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Antidiabetic Actions of an Estrogen Receptor beta Selective Agonist

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Author

  • Paloma Alonso-Magdalena
  • Ana B. Ropero
  • Marta Garcia-Arevalo
  • Sergi Soriano
  • Ivan Quesada
  • Sarheed Jabar Muhammed
  • S Albert Salehi
  • Jan-Ake Gustafsson
  • Angel Nadal

Summary, in English

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.

Department/s

Publishing year

2013

Language

English

Pages

2015-2025

Publication/Series

Diabetes

Volume

62

Issue

6

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Islet cell physiology

ISBN/ISSN/Other

  • ISSN: 1939-327X