Heparan sulfate fine-tuned interleukin-1 (IL-1) signaling inhibits insulin secretion of grafted pancreatic islets.

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 bind

SUBMITTER: Wrublewsky S 

PROVIDER: S-EPMC12333676 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature