Evidence map›Paper›PMID 24878748›Full record

ArticlePloS one2014

Deletion of ARNT (Aryl hydrocarbon receptor nuclear translocator) in β-cells causes islet transplant failure with impaired β-cell function.

Amit Lalwani, Rebecca A Stokes, Sue Mei Lau, Jenny E Gunton

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

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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

4 authors at 4 institutions in 1 country.

Amit LalwaniDiabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, Australia; Faculty of Medicine, Westmead Hospital, University of Sydney, Sydney, Australia.
Rebecca A StokesDiabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, Australia.
Sue Mei LauDiabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
Jenny E GuntonDiabetes and Transcription Factors Group, Garvan Institute of Medical Research (GIMR), Sydney, Australia; Faculty of Medicine, Westmead Hospital, University of Sydney, Sydney, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, Australia; Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, Australia.
Garvan Institute of Medical Research · AUSt Vincent's Clinic · AUUNSW Sydney · AUWestmead Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundReplacing β-cells by islet-transplantation can cure type 1 diabetes, but up to 70% of β-cells die within 10 days of transplantation. ARNT (Aryl hydrocarbon Receptor Nuclear Translocator) regulates β-cell function, and potentially survival. Lack of ARNT impairs the ability of β-cells to respond to physiological stress and potentiates the onset of diabetes, but the exact role of ARNT in graft outcome is unknown.

aimTo investigate the effect of β-cell deletion of ARNT on graft outcomes.

methodsIslets were isolated from donor mice which had β-cell specific ARNT-deletion (β-ARNT) or littermate floxed controls. The islets were transplanted into diabetic SCID recipients in ratios of (a) 3 donors: 1 recipient, (b) 1 donor: 1 recipient or (c) ½ of the islets from 1 donor: 1 recipient. After 28 days, the kidney containing the graft was removed (nephrectomy) to exclude regeneration of the endogenous pancreas.

resultsIn the supra-physiological-mass model (3:1), both groups achieved reasonable glycaemia, with slightly higher levels in β-ARNT-recipients. In adequate-mass model (1:1), β-ARNT recipients had poor glucose control versus floxed-control recipients and versus the β-ARNT donors. In the low-β-cell-mass model (½:1) β-ARNT transplants completely failed, whereas controls had good outcomes. Unexpectedly, there was no difference in the graft insulin content or β-cell mass between groups indicating that the defect was not due to early altered β-cell survival.

conclusionOutcomes for islet transplants lacking β-cell ARNT were poor, unless markedly supra-physiological masses of islets were transplanted. In the 1:1 transplant model, there was no difference in β-cell volume. This is surprising because transplants of islets lacking one of the ARNT-partners HIF-1α have increased apoptosis and decreased islet volume. ARNT also partners HIF-2α and AhR (aryl hydrocarbon receptor) to form active transcriptional complexes, and further work to understand the roles of HIF-2α and AhR in transplant outcomes is needed.

Indexed as

AnimalsAryl Hydrocarbon Receptor Nuclear TranslocatorBasic Helix-Loop-Helix ProteinsCell SurvivalDiabetes MellitusEndothelial PAS Domain-Containing Protein 1GlucoseHypoxia-Inducible Factor 1, alpha SubunitInsulinInsulin-Secreting CellsIslets of Langerhans TransplantationMiceMice, SCIDPancreasReceptors, Aryl HydrocarbonSequence DeletionArnt protein, mouseAryl Hydrocarbon Receptor Nuclear TranslocatorBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1GlucoseHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitInsulinReceptors, Aryl Hydrocarbon

Identifiers

PMID24878748
PMCPMC4039512
OpenAlexW2015279066

What OpenQuestion holds

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LicenceCC BY
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.