Bisphenol-S and Bisphenol-F alter mouse pancreatic beta-cell ion channel expression and activity and insulin release through an estrogen receptor ER beta mediated pathway
Por:
Marroqui, L, Martinez-Pinna, J, Castellano-Munoz, M, dos Santos, R, Medina-Gali, R, Soriano, S, Quesada, I, Gustafsson, J, Encinar, J and Nadal, A
Publicada:
1 feb 2021
Resumen:
Bisphenol-S (BPS) and Bisphenol-F (BPF) are current Bisphenol-A (BPA) substitutes. Here we used pancreatic beta-cells from wild type (WT) and estrogen receptor beta (ER beta) knockout (BERKO) mice to investigate the effects of BPS and BPF on insulin secretion, and the expression and activity of ion channels involved in beta-cell function. BPS or BPF rapidly increased insulin release and diminished ATP-sensitive K+ (K-ATP) channel activity. Similarly, 48 h treatment with BPS or BPF enhanced insulin release and decreased the expression of several ion channel subunits in beta-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 ER beta pathways. Molecular dynamics simulations indicated differences in ER beta ligand-binding domain dimer stabilization and solvation free energy among different bisphenols and PaPE-1. Our data suggest a mode of action involving ER beta whose activation alters three key cellular events in beta-cell, namely ion channel expression and activity, and insulin release. These results may help to improve the hazard identification of bisphenols. (C) 2020 Elsevier Ltd. All rights reserved.
Filiaciones:
Marroqui, L:
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Elche, Spain
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
Martinez-Pinna, J:
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Elche, Spain
Univ Alicante, Dept Fisiol Genet & Microbiol, Alicante, Spain
Castellano-Munoz, M:
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
dos Santos, R:
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Elche, Spain
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
Medina-Gali, R:
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Elche, Spain
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
Soriano, S:
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Elche, Spain
Univ Alicante, Dept Fisiol Genet & Microbiol, Alicante, Spain
Quesada, I:
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Elche, Spain
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
Gustafsson, J:
Univ Houston, Dept Cell Biol & Biochem, Ctr Nucl Receptors & Cell Signaling, Houston, TX USA
Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden
:
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Elche, Spain
Nadal, A:
Univ Miguel Hernandez, Inst Invest Desarrollo & Innovac Biotecnol Sanita, Elche, Spain
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
Green Published, Green Submitted
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