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Rapid Insulinotropic Action of Low Doses of Bisphenol-A on Mouse and Human Islets of Langerhans: Role of Estrogen Receptor beta

Soriano, Sergi ; Alonso-Magdalena, Paloma ; Garcia-Arevalo, Marta ; Novials, Anna ; Jabar Muhammed, Sarheed LU ; Salehi, S Albert LU orcid ; Gustafsson, Jan-Ake ; Quesada, Ivan and Nadal, Angel (2012) In PLoS ONE 7(2).
Abstract
Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic beta-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ER beta(-/-) mice to study whether ER beta is involved in the rapid regulation of K-ATP channel activity, calcium signals and insulin release elicited by environmentally relevant doses of BPA (1 nM). We also investigated these effects of BPA in beta-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased K-ATP channel activity, increased glucose-induced [Ca2+](i) signals and insulin release in beta-cells from WT mice but not in cells from ER beta(-/-) mice. The... (More)
Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic beta-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ER beta(-/-) mice to study whether ER beta is involved in the rapid regulation of K-ATP channel activity, calcium signals and insulin release elicited by environmentally relevant doses of BPA (1 nM). We also investigated these effects of BPA in beta-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased K-ATP channel activity, increased glucose-induced [Ca2+](i) signals and insulin release in beta-cells from WT mice but not in cells from ER beta(-/-) mice. The rapid reduction in the K-ATP channel activity and the insulinotropic effect was seen in human cells and islets. BPA actions were stronger in human islets compared to mouse islets when the same BPA concentration was used. Our findings suggest that BPA behaves as a strong estrogen via nuclear ER beta and indicate that results obtained with BPA in mouse beta-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
7
issue
2
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000302730100042
  • scopus:84856762350
  • pmid:22347437
ISSN
1932-6203
DOI
10.1371/journal.pone.0031109
language
English
LU publication?
yes
id
0c2a938b-009e-462b-ac03-54ed471da1dc (old id 2571418)
date added to LUP
2016-04-01 13:07:36
date last changed
2022-04-21 19:51:06
@article{0c2a938b-009e-462b-ac03-54ed471da1dc,
  abstract     = {{Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic beta-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ER beta(-/-) mice to study whether ER beta is involved in the rapid regulation of K-ATP channel activity, calcium signals and insulin release elicited by environmentally relevant doses of BPA (1 nM). We also investigated these effects of BPA in beta-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased K-ATP channel activity, increased glucose-induced [Ca2+](i) signals and insulin release in beta-cells from WT mice but not in cells from ER beta(-/-) mice. The rapid reduction in the K-ATP channel activity and the insulinotropic effect was seen in human cells and islets. BPA actions were stronger in human islets compared to mouse islets when the same BPA concentration was used. Our findings suggest that BPA behaves as a strong estrogen via nuclear ER beta and indicate that results obtained with BPA in mouse beta-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans.}},
  author       = {{Soriano, Sergi and Alonso-Magdalena, Paloma and Garcia-Arevalo, Marta and Novials, Anna and Jabar Muhammed, Sarheed and Salehi, S Albert and Gustafsson, Jan-Ake and Quesada, Ivan and Nadal, Angel}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Rapid Insulinotropic Action of Low Doses of Bisphenol-A on Mouse and Human Islets of Langerhans: Role of Estrogen Receptor beta}},
  url          = {{https://lup.lub.lu.se/search/files/3174496/3051607.pdf}},
  doi          = {{10.1371/journal.pone.0031109}},
  volume       = {{7}},
  year         = {{2012}},
}