Evidence mapPaperPMID 41667949Full record

ArticleMolecular medicine (Cambridge, Mass.)2026

Glucagon secretion by pancreatic alpha-cells requires an intact tubulin-cytoskeleton-primary cilium axis.

Elena Casanueva-Álvarez, Alba Sanz-González, Alicia Vilas, Patricia Cámara-Torres, Magalie A Ravier, Sara Eslava-Alcon, M Carmen Duran-Ruiz, Cristina M Ramírez, Peristera-Ioanna Petropoulou, Teresa Rodriguez-Calvo and 3 more

Abstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 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. 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

13 authors.

Elena Casanueva-Álvarez *Institute of Biomedicine and Molecular Genetics (Consejo Superior de Investigaciones Científicas-Universidad de Valladolid), Valladolid, Spain.
Alba Sanz-González *Institute of Biomedicine and Molecular Genetics (Consejo Superior de Investigaciones Científicas-Universidad de Valladolid), Valladolid, Spain.
Alicia VilasInstitute of Biomedicine and Molecular Genetics (Consejo Superior de Investigaciones Científicas-Universidad de Valladolid), Valladolid, Spain.
Patricia Cámara-TorresInstitute of Biomedicine and Molecular Genetics (Consejo Superior de Investigaciones Científicas-Universidad de Valladolid), Valladolid, Spain.
Magalie A RavierIGF, Univ Montpellier, CNRS, Inserm, Montpellier, France.
Sara Eslava-AlconBiomedicine, Biotechnology and Public Health Department, Cádiz University, Cádiz, Spain.
M Carmen Duran-RuizBiomedicine, Biotechnology and Public Health Department, Cádiz University, Cádiz, Spain.
Cristina M RamírezIMDEA Research Institute of Food & Health Sciences, Madrid, Spain.
Peristera-Ioanna PetropoulouInstitute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany.
Teresa Rodriguez-CalvoInstitute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany.
Beatriz MerinoInstitute of Biomedicine and Molecular Genetics (Consejo Superior de Investigaciones Científicas-Universidad de Valladolid), Valladolid, Spain.
Germán PerdomoInstitute of Biomedicine and Molecular Genetics (Consejo Superior de Investigaciones Científicas-Universidad de Valladolid), Valladolid, Spain.
Irene Cozar-CastellanoInstitute of Biomedicine and Molecular Genetics (Consejo Superior de Investigaciones Científicas-Universidad de Valladolid), Valladolid, Spain. irene.cozar@uva.es.

Funding

Agencia Estatal de Investigación PID2019-110496RB-C21Agencia Estatal de Investigación PID2019-110496RB-C22Agencia Estatal de Investigación PID2021-128264OB-I00Junta de Castilla y León VA129P24Juvenile Diabetes Research Foundation International 5-CDA-2020-949-A-N
6 · The paper itself

Abstract

backgroundHyperglucagonemia is a hallmark of diabetes mellitus, resulting from the dysregulation of glucagon secretion by pancreatic alpha-cells. Although glucose sensing and insulin signaling are well-established regulatory processes, the pathways that govern glucagon secretion remain unclear. Recent evidences suggest that insulin-degrading enzyme (IDE) regulates glucagon secretion via an unknown pathway.

methodsUsing IDE-immunoprecipitation proteomic data as a basis, we aimed to ascertain the molecular mechanisms downstream of IDE in the alpha-TC cell model. Knock-down studies of relevant genes involved in the functional pathways identified in the proteomic study, and its impact on glucagon secretion were performed. Primary cilium was stained and detected using confocal and STORM microscopies in alpha-TC cells and mouse pancreas.

resultsBased on proteomic studies we focus our efforts on the relationship between IDE, tubulin cytoskeleton, and the primary cilium. Although IDE was not localized to the primary cilium of alpha-cells using confocal microscopy and STORM, its absence resulted in impaired ciliogenesis. Consistent with lower protein levels of the insulin receptor, the counterregulatory effect of insulin on glucagon secretion was reduced in IDE-deficient alpha-cells. Two cellular models of ciliary dysfunction (ARL13B-KD and IFT88-KD) resulted in impaired glucagon secretion, as well as a failure of insulin to suppress glucagon secretion in alpha-cells. Importantly, IDE, tubulin, ciliary markers (AcTubulin, ARL13B) and insulin receptor levels were diminished in glucose conditions of physiological glucagon repression.

conclusionsIDE acts as a mechanistic link between glucose levels, tubulin, and the primary cilium, regulating glucagon secretion in alpha-cells. The dysregulation of the tubulin-primary cilium axis induces glucagon secretion impairment.

Indexed as

CiliaCytoskeletonGlucagonGlucagon-Secreting CellsTubulinADP-Ribosylation FactorsAnimalsInsulinMiceTumor Suppressor ProteinsADP-Ribosylation FactorsArl13b protein, mouseGlucagonInsulinTg737Rpw protein, mouseTubulinTumor Suppressor ProteinsDiabetes mellitusEndocrine pancreasGlucagonInsulin-degrading enzymePancreatic alpha-cellPrimary ciliumTubulin

Identifiers

PMID41667949
PMCPMC12990396

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.