Islet Gene View-a tool to facilitate islet research

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Olof Asplund - , Lund University (Author)
  • Petter Storm - , Lund University (Author)
  • Vikash Chandra - , University of Helsinki (Author)
  • Gad Hatem - , Lund University (Author)
  • Emilia Ottosson-Laakso - , Lund University (Author)
  • Dina Mansour-Aly - , Lund University (Author)
  • Ulrika Krus - , Lund University (Author)
  • Hazem Ibrahim - , University of Helsinki (Author)
  • Emma Ahlqvist - , Lund University (Author)
  • Tiinamaija Tuomi - , Lund University, University of Helsinki (Author)
  • Erik Renstrom - , Lund University (Author)
  • Olle Korsgren - , Uppsala University, University of Gothenburg (Author)
  • Nils Wierup - , Lund University (Author)
  • Mark Ibberson - , Swiss Institute of Bioinformatics (Author)
  • Michele Solimena - , Molecular Diabetology, German Center for Diabetes Research (DZD e.V.), Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Piero Marchetti - , University of Pisa (Author)
  • Claes Wollheim - , Lund University, University of Geneva (Author)
  • Isabella Artner - , Lund University (Author)
  • Hindrik Mulder - , Lund University (Author)
  • Ola Hansson - , Lund University, University of Helsinki (Author)
  • Timo Otonkoski - , University of Helsinki (Author)
  • Leif Groop - , Lund University, University of Helsinki (Author)
  • Rashmi B. Prasad - , Lund University, University of Helsinki (Author)

Abstract

Characterization of gene expression in pancreatic islets and its alteration in type 2 diabetes (T2D) are vital in understanding islet function and T2D pathogenesis. We leveraged RNA sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. Expression data were related to islet phenotypes, diabetes status, other isletexpressed genes, islet hormone-encoding genes and for expression in insulin target tissues. The IGW web application produces output graphs for a particular gene of interest. In IGW, 284 differentially expressed genes (DEGs) were identified in T2D donor islets compared with controls. Forty percent of DEGs showed cell-type enrichment and a large proportion significantly co-expressed with islet hormone-encoding genes; glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%), and somatostatin (SST, 24%). Inhibition of two DEGs, UNC5D and SERPINE2, impaired glucose-stimulated insulin secretion and impacted cell survival in a human β-cell model. The exploratory use of IGW could help designing more comprehensive functional follow-up studies and serve to identify therapeutic targets in T2D.

Details

Original languageEnglish
Article numbere202201376
JournalLife science alliance
Volume5
Issue number12
Publication statusPublished - Dec 2022
Peer-reviewedYes

External IDs

PubMed 35948367