microRNA-205-5p is a modulator of insulin sensitivity that inhibits FOXO function.

Détails

Ressource 1Télécharger: 1-s2.0-S2212877818307543-main.pdf (2315.07 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_12DBBA598245
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
microRNA-205-5p is a modulator of insulin sensitivity that inhibits FOXO function.
Périodique
Molecular Metabolism
Auteur(s)
Langlet F., Tarbier M., Haeusler R.A., Camastra S., Ferrannini E., Friedländer M.R., Accili D.
ISSN
2212-8778 (Electronic)
ISSN-L
2212-8778
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
17
Pages
49-60
Langue
anglais
Résumé
Hepatic insulin resistance is a hallmark of type 2 diabetes and obesity. Insulin receptor signaling through AKT and FOXO has important metabolic effects that have traditionally been ascribed to regulation of gene expression. However, whether all the metabolic effects of FOXO arise from its regulation of protein-encoding mRNAs is unknown.
To address this question, we obtained expression profiles of FOXO-regulated murine hepatic microRNAs (miRNAs) during fasting and refeeding using mice lacking Foxo1, 3a, and 4 in liver (L-Foxo1,3a, 4).
Out of 439 miRNA analyzed, 175 were differentially expressed in Foxo knockouts. Their functions were associated with insulin, Wnt, Mapk signaling, and aging. Among them, we report a striking increase of miR-205-5p expression in L-Foxo1,3a,4 knockouts, as well as in obese mice. We show that miR-205-5p gain-of-function increases AKT phosphorylation and decreases SHIP2 in primary hepatocytes, resulting in FOXO inhibition. This results in decreased hepatocyte glucose production. Consistent with these observations, miR-205-5p gain-of-function in mice lowered glucose levels and improved pyruvate tolerance.
These findings reveal a homeostatic miRNA loop regulating insulin signaling, with potential implications for in vivo glucose metabolism.
Mots-clé
Genetics, Glucose production, Insulin resistance, Liver metabolism, Transcriptional regulation, Type 2 diabetes
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/11/2018 8:58
Dernière modification de la notice
20/08/2019 12:41
Données d'usage