Evidence map›Paper›PMID 39508880›Full record

ArticleDiabetologia2025

Transcriptomic heterogeneity of non-beta islet cells is associated with type 2 diabetes development in mouse models.

Pascal Gottmann, Thilo Speckmann, Mandy Stadion, Prateek Chawla, Judith Saurenbach, Nikolay Ninov, Heiko Lickert, Annette Schürmann

Abstract read
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. Article
  2. Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.Clinical reviews in allergy & immunology · 2025
    Review
  3. Review
  4. 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

8 authors.

Pascal GottmannDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
Thilo SpeckmannDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
Mandy StadionDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
Prateek ChawlaGerman Center for Diabetes Research (DZD), München Neuherberg, Germany.
Judith SaurenbachDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
Nikolay NinovGerman Center for Diabetes Research (DZD), München Neuherberg, Germany.
Heiko LickertGerman Center for Diabetes Research (DZD), München Neuherberg, Germany.
Annette SchürmannDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. schuermann@dife.de.

Funding

Bundesministerium für Bildung und Forschung 82DZD03D03Deutsche Forschungsgemeinschaft 407395267Deutsche Forschungsgemeinschaft 525802829
6 · The paper itself

Abstract

aims/hypothesisThe aim of this work was to understand the role of non-beta cells in pancreatic islets at early stages of type 2 diabetes pathogenesis.

methodsSpecific clustering was employed to single-cell transcriptome data from islet cells of obese mouse strains differing in their diabetes susceptibility (diabetes-resistant B6.V.Lep

resultsRefined clustering analysis revealed several heterogeneous subpopulations for alpha cells, delta cells and macrophages, of which 133 mapped to human diabetes genes identified by genome-wide association studies. Importantly, a similar non-beta cell heterogeneity was found in a dataset of human islets from donors at different stages of type 2 diabetes. The predominant alpha cell cluster in NZO mice displayed signs of cellular stress and lower mitochondrial capacity (97 differentially expressed genes [DEGs]), whereas delta cells from these mice exhibited higher expression levels of maturation marker genes (Hhex and Sst) but lower somatostatin secretion than OB mice (184 DEGs). Furthermore, a cluster of macrophages was almost twice as abundant in islets of OB mice, and displayed extensive cell-cell communication with beta cells of OB mice. Treatment of beta cells with IL-15, predicted to be released by macrophages, activated signal transducer and activator of transcription (STAT3), which may mediate anti-apoptotic effects. Similar to mice, humans without diabetes possess a greater number of macrophages than those with prediabetes (39 mmol/mol [5.7%] < HbA CONCLUSIONS/

interpretationOur study indicates that the transcriptional heterogeneity of non-beta cells has an impact on intra-islet crosstalk and participates in beta cell (dys)function. DATA AVAILABILITY: scRNA-seq data from the previous study are available in gene expression omnibus under gene accession number GSE159211 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE159211 ).

Indexed as

Diabetes Mellitus, Type 2Islets of LangerhansTranscriptomeAnimalsDisease Models, AnimalGlucagon-Secreting CellsHumansInsulin-Secreting CellsMacrophagesMaleMiceMice, Inbred C57BLMice, ObeseBeta cell protectionCell–cell communicationHeterogeneity in isletsMacrophagesType 2 diabetes

Identifiers

PMID39508880
PMCPMC11663180

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.