TY - JOUR
T1 - Rapid insulinotropic action of low doses of Bisphenol-A on mouse and human islets of Langerhans
T2 - Role of estrogen receptor β
AU - Soriano, Sergi
AU - Alonso-Magdalena, Paloma
AU - García-Arévalo, Marta
AU - Novials, Anna
AU - Muhammed, Sarheed J.
AU - Salehi, Albert
AU - Gustafsson, Jan Ake
AU - Quesada, Ivan
AU - Nadal, Angel
PY - 2012/2/8
Y1 - 2012/2/8
N2 - Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic β-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ERβ-/- mice to study whether ERβ 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 β-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased K ATP channel activity, increased glucose-induced [Ca 2+] i signals and insulin release in β-cells from WT mice but not in cells from ERβ-/- 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 ERβ and indicate that results obtained with BPA in mouse β-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans.
AB - Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic β-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ERβ-/- mice to study whether ERβ 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 β-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased K ATP channel activity, increased glucose-induced [Ca 2+] i signals and insulin release in β-cells from WT mice but not in cells from ERβ-/- 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 ERβ and indicate that results obtained with BPA in mouse β-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans.
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U2 - 10.1371/journal.pone.0031109
DO - 10.1371/journal.pone.0031109
M3 - Article
C2 - 22347437
AN - SCOPUS:84856762350
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e31109
ER -