Evidence map›Paper›PMID 29396373›Full record

ArticleMolecular metabolism2018

Circular RNAs as novel regulators of β-cell functions in normal and disease conditions.

Lisa Stoll, Jonathan Sobel, Adriana Rodriguez-Trejo, Claudiane Guay, Kailun Lee, Morten Trillingsgaard Venø, Jørgen Kjems, D Ross Laybutt, Romano Regazzi

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 3 pooled it
13.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

127 citing papers in PubMed, 3 syntheses or guidelines pooled it, 228 citations in OpenAlex.

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67 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Lisa StollDepartment of Fundamental Neurosciences, University of Lausanne, Switzerland.
Jonathan SobelDepartment of Fundamental Neurosciences, University of Lausanne, Switzerland.
Adriana Rodriguez-TrejoDepartment of Fundamental Neurosciences, University of Lausanne, Switzerland.
Claudiane GuayDepartment of Fundamental Neurosciences, University of Lausanne, Switzerland.
Kailun LeeDiabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
Morten Trillingsgaard VenøInterdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Denmark.
Jørgen KjemsInterdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Denmark.
D Ross LaybuttDiabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
Romano RegazziDepartment of Fundamental Neurosciences, University of Lausanne, Switzerland. Electronic address: Romano.Regazzi@unil.ch.
University of Lausanne · CHAarhus University · DKGarvan Institute of Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThere is strong evidence for an involvement of different classes of non-coding RNAs, including microRNAs and long non-coding RNAs, in the regulation of β-cell activities and in diabetes development. Circular RNAs were recently discovered to constitute a substantial fraction of the mammalian transcriptome but the contribution of these non-coding RNAs in physiological and disease processes remains largely unknown. The goal of this study was to identify the circular RNAs expressed in pancreatic islets and to elucidate their possible role in the control of β-cells functions.

methodsWe used a microarray approach to identify circular RNAs expressed in human islets and searched their orthologues in RNA sequencing data from mouse islets. We then measured the level of four selected circular RNAs in the islets of different Type 1 and Type 2 diabetes models and analyzed the role of these circular transcripts in the regulation of insulin secretion, β-cell proliferation, and apoptosis.

resultsWe identified thousands of circular RNAs expressed in human pancreatic islets, 497 of which were conserved in mouse islets. The level of two of these circular transcripts, circHIPK3 and ciRS-7/CDR1as, was found to be reduced in the islets of diabetic db/db mice. Mimicking this decrease in the islets of wild type animals resulted in impaired insulin secretion, reduced β-cell proliferation, and survival. ciRS-7/CDR1as has been previously proposed to function by blocking miR-7. Transcriptomic analysis revealed that circHIPK3 acts by sequestering a group of microRNAs, including miR-124-3p and miR-338-3p, and by regulating the expression of key β-cell genes, such as Slc2a2, Akt1, and Mtpn.

conclusionsOur findings point to circular RNAs as novel regulators of β-cell activities and suggest an involvement of this novel class of non-coding RNAs in β-cell dysfunction under diabetic conditions.

Indexed as

AnimalsApoptosisCell LineCell ProliferationCells, CulturedDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2HumansInsulin-Secreting CellsInsulin SecretionMaleMiceMice, Inbred C57BLRatsRats, WistarRNARNARNA, CircularCircular RNADiabetesInsulinmicroRNAPancreatic islet

Identifiers

PMID29396373
PMCPMC5870096
OpenAlexW2792222116

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.