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Antidiabetic Actions of an Estrogen Receptor β Selective Agonist

The estrogen receptor β (ERβ) is emerging as an important player in the physiology of the endocrine pancreas. We evaluated the role and antidiabetic actions of the ERβ selective agonist WAY200070 as an insulinotropic molecule. We demonstrate that WAY200070 enhances glucose-stimulated insulin secreti...

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Autores principales: Alonso-Magdalena, Paloma, Ropero, Ana B., García-Arévalo, Marta, Soriano, Sergi, Quesada, Iván, Muhammed, Sarheed J., Salehi, Albert, Gustafsson, Jan-Ake, Nadal, Ángel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661616/
https://www.ncbi.nlm.nih.gov/pubmed/23349481
http://dx.doi.org/10.2337/db12-1562
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author Alonso-Magdalena, Paloma
Ropero, Ana B.
García-Arévalo, Marta
Soriano, Sergi
Quesada, Iván
Muhammed, Sarheed J.
Salehi, Albert
Gustafsson, Jan-Ake
Nadal, Ángel
author_facet Alonso-Magdalena, Paloma
Ropero, Ana B.
García-Arévalo, Marta
Soriano, Sergi
Quesada, Iván
Muhammed, Sarheed J.
Salehi, Albert
Gustafsson, Jan-Ake
Nadal, Ángel
author_sort Alonso-Magdalena, Paloma
collection PubMed
description The estrogen receptor β (ERβ) is emerging as an important player in the physiology of the endocrine pancreas. We evaluated the role and antidiabetic actions of the ERβ 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 β-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 β-cell mass. Studies performed in db/db mice demonstrated that this compound restored first-phase insulin secretion and enhanced pancreatic β-cell mass. We conclude that ERβ agonists should be considered as new targets for the treatment of diabetes.
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spelling pubmed-36616162014-06-01 Antidiabetic Actions of an Estrogen Receptor β Selective Agonist Alonso-Magdalena, Paloma Ropero, Ana B. García-Arévalo, Marta Soriano, Sergi Quesada, Iván Muhammed, Sarheed J. Salehi, Albert Gustafsson, Jan-Ake Nadal, Ángel Diabetes Original Research The estrogen receptor β (ERβ) is emerging as an important player in the physiology of the endocrine pancreas. We evaluated the role and antidiabetic actions of the ERβ 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 β-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 β-cell mass. Studies performed in db/db mice demonstrated that this compound restored first-phase insulin secretion and enhanced pancreatic β-cell mass. We conclude that ERβ agonists should be considered as new targets for the treatment of diabetes. American Diabetes Association 2013-06 2013-05-17 /pmc/articles/PMC3661616/ /pubmed/23349481 http://dx.doi.org/10.2337/db12-1562 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Alonso-Magdalena, Paloma
Ropero, Ana B.
García-Arévalo, Marta
Soriano, Sergi
Quesada, Iván
Muhammed, Sarheed J.
Salehi, Albert
Gustafsson, Jan-Ake
Nadal, Ángel
Antidiabetic Actions of an Estrogen Receptor β Selective Agonist
title Antidiabetic Actions of an Estrogen Receptor β Selective Agonist
title_full Antidiabetic Actions of an Estrogen Receptor β Selective Agonist
title_fullStr Antidiabetic Actions of an Estrogen Receptor β Selective Agonist
title_full_unstemmed Antidiabetic Actions of an Estrogen Receptor β Selective Agonist
title_short Antidiabetic Actions of an Estrogen Receptor β Selective Agonist
title_sort antidiabetic actions of an estrogen receptor β selective agonist
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661616/
https://www.ncbi.nlm.nih.gov/pubmed/23349481
http://dx.doi.org/10.2337/db12-1562
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