Bisphenol-S and Bisphenol-F alter mouse pancreatic β-cell ion channel expression and activity and insulin release through an estrogen receptor ERβ mediated pathway

Chemosphere. 2021 Feb;265:129051. doi: 10.1016/j.chemosphere.2020.129051. Epub 2020 Nov 20.


Bisphenol-S (BPS) and Bisphenol-F (BPF) are current Bisphenol-A (BPA) substitutes. Here we used pancreatic β-cells from wild type (WT) and estrogen receptor β (ERβ) knockout (BERKO) mice to investigate the effects of BPS and BPF on insulin secretion, and the expression and activity of ion channels involved in β-cell function. BPS or BPF rapidly increased insulin release and diminished ATP-sensitive K+ (KATP) channel activity. Similarly, 48 h treatment with BPS or BPF enhanced insulin release and decreased the expression of several ion channel subunits in β-cells from WT mice, yet no effects were observed in cells from BERKO mice. PaPE-1, a ligand designed to preferentially trigger extranuclear-initiated ER pathways, mimicked the effects of bisphenols, suggesting the involvement of extranuclear-initiated ERβ pathways. Molecular dynamics simulations indicated differences in ERβ ligand-binding domain dimer stabilization and solvation free energy among different bisphenols and PaPE-1. Our data suggest a mode of action involving ERβ whose activation alters three key cellular events in β-cell, namely ion channel expression and activity, and insulin release. These results may help to improve the hazard identification of bisphenols.

Keywords: Bisphenol; Endocrine disrupting chemicals; Estrogen receptors; Islet of langerhans; Molecular dynamics simulation.

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity
  • Estrogen Receptor beta* / genetics
  • Estrogen Receptor beta* / metabolism
  • Insulin
  • Ion Channels
  • Mice
  • Phenols
  • Receptors, Estrogen* / genetics


  • Benzhydryl Compounds
  • Estrogen Receptor beta
  • Insulin
  • Ion Channels
  • Phenols
  • Receptors, Estrogen
  • bisphenol F