Islet Gene View-a tool to facilitate islet research.

Details

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_1B289C537F38
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Islet Gene View-a tool to facilitate islet research.
Journal
Life science alliance
Author(s)
Asplund O., Storm P., Chandra V., Hatem G., Ottosson-Laakso E., Mansour-Aly D., Krus U., Ibrahim H., Ahlqvist E., Tuomi T., Renström E., Korsgren O., Wierup N., Ibberson M., Solimena M., Marchetti P., Wollheim C., Artner I., Mulder H., Hansson O., Otonkoski T., Groop L., Prasad R.B.
ISSN
2575-1077 (Electronic)
ISSN-L
2575-1077
Publication state
Published
Issued date
10/08/2022
Peer-reviewed
Oui
Volume
5
Number
12
Pages
e202201376
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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 islet-expressed 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 (<i>GCG</i>, 56%), amylin (<i>IAPP</i>, 52%), insulin (<i>INS</i>, 44%), and somatostatin (<i>SST</i>, 24%). Inhibition of two DEGs, <i>UNC5D</i> and <i>SERPINE2</i>, 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.
Keywords
Diabetes Mellitus, Type 2/genetics, Glucagon/genetics, Glucagon/metabolism, Humans, Insulin/genetics, Insulin/metabolism, Islets of Langerhans/metabolism, Serpin E2/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
22/08/2022 14:15
Last modification date
23/01/2024 8:21
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