Molecular phenotyping of multiple mouse strains under metabolic challenge uncovers a role for <i>Elovl2</i> in glucose-induced insulin secretion.

Détails

Ressource 1Télécharger: 1-s2.0-S221287781730008X-main.pdf (3033.87 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_0B44EFB14BA9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Molecular phenotyping of multiple mouse strains under metabolic challenge uncovers a role for <i>Elovl2</i> in glucose-induced insulin secretion.
Périodique
Molecular metabolism
Auteur(s)
Cruciani-Guglielmacci C., Bellini L., Denom J., Oshima M., Fernandez N., Normandie-Levi P., Berney X.P., Kassis N., Rouch C., Dairou J., Gorman T., Smith D.M., Marley A., Liechti R., Kuznetsov D., Wigger L., Burdet F., Lefèvre A.L., Wehrle I., Uphues I., Hildebrandt T., Rust W., Bernard C., Ktorza A., Rutter G.A., Scharfmann R., Xenarios I., Le Stunff H., Thorens B., Magnan C., Ibberson M.
ISSN
2212-8778 (Electronic)
ISSN-L
2212-8778
Statut éditorial
Publié
Date de publication
04/2017
Peer-reviewed
Oui
Volume
6
Numéro
4
Pages
340-351
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
In type 2 diabetes (T2D), pancreatic β cells become progressively dysfunctional, leading to a decline in insulin secretion over time. In this study, we aimed to identify key genes involved in pancreatic beta cell dysfunction by analyzing multiple mouse strains in parallel under metabolic stress.
Male mice from six commonly used non-diabetic mouse strains were fed a high fat or regular chow diet for three months. Pancreatic islets were extracted and phenotypic measurements were recorded at 2 days, 10 days, 30 days, and 90 days to assess diabetes progression. RNA-Seq was performed on islet tissue at each time-point and integrated with the phenotypic data in a network-based analysis.
A module of co-expressed genes was selected for further investigation as it showed the strongest correlation to insulin secretion and oral glucose tolerance phenotypes. One of the predicted network hub genes was <i>Elovl2</i> , encoding Elongase of very long chain fatty acids 2. <i>Elovl2</i> silencing decreased glucose-stimulated insulin secretion in mouse and human β cell lines.
Our results suggest a role for <i>Elovl2</i> in ensuring normal insulin secretory responses to glucose. Moreover, the large comprehensive dataset and integrative network-based approach provides a new resource to dissect the molecular etiology of β cell failure under metabolic stress.
Mots-clé
Acetyltransferases/genetics, Acetyltransferases/metabolism, Animals, Cell Line, Diabetes Mellitus, Type 2/genetics, Diabetes Mellitus, Type 2/metabolism, Gene Regulatory Networks, Glucose/metabolism, Humans, Insulin/metabolism, Insulin Secretion, Insulin-Secreting Cells/metabolism, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Phenotype, Beta cell dysfunction, Diabetes, Metabolic stress, Molecular phenotyping, Network analysis, Pancreas
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/04/2017 17:07
Dernière modification de la notice
20/08/2019 12:33
Données d'usage