Evidence map›Paper›PMID 29307512›Full record

ArticleMolecular metabolism2018

The EndoC-βH1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates.

Violeta Georgieva Tsonkova, Fredrik Wolfhagen Sand, Xenia Asbæk Wolf, Lars Groth Grunnet, Anna Kirstine Ringgaard, Camilla Ingvorsen, Louise Winkel, Mark Kalisz, Kevin Dalgaard, Christine Bruun and 26 more

Open access · goldAbstract readValidation Study
In one paragraph

Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
10.7field-weighted citation impact, top 1% 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

86 citing papers in PubMed, 137 citations in OpenAlex.

  1. Activation of GScience advances · 2026
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  2. Experimental models in diabetes research.Laboratory animal research · 2026
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  11. miRNA-642a-3p protects β cells from glucolipotoxicity.Molecular therapy. Nucleic acids · 2025
    Article
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26 more citing papers are in PubMed but not listed here.

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

36 authors at 6 institutions in 5 countries.

Violeta Georgieva TsonkovaNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark; University of Copenhagen, Department of Biomedical Sciences, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark.
Fredrik Wolfhagen SandNovo Nordisk A/S, Diabetes Research, GLP-1 & T2D Pharmacology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Xenia Asbæk WolfNovo Nordisk A/S, Diabetes Research, GLP-1 & T2D Pharmacology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Lars Groth GrunnetNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Anna Kirstine RinggaardNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark; University of Copenhagen, Department of Biomedical Sciences, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark.
Camilla IngvorsenNovo Nordisk A/S, Diabetes Research, Histology & Imaging, Novo Nordisk Park, 2760, Maaloev, Denmark.
Louise WinkelNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Mark KaliszNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Kevin DalgaardNovo Nordisk A/S, Diabetes Research, GLP-1 & T2D Pharmacology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Christine BruunNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Johannes Josef FelsNovo Nordisk A/S, Discovery Biology & Technology, Research Bioanalysis, Novo Nordisk Park, 2760, Maaloev, Denmark.
Charlotte HelgstrandNovo Nordisk A/S, Protein Engineering, Expression Technologies 1, Novo Nordisk Park, 2760, Maaloev, Denmark.
Sven HastrupNovo Nordisk A/S, Protein Engineering, Expression Technologies 1, Novo Nordisk Park, 2760, Maaloev, Denmark.
Fredrik Kryh ÖbergNovo Nordisk A/S, Protein Engineering, Expression Technologies 1, Novo Nordisk Park, 2760, Maaloev, Denmark.
Erik VernetNovo Nordisk Research Center Seattle Inc., Protein Engineering, NNRC Seattle, Inc., 530 Fairview Avenue North, 98109, Seattle, WA, USA.
Michael Paolo Bastner SandriniNovo Nordisk A/S, Protein Engineering, Upstream Technologies, Novo Nordisk Park, 2760, Maaloev, Denmark.
Allan Christian ShawNovo Nordisk A/S, Protein Engineering, Characterisation & Modelling Technology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Carsten JessenNovo Nordisk A/S, Protein Engineering, Protein & Peptide Chemistry 2, Novo Nordisk Park, 2760, Maaloev, Denmark.
Mads GrønborgNovo Nordisk A/S, Discovery Biology & Technology, Discovery ADME, Novo Nordisk Park, 2760, Maaloev, Denmark.
Jacob HaldNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Hanni WillenbrockNovo Nordisk A/S, Discovery Biology & Technology, Bioinformatics, Maaloev, Denmark.
Dennis MadsenNovo Nordisk A/S, Discovery Biology & Technology, Bioinformatics, Maaloev, Denmark.
Rasmus WernerssonIntomics A/S, Lottenborgvej 26, DK-2800, Lyngby, Denmark.
Lena HanssonIntomics A/S, Lottenborgvej 26, DK-2800, Lyngby, Denmark; Novo Nordisk Pharma Ltd., Research Centre Oxford, Bioinformatics, Novo Nordisk Ltd., 3 City Place Beehive Ring Road, Gatwick, RH6 0PA, West Sussex, United Kingdom.
Jan Nygaard JensenNovo Nordisk Pharma Ltd., Research Centre Oxford, Bioinformatics, Novo Nordisk Ltd., 3 City Place Beehive Ring Road, Gatwick, RH6 0PA, West Sussex, United Kingdom.
Annette PlesnerNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Tomas AlanentaloNovo Nordisk A/S, Diabetes Research, Histology & Imaging, Novo Nordisk Park, 2760, Maaloev, Denmark.
Maja Borup Kjær PetersenNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark; University of Copenhagen, DanStem, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark.
Anne Grapin-BottonUniversity of Copenhagen, DanStem, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark.
Christian HonoréNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Jonas Ahnfelt-RønneNovo Nordisk A/S, Diabetes Research, Histology & Imaging, Novo Nordisk Park, 2760, Maaloev, Denmark.
Jacob Hecksher-SørensenNovo Nordisk A/S, Diabetes Research, Histology & Imaging, Novo Nordisk Park, 2760, Maaloev, Denmark.
Philippe RavassardInstitut du cerveau et de la moelle (ICM) - Hôpital Pitié-Salpêtrière, Boulevard de l'Hôpital, Sorbonne Universités, Inserm, CNRS, UPMC Univ, Paris 06, Paris, France.
Ole D MadsenNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Claude RescanNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark.
Thomas FrogneNovo Nordisk A/S, Diabetes Research, Department of Islet & Stem Cell Biology, Novo Nordisk Park, 2760, Maaloev, Denmark. Electronic address: tfro@novonordisk.com.
Novo Nordisk (Denmark) · DKUniversity of Copenhagen · DKCentre National de la Recherche Scientifique · FRClinical Microbiomics (Denmark) · DKNovo Nordisk (United Kingdom) · GBNovo Nordisk (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates.

methodsEndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, and ER stress responses were assessed. Beta cell relevant mRNA and protein expression were investigated by qPCR and antibody staining. Hundreds of proteins or peptides were tested for their effect on insulin secretion and proliferation.

resultsTransplantation of EndoC-βH1 cells restored normoglycemia in streptozotocin induced diabetic mice. Both in vitro and in vivo, we observed a clear insulin response to glucose, and, in vitro, we found a significant increase in insulin secretion from EndoC-βH1 pseudoislets compared to monolayer cultures for both glucose and incretins. Apoptosis and ER stress were inducible in the cells and caspase 3/7 activity was elevated in response to cytokines, but not affected by the saturated fatty acid palmitate. By screening of various proteins and peptides, we found Bombesin (BB) receptor agonists and Pituitary Adenylate Cyclase-Activating Polypeptides (PACAP) to significantly induce insulin secretion and the proteins SerpinA6, STC1, and APOH to significantly stimulate proliferation. ER stress was readily induced by Tunicamycin and resulted in a reduction of insulin mRNA. Somatostatin (SST) was found to be expressed by 1% of the cells and manipulation of the SST receptors was found to significantly affect insulin secretion.

conclusionsOverall, the EndoC-βH1 cells strongly resemble human islet beta cells in terms of glucose and incretin stimulated insulin secretion capabilities. The cell line has an active cytokine induced caspase 3/7 apoptotic pathway and is responsive to ER stress initiation factors. The cells' ability to proliferate can be further increased by already known compounds as well as by novel peptides and proteins. Based on its robust performance during the functionality assessment assays, the EndoC-βH1 cell line was successfully used as a screening platform for identification of novel anti-diabetic drug candidates.

Indexed as

AnimalsCell Culture TechniquesCell LineCells, CulturedDiabetes Mellitus, ExperimentalDrug Evaluation, PreclinicalHumansHypoglycemic AgentsInsulin-Secreting CellsInsulin SecretionMiceMice, SCIDHypoglycemic AgentsEndoC-βH1Glucose stimulated insulin secretionProliferationPseudoisletsSomatostatin signaling

Identifiers

PMID29307512
PMCPMC5985049
OpenAlexW2781215248

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.