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Environ Health Perspect. 2019 May;127(5):57009. doi: 10.1289/EHP4591.

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

Author information

1
Department of Geriatric Endocrinology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
2
Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland, USA.
3
Department of Bile Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
4
Department of Occupational and Environmental Health, School of Public Health, Nantong University, Nantong, China.
5
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine , Baltimore, Maryland, USA.

Abstract

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.

PMID:
31095431
DOI:
10.1289/EHP4591
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