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 6weeks 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 100mg/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±5.3mg/dl, P=0.034) and exhibited a trend of increased glucose intolerance compared to control mice. Insulin tolerance test on non-fasted mice 3weeks 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±3.6mg/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 12weeks of phthalate exposure. Neither body weight nor atherosclerotic lesions of Apoe -/- mice was affected. Conclusion: 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.