Antidiabetic Actions of an Estrogen Receptor beta Selective Agonist

Research output: Contribution to journalArticle

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.

Details

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

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)2015-2025
JournalDiabetes
Volume62
Issue number6
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes