ArticleScience advances2025
Heparan sulfate fine-tuned interleukin-1 (IL-1) signaling inhibits insulin secretion of grafted pancreatic islets.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Inflammatory Cytokines Impair Glucagon Expression and Secretion in Pancreatic α-Cells.Diabetes, obesity & metabolism · 2026Article
- Urinary Extracellular Vesicle-Derived miRNAs as Regulators and Biomarkers in Diabetic Kidney Disease.International journal of molecular sciences · 2026Review
- Preclinical Analysis of Sex-Specific Differences in the Angiogenic and Inflammatory Tissue Response to Surgical Sutures.Journal of functional biomaterials · 2026Article
- Mitochondria-associated programmed cell death in pancreatic β cell of T2DM.Apoptosis : an international journal on programmed cell death · 2026Review
- Immunosenescence in Older Patients with Psoriasis: Mechanistic Insights and Opportunities for Biologic Therapy.Psoriasis (Auckland, N.Z.) · 2026Review
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Authors and funding
14 authors.
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Abstract
Islet-resident macrophages contribute to hypoxia-induced islet cell death during pancreatic islet transplantation. However, their specific role during this process remains elusive. Here, we report that interleukin-1α (IL-1α) and IL-1β are released by islet-resident macrophages, resulting in the suppression of insulin secretion. This may be due to a decreased inflammation-driven expression of pancreatic and duodenal homeobox 1 (PDX-1) and MafA in β cells. Islet-resident macrophages release significantly less IL-1α when compared to IL-1β. However, both cytokines inhibit insulin expression and secretion to a comparable extent. We identified heparan sulfate on the islet surface, which acts as a "molecular glue" potentiating the inhibitory action of IL-1α on insulin expression via specific binding to IL-1 receptor (IL-1R). In vivo analyses revealed that the loss of IL-1 signaling in isolated islets accelerates their revascularization and, thus, enhances their endocrine function. These findings indicate that heparan sulfate fine-tuned IL-1 signaling crucially determines the outcome of islet transplantation.
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