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Series GSE159984 Query DataSets for GSE159984
Status Public on Oct 24, 2020
Title Persistent or Transient Human β-cell Dysfunction Induced by Metabolic Stress Associated with Specific Signatures and Shared Gene Expression of Type 2 Diabetes
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Pancreatic β-cell failure is key to type 2 diabetes (T2D) onset and progression. We assessed whether human β-cell dysfunction induced by metabolic stress is reversible, evaluated the molecular pathways underlying persistent or transient damage, and explored the relationships with T2D islet traits. Twenty-six human islet preparations were exposed to several lipo- and/or glucotoxicity conditions, some of which impaired insulin release depending on stressor type, concentration and combination. Interestingly, reversal of dysfunction occurred after washout for some, but not for all, of the lipoglucotoxic insults. Islet transcriptomes assessed by RNA-sequencing and eQTL analysis identified specific pathways underlying β-cell failure and recovery. Notably, comparison of a large number of human T2D islet transcriptomes with those of persistent or reversible β-cell lipoglucotoxicity showed shared gene expression signatures. The identification of mechanisms associated with human β-cell dysfunction and recovery, and their overlap with T2D islet traits provide novel insights into T2D pathogenesis and should foster the development of improved β-cell targeted therapeutic strategies.
Overall design Human islets from 26 non-diabetic donors were exposed to 0.5 mM palmitate (P), 22.2 mM glucose (G), P+G, 1 mM palmitate+oleate, (1:2 ratio, P+O) and P+O+G for 2 days (n=2-5/condition) (D4), followed by 4 days of washout (D8). Glucose-stimulated insulin secretion and RNA-seq (llumina HiSeq 2500 instrument) transcriptomes of P, G, P+G conditions were assessed. The reads were assigned to reference and quantified by Salmon v.0.13.2. We run the bioconductor R package Deseq2 to generate a paired differential analysis between metabolic stress condition vs matched control. Data were compared to RNA-seq of islets from 29 type 2 diabetic and 59 non-diabetic donors by rank-rank hypergeometric overlap (RRHO)
Contributor(s) Marchetti P, Piron A, Suleiman M, Colli M, Yi X, Khamis A, Rutter G, Bugliani M, Giusti L, Ronci M, Ibberson M, Turatsinze J, Boggi U, De Simone P, De Tata V, De Luca C, Campani D, Lopes M, Nasteska D, Shulte A, Solimena M, Hecht P, Rady B, Bakaj I, Pocai A, Norquay L, Thorens B, Canouil M, Frogues P, Eizirik D, Cnop M, Marselli L
Citation(s) 33264613
Submission date Oct 23, 2020
Last update date Feb 23, 2021
Contact name Anthony Piron
Organization name Université Libre de Bruxelles
Department Faculté de Medecine
Lab Search Results Web result with site links ULB Center for Diabetes Research
Street address Route de Lennik 808 CP618
City Bruxelles
ZIP/Postal code 1070
Country Belgium
Platforms (2)
GPL9115 Illumina Genome Analyzer II (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (131)
GSM4852033 Human islets 1 from type 2 diabetic donor
GSM4852034 Human islets 2 from type 2 diabetic donor
GSM4852035 Human islets 3 from type 2 diabetic donor
BioProject PRJNA671458
SRA SRP288373

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MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource 1.7 Kb (ftp)(http) TAB
GSE159984_D4GD4C_RPKM.csv.gz 3.1 Kb (ftp)(http) CSV 19.7 Kb (ftp)(http) TAB
GSE159984_D4PD4C_RPKM.csv.gz 44.4 Kb (ftp)(http) CSV 46.2 Kb (ftp)(http) TAB
GSE159984_D4PGD4C_RPKM.csv.gz 76.0 Kb (ftp)(http) CSV 13.8 Kb (ftp)(http) TAB
GSE159984_D8GD4G_RPKM.csv.gz 19.5 Kb (ftp)(http) CSV 23.3 Kb (ftp)(http) TAB
GSE159984_D8PD4P_RPKM.csv.gz 47.6 Kb (ftp)(http) CSV 11.2 Kb (ftp)(http) TAB
GSE159984_D8PGD4PG_RPKM.csv.gz 17.0 Kb (ftp)(http) CSV
GSE159984_de-d4g.tsv.gz 2.2 Mb (ftp)(http) TSV
GSE159984_de-d4p.tsv.gz 1.9 Mb (ftp)(http) TSV
GSE159984_de-d4pg.tsv.gz 2.0 Mb (ftp)(http) TSV
GSE159984_de-d8g-d4g.tsv.gz 2.3 Mb (ftp)(http) TSV
GSE159984_de-d8g.tsv.gz 2.1 Mb (ftp)(http) TSV
GSE159984_de-d8p-d4p.tsv.gz 1.9 Mb (ftp)(http) TSV
GSE159984_de-d8p.tsv.gz 1.9 Mb (ftp)(http) TSV
GSE159984_de-d8pg-d4pg.tsv.gz 1.9 Mb (ftp)(http) TSV
GSE159984_de-d8pg.tsv.gz 1.9 Mb (ftp)(http) TSV
GSE159984_de-t2d.tsv.gz 1.8 Mb (ftp)(http) TSV
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