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Antidiabetic Actions of an Estrogen Receptor beta Selective Agonist

Alonso-Magdalena, Paloma ; Ropero, Ana B. ; Garcia-Arevalo, Marta ; Soriano, Sergi ; Quesada, Ivan ; Jabar Muhammed, Sarheed LU ; Salehi, S Albert LU orcid ; Gustafsson, Jan-Ake and Nadal, Angel (2013) In Diabetes 62(6). p.2015-2025
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... (More)
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. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
62
issue
6
pages
2015 - 2025
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000319845000031
  • scopus:84878237251
  • pmid:23349481
ISSN
1939-327X
DOI
10.2337/db12-1562
language
English
LU publication?
yes
id
fe2f4a6a-1e02-4741-a890-89d9989a98c1 (old id 3927066)
date added to LUP
2016-04-01 13:28:11
date last changed
2022-01-27 19:25:17
@article{fe2f4a6a-1e02-4741-a890-89d9989a98c1,
  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.}},
  author       = {{Alonso-Magdalena, Paloma and Ropero, Ana B. and Garcia-Arevalo, Marta and Soriano, Sergi and Quesada, Ivan and Jabar Muhammed, Sarheed and Salehi, S Albert and Gustafsson, Jan-Ake and Nadal, Angel}},
  issn         = {{1939-327X}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{2015--2025}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Antidiabetic Actions of an Estrogen Receptor beta Selective Agonist}},
  url          = {{http://dx.doi.org/10.2337/db12-1562}},
  doi          = {{10.2337/db12-1562}},
  volume       = {{62}},
  year         = {{2013}},
}