• The epigenetic effects of the combination of diesel exhaust exposure and excess nutrition in development of insulin resistance
  • Anahid Hemmatpur,1 Sima Ghaneie,2 Alireza Karimollah,3 Marzieh Nemati,4 Javad Zavarreza,5,*
    1. Shahid Sadoughi University of medical sciences and Health Services
    2. Shahid Sadoughi University of medical sciences and Health Services
    3. Shahid Sadoughi University of medical sciences and Health Services
    4. Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz
    5. Shahid Sadoughi University of medical sciences and Health Services


  • Introduction: Numerous investigations have been conducted to disclose risk factors for type 2 diabetes. Overnutrition is the most well-known contributor to its development. Meanwhile, exposure to air pollution (PM) has recently been shown to trigger insulin resistance, leading to diabetes; however, its underlying mechanisms are not fully understood. Nutrient-induced insulin production is aided by incretin hormone receptors (GLP-1R and GIPR) working in tandem with transcription factor7-like 2 (TCF7L2). We hypothesize that insulin resistance may be triggered as a result of PM tampering the modulators of the nutrient-induced insulin secretion. Thus, focusing on pancreas malfunction, we examined the mechanism by which PM exposure in conjunction with high-fat feeding may induce insulin resistance.
  • Methods: The experiment involved four groups of C57BL/6 mice, namely (N/F, H/F, N/P, and H/P). The mice were fed a control/high-fat diet and exposed to PM/filtered air for 10 weeks to examine pancreatic Gipr, Glp-1r, and Tcf7l2-E4 gene expression. Fasting blood glucose and insulin sensitivity were evaluated via insulin surrogate indices. Pancreatic concentration of TCF7L2 was also assessed.
  • Results: High-fat-fed mice displayed lower Gipr and pancreatic TCF7L2 protein expression associated with impaired glucose tolerance despite preserved insulin tolerance. PM exposure led to a downward trend in Gipr, Glp-1r, and Tcf7l2-E4 expression, while their glucose tolerance and insulin sensitivity state were steady. Moreover, pancreatic TCF7L2 protein level increased significantly in response to PM.
  • Conclusion: Present findings suggest that sub-acute exposure to diesel exhaust PM can disrupt the normal gene expression in the pancreas, which due the importance of the genes might cause susceptibility to the development of insulin resistance.
  • Keywords: Air pollution; High-fat diet; Gipr; Glp-1r; Tcf7l2