Klf6 protects β-cells against insulin resistance-induced dedifferentiation.

Détails

Ressource 1Télécharger: Dumayne_et_al.__2020.pdf (2849.33 [Ko])
Etat: Public
Version: de l'auteur
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_48A38BFBF2D1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Klf6 protects β-cells against insulin resistance-induced dedifferentiation.
Périodique
Molecular metabolism
Auteur(s)
Dumayne C., Tarussio D., Sanchez-Archidona A.R., Picard A., Basco D., Berney X.P., Ibberson M., Thorens B.
ISSN
2212-8778 (Electronic)
ISSN-L
2212-8778
Statut éditorial
Publié
Date de publication
05/2020
Peer-reviewed
Oui
Volume
35
Pages
100958
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
In the pathogenesis of type 2 diabetes, development of insulin resistance triggers an increase in pancreatic β-cell insulin secretion capacity and β-cell number. Failure of this compensatory mechanism is caused by a dedifferentiation of β-cells, which leads to insufficient insulin secretion and diabetic hyperglycemia. The β-cell factors that normally protect against dedifferentiation remain poorly defined. Here, through a systems biology approach, we identify the transcription factor Klf6 as a regulator of β-cell adaptation to metabolic stress.
We used a β-cell specific Klf6 knockout mouse model to investigate whether Klf6 may be a potential regulator of β-cell adaptation to a metabolic stress.
We show that inactivation of Klf6 in β-cells blunts their proliferation induced by the insulin resistance of pregnancy, high-fat high-sucrose feeding, and insulin receptor antagonism. Transcriptomic analysis showed that Klf6 controls the expression of β-cell proliferation genes and, in the presence of insulin resistance, it prevents the down-expression of genes controlling mature β-cell identity and the induction of disallowed genes that impair insulin secretion. Its expression also limits the transdifferentiation of β-cells into α-cells.
Our study identifies a new transcription factor that protects β-cells against dedifferentiation, and which may be targeted to prevent diabetes development.
Mots-clé
Dedifferentiation, Insulin resistance, Transdifferentiation, Type 2 diabetes, β-Cell proliferation
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/04/2020 21:51
Dernière modification de la notice
06/10/2020 6:08
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