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Glucose Homeostasis following Diesel Exhaust Particulate Matter Exposure in a Lung Epithelial Cell-Specific IKK2-Deficient Mouse Model

BACKGROUND: Pulmonary inflammation is believed to be central to the pathogenesis due to exposure to fine particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]). This central role, however, has not yet been systemically examined. OBJECTIVE: In the present study, we exp...

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Autores principales: Chen, Sufang, Chen, Minjie, Wei, Wei, Qiu, Lianglin, Zhang, Li, Cao, Qi, Ying, Zhekang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Environmental Health Perspectives 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791567/
https://www.ncbi.nlm.nih.gov/pubmed/31095431
http://dx.doi.org/10.1289/EHP4591
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author Chen, Sufang
Chen, Minjie
Wei, Wei
Qiu, Lianglin
Zhang, Li
Cao, Qi
Ying, Zhekang
author_facet Chen, Sufang
Chen, Minjie
Wei, Wei
Qiu, Lianglin
Zhang, Li
Cao, Qi
Ying, Zhekang
author_sort Chen, Sufang
collection PubMed
description BACKGROUND: Pulmonary inflammation is believed to be central to the pathogenesis due to exposure to fine particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]). This central role, however, has not yet been systemically examined. OBJECTIVE: In the present study, we exploited a lung epithelial cell-specific inhibitor [Formula: see text] kinase 2 (IKK2) knockout mouse model to determine the role of pulmonary inflammation in the pathophysiology due to exposure to diesel exhaust particulate matter (DEP). METHODS: [Formula: see text] (lung epithelial cell-specific IKK2 knockout, KO) and [Formula: see text] (wild-type, tgWT) mice were intratracheally instilled with either vehicle or DEP for 4 months, and their inflammatory response and glucose homeostasis were then assessed. RESULTS: In comparison with tgWT mice, lung epithelial cell-specific IKK2-deficient mice had fewer DEP exposure-induced bronchoalveolar lavage fluid immune cells and proinflammatory cytokines as well as fewer DEP exposure-induced circulating proinflammatory cytokines. Glucose and insulin tolerance tests revealed that lung epithelial cell-specific IKK2 deficiency resulted in markedly less DEP exposure–induced insulin resistance and greater glucose tolerance. Akt phosphorylation analyses of insulin-responsive tissues showed that DEP exposure primarily targeted hepatic insulin sensitivity. Lung epithelial cell–specific IKK2-deficient mice had significantly lower hepatic insulin resistance than tgWT mice had. Furthermore, this difference in insulin resistance was accompanied by consistent differences in hepatic insulin receptor substrate 1 serine phosphorylation and inflammatory marker expression. DISCUSSION: Our findings suggest that in a tissue-specific knockout mouse model, an IKK2-dependent pulmonary inflammatory response was essential for the development of abnormal glucose homeostasis due to exposure to DEP. https://doi.org/10.1289/EHP4591
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spelling pubmed-67915672019-10-16 Glucose Homeostasis following Diesel Exhaust Particulate Matter Exposure in a Lung Epithelial Cell-Specific IKK2-Deficient Mouse Model Chen, Sufang Chen, Minjie Wei, Wei Qiu, Lianglin Zhang, Li Cao, Qi Ying, Zhekang Environ Health Perspect Research BACKGROUND: Pulmonary inflammation is believed to be central to the pathogenesis due to exposure to fine particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]). This central role, however, has not yet been systemically examined. OBJECTIVE: In the present study, we exploited a lung epithelial cell-specific inhibitor [Formula: see text] kinase 2 (IKK2) knockout mouse model to determine the role of pulmonary inflammation in the pathophysiology due to exposure to diesel exhaust particulate matter (DEP). METHODS: [Formula: see text] (lung epithelial cell-specific IKK2 knockout, KO) and [Formula: see text] (wild-type, tgWT) mice were intratracheally instilled with either vehicle or DEP for 4 months, and their inflammatory response and glucose homeostasis were then assessed. RESULTS: In comparison with tgWT mice, lung epithelial cell-specific IKK2-deficient mice had fewer DEP exposure-induced bronchoalveolar lavage fluid immune cells and proinflammatory cytokines as well as fewer DEP exposure-induced circulating proinflammatory cytokines. Glucose and insulin tolerance tests revealed that lung epithelial cell-specific IKK2 deficiency resulted in markedly less DEP exposure–induced insulin resistance and greater glucose tolerance. Akt phosphorylation analyses of insulin-responsive tissues showed that DEP exposure primarily targeted hepatic insulin sensitivity. Lung epithelial cell–specific IKK2-deficient mice had significantly lower hepatic insulin resistance than tgWT mice had. Furthermore, this difference in insulin resistance was accompanied by consistent differences in hepatic insulin receptor substrate 1 serine phosphorylation and inflammatory marker expression. DISCUSSION: Our findings suggest that in a tissue-specific knockout mouse model, an IKK2-dependent pulmonary inflammatory response was essential for the development of abnormal glucose homeostasis due to exposure to DEP. https://doi.org/10.1289/EHP4591 Environmental Health Perspectives 2019-05-16 /pmc/articles/PMC6791567/ /pubmed/31095431 http://dx.doi.org/10.1289/EHP4591 Text en EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.
spellingShingle Research
Chen, Sufang
Chen, Minjie
Wei, Wei
Qiu, Lianglin
Zhang, Li
Cao, Qi
Ying, Zhekang
Glucose Homeostasis following Diesel Exhaust Particulate Matter Exposure in a Lung Epithelial Cell-Specific IKK2-Deficient Mouse Model
title Glucose Homeostasis following Diesel Exhaust Particulate Matter Exposure in a Lung Epithelial Cell-Specific IKK2-Deficient Mouse Model
title_full Glucose Homeostasis following Diesel Exhaust Particulate Matter Exposure in a Lung Epithelial Cell-Specific IKK2-Deficient Mouse Model
title_fullStr Glucose Homeostasis following Diesel Exhaust Particulate Matter Exposure in a Lung Epithelial Cell-Specific IKK2-Deficient Mouse Model
title_full_unstemmed Glucose Homeostasis following Diesel Exhaust Particulate Matter Exposure in a Lung Epithelial Cell-Specific IKK2-Deficient Mouse Model
title_short Glucose Homeostasis following Diesel Exhaust Particulate Matter Exposure in a Lung Epithelial Cell-Specific IKK2-Deficient Mouse Model
title_sort glucose homeostasis following diesel exhaust particulate matter exposure in a lung epithelial cell-specific ikk2-deficient mouse model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791567/
https://www.ncbi.nlm.nih.gov/pubmed/31095431
http://dx.doi.org/10.1289/EHP4591
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