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Islet Gene View—a tool to facilitate islet research

Authors: Olof Asplund; Petter Storm; Vikash Chandra; Gad Hatem; Emilia Ottosson-Laakso; Dina Mansour-Aly; Ulrika Krus; +16 Authors

Islet Gene View—a tool to facilitate islet research

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 ( 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.

Countries
Sweden, Finland, Germany, Italy
Keywords

EXPRESSION, Endocrinology and Diabetes, VARIANTS, Glucagon, INSULIN-SECRETION, Resources, Biomedicine, Islets of Langerhans, Diabetes Mellitus, Type 2, HUMAN PANCREATIC-ISLETS, Endokrinologi och diabetes, Serpin E2, Humans, Insulin, TRANSCRIPTION, GENOME-WIDE ASSOCIATION, Diabetes Mellitus, Type 2/genetics; Glucagon/genetics; Glucagon/metabolism; Humans; Insulin/genetics; Insulin/metabolism; Islets of Langerhans/metabolism; Serpin E2/metabolism

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    popularity
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    influence
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
35
Top 10%
Top 10%
Top 1%
Green
gold