| Literature DB >> 26015547 |
Yixing Yuchi1, Ying Cai1, Bart Legein1, Sofie De Groef1, Gunter Leuckx1, Violette Coppens1, Eva Van Overmeire2, Willem Staels3, Nico De Leu4, Geert Martens1, Jo A Van Ginderachter2, Harry Heimberg5, Mark Van de Casteele1.
Abstract
Identifying pathways for β-cell generation is essential for cell therapy in diabetes. We investigated the potential of 17β-estradiol (E2) and estrogen receptor (ER) signaling for stimulating β-cell generation during embryonic development and in the severely injured adult pancreas. E2 concentration, ER activity, and number of ERα transcripts were enhanced in the pancreas injured by partial duct ligation (PDL) along with nuclear localization of ERα in β-cells. PDL-induced proliferation of β-cells depended on aromatase activity. The activation of Neurogenin3 (Ngn3) gene expression and β-cell growth in PDL pancreas were impaired when ERα was turned off chemically or genetically (ERα(-/-)), whereas in situ delivery of E2 promoted β-cell formation. In the embryonic pancreas, β-cell replication, number of Ngn3(+) progenitor cells, and expression of key transcription factors of the endocrine lineage were decreased by ERα inactivation. The current study reveals that E2 and ERα signaling can drive β-cell replication and formation in mouse pancreas.Entities:
Mesh：
Substances：
Year: 2015 PMID： 26015547 DOI： 10.2337/db14-1798
Source DB: PubMed Journal: Diabetes ISSN： 0012-1797 Impact factor: 9.461