Airborne PM 2.5 -Induced Hepatic Insulin Resistance by Nrf2/JNK-Mediated Signaling Pathway

Jinxia Xu, Wei Zhang, Zhongbing Lu, Fang Zhang and Wenjun Ding
Additional contact information
Jinxia Xu: Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
Wei Zhang: Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
Zhongbing Lu: Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
Fang Zhang: Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
Wenjun Ding: Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China

IJERPH, 2017, vol. 14, issue 7, 1-15

Abstract: Animal and epidemiological studies have suggested that exposure to airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 ?m (PM 2.5 ) is associated with the risk of developing type 2 diabetes. However, the mechanism underlying this risk is poorly understood. In the present study, we investigated the effects of PM 2.5 exposure on glucose homeostasis and related signaling pathways in mice. Wild-type and nuclear factor erythroid 2-related factor 2 (Nrf2) knockout (Nrf2 ? / ? ) C57BL/6 male mice were exposed to either ambient concentrated PM 2.5 or filtered air (FA) for 12 weeks through a whole-body PM exposure system. At the end of the exposure, we assessed liver damage, and performed metabolic studies, gene expressions, as well as molecular signal transductions to determine the signaling pathways involving oxidative responses, insulin signaling, and glucose metabolism. Our results indicated that PM 2.5 exposure for 12 weeks caused significant liver damage as evidenced by elevated levels of aminotransferase (AST) and alanine aminotransferase (ALT). Furthermore, PM 2.5 exposure induced impaired glucose tolerance and inhibited glycogen synthesis, leading to hepatic insulin resistance indicated by higher glucose levels, higher area under the curve (AUC), and homeostasis model assessment of insulin resistance (HOMA-IR) values. We further found that PM 2.5 exposure significantly increased the expressions of Nrf2 and Nrf2-regulated antioxidant genes. Moreover, PM 2.5 exposure activated the c-Jun N-terminal kinase (JNK) signaling pathway and increased insulin receptor substrate-1 (IRS-1) phosphorylation at Ser 307 , but reduced protein kinase B phosphorylation at Ser 473 . Taken together, our study demonstrated PM 2.5 exposure triggered Nrf2-mediated oxidative responses and activated the JNK-mediated inhibitory signaling pathway, resulting in hepatic insulin resistance.

Keywords: PM2.5; liver; insulin resistance; oxidative stress; Nrf2; JNK/IRS-1/AKT (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2017
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.mdpi.com/1660-4601/14/7/787/pdf (application/pdf)
https://www.mdpi.com/1660-4601/14/7/787/ (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:gam:jijerp:v:14:y:2017:i:7:p:787-:d:104706

Access Statistics for this article

IJERPH is currently edited by Ms. Jenna Liu

More articles in IJERPH from MDPI
Bibliographic data for series maintained by MDPI Indexing Manager ().