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- Title
Benzene Exposure Induces Insulin Resistance in Mice.
- Authors
Abplanalp, Wesley T; Wickramasinghe, Nalinie S; Sithu, Srinivas D; Conklin, Daniel J; Xie, Zhengzhi; Bhatnagar, Aruni; Srivastava, Sanjay; O'Toole, Timothy E
- Abstract
Benzene is a ubiquitous pollutant associated with hematotoxicity but its metabolic effects are unknown. We sought to determine if and how exposure to volatile benzene impacted glucose handling. We exposed wild type C57BL/6 mice to volatile benzene (50 ppm × 6 h/day) or HEPA-filtered air for 2 or 6 weeks and measured indices of oxidative stress, inflammation, and insulin signaling. Compared with air controls, we found that mice inhaling benzene demonstrated increased plasma glucose (p =.05), insulin (p =.03), and HOMA-IR (p =.05), establishing a state of insulin and glucose intolerance. Moreover, insulin-stimulated Akt phosphorylation was diminished in the liver (p =.001) and skeletal muscle (p =.001) of benzene-exposed mice, accompanied by increases in oxidative stress and Nf-κb phosphorylation (p =.025). Benzene-exposed mice also demonstrated elevated levels of Mip1-α transcripts and Socs1 (p =.001), but lower levels of Irs-2 tyrosine phosphorylation (p =.0001). Treatment with the superoxide dismutase mimetic, TEMPOL, reversed benzene-induced effects on oxidative stress, Nf-κb phosphorylation, Socs1 expression, Irs-2 tyrosine phosphorylation, and systemic glucose intolerance. These findings suggest that exposure to benzene induces insulin resistance and that this may be a sensitive indicator of inhaled benzene toxicity. Persistent ambient benzene exposure may be a heretofore unrecognized contributor to the global human epidemics of diabetes and cardiovascular disease.
- Subjects
BENZENE; ANIMAL models of insulin resistance; DIABETES; CARDIOVASCULAR diseases; TYPE 2 diabetes risk factors; OXIDATIVE stress
- Publication
Toxicological Sciences, 2019, Vol 167, Issue 2, p426
- ISSN
1096-6080
- Publication type
Article
- DOI
10.1093/toxsci/kfy252