In an article published on December 23, 2016 in the peer-reviewed journal Toxicology and Applied Pharmacology, Wang Zhang and colleagues from the Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui, China investigated the influence of chronic exposure to phthalates on glucose homeostasis and insulin sensitivity.
Adult rats were exposed daily for 15 weeks to di-(2-ethylhexyl)-phthalate (DEHP, CAS 117-81-7) by gastric intubation to 0.05, 5 and 500 mg/kg body weight. The lowest dose approaches the current limits for human intake. Insulin sensitivity was analyzed at several time points through the oral glucose tolerance test and insulin tolerance test. Molecular mechanisms were also investigated, both in vivo (in tissues of the exposed rats) and in vitro (in normal human hepatocyte cell line L02).
At the end of the exposure period, increased insulin resistance was observed in DEHP-exposed rats at all doses tested, coinciding with liver damage and decreased expression of insulin receptor and glucose transporter 4 (GLUT4) protein. Previously, impairment of insulin tolerance by DEHP has been observed in mice as well (FPF reported). In vitro experiments demonstrated the involvement of peroxisome proliferator activated receptor γ (PPARγ) in the molecular mechanism underlying the observed effects of DEHP on insulin receptor and GLUT4 expression. PPARγ is involved in the regulation of adipogenesis and glucose metabolism, and its activation by phthalates has been implicated in the etiology of obesity previously (FPF reported).
Zhang, W., et al. (2017). “Di-(2-ethylhexyl) phthalate could disrupt the insulin signaling pathway in liver of SD rats and L02 cells via PPARγ.” Toxicology and Applied Pharmacology 316: 17-26.