introduction 30
1.3 Methods 31
1.4 Results 36
1.5 Discussions 37
1.6 Conclusion 39
1.7 Tables and Figures 41
Chapter IV. Subchronic effects of straight ambient PM2.5 inhalation exposure on glucose homeostasis and target organ damage in the streptozotocin-diabetic rat model (Type 1 diabetes rat model) 49
1.1 Abstract 50
1.2 Introduction 51
1.3 Methods 51
1.4 Results 56
1.5 Discussion 57
1.6 Conclusions 60
1.7 Tables and Figures 61
Chapter V. Induced insulin resistance and organ damage in healthy Sprague Dawley rats exposed to low levels of ambient fine particulate matter 67
1.1 Abstract 68
1.2 Introduction 68
1.3 Methods 69
1.4 Results 73
1.5 Discussion 74
1.6 Conclusion 77
1.7 Tables and Figures 78
Chapter VI. Discussion and Conclusion 82
6.1 Overall research findings 82
6.2 Proposed mechanisms of PM-induced cardiovascular effects 83
6.3 PM effects on heart and aorta using histopathology 85
6.4 PM effects on kidney 85
6.5 Effects of subchronic, low levels of real-world ambient PM 87
6.6 Strength and limitation 89
參考文獻 90
附錄 100


Amann, K., Tornig, J., Kugel, B., Gross, M. L., Tyralla, K., El-Shakmak, A., Szabo, A., and Ritz, E. (2003). Hyperphosphatemia aggravates cardiac fibrosis and microvascular disease in experimental uremia. Kidney international 63, 1296-1301.
Amann, K., Wolf, B., Nichols, C., Tornig, J., Schwarz, U., Zeier, M., Mall, G., and Ritz, E. (1997). Aortic changes in experimental renal failure: hyperplasia or hypertrophy of smooth muscle cells? Hypertension 29, 770-775.
Amar, J., Perez, L., Burcelin, R., and Chamontin, B. (2006). Arteries, inflammation and insulin resistance. Journal of hypertension. Supplement : official journal of the International Society of Hypertension 24, S18-20.
Andersen, Z. J., Raaschou-Nielsen, O., Ketzel, M., Jensen, S. S., Hvidberg, M., Loft, S., Tjonneland, A., Overvad, K., and Sorensen, M. (2012). Diabetes incidence and long-term exposure to air pollution: a cohort study. Diabetes care 35, 92-98.
Araujo, J. A., Barajas, B., Kleinman, M., Wang, X., Bennett, B. J., Gong, K. W., Navab, M., Harkema, J., Sioutas, C., Lusis, A. J., and Nel, A. E. (2008). Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress. Circulation research 102, 589-596.
Aronson, D. (2008). Hyperglycemia and the pathobiology of diabetic complications. Advances in cardiology 45, 1-16.
Batalha, J. R. F., Saldiva, P. H. N., Clarke, R. W., Coull, B. A., Stearns, R. C., Lawrence, J., Murthy, G. G. K., Koutrakis, P., and Godleski, J. J. (2002). Concentrated ambient air particles induce vasoconstriction of small pulmonary arteries in rats. Environmental health perspectives 110, 1191-1197.
Becker, S., Dailey, L., Soukup, J. M., Silbajoris, R., and Devlin, R. B. (2005). TLR-2 is involved in airway epithelial cell response to air pollution particles. Toxicol Appl Pharm 203, 45-52.
Belmin, J., Michel, J. B., Curmi, P. A., Salzmann, J. L., Juan, L., and Tedgui, A. (1991). Reduction of transmural 125I-albumin concentration in rat aortic media by chronic hypertension. Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association 11, 334-343.
Bhatnagar, A. (2009). Could Dirty Air Cause Diabetes? Circulation 119, 492-494.
Bind, M. A., Baccarelli, A., Zanobetti, A., Tarantini, L., Suh, H., Vokonas, P., and Schwartz, J. (2012). Air Pollution and Markers of Coagulation, Inflammation, and Endothelial Function Associations and Epigene-environment Interactions in an Elderly Cohort. Epidemiology 23, 332-340.
Brook, R. D., and Rajagopalan, S. (2010). Particulate matter air pollution and atherosclerosis. Current atherosclerosis reports 12, 291-300.
Brook, R. D., Rajagopalan, S., Pope, C. A., 3rd, Brook, J. R., Bhatnagar, A., Diez-Roux, A. V., Holguin, F., Hong, Y., Luepker, R. V., Mittleman, M. A., Peters, A., Siscovick, D., Smith, S. C., Jr., Whitsel, L., and Kaufman, J. D. (2010a). Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation 121, 2331-2378.
