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Article History

Received: 13 March 2026

Accepted: 15 June 2026

First Online: 21 September 2026

Ethics

Acknowledgements: The authors wish to thank B. and J. Bergstein, L. and T. Schwartz, and M. and F. Farkouh families for their constant support of this research. We thank S. Mueller at Evotec in Munich, Germany, for help with proteomics. We also thank the NIDDK-supported Human Islet and Adenovirus Core (HIAC) of the Einstein-Sinai Diabetes Research Center (ES-DRC), the NIDDK Integrated Islet Distribution Program (IIDP), Prodo Laboratories, P. MacDonald at the Alberta Diabetes Institute Islet Core at the University of Alberta in Edmonton ( ) with the assistance of the Human Organ Procurement and Exchange (HOPE) program, Trillium Gift of Life Network (TGLN), and other Canadian organ procurement organisations. We also thank T. Kin (University of Alberta, Edmonton, AB, Canada), P. Witkowski (University of Chicago, Chicago, IL, USA) and. F. Kandeel (City of Hope Medical Center, Duarte, CA, USA) for providing human organ donor islets.

Data availability: The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request. Data will be made available upon publication of this article and will remain available for at least 5 years following publication. Data will be shared with qualified researchers for academic, non-commercial research purposes, subject to institutional approvals, material transfer agreements where applicable, and compliance with relevant ethical and data-sharing regulations.

Funding: This work was supported by NIH grants P30DK020541, R01DK116873, R01DK116904, R01DK125285, R01DK105015, R01DK129196, R01 GM132129, R01DK139631, R35GM124838, R35CA232128 and P01CA203655.

Authors’ relationships and activities: PW, AFS, KK, RJD and AGO are inventors on patents filed by The Icahn School of Medicine at Mount Sinai. PaulexBio has licensed this patent portfolio from The Icahn School of Medicine at Mount Sinai. AFS, RJD and AGO are consultants for PaulexBio. AGO consults for Sun Pharmaceuticals. The other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

Contribution statement: PW, KK, RJD and AFS conceived and designed the study. PW, OW, HL, AP, SC, MBL, SK, EK and SM acquired data and performed experiments. PW, LL and AFS analysed and interpreted data. KK, RJD, DKS, AGO and EK contributed critical reagents, technical expertise and interpretation of data. JAP and SPG contributed to proteomic analyses, technical expertise and interpretation of data. PW and AFS drafted the manuscript. All authors critically reviewed and revised the manuscript for important intellectual content and approved the final version for publication. PW and AFS guarantee the data in this manuscript.