Di-(2-ethylhexyl)-phthalate induces glucose metabolic disorder in adolescent rats

Environ Sci Pollut Res Int. 2018 Feb;25(4):3596-3607. doi: 10.1007/s11356-017-0738-z. Epub 2017 Nov 21.


As a plasticizer, di-(2-ethylhexyl)-phthalate (DEHP) is widely added in various commercial products. Some researchers had suggested that DEHP has adverse effects on the glucose metabolism, but the mechanisms remain unclear. Adolescent Wistar rats were divided into four groups and administered DEHP by gavage at 0, 5, 50, and 500 mg kg-1 d-1 for 28 days. ELISA was used to quantify the serum insulin and leptin levels; RT-PCR, immunohistochemistry, and Western blot were used to detect the mRNA and protein expressions of Janus-activated kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signaling 3 (SOCS3), leptin receptor (Ob-R), and insulin receptor (IR) in liver and pancreas In comparison to the control group, the DEHP-treated rats showed the following: (1) higher organ coefficient of liver; (2) higher fasting blood glucose levels, higher fasting serum insulin and leptin levels, higher insulin resistance index homeostasis model assessment; (3) lower protein levels of Ob-R and IR in the liver and pancreas; (4) higher protein levels of JAK2 and STAT3 in the liver; and (5) higher protein and mRNA levels of SOCS3 in the liver and pancreas. Exposure to DEHP induced glucose metabolic disorder in the adolescent rats, and the mechanism is that DEHP may interfere with the JAK2/STAT3/SOCS3 pathway, regulated the sensitivity of the insulin receptor and leptin receptor.

Keywords: Di-(2-ethylhexyl)-phthalate; Glucose homeostasis; Insulin resistance; JAK2/STAT3/SOCS3; Leptin sensitivity.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diethylhexyl Phthalate / toxicity*
  • Glucose Metabolism Disorders / chemically induced*
  • Glucose Metabolism Disorders / metabolism
  • Insulin / blood
  • Insulin Resistance
  • Leptin / blood
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Plasticizers / toxicity*
  • Rats
  • Rats, Wistar
  • Receptor, Insulin / metabolism
  • Receptors, Leptin / metabolism


  • Blood Glucose
  • Insulin
  • Leptin
  • Plasticizers
  • Receptors, Leptin
  • Diethylhexyl Phthalate
  • Receptor, Insulin