Brook, R. D., Rajagopalan, S., Pope, C. A., Brook, J. R., Bhatnagar, A., Diez-Roux, A. V., Holguin, F., Hong, Y. L., Luepker, R. V., Mittleman, M. A., Peters, A., Siscovick, D., Smith, S. C., Whitsel, L., Kaufman, J. D., Epidemiol, A. H. A. C., Dis, C. K. C., and Metab, C. N. P. A. (2010b). Particulate Matter Air Pollution and Cardiovascular Disease An Update to the Scientific Statement From the American Heart Association. Circulation 121, 2331-2378.
Brook, R. D., Xu, X., Bard, R. L., Dvonch, J. T., Morishita, M., Kaciroti, N., Sun, Q., Harkema, J., and Rajagopalan, S. (2012). Reduced metabolic insulin sensitivity following sub-acute exposures to low levels of ambient fine particulate matter air pollution. The Science of the total environment.
Brownlee, M. (2005). The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54, 1615-1625.
Bruno, G., Fornengo, P., Novelli, G., Panero, F., Perotto, M., Segre, O., Zucco, C., Deambrogio, P., Bargero, G., and Perin, P. C. (2009). C-reactive protein and 5-year survival in type 2 diabetes: the Casale Monferrato Study. Diabetes 58, 926-933.
Budinger, G. R. S., McKell, J. L., Urich, D., Foiles, N., Weiss, I., Chiarella, S. E., Gonzalez, A., Soberanes, S., Ghio, A. J., Nigdelioglu, R., Mutlu, E. A., Radigan, K. A., Green, D., Kwaan, H. C., and Mutlu, G. M. (2011). Particulate Matter-Induced Lung Inflammation Increases Systemic Levels of PAI-1 and Activates Coagulation Through Distinct Mechanisms. PloS one 6.
Cacho, J., Sevillano, J., de Castro, J., Herrera, E., and Ramos, M. P. (2008). Validation of simple indexes to assess insulin sensitivity during pregnancy in Wistar and Sprague-Dawley rats. American journal of physiology. Endocrinology and metabolism 295, E1269-1276.
Ceriello, A. (1997). Fibrinogen and diabetes mellitus: Is it time for intervention trials? Diabetologia 40, 731-734.
Chang, S. C., Chou, C. C. K., Chan, C. C., and Lee, C. T. (2010). Temporal characteristics from continuous measurements of PM2.5 and speciation at the Taipei Aerosol Supersite from 2002 to 2008. Atmos Environ 44, 1088-1096.
Chen, J., Muntner, P., Hamm, L. L., Fonseca, V., Batuman, V., Whelton, P. K., and He, J. (2003). Insulin resistance and risk of chronic kidney disease in nondiabetic US adults. Journal of the American Society of Nephrology : JASN 14, 469-477.
Chen, J. C., and Schwartz, J. (2008a). Metabolic syndrome and inflammatory responses to long-term particulate air pollutants. Environmental health perspectives 116, 612-617.
Chen, J. C., and Schwartz, J. (2008b). Metabolic syndrome and inflammatory responses to long-term particulate air pollutants. Environ Health Persp 116, 612-617.
Chou, C. C. K., Lee, C. T., Cheng, M. T., Yuan, C. S., Chen, S. J., Wu, Y. L., Hsu, W. C., Lung, S. C., Hsu, S. C., Lin, C. Y., and Liu, S. C. (2010). Seasonal variation and spatial distribution of carbonaceous aerosols in Taiwan. Atmos Chem Phys 10, 9563-9578.
Chou, C. C. K., Lee, C. T., Yuan, C. S., Hsu, W. C., Lin, C. Y., Hsu, S. C., and Liu, S. C. (2008). Implications of the chemical transformation of Asian outflow aerosols for the long-range transport of inorganic nitrogen species. Atmos Environ 42, 7508-7519.
Chow, J. C., Watson, J. G., Crow, D., Lowenthal, D. H., and Merrifield, T. (2001). Comparison of IMPROVE and NIOSH carbon measurements. Aerosol Sci Tech 34, 23-34.
Chuang, K. J., Chan, C. C., Su, T. C., Lee, C. T., and Tang, C. S. (2007). The effect of urban air pollution on inflammation, oxidative stress, coagulation, and autonomic dysfunction in young adults. American journal of respiratory and critical care medicine 176, 370-376.
Chuang, K. J., Yan, Y. H., and Cheng, T. J. (2010). Effect of air pollution on blood pressure, blood lipids, and blood sugar: a population-based approach. Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine 52, 258-262.
Chuang, K. J., Yan, Y. H., Chiu, S. Y., and Cheng, T. J. (2011). Long-term air pollution exposure and risk factors for cardiovascular diseases among the elderly in Taiwan. Occup Environ Med 68, 64-68.
Coogan, P. F., White, L. F., Jerrett, M., Brook, R. D., Su, J. G., Seto, E., Burnett, R., Palmer, J. R., and Rosenberg, L. (2012). Air pollution and incidence of hypertension and diabetes mellitus in black women living in Los Angeles. Circulation 125, 767-772.
