Benzene Exposure Induces Insulin Resistance in Mice

Toxicol Sci. 2019 Feb 1;167(2):426-437. doi: 10.1093/toxsci/kfy252.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Air Pollutants / toxicity*
  • Animals
  • Benzene / toxicity*
  • Blood Cell Count
  • Blood Glucose / analysis
  • Inhalation Exposure / adverse effects*
  • Insulin / blood
  • Insulin Resistance*
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects*


  • Air Pollutants
  • Blood Glucose
  • Insulin
  • Benzene