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
Published In Toxicol Sci, (2019 02 01)
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.
PubMed ID: 30346588
MeSH Terms: Air Pollutants/toxicity*; Animals; Benzene/toxicity*; Blood Cell Count; Blood Glucose/analysis; Inhalation Exposure/adverse effects*; Insulin Resistance*; Insulin/blood; Mice, Inbred C57BL; Oxidative Stress/drug effects*