Antidiabetic Actions of an Estrogen Receptor beta Selective Agonist

作者：Alonso Magdalena Paloma^*; Ropero Ana B; Garcia Arevalo Marta; Soriano Sergi; Quesada Ivan; Muhammed Sarheed J; Salehi Albert; Gustafsson Jan Ake; Nadal Angel

来源：Diabetes, 2013, 62(6): 2015-2025.

DOI：10.2337/db12-1562

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.

• 出版日期2013-6