Evidence map›Paper›PMID 39441374›Full record

ArticleDiabetologia2025

Molecular mechanisms underlying glucose-dependent insulinotropic polypeptide secretion in human duodenal organoids.

Nunzio Guccio, Constanza Alcaino, Emily L Miedzybrodzka, Marta Santos-Hernández, Christopher A Smith, Adam Davison, Rula Bany Bakar, Richard G Kay, Frank Reimann, Fiona M Gribble

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Altered GScience advances · 2026
    Article
  2. Review
  3. Review
  4. Incretin hormones and obesity.The Journal of physiology · 2025
    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

10 authors.

Nunzio GuccioInstitute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Constanza AlcainoInstitute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Emily L MiedzybrodzkaInstitute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Marta Santos-HernándezInstitute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Christopher A SmithInstitute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Adam DavisonInstitute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Rula Bany BakarInstitute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Richard G KayInstitute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Frank ReimannInstitute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. fr222@cam.ac.uk.
Fiona M GribbleInstitute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. fmg23@cam.ac.uk.

Funding

Medical Research Council MRC_MC_UU_00014/5Medical Research Council MRC_MC_UU_12012/3Medical Research Council MR/M009041/1Wellcome TrustWellcome Trust 100574/Z/12/ZWellcome Trust 220271/Z/20/Z
6 · The paper itself

Abstract

aims/hypothesisGlucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by enteroendocrine K cells in the proximal small intestine. This study aimed to explore the function of human K cells at the molecular and cellular levels.

methodsCRISPR-Cas9 homology-directed repair was used to insert transgenes encoding a yellow fluorescent protein (Venus) or an Epac-based cAMP sensor (Epac-S-H187) in the GIP locus in human duodenal-derived organoids. Fluorescently labelled K cells were purified by FACS for RNA-seq and peptidomic analysis. GIP reporter organoids were employed for GIP secretion assays, live-cell imaging of Ca

resultsRNA-seq of human duodenal K cells revealed enrichment of several G protein-coupled receptors involved in nutrient sensing, including FFAR1, GPBAR1, GPR119, CASR and GPR142. Glucose induced action potential firing and cytosolic Ca CONCLUSIONS/

interpretationThe newly generated human organoid K cell model enables transcriptomic and functional characterisation of nutrient-sensing pathways involved in human GIP secretion. Both calcium-sensing receptor (CASR) and G protein-coupled receptor 142 (GPR142) contribute to protein-stimulated GIP secretion. This model will be further used to identify potential targets for modulation of native GIP secretion in diabetes and obesity.

Indexed as

DuodenumEnteroendocrine CellsGastric Inhibitory PolypeptideOrganoidsReceptors, G-Protein-CoupledCalciumCRISPR-Cas SystemsCyclic AMPGlucoseHumansReceptors, Calcium-SensingCalciumCyclic AMPFFAR1 protein, humanGastric Inhibitory PolypeptideGlucoseReceptors, Calcium-SensingReceptors, G-Protein-CoupledCASRGIPGPR142OrganoidSGLT1

Identifiers

PMID39441374
PMCPMC11663192

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.