Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans: role of estrogen receptor β

• Published in: PloS one 2012, Vol.7 (2), p.e31109
• Main Authors: Soriano, Sergi, Alonso-Magdalena, Paloma, García-Arévalo, Marta, Novials, Anna, Muhammed, Sarheed J, Salehi, Albert, Gustafsson, Jan-Ake, Quesada, Ivan, Nadal, Angel
• Format: Article
• Language: English
• Subjects: Air Pollutants, Occupational - toxicity; Animals; Benzhydryl Compounds; Biology; Bisphenol A; Calcium; Calcium (intracellular); Calcium Signaling; Calcium signalling; Channel gating; Clinical Medicine; Diabetes mellitus; Diabetes Mellitus, Type 2 - chemically induced; Endocrine disruptors; Endocrine Disruptors - toxicity; Endocrinology and Diabetes; Endokrinologi och diabetes; Estrogen Receptor beta - physiology; Estrogens; Estrogens, Non-Steroidal; Glucose; Gustafsson, Jan-Ake; Health risks; Humans; Insulin; Insulin - metabolism; Insulin resistance; Islets of Langerhans; Islets of Langerhans - drug effects; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine; Metabolic disorders; Mice; Mice, Knockout; Pancreas; Phenols; Phenols - administration & dosage; Phenols - toxicity; Polycarbonate; Polymers; Potassium; Potassium Channels; Risk factors; Rodents
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0031109

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.