title: Long-term exposure to nonylphenol affects insulin signaling in the liver of adult male rats.
abstract: In the present study, we sought to investigate the long-term effects of nonylphenol (NP) on insulin signaling and glucose metabolism in liver. Furthermore, reactive oxygen species (ROS) in liver was evaluated as it is known to induce insulin resistance. Rats were administered NP by oral gavage at the doses of 15, 150 and 1500 μg/ kg body weight per day for 45 days. Hydrogen peroxide (H(2)O(2)) generation and lipid peroxidation were increased, and the activities of antioxidant enzymes were decreased in the liver of NP-treated rats. NP increased the plasma glucose and insulin levels and altered the enzymes of carbohydrate metabolism. Decrease in the protein levels of insulin signaling molecules insulin receptor (IR), IR substrate (IRS)-1, IRS-2 and phosphatidylinositol-3-kinase were observed with parallel increase in H(2)O(2) levels in the liver of NP-treated rats. These results suggest that NP downregulates insulin signaling in liver, which could be due to ROS production and oxidative damage.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry, India.
authors.forename: R
authors.initials: R
authors.lastname: Jubendradass
authors.forename: S C
authors.initials: SC
authors.lastname: D'Cruz
authors.forename: P P
authors.initials: PP
authors.lastname: Mathur
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002374:Catalase / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004785:Environmental Pollutants; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D010636:Phenols; C025256:nonylphenol; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D005947:Glucose