Crouse, D. L., Peters, P. A., van Donkelaar, A., Goldberg, M. S., Villeneuve, P. J., Brion, O., Khan, S., Atari, D. O., Jerrett, M., Pope, C. A., Brauer, M., Brook, J. R., Martin, R. V., Stieb, D., and Burnett, R. T. (2012). Risk of nonaccidental and cardiovascular mortality in relation to long-term exposure to low concentrations of fine particulate matter: a Canadian national-level cohort study. Environmental health perspectives 120, 708-714.
Dales, R. E., Cakmak, S., Vidal, C. B., and Rubio, M. A. (2012). Air pollution and hospitalization for acute complications of diabetes in Chile. Environment international 46, 1-5.
Danaei, G., Finucane, M. M., Lu, Y., Singh, G. M., Cowan, M. J., Paciorek, C. J., Lin, J. K., Farzadfar, F., Khang, Y. H., Stevens, G. A., Rao, M., Ali, M. K., Riley, L. M., Robinson, C. A., and Ezzati, M. (2011). National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 378, 31-40.
Danesh, J., Lewington, S., Thompson, S. G., Lowe, G. D., Collins, R., Kostis, J. B., Wilson, A. C., Folsom, A. R., Wu, K., Benderly, M., Goldbourt, U., Willeit, J., Kiechl, S., Yarnell, J. W., Sweetnam, P. M., Elwood, P. C., Cushman, M., Psaty, B. M., Tracy, R. P., Tybjaerg-Hansen, A., Haverkate, F., de Maat, M. P., Fowkes, F. G., Lee, A. J., Smith, F. B., Salomaa, V., Harald, K., Rasi, R., Vahtera, E., Jousilahti, P., Pekkanen, J., D''Agostino, R., Kannel, W. B., Wilson, P. W., Tofler, G., Arocha-Pinango, C. L., Rodriguez-Larralde, A., Nagy, E., Mijares, M., Espinosa, R., Rodriquez-Roa, E., Ryder, E., Diez-Ewald, M. P., Campos, G., Fernandez, V., Torres, E., Marchioli, R., Valagussa, F., Rosengren, A., Wilhelmsen, L., Lappas, G., Eriksson, H., Cremer, P., Nagel, D., Curb, J. D., Rodriguez, B., Yano, K., Salonen, J. T., Nyyssonen, K., Tuomainen, T. P., Hedblad, B., Lind, P., Loewel, H., Koenig, W., Meade, T. W., Cooper, J. A., De Stavola, B., Knottenbelt, C., Miller, G. J., Bauer, K. A., Rosenberg, R. D., Sato, S., Kitamura, A., Naito, Y., Palosuo, T., Ducimetiere, P., Amouyel, P., Arveiler, D., Evans, A. E., Ferrieres, J., Juhan-Vague, I., Bingham, A., Schulte, H., Assmann, G., Cantin, B., Lamarche, B., Despres, J. P., Dagenais, G. R., Tunstall-Pedoe, H., Woodward, M., Ben-Shlomo, Y., Davey Smith, G., Palmieri, V., Yeh, J. L., Rudnicka, A., Ridker, P., Rodeghiero, F., Tosetto, A., Shepherd, J., Ford, I., et al. (2005). Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA : the journal of the American Medical Association 294, 1799-1809.
DeFronzo, R. A. (2010). Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia 53, 1270-1287.
Delfino, R. J., Staimer, N., Tjoa, T., Polidori, A., Arhami, M., Gillen, D. L., Kleinman, M. T., Vaziri, N. D., Longhurst, J., Zaldivar, F., and Sioutas, C. (2008). Circulating biomarkers of inflammation, antioxidant activity, and platelet activation are associated with primary combustion aerosols in subjects with coronary artery disease. Environ Health Perspect 116, 898-906.
Dijkema, M. B. A., Mallant, S. F., Gehring, U., van den Hurk, K., Alssema, M., van Strien, R. T., Fischer, P. H., Nijpels, G., Stehouwer, C. D. A., Hoek, G., Dekker, J. M., and Brunekreef, B. (2011). Long-term Exposure to Traffic-related Air Pollution and Type 2 Diabetes Prevalence in a Cross-sectional Screening-study in the Netherlands. Environ Health-Glob 10.
Ding, H., and Triggle, C. R. (2005). Endothelial cell dysfunction and the vascular complications associated with type 2 diabetes: assessing the health of the endothelium. Vascular health and risk management 1, 55-71.
