Maintenance of hepatic nuclear factor 6 in postnatal islets impairs terminal differentiation and function of beta-cells.

Détails

ID Serval
serval:BIB_17F1B0E4FB6D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Maintenance of hepatic nuclear factor 6 in postnatal islets impairs terminal differentiation and function of beta-cells.
Périodique
Diabetes
Auteur(s)
Tweedie E., Artner I., Crawford L., Poffenberger G., Thorens B., Stein R., Powers A.C., Gannon M.
ISSN
0012-1797
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
55
Numéro
12
Pages
3264-3270
Langue
anglais
Résumé
The Onecut homeodomain transcription factor hepatic nuclear factor 6 (Hnf6) is necessary for proper development of islet beta-cells. Hnf6 is initially expressed throughout the pancreatic epithelium but is downregulated in endocrine cells at late gestation and is not expressed in postnatal islets. Transgenic mice in which Hnf6 expression is maintained in postnatal islets (pdx1(PB)Hnf6) show overt diabetes and impaired glucose-stimulated insulin secretion (GSIS) at weaning. We now define the mechanism whereby maintenance of Hnf6 expression postnatally leads to beta-cell dysfunction. We provide evidence that continued expression of Hnf6 impairs GSIS by altering insulin granule biosynthesis, resulting in a reduced response to secretagogues. Sustained expression of Hnf6 also results in downregulation of the beta-cell-specific transcription factor MafA and a decrease in total pancreatic insulin. These results suggest that downregulation of Hnf6 expression in beta-cells during development is essential to achieve a mature, glucose-responsive beta-cell.
Mots-clé
Animals, Cell Differentiation, Gene Expression Regulation, Developmental, Glucose, Glucose Transporter Type 2, Hepatocyte Nuclear Factor 6, Homeodomain Proteins, Homeostasis, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Mice, Mice, Transgenic, Trans-Activators
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:41
Dernière modification de la notice
20/08/2019 12:48
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