Evidence mapPaperPMID 33182425Full record

ArticleInternational journal of molecular sciences2020

Ligand-Specific Factors Influencing GLP-1 Receptor Post-Endocytic Trafficking and Degradation in Pancreatic Beta Cells.

Zijian Fang, Shiqian Chen, Yusman Manchanda, Stavroula Bitsi, Philip Pickford, Alessia David, Maria M Shchepinova, Ivan R Corrêa, David J Hodson, Johannes Broichhagen and 8 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

24 citing papers in PubMed, 45 citations in OpenAlex.

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  19. The therapeutic potential of GLP-1 receptor biased agonism.British journal of pharmacology · 2022 · on this map
    Review
  20. 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

18 authors at 8 institutions in 4 countries.

Zijian FangSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Shiqian ChenSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Yusman ManchandaSection of Cell Biology and Functional Genomics, Imperial College London, London W12 0NN, UK.
Stavroula BitsiSection of Cell Biology and Functional Genomics, Imperial College London, London W12 0NN, UK.
Philip PickfordSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Alessia DavidCentre for Bioinformatics and System Biology, Department of Life Sciences, Imperial College London, London SW7 2BX, UK.
Maria M ShchepinovaDepartment of Chemistry, Imperial College London, Molecular Sciences Research Hub, 80 Wood Lane, London W12 0BZ, UK.
Ivan R CorrêaNew England Biolabs, Ipswich, MA 01938, USA.ORCID 0000-0002-3169-6878
David J HodsonInstitute of Metabolism and Systems Research (IMSR), and Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham B15 2TT, UK.ORCID 0000-0002-8641-8568
Johannes BroichhagenDepartment of Chemical Biology, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, 13125 Berlin, Germany.ORCID 0000-0003-3084-6595
Edward W TateDepartment of Chemistry, Imperial College London, Molecular Sciences Research Hub, 80 Wood Lane, London W12 0BZ, UK.
Frank ReimannInstitute of Metabolic Science & MRC Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
Victoria SalemSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Guy A RutterSection of Cell Biology and Functional Genomics, Imperial College London, London W12 0NN, UK.
Tricia TanSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Stephen R BloomSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Alejandra TomasSection of Cell Biology and Functional Genomics, Imperial College London, London W12 0NN, UK.
Ben JonesSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Imperial College London · GBGenomics (United Kingdom) · GBMax Planck Institute for Medical Research · DENanyang Technological University · SGNew England Biolabs (United States) · USUniversity of Birmingham · GBUniversity of Cambridge · GBWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

Academy of Medical Sciences N/ABiotechnology and Biological Sciences Research Council BB/N016947/1 and BB/S001565/1Biotechnology and Biological Sciences Research Council N/ABritish Society for Neuroendocrinology N/ADiabetes UK 17/0005681Diabetes UK BDA/11/0004210, BDA/15/0005275, BDA 16/0005485Diabetes UK Harry Keen FellowshipDiabetes UK N/AEPSRC N/AEU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking RHAPSODY grant No 11581European Federation for the Study of Diabetes N/AFP7-HEALTH-2009-241592 EuroCHIP N/AH2020 European Research Council Starting Grant 715884Medical Research Council DIVA, MR/L02036X/1Medical Research Council MC_UU_00014/3Medical Research Council MC_UU_12012/3Medical Research Council MRC_MC_UU_12012/3Medical Research Council MR/K001981/1Medical Research Council MR/K023667/1Medical Research Council MR/L02036X/1Medical Research Council MR/M012646/1Medical Research Council MR/N00275X/1Medical Research Council MR/N00275X/1 and MR/S025618/1Medical Research Council MR/N020472/1Medical Research Council MR/R010676/1Medical Research Council MR/R022259/1Medical Research Council MR/S025618/1NIHR N/ANIHR Biomedical Research Centre N/ASociety for Endocrinology N/AWellcome Trust 106262/Z/14/Z, 106263/Z/14/ZWellcome Trust 212625/Z/18/Z
6 · The paper itself

Abstract

The glucagon-like peptide-1 receptor (GLP-1R) is an important regulator of blood glucose homeostasis. Ligand-specific differences in membrane trafficking of the GLP-1R influence its signalling properties and therapeutic potential in type 2 diabetes. Here, we have evaluated how different factors combine to control the post-endocytic trafficking of GLP-1R to recycling versus degradative pathways. Experiments were performed in primary islet cells, INS-1 832/3 clonal beta cells and HEK293 cells, using biorthogonal labelling of GLP-1R to determine its localisation and degradation after treatment with GLP-1, exendin-4 and several further GLP-1R agonist peptides. We also characterised the effect of a rare GLP1R coding variant, T149M, and the role of endosomal peptidase endothelin-converting enzyme-1 (ECE-1), in GLP1R trafficking. Our data reveal how treatment with GLP-1 versus exendin-4 is associated with preferential GLP-1R targeting towards a recycling pathway. GLP-1, but not exendin-4, is a substrate for ECE-1, and the resultant propensity to intra-endosomal degradation, in conjunction with differences in binding affinity, contributes to alterations in GLP-1R trafficking behaviours and degradation. The T149M GLP-1R variant shows reduced signalling and internalisation responses, which is likely to be due to disruption of the cytoplasmic region that couples to intracellular effectors. These observations provide insights into how ligand- and genotype-specific factors can influence GLP-1R trafficking.

Indexed as

AnimalsCell LineCytoplasmEndocytosisEndosomesEndothelin-Converting EnzymesGlucagon-Like Peptide-1 ReceptorHEK293 CellsHumansInsulin-Secreting CellsLigandsMiceProtein TransportEndothelin-Converting EnzymesGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorLigandsbiased agonismdegradationendothelin converting enzyme-1exendin-4glucagon-like peptide-1trafficking

Identifiers

PMID33182425
PMCPMC7664906
OpenAlexW3100966455

What Socratic 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 Socratic graph.