Dubowsky, S. D., Suh, H., Schwartz, J., Coull, B. A., and Gold, D. R. (2006). Diabetes, obesity, and hypertension may enhance associations between air pollution and markers of systemic inflammation. Environ Health Persp 114, 992-998.
el Nahas, A. M., Bassett, A. H., Cope, G. H., and Le Carpentier, J. E. (1991). Role of growth hormone in the development of experimental renal scarring. Kidney international 40, 29-34.
Englert, N. (2004). Fine particles and human health--a review of epidemiological studies. Toxicology letters 149, 235-242.
Gardner, S. Y., Lehmann, J. R., and Costa, D. L. (2000). Oil fly ash-induced elevation of plasma fibrinogen levels in rats. Toxicological sciences : an official journal of the Society of Toxicology 56, 175-180.
Gerlofs-Nijland, M. E., Dormans, J. A., Bloemen, H. J., Leseman, D. L., John, A., Boere, F., Kelly, F. J., Mudway, I. S., Jimenez, A. A., Donaldson, K., Guastadisegni, C., Janssen, N. A., Brunekreef, B., Sandstrom, T., van Bree, L., and Cassee, F. R. (2007). Toxicity of coarse and fine particulate matter from sites with contrasting traffic profiles. Inhalation toxicology 19, 1055-1069.
Goldberg, M. S., Burnett, R. T., Bailar, J. C., Brook, J., Bonvalot, Y., Tamblyn, R., Singh, R., Valois, M. F., and Vincent, R. (2001). The association between daily mortality and ambient air particle pollution in Montreal, Quebec 2. Cause-specific mortality. Environ Res 86, 26-36.
Hampel, R., Breitner, S., Schneider, A., Zareba, W., Kraus, U., Cyrys, J., Geruschkat, U., Belcredi, P., Muller, M., Wichmann, H. E., and Peters, A. (2012). Acute air pollution effects on heart rate variability are modified by SNPs involved in cardiac rhythm in individuals with diabetes or impaired glucose tolerance. Environmental research 112, 177-185.
Happo, M. S., Salonen, R. O., Halinen, A. I., Jalava, P. I., Pennanen, A. S., Dormans, J. A. M. A., Gerlofs-Nijland, M. E., Cassee, F. R., Kosma, V. M., Sillanpaa, M., Hillamo, R., and Hirvonen, M. R. (2010). Inflammation and tissue damage in mouse lung by single and repeated dosing of urban air coarse and fine particles collected from six European cities. Inhalation toxicology 22, 402-416.
Hard, G. C., Rodgers, I. S., Baetcke, K. P., Richards, W. L., Mcgaughy, R. E., and Valcovic, L. R. (1993). Hazard Evaluation of Chemicals That Cause Accumulation of Alpha-2u-Globulin, Hyaline Droplet Nephropathy, and Tubule Neoplasia in the Kidneys of Male-Rats. Environ Health Persp 99, 313-349.
Hoffmann, B., Moebus, S., Dragano, N., Stang, A., Mohlenkamp, S., Schmermund, A., Memmesheimer, M., Brocker-Preuss, M., Mann, K., Erbel, R., and Jockel, K. H. (2009). Chronic residential exposure to particulate matter air pollution and systemic inflammatory markers. Environmental health perspectives 117, 1302-1308.
Hu, C. W., Wang, C. J., Chang, L. W., and Chao, M. R. (2006). Clinical-scale high-throughput analysis of urinary 8-oxo-7,8-dihydro-2''-deoxyguanosine by isotope-dilution liquid chromatography-tandem mass spectrometry with on-line solid-phase extraction. Clinical chemistry 52, 1381-1388.
Huang, C. H., Lin, L. Y., Tsai, M. S., Hsu, C. Y., Chen, H. W., Wang, T. D., Chang, W. T., Cheng, T. J., and Chen, W. J. (2010). Acute cardiac dysfunction after short-term diesel exhaust particles exposure. Toxicology letters 192, 349-355.
Huttunen, K., Siponen, T., Salonen, I., Yli-Tuomi, T., Aurela, M., Dufva, H., Hillamo, R., Linkola, E., Pekkanen, J., Pennanen, A., Peters, A., Salonen, R. O., Schneider, A., Tiittanen, P., Hirvonen, M. R., and Lanki, T. (2012). Low-level exposure to ambient particulate matter is associated with systemic inflammation in ischemic heart disease patients. Environ Res 116, 44-51.
Iannuzzi, A., Licenziati, M. R., Acampora, C., Salvatore, V., Auriemma, L., Romano, M. L., Panico, S., Rubba, P., and Trevisan, M. (2004). Increased carotid intima-media thickness and stiffness in obese children. Diabetes care 27, 2506-2508.
Jacobs, L., Emmerechts, J., Mathieu, C., Hoylaerts, M. F., Fierens, F., Hoet, P. H., Nemery, B., and Nawrot, T. S. (2010). Air Pollution-Related Prothrombotic Changes in Persons with Diabetes. Environ Health Persp 118, 191-196.
