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Toxicol Lett. 2018 Jun 15;290:1-9. doi: 10.1016/j.toxlet.2018.03.004. Epub 2018 Mar 8.

Dibutyl phthalate exposure aggravates type 2 diabetes by disrupting the insulin-mediated PI3K/AKT signaling pathway.

Author information

1
Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei, China.
2
College of Basic Medical Sciences, Hubei University of Science and Technology, Xianning 437100, China.
3
Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei, China. Electronic address: chenmq@mail.ccnu.edu.cn.

Abstract

Epidemiological studies suggest a positive relationship between phthalate exposure and diabetes. However, little is known about the impact of dibutyl phthalate (DBP) exposure on the development of diabetes. To determine the role of DBP exposure on the development of type 2 diabetes, mice were orally exposed to DBP dosages of 0.5, 5, 50 mg/kg/day for 7 weeks, combined with a high fat diet and injections of a low dose of streptozotocin (STZ). The results showed that exposure to 50 mg/kg/day DBP alone induced a marked decrease in insulin secretion and glucose intolerance, but had no influence on insulin resistance. However, combined with a high fat diet and STZ treatment, DBP exposure markedly aggravated glucose intolerance, insulin tolerance and insulin resistance and induced lesions in the pancreas and kidney. Investigation of the role of DBP on the insulin signaling pathway, we found that DBP exposure could disrupt the PI3K expression and AKT phosphorylation, and decrease the level of GLUT-2 in the pancreas. Administering demethylasterriquinone B1, significantly increased the level of PI3K, AKT phosphorylation and GLUT-2 expression, effectively inhibiting the aggravation of diabetes. Our results suggested that DBP aggravated type 2 diabetes by disrupting the insulin signaling pathway and impairing insulin secretion.

KEYWORDS:

Dibutyl phthalate; Insulin resistance; Insulin secretion; Insulin signal transduction; Type 2 diabetes

PMID:
29526571
DOI:
10.1016/j.toxlet.2018.03.004
[Indexed for MEDLINE]

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