TABLE 2

Animal studies demonstrating EDC-induced changes in glucose homeostasis

AuthorEDCModel systemDisruption of glucose homeostasis
Weber et al., Toxicology 1991;66:133–144TCDDWild-type male Sprague Dawley ratsInjection of 25 μg/kg TCDD resulted in decreased activity of PEPCK and G-6-Pase after 2 and 8 days of treatment, respectively.
Liu et al., Mol Pharmacol 1995;47:65–73TCDDWild-type male C57BL/6 and DBA/2J miceA single dose of 116 μg/kg i.p. TCDD resulted in the significant decrease in glucose transport in adipose tissue and brain after 24 h that was sustained for at least 30 days. The effect was AhR mediated.
Gayathri et al., Indian J Med Res 2004;119:139–144DEHPWild-type female Wistar Kyoto ratsAdministration of 75 μg/kg DEHP every other day for 14 days resulted in a decrease in serum insulin and cortisol as well as liver glycogen; blood glucose was increased. The effects were reversible upon stopping treatment.
Alonso-Magdalena et al., Environ Health Perspect 2006;114:106–112BPAWild-type male Swiss albino OF1 miceAdministration of a single 10 μg/kg dose of BPA produced a rapid rise in plasma insulin and a corresponding decrease in plasma glucose; however, 4-day treatment with 100 μg/kg/day of BPA impaired glucose tolerance on an intraperitoneal glucose tolerance test and reduced the hypoglycemic effect of insulin in an insulin tolerance test.
Hoppe and Carey, Obesity 2007;15:2942–2950Penta-BDEWild-type male Sprague Dawley ratsDaily gavage of 14 mg/kg penta-BDE for 4 weeks resulted in a 30% increase in isoproterenol-stimulated lipolysis and a 59% decrease in insulin-stimulated glucose oxidation in adipocytes.
Alonso-Magdalena et al., PLoS One 2008;3:e2069BPAWild-type male Swiss albino OF1 mice and ERα and ERβ KO miceAdministration of 100 μg/kg BPA twice per day for 4 days resulted in a significant increase in β-cell insulin content that was ERα dependent. Isolated islets treated with 1 nmol/L BPA had an increase in insulin content.
Sato et al., Toxicol Appl Pharmacol 2008;229:1019TCDDWild-type male C57BL/6 and AhR KO mouseOral administration of 500 ng/kg TCDD once a day for 18 days resulted in significantly increased CYP1A1 expression in the liver and changes in energy metabolism gene expression that was AhR-mediated.
Ruzzin et al., Environ Health Perspect 2010;118:465–471General POPsWild-type male Sprague Dawley ratsAdministration of a crude fish oil diet for 28 days resulted in systemic insulin resistance, visceral fat accumulation, and hepatosteatosis. Several genes regulating hepatic lipid metabolism were altered. Isolated POP classes impaired insulin-stimulated glucose uptake in 3T3-L1 adipocytes.
Fried et al., Drug Chem Toxicol 2010;33:261–268TCDDWild-type male Sprague Dawley ratsDiabetic rats (high-fat diet/streptozotocin treatment) dosed with 12.8 μg/kg TCDD had significantly reduced serum glucose levels by day 8 of treatment.
Zuo et al., Environ Toxicol 2011;26:79–85TBTWild-type male KM miceOral administration once every 3 days for 45 days of 0.5–50 μg/kg TBT resulted in body weight gain, hepatic steatosis, hyperinsulinemia, hyperleptinemia, and a reduction in hepatic adiponectin levels in a dose-dependent fashion.
  • BDE, bromodiphenyl ether; DEHP, di(2-ethylhexyl)-phthalate; G-6-Pase, glucose-6-phosphatase.