Central IKKβ inhibition prevents air pollution mediated peripheral inflammation and exaggeration of type II diabetes
dc.contributor.author | Liu, Cuiqing | |
dc.contributor.author | Fonken, Laura K | |
dc.contributor.author | Wang, Aixia | |
dc.contributor.author | Maiseyeu, Andrei | |
dc.contributor.author | Bai, Yuntao | |
dc.contributor.author | Wang, Tse-Yao | |
dc.contributor.author | Maurya, Santosh | |
dc.contributor.author | Ko, Yi-An | |
dc.contributor.author | Periasamy, Muthu | |
dc.contributor.author | Dvonch, Timothy | |
dc.contributor.author | Morishita, Masako | |
dc.contributor.author | Brook, Robert D | |
dc.contributor.author | Harkema, Jack | |
dc.contributor.author | Ying, Zhekang | |
dc.contributor.author | Mukherjee, Bhramar | |
dc.contributor.author | Sun, Qinghua | |
dc.contributor.author | Nelson, Randy J | |
dc.contributor.author | Rajagopalan, Sanjay | |
dc.date.accessioned | 2014-12-08T17:45:42Z | |
dc.date.available | 2014-12-08T17:45:42Z | |
dc.date.issued | 2014-10-30 | |
dc.identifier.citation | Particle and Fibre Toxicology. 2014 Oct 30;11(1):53 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/109486 | en_US |
dc.description.abstract | Abstract Background 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 (Type II DM). We investigated the role of hypothalamic inflammation in PM2.5-mediated diabetes development. Methods KKay mice, a genetically susceptible model of Type II DM, were assigned to either concentrated PM2.5 or filtered air (FA) for 4–8 weeks via a versatile aerosol concentrator and exposure system, or administered intra-cerebroventricular with either IKKβ inhibitor (IMD-0354) or TNFα antibody (infliximab) for 4–5 weeks simultaneously with PM2.5 exposure. Glucose tolerance, insulin sensitivity, oxygen consumption and heat production were evaluated. At euthanasia, blood, spleen, visceral adipose tissue and hypothalamus were collected to measure inflammatory cells using flow cytometry. Standard immunohistochemical methods and quantitative PCR were used to assess targets of interest. Results PM2.5 exposure led to hyperglycemia and insulin resistance, which was accompanied by increased hypothalamic IL-6, TNFα, and IKKβ mRNA expression and microglial/astrocyte reactivity. Targeting the NFκB pathway with intra-cerebroventricular administration of an IKKβ inhibitor [IMD-0354, n = 8 for each group)], but not TNFα blockade with infliximab [(n = 6 for each group], improved glucose tolerance, insulin sensitivity, rectified energy homeostasis (O2 consumption, CO2 production, respiratory exchange ratio and heat generation) and reduced peripheral inflammation in response to PM2.5. Conclusions Central inhibition of IKKβ prevents PM2.5 mediated peripheral inflammation and exaggeration of type II diabetes. These results provide novel insights into how air pollution may mediate susceptibility to insulin resistance and Type II DM. | |
dc.title | Central IKKβ inhibition prevents air pollution mediated peripheral inflammation and exaggeration of type II diabetes | |
dc.type | Article | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/109486/1/12989_2014_Article_53.pdf | |
dc.identifier.doi | 10.1186/s12989-014-0053-5 | en_US |
dc.language.rfc3066 | en | |
dc.rights.holder | Liu et al.; licensee BioMed Central Ltd. | |
dc.date.updated | 2014-12-08T17:45:42Z | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.