دورية أكاديمية
Oestrogen receptor β mediates the actions of bisphenol-A on ion channel expression in mouse pancreatic beta cells
| العنوان: | Oestrogen receptor β mediates the actions of bisphenol-A on ion channel expression in mouse pancreatic beta cells |
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| المؤلفون: | Martinez-Pinna, Juan, Marroquí, Laura, Hmadcha, Abdelkrim, Lopez-Beas, Javier, Soriano, Sergi, Villar-Pazos, Sabrina, Alonso Magdalena, Paloma, Dos Santos, Reinaldo S., Quesada, Iván, Martin, Franz, Soria, Bernat, Gustafsson, Jan-Ake, Nadal, Ángel |
| المساهمون: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología, Fisiología Neuroendocrina (FINE) |
| بيانات النشر: | Springer Berlin Heidelberg |
| سنة النشر: | 2019 |
| المجموعة: | RUA - Repositorio Institucional de la Universidad de Alicante |
| مصطلحات موضوعية: | Beta cell, Bisphenol-A, Diabetes, Endocrine-disrupting chemicals, K+ channels, Na+ channels, Oestrogen receptor β, Fisiología |
| الوصف: | Aims/hypothesis Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical that has been associated with type 2 diabetes development. Low doses of BPA modify pancreatic beta cell function and induce insulin resistance; some of these effects are mediated via activation of oestrogen receptors α (ERα) and β (ERβ). Here we investigated whether low doses of BPA regulate the expression and function of ion channel subunits involved in beta cell function. Methods Microarray gene profiling of isolated islets from vehicle- and BPA-treated (100 μg/kg per day for 4 days) mice was performed using Affymetrix GeneChip Mouse Genome 430.2 Array. Expression level analysis was performed using the normalisation method based on the processing algorithm ‘robust multi-array average’. Whole islets or dispersed islets from C57BL/6J or oestrogen receptor β (ERβ) knockout (Erβ−/−) mice were treated with vehicle or BPA (1 nmol/l) for 48 h. Whole-cell patch-clamp recordings were used to measure Na+ and K+ currents. mRNA expression was evaluated by quantitative real-time PCR. Results Microarray analysis showed that BPA modulated the expression of 1440 probe sets (1192 upregulated and 248 downregulated genes). Of these, more than 50 genes, including Scn9a, Kcnb2, Kcnma1 and Kcnip1, encoded important Na+ and K+ channel subunits. These findings were confirmed by quantitative RT-PCR in islets from C57BL/6J BPA-treated mice or whole islets treated ex vivo. Electrophysiological measurements showed a decrease in both Na+ and K+ currents in BPA-treated islets. The pharmacological profile indicated that BPA reduced currents mediated by voltage-activated K+ channels (Kv2.1/2.2 channels) and large-conductance Ca2+-activated K+ channels (KCa1.1 channels), which agrees with BPA’s effects on gene expression. Beta cells from ERβ−/− mice did not present BPA-induced changes, suggesting that ERβ mediates BPA’s effects in pancreatic islets. Finally, BPA increased burst duration, reduced the amplitude of the action potential and enlarged the action ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1007/s00125-019-4925-yTest; Diabetologia. 2019, 62(9): 1667-1680. doi:10.1007/s00125-019-4925-y; 0012-186X (Print); 1432-0428 (Online); http://hdl.handle.net/10045/95669Test |
| DOI: | 10.1007/s00125-019-4925-y |
| الإتاحة: | https://doi.org/10.1007/s00125-019-4925-yTest http://hdl.handle.net/10045/95669Test |
| حقوق: | © Springer-Verlag GmbH Germany, part of Springer Nature 2019 ; info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.FB9A52F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s00125-019-4925-y |
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