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Record W4412441493 · doi:10.1016/j.cmet.2025.06.009

Localized GLP1 receptor pre-internalization directs pancreatic alpha cell to beta cell communication

2025· article· en· W4412441493 on OpenAlexafffund
Charlotte Frazer-Morris, Ali H. Shilleh, Katrina Viloria, Anne de Bray, Paul Johnson, Rebecca Spiers, Ahmad Kobiita, Oladapo E. Olaniru, Shanta J. Persaud, Robert Hauffe, André Kleinridders, Carsten Schultz, C. Bruce Verchere, Canqi Cui, Jonathan E. Campbell, Małgorzata Cyranka, Alexey Epanchintsev, Carina Ämmälä, Johannes Broichhagen, David J. Hodson

Bibliographic record

VenueCell Metabolism · 2025
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsBC Children's Hospital
FundersDiabetes Research Wellness FoundationH2020 European Research CouncilNational Institute of Diabetes and Digestive and Kidney DiseasesMedical Research CouncilNational Institutes of HealthNational Institute for Health and Care ResearchNovo NordiskCanadian Institutes of Health ResearchDiabetes Research and Wellness FoundationDeutsche ForschungsgemeinschaftDiabetes UKAstraZenecaUK Research and InnovationHORIZON EUROPE Framework ProgrammeSaint Mary's Foundation
KeywordsAlpha cellGlucagonBeta cellParacrine signallingCell biologyInternalizationBiologyReceptorBETA (programming language)EndocrinologySignal transductionInternal medicinePancreatic isletsIsletAlpha (finance)InsulinBiochemistryMedicine

Abstract

fetched live from OpenAlex

Pancreatic alpha cells modulate beta cell function in a paracrine manner through the release of glucagon. However, the detailed molecular architecture underlying alpha-to-beta cell regulation remains poorly characterized. Here, we show that the glucagon-like peptide-1 receptor (GLP1R) is enriched as nanodomains on beta cell membranes that contact alpha cells, in keeping with increased single-molecule transcript expression. At low glucose, beta cells next to alpha cells directly sense micromolar glucagon release by pre-internalizing GLP1R. Pre-internalized GLP1R is associated with earlier beta cell Ca 2+ responses to high glucose, which are then propagated across the islet. Beta cells adjacent to alpha cells are more secretory than beta cells next to other beta cells. Localized GLP1R signaling occurs in vitro and in vivo , is operative in the post-prandial state, and GLP1R contacts decrease between beta cells and alpha cells during metabolic stress. Thus, we detail a regulated pathway through which glucagon modulates insulin release.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.191
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.008
GPT teacher head0.256
Teacher spread0.248 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations15
Published2025
Admission routes2
Has abstractyes

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