Insulin production is sustained during DNA damage-mediated senescence in adult human beta cells.

ABSTRACT:

Aims/hypothesis

Residual pancreatic beta cells in type 1 diabetes show reduced insulin production but the mechanisms remain unclear. Beta cells undergo stress responses during type 1 diabetes, including endoplasmic reticulum (ER) stress and DNA damage-associated senescence, which may affect insulin production. ER stress reduces insulin production but whether senescence disrupts insulin production in human beta cells has not been investigated.

Methods

DNA damage-mediated senescence was induced using bleomycin in human donor islets. Relative levels of prohormone convertase 1/3 (PC1/3), prohormone convertase 2 (PC2), carboxypeptidase E (CPE) and the endogenous PC1/3 inhibitor, proprotein convertase subtilisin/kexin type 1 inhibitor (proSAAS), were quantified by western blot. Le

SUBMITTER: Prefontaine C 

PROVIDER: S-EPMC12779684 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature