Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus.
Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus.
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DOI：
10.1186/1743-8977-11-27
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发表时间：
2014-05-30
影响因子：
10
通讯作者：
Rajagopalan S
中科院分区：
文献类型：
--
作者：
Liu C;Bai Y;Xu X;Sun L;Wang A;Wang TY;Maurya SK;Periasamy M;Morishita M;Harkema J;Ying Z;Sun Q;Rajagopalan S
先前的实验和流行病学数据支持暴露于细微的环境颗粒物（空气动力学直径<2.5 μm，PM2.5）与胰岛素抵抗/II型糖尿病之间的联系。本研究旨在研究在遗传易感动物模型中吸入高浓度PM2.5是否会导致能量代谢异常和外周血糖控制恶化。通过全身暴露系统，将易患II型DM的KKay小鼠分配到浓缩的环境PM2.5或过滤的空气（FA）中5-8周。评估葡萄糖耐量、胰岛素敏感性、耗氧量和产热率。安乐死时，采集血液、脾脏和内脏脂肪组织，使用流式细胞术测量炎症细胞。采用标准免疫组织化学方法、蛋白质印迹法和定量PCR来评估感兴趣的靶标。PM2.5暴露影响能量代谢，包括O2消耗、CO2产生、呼吸交换率和产热。这些变化伴随着胰岛素抵抗恶化、内脏脂肪过多以及脾脏和内脏脂肪库的炎症。血浆脂联素水平下降，而瘦素水平增加响应PM2.5暴露。PM2.5暴露导致KKay小鼠棕色脂肪组织中炎症基因表达显著增加，UCP 1表达减少，肝脏中p38和ERK通路活化。在遗传易感的糖尿病模型中，集中的环境PM2.5暴露损害能量代谢，伴随葡萄糖稳态异常，胰岛素反应器官中的炎症增加，棕色脂肪炎症，并导致循环瘦素/脂联素水平失衡。这些结果提供了额外的见解周围的空气污染介导的易感性II型糖尿病的机制。
Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (<2.5 μm in aerodynamic diameter, PM2.5) and development of insulin resistance/Type II diabetes mellitus. This study was designed to investigate whether inhalational exposure of concentrated PM2.5 in a genetically susceptible animal model would result in abnormalities in energy metabolism and exacerbation of peripheral glycemic control. KKay mice, which are susceptible to Type II DM, were assigned to either concentrated ambient PM2.5 or filtered air (FA) for 5–8 weeks via a whole body exposure system. Glucose tolerance, insulin sensitivity, oxygen consumption and heat production were evaluated. At euthanasia, blood, spleen and visceral adipose tissue were collected to measure inflammatory cells using flow cytometry. Standard immnunohistochemical methods, western blotting and quantitative PCR were used to assess targets of interest. PM2.5 exposure influenced energy metabolism including O2 consumption, CO2 production, respiratory exchange ratio and thermogenesis. These changes were accompanied by worsened insulin resistance, visceral adiposity and inflammation in spleen and visceral adipose depots. Plasma adiponectin were decreased in response to PM2.5 exposure while leptin levels increased. PM2.5 exposure resulted in a significant increase in expression of inflammatory genes and decreased UCP1 expression in brown adipose tissue and activated p38 and ERK pathways in the liver of the KKay mice. Concentrated ambient PM2.5 exposure impairs energy metabolism, concomitant with abnormalities in glucose homeostasis, increased inflammation in insulin responsive organs, brown adipose inflammation and results in imbalance in circulating leptin/adiponectin levels in a genetically susceptible diabetic model. These results provide additional insights into the mechanisms surrounding air pollution mediated susceptibility to Type II DM.
