Evidence map›Paper›PMID 33087848›Full record

ArticleScientific reports2020

TBC1D1 interacting proteins, VPS13A and VPS13C, regulate GLUT4 homeostasis in C2C12 myotubes.

Sharon C Hook, Alexandra Chadt, Kate J Heesom, Shosei Kishida, Hadi Al-Hasani, Jeremy M Tavaré, Elaine C Thomas

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.6field-weighted citation impact, top 17% 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, 29 citations in OpenAlex.

  1. Trial
  2. Triglycerides, Glucose Metabolism, and Type 2 Diabetes.International journal of molecular sciences · 2025
    Review
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  12. Genes · 2022
    Article
  13. Article
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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

7 authors at 4 institutions in 3 countries.

Sharon C HookSchool of Biochemistry, Biomedical Sciences Building, University of Bristol, University Walk, Bristol, BS8 1TD, UK.
Alexandra ChadtInstitute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
Kate J HeesomSchool of Biochemistry, Biomedical Sciences Building, University of Bristol, University Walk, Bristol, BS8 1TD, UK.
Shosei KishidaDepartment of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Hadi Al-HasaniInstitute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
Jeremy M TavaréSchool of Biochemistry, Biomedical Sciences Building, University of Bristol, University Walk, Bristol, BS8 1TD, UK.
Elaine C ThomasSchool of Biochemistry, Biomedical Sciences Building, University of Bristol, University Walk, Bristol, BS8 1TD, UK. elaine.thomas@bristol.ac.uk.
University of Bristol · GBDeutsches Diabetes-Zentrum e.V. · DEGerman Center for Diabetes Research · DEKagoshima University · JP

Funding

British Heart Foundation PG/10/008/28186Diabetes UK 14/0004877
6 · The paper itself

Abstract

Proteins involved in the spaciotemporal regulation of GLUT4 trafficking represent potential therapeutic targets for the treatment of insulin resistance and type 2 diabetes. A key regulator of insulin- and exercise-stimulated glucose uptake and GLUT4 trafficking is TBC1D1. This study aimed to identify proteins that regulate GLUT4 trafficking and homeostasis via TBC1D1. Using an unbiased quantitative proteomics approach, we identified proteins that interact with TBC1D1 in C2C12 myotubes including VPS13A and VPS13C, the Rab binding proteins EHBP1L1 and MICAL1, and the calcium pump SERCA1. These proteins associate with TBC1D1 via its phosphotyrosine binding (PTB) domains and their interactions with TBC1D1 were unaffected by AMPK activation, distinguishing them from the AMPK regulated interaction between TBC1D1 and AMPKα1 complexes. Depletion of VPS13A or VPS13C caused a post-transcriptional increase in cellular GLUT4 protein and enhanced cell surface GLUT4 levels in response to AMPK activation. The phenomenon was specific to GLUT4 because other recycling proteins were unaffected. Our results provide further support for a role of the TBC1D1 PTB domains as a scaffold for a range of Rab regulators, and also the VPS13 family of proteins which have been previously linked to fasting glycaemic traits and insulin resistance in genome wide association studies.

Indexed as

AMP-Activated Protein KinasesAnimalsCells, CulturedDiabetes Mellitus, Type 2Glucose Transporter Type 4GTPase-Activating ProteinsHEK293 CellsHomeostasisHumansInsulin ResistanceMaleMice, TransgenicMuscle Fibers, SkeletalProteinsVesicular Transport ProteinsAMP-Activated Protein KinasesGlucose Transporter Type 4GTPase-Activating ProteinsProteinsTBC1D1 protein, humanVesicular Transport ProteinsVPS13A protein, humanVPS13C protein, human

Identifiers

PMID33087848
PMCPMC7578007
OpenAlexW3087680657

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.