Developmental beta-cell death orchestrates the islet's inflammatory milieu by regulating immune system crosstalk.

ABSTRACT: While pancreatic beta-cell proliferation has been extensively studied, the role of cell death during islet development remains incompletely understood. Using a genetic model of caspase inhibition in beta cells coupled with mathematical modeling, we here discover an onset of beta-cell death in juvenile zebrafish, which regulates beta-cell mass. Histologically, this beta-cell death is underestimated due to phagocytosis by resident macrophages. To investigate beta-cell apoptosis at the molecular level, we implement a conditional model of beta-cell death linked to Ca²⁺ overload. Transcriptomic analysis reveals that metabolically-stressed beta cells follow paths to either de-differentiation or apoptosis. Beta cells destined to die activate inflammatory and immuno-regulatory pathways,

SUBMITTER: Akhtar MN 

PROVIDER: S-EPMC11833124 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature