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Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus.

ABSTRACT: Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (<2.5 ?m 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.

SUBMITTER: Liu C

PROVIDER: S-EPMC4049808 | biostudies-other | 2014 May

REPOSITORIES: biostudies-other

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Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus.

Liu Cuiqing C Bai Yuntao Y Xu Xiaohua X Sun Lixian L Wang Aixia A Wang Tse-Yao TY Maurya Santosh K SK Periasamy Muthu M Morishita Masako M Harkema Jack J Ying Zhekang Z Sun Qinghua Q Rajagopalan Sanjay S

Particle and fibre toxicology 20140530

<h4>Background</h4>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.<h4>Methods</h4>KKay mice, which a ...[more]

PMID: 24886175

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Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus.

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Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus.

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