Jorgensen, L., Jenssen, T., Joakimsen, O., Heuch, I., Ingebretsen, O. C., and Jacobsen, B. K. (2004). Glycated hemoglobin level is strongly related to the prevalence of carotid artery plaques with high echogenicity in nondiabetic individuals - The Tromso Study. Circulation 110, 466-470.
Kan, H. D., Chen, B. H., and Hong, C. J. (2009). Health Impact of Outdoor Air Pollution in China: Current Knowledge and Future Research Needs. Environ Health Persp 117, A187-A187.
Kaparianos, A., Argyropoulou, E., Sampsonas, F., Karkoulias, K., Tsiamita, M., and Spiropoulos, K. (2008). Pulmonary complications in diabetes mellitus. Chronic respiratory disease 5, 101-108.
Kelishadi, R., Mirghaffari, N., Poursafa, P., and Gidding, S. S. (2009). Lifestyle and environmental factors associated with inflammation, oxidative stress and insulin resistance in children. Atherosclerosis 203, 311-319.
Kittel, B., Ruehl-Fehlert, C., Morawietz, G., Klapwijk, J., Elwell, M. R., Lenz, B., O''Sullivan, M. G., Roth, D. R., and Wadsworth, P. F. (2004a). Revised guides for organ sampling and trimming in rats and mice--Part 2. A joint publication of the RITA and NACAD groups. Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie 55, 413-431.
Kittel, B., Ruehl-Fehlert, C., Morawietz, G., Klapwijk, J., Elwell, M. R., Lenz, B., O''Sullivan, M. G., Roth, D. R., and Wadsworth, P. F. (2004b). Revised guides for organ sampling and trimming in rats and mice - Part 2 - A joint publication of the RITA and NACAD groups. Exp Toxicol Pathol 55, 413-431.
Kodavanti, U. P., Moyer, C. F., Ledbetter, A. D., Schladweiler, M. C., Costa, D. L., Hauser, R., Christiani, D. C., and Nyska, A. (2003). Inhaled environmental combustion particles cause myocardial injury in the Wistar Kyoto rat. Toxicological sciences : an official journal of the Society of Toxicology 71, 237-245.
Kodavanti, U. P., Schladweiler, M. C., Gilmour, P. S., Wallenborn, J. G., Mandavilli, B. S., Ledbetter, A. D., Christiani, D. C., Runge, M. S., Karoly, E. D., Costa, D. L., Peddada, S., Jaskot, R., Richards, J. H., Thomas, R., Madamanchi, N. R., and Nyska, A. (2008). The role of particulate matter-associated zinc in cardiac injury in rats. Environmental health perspectives 116, 13-20.
Kramer, U., Herder, C., Sugiri, D., Strassburger, K., Schikowski, T., Ranft, U., and Rathmann, W. (2010). Traffic-related air pollution and incident type 2 diabetes: results from the SALIA cohort study. Environmental health perspectives 118, 1273-1279.
Kunzli, N., Jerrett, M., Mack, W. J., Beckerman, B., LaBree, L., Gilliland, F., Thomas, D., Peters, J., and Hodis, H. N. (2005). Ambient air pollution and atherosclerosis in Los Angeles. Environmental health perspectives 113, 201-206.
Lee, C. T., Chuang, M. T., Chan, C. C., Cheng, T. J., and Huang, S. L. (2006). Aerosol characteristics from the Taiwan aerosol supersite in the Asian yellow-dust periods of 2002. Atmos Environ 40, 3409-3418.
Lei, Y. C., Hwang, J. S., Chan, C. C., Lee, C. T., and Cheng, T. J. (2005). Enhanced oxidative stress and endothelial dysfunction in streptozotocin-diabetic rats exposed to fine particles. Environ Res 99, 335-343.
Lippmann, M., and Chen, L. C. (2009). Health effects of concentrated ambient air particulate matter (CAPs) and its components. Critical reviews in toxicology 39, 865-913.
Liu, L., Ruddy, T. D., Dalipaj, M., Szyszkowicz, M., You, H., Poon, R., Wheeler, A., and Dales, R. (2007a). Influence of personal exposure to particulate air pollution on cardiovascular physiology and biomarkers of inflammation and oxidative stress in subjects with diabetes. Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine 49, 258-265.
Liu, L., Ruddy, T. D., Dalipaj, M., Szyszkowicz, M., You, H., Poon, R., Wheeler, A., and Dales, R. (2007b). Influence of personal exposure to particulate air pollution on cardiovascular physiology and biomarkers of inflammation and oxidative stress in subjects with diabetes. J Occup Environ Med 49, 258-265.
Madonna, R., and De Caterina, R. (2011a). Cellular and molecular mechanisms of vascular injury in diabetes--part I: pathways of vascular disease in diabetes. Vascular pharmacology 54, 68-74.
