Evidence map›Paper›PMID 27329800›Full record

ArticleAmerican journal of physiology. Endocrinology and metabolism2016

Changes in the expression of the type 2 diabetes-associated gene VPS13C in the β-cell are associated with glucose intolerance in humans and mice.

Zenobia B Mehta, Nicholas Fine, Timothy J Pullen, Matthew C Cane, Ming Hu, Pauline Chabosseau, Gargi Meur, Antonio Velayos-Baeza, Anthony P Monaco, Lorella Marselli and 2 more

Open access · hybridAbstract read
In one paragraph

Article in American journal of physiology. Endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 11% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
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  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Identification ofProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  11. Transcription factor-7-like 2 (The Journal of biological chemistry · 2018
    Article
  12. Article
  13. Article
  14. The role of CaDisease models & mechanisms · 2017
    Review
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

12 authors at 4 institutions in 2 countries.

Zenobia B MehtaSection of Cell Biology and Functional Genomics, Imperial College London, London, United Kingdom;
Nicholas FineSection of Cell Biology and Functional Genomics, Imperial College London, London, United Kingdom;
Timothy J PullenSection of Cell Biology and Functional Genomics, Imperial College London, London, United Kingdom;
Matthew C CaneSection of Cell Biology and Functional Genomics, Imperial College London, London, United Kingdom;
Ming HuSection of Cell Biology and Functional Genomics, Imperial College London, London, United Kingdom;
Pauline ChabosseauSection of Cell Biology and Functional Genomics, Imperial College London, London, United Kingdom;
Gargi MeurSection of Cell Biology and Functional Genomics, Imperial College London, London, United Kingdom;
Antonio Velayos-BaezaWellcome Trust Centre for Human Genetics, Oxford, United Kingdom; and.
Anthony P MonacoWellcome Trust Centre for Human Genetics, Oxford, United Kingdom; and.
Lorella MarselliDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Piero MarchettiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Guy A RutterSection of Cell Biology and Functional Genomics, Imperial College London, London, United Kingdom; g.rutter@imperial.ac.uk.
Genomics (United Kingdom) · GBImperial College London · GBCentre for Human Genetics · GBUniversity of Pisa · IT

Funding

Biotechnology and Biological Sciences Research Council BB/J015873/1Medical Research Council MR/J0003042/1Medical Research Council MR/K001981/1Wellcome TrustWellcome Trust 075491/Z/04Wellcome Trust WT098424AIA
6 · The paper itself

Abstract

Single nucleotide polymorphisms (SNPs) close to the VPS13C, C2CD4A and C2CD4B genes on chromosome 15q are associated with impaired fasting glucose and increased risk of type 2 diabetes. eQTL analysis revealed an association between possession of risk (C) alleles at a previously implicated causal SNP, rs7163757, and lowered VPS13C and C2CD4A levels in islets from female (n = 40, P < 0.041) but not from male subjects. Explored using promoter-reporter assays in β-cells and other cell lines, the risk variant at rs7163757 lowered enhancer activity. Mice deleted for Vps13c selectively in the β-cell were generated by crossing animals bearing a floxed allele at exon 1 to mice expressing Cre recombinase under Ins1 promoter control (Ins1Cre). Whereas Vps13c(fl/fl):Ins1Cre (βVps13cKO) mice displayed normal weight gain compared with control littermates, deletion of Vps13c had little effect on glucose tolerance. Pancreatic histology revealed no significant change in β-cell mass in KO mice vs. controls, and glucose-stimulated insulin secretion from isolated islets was not altered in vitro between control and βVps13cKO mice. However, a tendency was observed in female null mice for lower insulin levels and β-cell function (HOMA-B) in vivo. Furthermore, glucose-stimulated increases in intracellular free Ca(2+) were significantly increased in islets from female KO mice, suggesting impaired Ca(2+) sensitivity of the secretory machinery. The present data thus provide evidence for a limited role for changes in VPS13C expression in conferring altered disease risk at this locus, particularly in females, and suggest that C2CD4A may also be involved.

Indexed as

AnimalsBlotting, WesternCalciumCalcium-Binding ProteinsDiabetes Mellitus, Type 2FemaleGlucagon-Secreting CellsGlucose IntoleranceInsulinInsulin ResistanceInsulin-Secreting CellsInsulin SecretionMaleMiceMice, KnockoutNerve Tissue ProteinsCalciumCalcium-Binding ProteinsInsulinNerve Tissue ProteinsProteinsVesicular Transport ProteinsVps13a protein, mouseVPS13C protein, humanC2CD4AGWAStype 2 diabetesVPS13Cβ-cell

Identifiers

PMID27329800
PMCPMC5005967
OpenAlexW2468942193

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.