Evidence mapPaperPMID 42271608Full record

ArticleEndocrinology2026

eNAMPT induces alpha-cell mass expansion but impaired glucagon counter regulatory response.

Sophie R Sayers, Vesela S Gesheva, Jithu J Varghese, Rebecca Beavil, Min Zhao, Yee Cheah, David Hopkins, Nicholas H F Fine, Annie Hasib, David J Hodson and 1 more

Abstract read
In one paragraph

Article in Endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

1 citing paper in PubMed.

  1. Article
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

11 authors.

Sophie R SayersDiabetes and Obesity Theme, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London SE1 1UL, UK.
Vesela S GeshevaDiabetes and Obesity Theme, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London SE1 1UL, UK.
Jithu J VargheseDiabetes and Obesity Theme, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London SE1 1UL, UK.
Rebecca BeavilProtein Production Facility, Randall Centre for Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
Min ZhaoDiabetes and Obesity Theme, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London SE1 1UL, UK.
Yee CheahDiabetes and Obesity Theme, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London SE1 1UL, UK.
David HopkinsDiabetes and Obesity Theme, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London SE1 1UL, UK.
Nicholas H F FineInstitute of Metabolism and Systems Research (IMSR), and Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham B15 2TT, UK.
Annie HasibInstitute of Metabolism and Systems Research (IMSR), and Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham B15 2TT, UK.
David J HodsonOxford Center for Diabetes, Endocrinology and Metabolism (OCDEM), NIHR Oxford Biomedical Research Centre, Churchill Hospital, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK.
Paul W CatonDiabetes and Obesity Theme, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London SE1 1UL, UK.ORCID 0000-0003-0902-0676

Funding

Department of HealthDiabetes UK 17/0005681Diabetes UK 18/0005865Diabetes UK 20/0006297Diabetes UK 22/0006389DRWFEFSD/Lilly European Diabetes Research ProgramEuropean Research Council (ERC)European Union's Horizon 2020 715884King's College London Human Islet Research Tissue Bank 20/SW/0074MRC MR/S025618/1National Institute for Health Research (NIHR)NHSOxford Biomedical Research Centre (BRC)SMF 23/0006627UKRI ERC Frontier Research Guarantee EP/X026833/1Wellcome King's Clinical Research Facility
6 · The paper itself

Abstract

contextLoss of functional beta-cell mass, coupled with alpha-cell dysfunction are key factors in pathophysiology of type 1 and type 2 diabetes. We have reported that extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is elevated in type 2 diabetes and that elevated eNAMPT levels promote beta-cell dysfunction.

objectiveTo further investigate the effects of eNAMPT on beta-cell mass.

methodsIslets isolated from CD1 and Ins1tm1.1(cre)Thor+/-; mTmGfl/- mice and human donors were exposed to eNAMPT (48-96 hours). CD1 mice were administered eNAMPT for 14 days. Alpha-, beta-, and delta-cell numbers were determined by glucagon, insulin, and somatostatin staining, respectively. Alpha-cell proliferation was assessed by bromodeoxyuridine (BrDU) uptake and Ki67 expression. Glucagon secretion was assessed via radioimmunoassay. Trans-differentiation was assessed by determining changes in presence of bi-hormonal cells in CD1/human islets and using Ins1tm1.1(cre)Thor+/-; mTmGfl/- islets to determine changes in GLU+/GFP+ and GLU+/TdT+ cells.

resultseNAMPT treatment reduced beta-cell number and induced corresponding increases in alpha-cell number. Indicative of beta- to alpha-cell trans-differentiation eNAMPT induced increased presence of bi-hormonal INS+/GLU+ cells and PDX1+/GLU+ cells, and increased GLU+/GFP+ cells in Ins1tm1.1(cre)Thor+/-; mTmGfl/- mouse islets. In addition, eNAMPT induced alpha-cell proliferation, indicated by increased BrDU uptake. Despite marked elevation in alpha-cell number, alpha-cell function was compromised following eNAMPT exposure, indicated by impaired glucagon counterregulatory response (CCR) to low glucose levels.

conclusionThis data supports a role for elevated eNAMPT levels in driving increased alpha-cell mass via a combination of beta- to alpha-cell trans-differentiation and alpha-cell proliferation. When combined with observed impaired CCR, these data have implications for both type 1 and type 2 diabetes pathophysiology.

Indexed as

GlucagonGlucagon-Secreting CellsAnimalsCell ProliferationFemaleHumansInsulinInsulin-Secreting CellsMaleMiceGlucagonInsulinalpha-cellsbeta-cellsglucagonNAMPTtype 1 diabetestype 2 diabetes

Identifiers

PMID42271608
PMCPMC13268769

What Socratic holds

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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 Socratic graph.