Madonna, R., and De Caterina, R. (2011b). Cellular and molecular mechanisms of vascular injury in diabetes--part II: cellular mechanisms and therapeutic targets. Vascular pharmacology 54, 75-79.
Mauad, T., Rivero, D. H., de Oliveira, R. C., Lichtenfels, A. J., Guimaraes, E. T., de Andre, P. A., Kasahara, D. I., Bueno, H. M., and Saldiva, P. H. (2008). Chronic exposure to ambient levels of urban particles affects mouse lung development. American journal of respiratory and critical care medicine 178, 721-728.
Mauer, S. M., Lee, C. S., Najarian, J. S., and Brown, D. M. (1974). Induction of malignant kidney tumors in rats with streptozotocin. Cancer research 34, 158-160.
McNeely, M. J., McClelland, R. L., Bild, D. E., Jacobs, D. R., Tracy, R. P., Cushman, M., Goff, D. C., Astor, B. C., Shea, S., and Siscovick, D. S. (2009). The Association Between A1C and Subclinical Cardiovascular Disease The Multi-Ethnic Study of Atherosclerosis. Diabetes Care 32, 1727-1733.
Mertens, I., and Van Gaal, L. F. (2002). Obesity, haemostasis and the fibrinolytic system. Obesity reviews : an official journal of the International Association for the Study of Obesity 3, 85-101.
Muniyappa, R., Chen, H., Muzumdar, R. H., Einstein, F. H., Yan, X., Yue, L. Q., Barzilai, N., and Quon, M. J. (2009). Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats. Am J Physiol-Endoc M 297, E1023-E1029.
Nishikawa, T., Edelstein, D., and Brownlee, M. (2000). The missing link: a single unifying mechanism for diabetic complications. Kidney international. Supplement 77, S26-30.
O''Neill, M. S., Diez-Roux, A. V., Auchincloss, A. H., Franklin, T. G., Jacobs, D. R., Jr., Astor, B. C., Dvonch, J. T., and Kaufman, J. (2008). Airborne particulate matter exposure and urinary albumin excretion: the Multi-Ethnic Study of Atherosclerosis. Occup Environ Med 65, 534-540.
O''Neill, M. S., Veves, A., Sarnat, J. A., Zanobetti, A., Gold, D. R., Economides, P. A., Horton, E. S., and Schwartz, J. (2007). Air pollution and inflammation in type 2 diabetes: a mechanism for susceptibility. Occup Environ Med 64, 373-379.
O''Neill, M. S., Veves, A., Zanobetti, A., Sarnat, J. A., Gold, D. R., Economides, P. A., Horton, E. S., and Schwartz, J. (2005). Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function. Circulation 111, 2913-2920.
Pearson, J. F., Bachireddy, C., Shyamprasad, S., Goldfine, A. B., and Brownstein, J. S. (2010). Association Between Fine Particulate Matter and Diabetes Prevalence in the U.S. Diabetes care 33, 2196-2201.
Proctor, S. D., Dreher, K. L., Kelly, S. E., and Russell, J. C. (2006). Hypersensitivity of prediabetic JCR : LA-cp rats to fine airborne combustion particle-induced direct and noradrenergic-mediated vascular contraction. Toxicological Sciences 90, 385-391.
Puett, R. C., Hart, J. E., Schwartz, J., Hu, F. B., Liese, A. D., and Laden, F. (2011). Are particulate matter exposures associated with risk of type 2 diabetes? Environmental health perspectives 119, 384-389.
Raaschou-Nielsen, O., Sorensen, M., Ketzel, M., Hertel, O., Loft, S., Tjonneland, A., Overvad, K., and Andersen, Z. J. (2013). Long-term exposure to traffic-related air pollution and diabetes-associated mortality: a cohort study. Diabetologia 56, 36-46.
Reaven, G. M. (2008). Insulin Resistance: the Link Between Obesity and Cardiovascular Disease. Endocrin Metab Clin 37, 581-+.
Reed, M. J., Meszaros, K., Entes, L. J., Claypool, M. D., Pinkett, J. G., Gadbois, T. M., and Reaven, G. M. (2000). A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism: clinical and experimental 49, 1390-1394.
Rivero, D. H., Soares, S. R., Lorenzi-Filho, G., Saiki, M., Godleski, J. J., Antonangelo, L., Dolhnikoff, M., and Saldiva, P. H. (2005). Acute cardiopulmonary alterations induced by fine particulate matter of Sao Paulo, Brazil. Toxicological sciences : an official journal of the Society of Toxicology 85, 898-905.
