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Series GSE78183 Query DataSets for GSE78183
Status Public on Apr 28, 2017
Title Molecular phenotyping of multiple mouse strains under metabolic challenge uncovers Elovl2 as a novel regulator of glucose-induced insulin secretion
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Defective insulin secretion by pancreatic β cells underlies the development of type 2 diabetes (T2D). High fat diet-fed mice are commonly used to study diabetes progression, but studies are usually limited to a single strain, such as C57Bl/6J. Here, we use a systems biology approach to integrate large phenotypic and islet transcriptomic data sets from six commonly used strains fed a high fat or regular chow diet to identify genes associated with glucose intolerance and insulin secretion. One of these genes is Elovl2, encoding very long chain fatty acid elongase 2. ELOVL2 is responsible for the synthesis of the polyunsaturated fatty acid, docosahexaenoic acid (DHA). We show that DHA rescues glucose-induced insulin secretion and cytosolic Ca2+ influx impaired by glucolipotoxicity, and that Elovl2 over-expression is able to restore the insulin secretion defect under these conditions. We propose that increased endogenous DHA levels resulting from Elovl2 up-regulation counteracts the insulin secretion defect associated with glucolipotoxicity. Although we focus our experimental validation on Elovl2, the comprehensive data set and integrative network model we used to identify this candidate gene represents an important novel resource to dissect the molecular aetiology of β cell failure in murine models.
 
Overall design 6 mouse strains, 4 time points, 2 diets
 
Contributor(s) Bellini L, Cruciani-Guglielmacci C, Denom J, Fernandez N, Normandie-Levi P, Kassis N, Gorman T, Smith DM, Marley A, Liechti R, Wigger L, Burdet F, Lefèvre A, Werlhe I, Uphues I, Hildebrandt T, Rust W, Bernard C, Ktorza A, Xenarios I, Marmugi A, Leclerc I, Rutter GA, Le Stunff H, Magnan C, Thorens B, Ibberson M
Citation(s) 28377873
Submission date Feb 22, 2016
Last update date May 15, 2019
Contact name Mark Ibberson
Organization name SIB Swiss Institute of Bioinformatics
Department Vital-IT
Street address Genopode building
City Lausanne
ZIP/Postal code CH-1015
Country Switzerland
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (338)
GSM2068872 Mouse: 1HF135; Strain: C57Bl/6J; Diet: High Fat, High Sugar (HFHS); Time-point: D02
GSM2068873 Mouse: 1HF136; Strain: C57Bl/6J; Diet: High Fat, High Sugar (HFHS); Time-point: D02
GSM2068874 Mouse: 1HF137; Strain: C57Bl/6J; Diet: High Fat, High Sugar (HFHS); Time-point: D02
Relations
BioProject PRJNA312845
SRA SRP070673

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE78183_normalized_counts_338samples.txt.gz 37.2 Mb (ftp)(http) TXT
GSE78183_raw_counts_338samples.txt.gz 9.0 Mb (ftp)(http) TXT
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