title: Influence of phthalates on glucose homeostasis and atherosclerosis in hyperlipidemic mice.
abstract: BACKGROUND
  Phthalates are widely used as plasticizer and are considered as a typical endocrine-disrupting chemical. Epidemiological studies have associated serum or urinary phthalate metabolites with the prevalence of type 2 diabetes or related phenotypes. However, direct evidence supporting a causal role for exposure to phthalates in type 2 diabetes is lacking.
  
  
  METHODS
  To determine the potential influence of phthalates on glucose homeostasis and atherosclerosis, female apolipoprotein E-deficient (Apoe(-/-)) mice were started at 6 weeks of age on a Western diet together with or without Bis-(2-ethylhexyl) phthalate. Phthalate was administered in drinking water at a daily dosage of 100 mg/kg. We examined glucose and insulin tolerance, plasma glucose and triglyceride levels, body weight, and atherosclerotic lesions in the aortic root.
  
  
  RESULTS
  Two weeks after treatment, phthalate-exposed mice had significantly higher fasting blood glucose level (97.9 ± 2.1 vs. 84.3 ± 5.3 mg/dl, P = 0.034) and exhibited a trend of increased glucose intolerance compared to control mice. Insulin tolerance test on non-fasted mice 3 weeks after treatment revealed that phthalate had little influence on insulin sensitivity though phthalate-treated mice had a higher glucose concentration (159.2 ± 6.0 vs. 145.2 ± 3.6 mg/dl; P = 0.086). On the Western diet, Apoe(-/-) mice showed a time-dependent rise in fasting plasma glucose and triglyceride levels. However, no significant differences were observed between phthalate-treated and control mice in either phenotype after 4, 8, and 12 weeks of phthalate exposure. Neither body weight nor atherosclerotic lesions of Apoe(-/-) mice was affected.
  
  
  CONCLUSIONS
  This study indicates that exposure to phthalates gives rise to a brief interference of glucose homeostasis but has little impact on the development of type 2 diabetes and atherosclerosis in Apoe(-/-) mice.
authors.affiliation: Departments of Radiology & Medical Imaging and of Biochemistry & Molecular Genetics, University of Virginia, PO Box 801339, , 266 Snyder Bldg, 480 Ray C Hunt Drive, Charlottesville, VA, 22908, USA. wz4m@Virginia.EDU.|Department of Endocrinology of Jianghuai Hospital, Huaian, Jiangsu Province, 223001, China. wz4m@Virginia.EDU.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Departments of Radiology & Medical Imaging and of Biochemistry & Molecular Genetics, University of Virginia, PO Box 801339, , 266 Snyder Bldg, 480 Ray C Hunt Drive, Charlottesville, VA, 22908, USA. mc2xc@Virginia.EDU.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Departments of Radiology & Medical Imaging and of Biochemistry & Molecular Genetics, University of Virginia, PO Box 801339, , 266 Snyder Bldg, 480 Ray C Hunt Drive, Charlottesville, VA, 22908, USA. ws4v@virginia.edu.
authors.forename: Weibin
authors.initials: W
authors.lastname: Shi
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology; D004785:Environmental Pollutants / Q000494:pharmacology*; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D006949:Hyperlipidemias / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010795:Phthalic Acids / Q000494:pharmacology*; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D010795:Phthalic Acids; C032279:phthalic acid