ArticleMolecular metabolism2025
Constructing chimeric mouse islets to study alpha- and delta-cell influence on beta-cell feature.
Article in Molecular metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Transient ER stress cell-autonomously promotes beta cell cycling in mice.Diabetologia · 2026Article
- Biological sex affects human islet gene expression and mitochondrial function in type 2 diabetes.Endocrinology · 2026Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThis study aimed to evaluate the role of alpha- and delta-cell signals on beta-cells within pancreatic mouse islets. Specifically, we investigated how these signals regulate glucose sensitivity, gene expression and function in beta-cells.
methodsWe first implemented our previous protocol to FACS purify alpha-, beta-, and delta-cells by adding CD81 as a positive marker for alpha-cells. We next developed an approach to reaggregate these sorted cell populations, creating chimeric islets with different proportions of each endocrine cell type. We used these chimeric islets to study the effect of alpha- and delta-cells on glucose sensitivity, gene expression and function in beta-cells.
resultsWe generated chimeric islets containing either all three endocrine cell types, alpha- + beta-cells or only beta-cells. We demonstrate that beta-cell glucose sensitivity and identity are independent of signals from alpha- and delta-cells. We identified a subset of genes including Pro-dynorphin, Fumarate hydratase and Txnip whose expression in beta-cells depends on alpha-cells signals acting through the glucagon- and glucagon-like peptide receptors. Finally, we demonstrated that in mouse beta-cell, KCl-mediated insulin secretion relies on an activation of the glucagon-receptor, while glucose-stimulated insulin secretion depends on glucagon-like peptide receptor activation.
conclusionsWe developed an innovative and easy-to-use model to reconstruct chimeric islets containing different frequencies of alpha-, beta- and delta-cells. Through this approach, we provide new insights into the complex regulatory mechanisms governing the role of alpha and delta cells on beta-cell features within islets.
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Registered trials
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