title: Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans: role of estrogen receptor β.
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 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.
authors.affiliation: Instituto Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Universidad Miguel Hernández de Elche, Elche, Alicante, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Soriano
authors.forename: Paloma
authors.initials: P
authors.lastname: Alonso-Magdalena
authors.forename: Marta
authors.initials: M
authors.lastname: García-Arévalo
authors.forename: Anna
authors.initials: A
authors.lastname: Novials
authors.forename: Sarheed J
authors.initials: SJ
authors.lastname: Muhammed
authors.forename: Albert
authors.initials: A
authors.lastname: Salehi
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Ivan
authors.initials: I
authors.lastname: Quesada
authors.forename: Angel
authors.initials: A
authors.lastname: Nadal
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity; D000818:Animals; D001559:Benzhydryl Compounds; D020013:Calcium Signaling; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced; D052244:Endocrine Disruptors / Q000633:toxicity; D047629:Estrogen Receptor beta / Q000502:physiology*; D004968:Estrogens, Non-Steroidal; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D015221:Potassium Channels; D000098826:Bisphenol A Compounds
chemical_list: D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal; D007328:Insulin; D010636:Phenols; D015221:Potassium Channels; C006780:bisphenol A; D000098826:Bisphenol A Compounds