biostudies-literaturePrefontaine CCanada Foundation for Innovation John R. Evans Leaders FundCanadian Institutes of Health Research and Breakthrough T1DCanadian Islet Research and Training Network and NSERC-CREATE programInstitute of Nutrition, Metabolism and DiabetesBreakthrough T1D Advanced Postdoctoral FellowshipManitoba Medical Service FoundationCanadian Islet Research and Training Network and Breakthrough T1DDiabetes Canada421-435https://www.ebi.ac.uk/biostudies/studies/S-EPMC12779684biostudies-literatureUnknown69(2)<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>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. LeDiabetologiaInsulin production is sustained during DNA damage-mediated senescence in adult human beta cells.PMC12779684431683-APF-2022–1141-A-NPJT-4796412023 Allen Rouse Basic Science Career DevelopmentMSc training award197485OG-3-22-5694-PT3-APF-2022-1141-A-Npostdoctoral fellowship awardTDP-1863593-COE-2022-1103-M-BPJT-485915Thompson PJChen YCPrefontaine CPipella JRampazzo Morelli NVerchere CBfalseInsulin production is sustained during DNA damage-mediated senescence in adult human beta cells.<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>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. Le2026-01-01T00:00:00Z2026 Feb2026-07-15T07:48:54.114Z2026-07-01T03:07:42.164ZS-EPMC127796844123125610.1007/s00125-025-06603-3