ArticleDiabetologia2025
Transcriptomic heterogeneity of non-beta islet cells is associated with type 2 diabetes development in mouse models.
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.
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Who cites it
4 citing papers in PubMed.
- Exercise Resistance in Obese Male NZO Mice Manifests as Local Muscle Remodelling Without Glycaemic Improvements.Diabetes, obesity & metabolism · 2026Article
- Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.Clinical reviews in allergy & immunology · 2025Review
- Application and Progression of Single-Cell RNA Sequencing in Diabetes Mellitus and Diabetes Complications.Journal of diabetes research · 2025Review
- Interactions between islet-resident macrophages and β cells in diabetes.Frontiers in immunology · 2025Review
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Authors and funding
8 authors.
Funding
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 ).
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