Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Effect of Bisphenol A on Insulin-Mediated Glucose Metabolism In Vivo and In Vitro

  • Ko, Jeong-Hyeon (Department of Pharmacology, Medicinal Toxicology Research Center, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project) ;
  • Kang, Ju-Hee (Department of Pharmacology, Medicinal Toxicology Research Center, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project) ;
  • Park, Chang-Shin (Department of Pharmacology, Medicinal Toxicology Research Center, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project) ;
  • Shin, Dong-Wun (Department of Emergency Medicine, Inje University Ilsan Paik Hospital) ;
  • Kim, Ji-Hye (Department of Emergency Medicine, Inha University College of Medicine) ;
  • Kim, Hoon (Department of Emergency Medicine, Inha University College of Medicine) ;
  • Han, Seung-Baik (Department of Emergency Medicine, Inha University College of Medicine)
  • Published : 2008.12.31
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Abstract

Bisphenol A (BPA), an environmental endocrine disrupter, enters the human body continuously in food and drink. Young children are likely to be more vulnerable than adults to chemical exposure due to the immaturities of their organ systems, rapid physical development, and higher ventilation, metabolic rates, and activity levels. The direct effect of BPA on peripheral tissue might also be of importance to the development of insulin resistance. However, the influence that BPA has on insulin signaling molecules in skeletal muscle has not been previously investigated. In this study, we examined the effect of BPA on fasting blood glucose (FBG) in post-weaned Wistar rats and on insulin signaling proteins in C2C12 skeletal muscle cells. Subsequently, we investigated the effects of BPA on insulin-mediated Akt phosphorylation in C2C12 myotubes. In rats, BPA treatment (0.1-1,000 ng/mL for 24 hours) resulted in the increase of FBG and plasma insulin levels, and reduced insulin-mediated Akt phosphorylation. Furthermore, the mRNA expression of insulin receptor (IR) was decreased after 24 hours of BPA treatment in C2C12 cells in a dose-dependent manner, whereas the mRNA levels of other insulin signaling proteins, including insulin receptor substrate-1 (IRS-1) and 5'-AMP-dependent protein kinase (AMPK), were unaffected. Treatment with BPA increased GLUT4 expression and protein tyrosine phosphatase 1B (PTP1B) activity in C2C12 myotubes, but not in protein levels. We conclude that exposure to BPA can induce insulin resistance by decreasing IR gene expression, which is followed by a decrease in insulin- mediated Akt activation and increased PTP1B activity.

Keywords

References

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