title: Di(2-ethylhexyl)phthalate exposure impairs insulin receptor and glucose transporter 4 gene expression in L6 myotubes.
abstract: Di(2-ethyl hexyl)-phthalate (DEHP) is an endocrine disrupter and is the most abundantly used phthalate derivative, which is suspected to be an inevitable environmental exposure contributing to the increasing incidence of type-2 diabetes in humans. Therefore, the present study was designed to address the dose-dependent effects of DEHP on insulin signaling molecules in L6 myotubes. L6 myotubes were exposed to different concentrations (25, 50, and 100 μM) of DEHP for 24 h. At the end of exposure, cells were utilized for assessing various parameters. Insulin receptor and glucose transporter4 (GLUT4) gene expression, insulin receptor protein concentration, glucose uptake and oxidation, and enzymatic and nonenzymatic antioxidants were significantly reduced, but glutamine fructose-6-phosphate amidotransferase, nitric oxide, lipid peroxidation, and reactive oxygen species levels were elevated in a dose-dependent manner in L6 myotubes exposed to DEHP. The present study in turn shows the direct adverse effect of DEHP on the expression of insulin receptor and GLUT4 gene, glucose uptake, and oxidation in L6 myotubes suggesting that DEHP exposure may have a negative influence on insulin signaling.
authors.affiliation: Department of Endocrinology, Dr A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India.
authors.forename: P
authors.initials: P
authors.lastname: Rajesh
authors.affiliation: Department of Endocrinology, Dr A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India kbala82@rediffmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Balasubramanian
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007333:Insulin Resistance; D015227:Lipid Peroxidation / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000975:Antioxidants; D052244:Endocrine Disruptors; D051275:Glucose Transporter Type 4; D017382:Reactive Oxygen Species; C495694:Slc2a4 protein, rat; D006003:Glycogen; D004051:Diethylhexyl Phthalate; D011972:Receptor, Insulin; D005947:Glucose
keywords: L6 myotubes; di(2-ethylhexyl)phthalate; glucose oxidation; glucose transporter4; insulin receptor; insulin signal transduction; reactive oxygen species