Ruckerl, R., Greven, S., Ljungman, P., Aalto, P., Antoniades, C., Bellander, T., Berglind, N., Chrysohoou, C., Forastiere, F., Jacquemin, B., von Klot, S., Koenig, W., Kuchenhoff, H., Lanki, T., Pekkanen, J., Perucci, C. A., Schneider, A., Sunyer, J., and Peters, A. (2007a). Air pollution and inflammation (interleukin-6, C-reactive protein, fibrinogen) in myocardial infarction survivors. Environmental health perspectives 115, 1072-1080.
Ruckerl, R., Greven, S., Ljungman, P., Aalto, P., Antoniades, C., Bellander, T., Berglind, N., Chrysohoou, C., Forastiere, F., Jacquemin, B., von Klot, S., Koenig, W., Kuchenhoff, H., Lanki, T., Pekkanen, J., Perucci, C. A., Schneider, A., Sunyer, J., and Peters, A. (2007b). Air pollution and inflammation (interleukin-6,C-reactive protein, fibrinogen) in myocardial infarction survivors. Environ Health Persp 115, 1072-1080.
Sattar, N., and Hingorani, A. D. (2009). C-Reactive Protein and Prognosis in Diabetes: Getting to the Heart of the Matter. Diabetes 58, 798-799.
Schneider, A., Neas, L., Herbst, M. C., Case, M., Williams, R. W., Cascio, W., Hinderliter, A., Holguin, F., Buse, J. B., Dungan, K., Styner, M., Peters, A., and Devlin, R. B. (2008a). Endothelial Dysfunction: Associations with Exposure to Ambient Fine Particles in Diabetic Individuals. Environ Health Persp 116, 1666-1674.
Schneider, A., Neas, L., Herbst, M. C., Case, M., Williams, R. W., Cascio, W., Hinderliter, A., Holguin, F., Buse, J. B., Dungan, K., Styner, M., Peters, A., and Devlin, R. B. (2008b). Endothelial dysfunction: associations with exposure to ambient fine particles in diabetic individuals. Environ Health Perspect 116, 1666-1674.
Schneider, A., Neas, L. M., Graff, D. W., Herbst, M. C., Cascio, W. E., Schmitt, M. T., Buse, J. B., Peters, A., and Devlin, R. B. (2010). Association of cardiac and vascular changes with ambient PM2.5 in diabetic individuals. Part Fibre Toxicol 7.
Segal, S. S., Kurjiaka, D. T., and Caston, A. L. (1993). Endurance training increases arterial wall thickness in rats. J Appl Physiol 74, 722-726.
Shoelson, S. E., Lee, J., and Goldfine, A. B. (2006). Inflammation and insulin resistance. The Journal of clinical investigation 116, 1793-1801.
Sibay, T. M., and Hayes, J. A. (1969). Potential carcinogenic effect of streptozotocin. Lancet 2, 912.
Smith, K. R., Veranth, J. M., Kodavanti, U. P., Aust, A. E., and Pinkerton, K. E. (2006). Acute pulmonary and systemic effects of inhaled coal fly ash in rats: Comparison to ambient environmental particles. Toxicological Sciences 93, 390-399.
Song, C. H., and Carmichael, G. R. (2001). A three-dimensional modeling investigation of the evolution processes of dust and sea-salt particles in east Asia. J Geophys Res-Atmos 106, 18131-18154.
Srinivasan, K., Viswanad, B., Asrat, L., Kaul, C. L., and Ramarao, P. (2005). Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacological research : the official journal of the Italian Pharmacological Society 52, 313-320.
Stanek, L. W., Brown, J. S., Stanek, J., Gift, J., and Costa, D. L. (2011). Air pollution toxicology--a brief review of the role of the science in shaping the current understanding of air pollution health risks. Toxicological sciences : an official journal of the Society of Toxicology 120 Suppl 1, S8-27.
Sun, Q., Hong, X., and Wold, L. E. (2010). Cardiovascular effects of ambient particulate air pollution exposure. Circulation 121, 2755-2765.
Sun, Q., Wang, A., Jin, X., Natanzon, A., Duquaine, D., Brook, R. D., Aguinaldo, J. G., Fayad, Z. A., Fuster, V., Lippmann, M., Chen, L. C., and Rajagopalan, S. (2005). Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. JAMA : the journal of the American Medical Association 294, 3003-3010.
Sun, Q., Yue, P., Deiuliis, J. A., Lumeng, C. N., Kampfrath, T., Mikolaj, M. B., Cai, Y., Ostrowski, M. C., Lu, B., Parthasarathy, S., Brook, R. D., Moffatt-Bruce, S. D., Chen, L. C., and Rajagopalan, S. (2009a). Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity. Circulation 119, 538-546.
Sun, Q. H., Yue, P., Deiuliis, J. A., Lumeng, C. N., Kampfrath, T., Mikolaj, M. B., Cai, Y., Ostrowski, M. C., Lu, B., Parthasarathy, S., Brook, R. D., Moffatt-Bruce, S. D., Chen, L. C., and Rajagopalan, S. (2009b). Ambient Air Pollution Exaggerates Adipose Inflammation and Insulin Resistance in a Mouse Model of Diet-Induced Obesity. Circulation 119, 538-U591.
