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Diabetes. 2015 Sep;64(9):3218-28. doi: 10.2337/db14-1798. Epub 2015 May 26.

Estrogen Receptor α Regulates β-Cell Formation During Pancreas Development and Following Injury.

Author information

1
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
2
Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
3
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium Department of Pediatrics, Division of Pediatric Endocrinology, Ghent University Hospital, and Department of Pediatrics and Medical Genetics, Ghent University, Ghent, Belgium.
4
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
5
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium harry.heimberg@vub.ac.be.

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.

PMID:
26015547
DOI:
10.2337/db14-1798
[Indexed for MEDLINE]
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