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- Alonso-Magdalena, Paloma, et al.
(författare)
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Antidiabetic Actions of an Estrogen Receptor beta Selective Agonist
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:6, s. 2015-2025
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Tidskriftsartikel (refereegranskat)abstract
- The estrogen receptor beta (ER beta) is emerging as an important player in the physiology of the endocrine pancreas. We evaluated the role and antidiabetic actions of the ER beta selective agonist WAY200070 as an insulinotropic molecule. We demonstrate that WAY200070 enhances glucose-stimulated insulin secretion both in mouse and human islets. In vivo experiments showed that a single administration of WAY200070 leads to an increase in plasma insulin levels with a concomitant improved response to a glucose load. Two-week treatment administration increased glucose-induced insulin release and pancreatic beta-cell mass and improved glucose and insulin sensitivity. In addition, streptozotocin-nicotinamide-induced diabetic mice treated with WAY200070 exhibited a significant improvement in plasma insulin levels and glucose tolerance as well as a regeneration of pancreatic beta-cell mass. Studies performed in db/db mice demonstrated that this compound restored first-phase insulin secretion and enhanced pancreatic beta-cell mass. We conclude that ER beta agonists should be considered as new targets for the treatment of diabetes.
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| 2. |
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| 3. |
- Soriano, Sergi, et al.
(författare)
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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
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2
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Tidskriftsartikel (refereegranskat)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.
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