Evidence map›Paper›PMID 25058609›Full record

ArticlePloS one2014

Gluco-incretins regulate beta-cell glucose competence by epigenetic silencing of Fxyd3 expression.

David Vallois, Guy Niederhäuser, Mark Ibberson, Vini Nagaraj, Vini Nagaray, Lorella Marselli, Piero Marchetti, Jean-Yves Chatton, Bernard Thorens

Erratum issuedOpen 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. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.3field-weighted citation impact, top 39% 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

10 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. The MODY-associatedeLife · 2024
    Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
4 · The record

Corrections and comments

  • Erratum issued
    Nagaray, Vini [corrected to Nagaraj, Vini]
5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

David ValloisCenter for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
Guy NiederhäuserCenter for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
Mark IbbersonCenter for Integrative Genomics, University of Lausanne, Lausanne, Switzerland; Vital-IT group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Vini Nagaraj
Vini NagarayLund University Diabetes Center, Malmö, Sweden.
Lorella MarselliDepartment of Endocrinology and Metabolism, Ospedale di Cisanello, Pisa, Italy.
Piero MarchettiDepartment of Endocrinology and Metabolism, Ospedale di Cisanello, Pisa, Italy.
Jean-Yves ChattonDepartment of Cell Biology and Morphology, University of Lausanne, Lausanne, Switzerland.
Bernard ThorensCenter for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
University of Lausanne · CHOspedale Cisanello · ITLund University · SESIB Swiss Institute of Bioinformatics · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

aimsGluco-incretin hormones increase the glucose competence of pancreatic beta-cells by incompletely characterized mechanisms.

methodsWe searched for genes that were differentially expressed in islets from control and Glp1r-/-; Gipr-/- (dKO) mice, which show reduced glucose competence. Overexpression and knockdown studies; insulin secretion analysis; analysis of gene expression in islets from control and diabetic mice and humans as well as gene methylation and transcriptional analysis were performed.

resultsFxyd3 was the most up-regulated gene in glucose incompetent islets from dKO mice. When overexpressed in beta-cells Fxyd3 reduced glucose-induced insulin secretion by acting downstream of plasma membrane depolarization and Ca++ influx. Fxyd3 expression was not acutely regulated by cAMP raising agents in either control or dKO adult islets. Instead, expression of Fxyd3 was controlled by methylation of CpGs present in its proximal promoter region. Increased promoter methylation reduced Fxyd3 transcription as assessed by lower abundance of H3K4me3 at the transcriptional start site and in transcription reporter assays. This epigenetic imprinting was initiated perinatally and fully established in adult islets. Glucose incompetent islets from diabetic mice and humans showed increased expression of Fxyd3 and reduced promoter methylation. CONCLUSIONS/

interpretationBecause gluco-incretin secretion depends on feeding the epigenetic regulation of Fxyd3 expression may link nutrition in early life to establishment of adult beta-cell glucose competence; this epigenetic control is, however, lost in diabetes possibly as a result of gluco-incretin resistance and/or de-differentiation of beta-cells that are associated with the development of type 2 diabetes.

Indexed as

AnimalsAnimals, NewbornCells, CulturedDNA MethylationEatingEpigenesis, GeneticGene SilencingGlucoseHumansIncretinsInsulin-Secreting CellsMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutNeoplasm ProteinsFxyd3 protein, mouseGlucoseIncretinsMembrane ProteinsNeoplasm Proteins

Identifiers

PMID25058609
PMCPMC4110016
OpenAlexW1998105891

What OpenQuestion holds

Textmetadata
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.