Photo by mykjohnson from unsplash
Abstract Di‐(2‐ethylhexyl)‐phthalate (DEHP), a ubiquitous industrial pollutant in our daily life, has been reported to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies previously. Recently, it… Click to show full abstract
Abstract Di‐(2‐ethylhexyl)‐phthalate (DEHP), a ubiquitous industrial pollutant in our daily life, has been reported to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies previously. Recently, it has been reported to be an endocrine disrupter and ligand to peroxisome proliferator activated receptor, which could influence the homeostasis of liver metabolic systems and contribute to the development of type‐2 diabetes. However, the potential mechanisms are not known yet. This study was designed to solve these problems with male SD rats and normal human hepatocyte line, L02 cells, exposed to DEHP for toxicological experiments. Adult male SD rats were divided into four groups, normal group fed with regular diets and three DEHP‐treated groups (dissolved in olive oil at doses of 0.05, 5 and 500 mg/kg body weight, respectively, once daily through gastric intubations for 15 weeks). L02 cells were divided into 6 groups, normal group with 5, 10, 25, 50, and 100 &mgr;mol/l DEHP groups. DEHP‐exposed rats exhibited significant liver damage, glucose tolerance, and insulin tolerance along with reduced expression of insulin receptor and GLUT4 proteins in the liver tissues. The results of in vitro experiments could determine that the DEHP‐induced activation of peroxisome proliferator activated receptor &ggr; (PPAR&ggr;) played a key role in the production of oxidative stress and down‐regulated expression of insulin receptor and GLUT4 proteins in L02 cells. This conclusion could be supported by the results of in vitro experiments, in which the cells were exposed to DEHP with GW9662 (PPAR&ggr; inhibitor). In general, these results highlight the key role of PPAR&ggr; in the process of insulin resistance induced by DEHP. HighlightsDEHP exacerbates insulin resistance both in liver tissues and cells.Expression of insulin receptor and GLUT4 were altered with PPAR&ggr;.DEHP can induce oxidative stress to disrupt the metabolic homeostasis.The dose of exposed DEHP is closed to daily exposure by human.Determine the key role of PPAR&ggr; to insulin resistance.