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Article History

Received: 7 August 2025

Accepted: 5 September 2025

First Online: 13 November 2025

Acknowledgements

: We thank the organ donors and their families. We thank the Network for Pancreatic Organ Donors (nPOD) (University of Florida, USA) for fixed pancreatic tissue sample procurement and distribution. We also thank the Alberta Diabetes Institute IsletCore for providing human islets for research with the assistance of the Human Organ Procurement and Exchange (HOPE) program, Trillium Gift of Life Network (TGLN) and other Canadian organ procurement organisations. The authors thank the NIDDK-funded Integrated Islet Distribution Program (IIDP) (RRID:SCR _014387) at City of Hope, NIH grant no. U24DK098085 and the Breakthrough T1D (formerly JDRF)-funded IIDP Islet Award Initiative for providing human islets for research for this study. This manuscript used data acquired from the database ( ) of the Human Pancreas Analysis Program (HPAP; RRID:SCR_016202; PMID: 31127054; PMID: 36206763). HPAP is part of a Human Islet Research Network (RRID:SCR_014393) consortium (UC4-DK112217, U01-DK123594, UC4-DK112232 and U01-DK123716). This work also includes data and/or analyses from HumanIslets.com funded by the Canadian Institutes of Health Research, Breakthrough T1D Canada, and Diabetes Canada (5-SRA-2021-1149-S-B/TG 179092) with data from islets isolated by the Alberta Diabetes Institute IsletCore with the support of the Human Organ Procurement and Exchange program, Trillium Gift of Life Network, BC Transplant, Quebec Transplant and other Canadian organ procurement organisations with written informed donor consent as approved by the Human Research Ethics Board at the University of Alberta (Pro00013094). The graphical abstract was created in BioRender.com.

: All data related to the manuscript are included in the text or in the .

: CP was supported by a Canadian Islet Research Network NSERC-CREATE MSc studentship award. JP was supported by a PhD studentship in Health Research from Research Manitoba. NRM was supported by a Canadian Islet Research Network-Breakthrough T1D postdoctoral fellowship award. CBV was supported by grants from the Canadian Institutes of Health Research and Breakthrough T1D (TDP-186359; 3-COE-2022-1103-M-B). Y-CC was supported by an Advanced Post-doctoral Fellowship from Breakthrough T1D (3-APF-2022–1141-A-N) and a Research Excellence, Diversity, and Independence (REDI) Early Career Transition Award from the Canadian Institutes of Health Research and Breakthrough T1D (197485). The laboratory of PJT was supported by a Diabetes Canada End Diabetes 2022 grant (OG-3-22-5694-PT), grants from the Canadian Institutes of Health Research (PJT-479641 and PJT-485915) and Breakthrough T1D Canada (4-SRA-2023-1184-S-N), the 2023 Allen Rouse Basic Science Career Award from the Manitoba Medical Services Foundation and the Canada Foundation for Innovation John Evan Leaders Fund award (43168).

: CBV receives a salary award from the BC Children’s Hospital Research Institute. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.

: CP, JP, NRM and PJT designed the experiments. CP, JP, NRM and YCC performed the experiments with input and guidance from PJT. CBV, PJT and CP wrote the manuscript with editing by JP, NRM, YCC and CBV. All authors approved the final manuscript for submission. PJT is the guarantor of this work.