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

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Serval ID
serval:BIB_0B44EFB14BA9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Molecular phenotyping of multiple mouse strains under metabolic challenge uncovers a role for <i>Elovl2</i> in glucose-induced insulin secretion.
Journal
Molecular metabolism
Author(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
Publication state
Published
Issued date
04/2017
Peer-reviewed
Oui
Volume
6
Number
4
Pages
340-351
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Create date
11/04/2017 18:07
Last modification date
20/08/2019 13:33
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