Thomas, M. C., Burns, W. C., and Cooper, M. E. (2005). Tubular changes in early diabetic nephropathy. Advances in chronic kidney disease 12, 177-186.
Tong, P. C., Lee, K. F., So, W. Y., Ng, M. H., Chan, W. B., Lo, M. K., Chan, N. N., and Chan, J. C. (2004). White blood cell count is associated with macro- and microvascular complications in Chinese patients with type 2 diabetes. Diabetes Care 27, 216-222.
Tornig, J., Amann, K., Ritz, E., Nichols, C., Zeier, M., and Mall, G. (1996). Arteriolar wall thickening, capillary rarefaction and interstitial fibrosis in the heart of rats with renal failure:the effects of ramipril, nifedipine and moxonidine. Journal of the American Society of Nephrology : JASN 7, 667-675.
Turpin, B. J., and Lim, H. J. (2001). Species contributions to PM2.5 mass concentrations: Revisiting common assumptions for estimating organic mass. Aerosol Sci Tech 35, 602-610.
Tzeng, H. P., Yang, R. S., Ueng, T. H., Lin-Shiau, S. Y., and Liu, S. H. (2003). Motorcycle exhaust particulates enhance vasoconstriction in organ culture of rat aortas and involve reactive oxygen species. Toxicological sciences : an official journal of the Society of Toxicology 75, 66-73.
Ulrich, M. M. W., Alink, G. M., Kumarathasan, P., Vincent, R., Boere, A. J. F., and Cassee, F. R. (2002). Health effects and time course of particulate matter on the cardiopulmonary system in rats with lung inflammation. J Toxicol Env Heal A 65, 1571-1595.
Vozarova, B., Weyer, C., Lindsay, R. S., Pratley, R. E., Bogardus, C., and Tataranni, P. A. (2002). High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes. Diabetes 51, 455-461.
Wegesser, T. C., Franzi, L. M., Mitloehner, F. M., Eiguren-Fernandez, A., and Last, J. A. (2010). Lung antioxidant and cytokine responses to coarse and fine particulate matter from the great California wildfires of 2008. Inhalation toxicology 22, 561-570.
Witteles, R. M., and Fowler, M. B. (2008). Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options. Journal of the American College of Cardiology 51, 93-102.
Xu, X., Deng, F., Guo, X., Lv, P., Zhong, M., Liu, C., Wang, A., Tzan, K., Jiang, S. Y., Lippmann, M., Rajagopalan, S., Qu, Q., Chen, L. C., and Sun, Q. (2012). Association of systemic inflammation with marked changes in particulate air pollution in Beijing in 2008. Toxicology letters 212, 147-156.
Xu, X., Liu, C., Xu, Z., Tzan, K., Zhong, M., Wang, A., Lippmann, M., Chen, L. C., Rajagopalan, S., and Sun, Q. (2011a). Long-term exposure to ambient fine particulate pollution induces insulin resistance and mitochondrial alteration in adipose tissue. Toxicological sciences : an official journal of the Society of Toxicology 124, 88-98.
Xu, X., Yavar, Z., Verdin, M., Ying, Z., Mihai, G., Kampfrath, T., Wang, A., Zhong, M., Lippmann, M., Chen, L. C., Rajagopalan, S., and Sun, Q. (2010). Effect of early particulate air pollution exposure on obesity in mice: role of p47phox. Arteriosclerosis, thrombosis, and vascular biology 30, 2518-2527.
Xu, Z., Xu, X., Zhong, M., Hotchkiss, I. P., Lewandowski, R. P., Wagner, J. G., Bramble, L. A., Yang, Y., Wang, A., Harkema, J. R., Lippmann, M., Rajagopalan, S., Chen, L. C., and Sun, Q. (2011b). Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues. Particle and fibre toxicology 8, 20.
Yan, Y. H., Chou, C. C., Lee, C. T., Liu, J. Y., and Cheng, T. J. (2011). Enhanced insulin resistance in diet-induced obese rats exposed to fine particles by instillation. Inhalation toxicology 23, 507-519.
Zhang, M., Lv, X. Y., Li, J., Xu, Z. G., and Chen, L. (2008). The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Experimental diabetes research 2008, 704045.
Zuo, L., Youtz, D. J., and Wold, L. E. (2011a). Particulate Matter Exposure Exacerbates High Glucose-Induced Cardiomyocyte Dysfunction through ROS Generation. Plos One 6.
Zuo, L., Youtz, D. J., and Wold, L. E. (2011b). Particulate matter exposure exacerbates high glucose-induced cardiomyocyte dysfunction through ROS generation. PloS one 6, e23116.




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