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DOI：
10.1097/med.0b013e328337a81f
发表时间：
2010-04
期刊：
Current opinion in endocrinology, diabetes, and obesity
影响因子：
--
作者：
Cypess AM;Kahn CR
通讯作者：
Kahn CR
影响因子：
5.8
作者：
Bremer, Andrew A.;Devaraj, Sridevi;Jialal, Ishwarlal
通讯作者：
Jialal, Ishwarlal
DOI：
10.1038/nri3070
发表时间：
2011-10-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
168.9
作者：
Lim, Stephen S.;Vos, Theo;Flaxman, Abraham D.;Danaei, Goodarz;Shibuya, Kenji;Adair-Rohani, Heather;Amann, Markus;Anderson, H. Ross;Andrews, Kathryn G.;Aryee, Martin;Atkinson, Charles;Bacchus, Loraine J.;Bahalim, Adil N.;Balakrishnan, Kalpana;Balmes, John;Barker-Collo, Suzanne;Baxter, Amanda;Bell, Michelle L.;Blore, Jed D.;Blyth, Fiona;Bonner, Carissa;Borges, Guilherme;Bourne, Rupert;Boussinesq, Michel;Brauer, Michael;Brooks, Peter;Bruce, Nigel G.;Brunekreef, Bert;Bryan-Hancock, Claire;Bucello, Chiara;Buchbinder, Rachelle;Bull, Fiona;Burnett, Richard T.;Byers, Tim E.;Calabria, Bianca;Carapetis, Jonathan;Carnahan, Emily;Chafe, Zoe;Charlson, Fiona;Chen, Honglei;Chen, Jian Shen;Cheng, Andrew Tai-Ann;Child, Jennifer Christine;Cohen, Aaron;Colson, K. Ellicott;Cowie, Benjamin C.;Darby, Sarah;Darling, Susan;Davis, Adrian;Degenhardt, Louisa;Dentener, Frank;Des Jarlais, Don C.;Devries, Karen;Dherani, Mukesh;Ding, Eric L.;Dorsey, E. Ray;Driscoll, Tim;Edmond, Karen;Ali, Suad Eltahir;Engell, Rebecca E.;Erwin, Patricia J.;Fahimi, Saman;Falder, Gail;Farzadfar, Farshad;Ferrari, Alize;Finucane, Mariel M.;Flaxman, Seth;Fowkes, Francis Gerry R.;Freedman, Greg;Freeman, Michael K.;Gakidou, Emmanuela;Ghosh, Santu;Giovannucci, Edward;Gmel, Gerhard;Graham, Kathryn;Grainger, Rebecca;Grant, Bridget;Gunnell, David;Gutierrez, Hialy R.;Hall, Wayne;Hoek, Hans W.;Hogan, Anthony;Hosgood, H. Dean, III;Hoy, Damian;Hu, Howard;Hubbell, Bryan J.;Hutchings, Sally J.;Ibeanusi, Sydney E.;Jacklyn, Gemma L.;Jasrasaria, Rashmi;Jonas, Jost B.;Kan, Haidong;Kanis, John A.;Kassebaum, Nicholas;Kawakami, Norito;Khang, Young-Ho;Khatibzadeh, Shahab;Khoo, Jon-Paul;Kok, Cindy;Laden, Francine;Lalloo, Ratilal;Lan, Qing;Lathlean, Tim;Leasher, Janet L.;Leigh, James;Li, Yang;Lin, John Kent;Lipshultz, Steven E.;London, Stephanie;Lozano, Rafael;Lu, Yuan;Mak, Joelle;Malekzadeh, Reza;Mallinger, Leslie;Marcenes, Wagner;March, Lyn;Marks, Robin;Martin, Randall;McGale, Paul;McGrath, John;Mehta, Sumi;Mensah, George A.;Merriman, Tony R.;Micha, Renata;Michaud, Catherine;Mishra, Vinod;Hanafiah, Khayriyyah Mohd;Mokdad, Ali A.;Morawska, Lidia;Mozaffarian, Dariush;Murphy, Tasha;Naghavi, Mohsen;Neal, Bruce;Nelson, Paul K.;Miquel Nolla, Joan;Norman, Rosana;Olives, Casey;Omer, Saad B.;Orchard, Jessica;Osborne, Richard;Ostro, Bart;Page, Andrew;Pandey, Kiran D.;Parry, Charles D. H.;Passmore, Erin;Patra, Jayadeep;Pearce, Neil;Pelizzari, Pamela M.;Petzold, Max;Phillips, Michael R.;Pope, Dan;Pope, C. Arden, III;Powles, John;Rao, Mayuree;Razavi, Homie;Rehfuess, Eva A.;Rehm, Juergen T.;Ritz, Beate;Rivara, Frederick P.;Roberts, Thomas;Robinson, Carolyn;Rodriguez-Portales, Jose A.;Romieu, Isabelle;Room, Robin;Rosenfeld, Lisa C.;Roy, Ananya;Rushton, Lesley;Salomon, Joshua A.;Sampson, Uchechukwu;Sanchez-Riera, Lidia;Sanman, Ella;Sapkota, Amir;Seedat, Soraya;Shi, Peilin;Shield, Kevin;Shivakoti, Rupak;Singh, Gitanjali M.;Sleet, David A.;Smith, Emma;Smith, Kirk R.;Stapelberg, Nicolas J. C.;Steenland, Kyle;Stoeckl, Heidi;Stovner, Lars Jacob;Straif, Kurt;Straney, Lahn;Thurston, George D.;Tran, Jimmy H.;Van Dingenen, Rita;van Donkelaar, Aaron;Veerman, J. Lennert;Vijayakumar, Lakshmi;Weintraub, Robert;Weissman, Myrna M.;White, Richard A.;Whiteford, Harvey;Wiersma, Steven T.;Wilkinson, James D.;Williams, Hywel C.;Williams, Warwick;Wilson, Nicholas;Woolf, Anthony D.;Yip, Paul;Zielinski, Jan M.;Lopez, Alan D.;Murray, Christopher J. L.;Ezzati, Majid
通讯作者：
Ezzati, Majid
棕色脂肪组织在能量稳态中的作用和重要性。
影响因子：
3.6
作者：
Cypess AM;Kahn CR
通讯作者：
Kahn CR