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  • 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.

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 (2020-12-01)
Laura Marroqui, Juan Martinez-Pinna, Manuel Castellano-Muñoz, Reinaldo S Dos Santos, Regla M Medina-Gali, Sergi Soriano, Ivan Quesada, Jan-Ake Gustafsson, José A Encinar, Angel Nadal
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
PaPE-1, ≥98% (HPLC)
Supelco
Bisphenol F, analytical standard
Sigma-Aldrich
4,4′-Sulfonyldiphenol, 98%
Sigma-Aldrich
Collagenase from Clostridium histolyticum, Type V, ≥1 FALGPA units/mg solid, >125 CDU/mg solid