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Article History

Received: 13 September 2025

Accepted: 3 April 2026

First Online: 5 June 2026

Acknowledgements

: We extend our deepest gratitude to the courageous families who generously donated their loved one’s organs and tissues for biomedical research. Such necessary research as this would not be possible without this selfless gift of hope. Thanks to the efforts of IIDP and Network for Hope (Louisville and Cincinnati) and Lifeline of Ohio, Columbus, for supporting these special families and providing human research pancreases to A. N. Balamurugan’s islet laboratory. We also thank members of A. N. Balamurugan’s islet laboratory for their contributions to islet research and transplant.

: The RNA-seq data were deposited in the Gene Expression Omnibus (GEO) (GSE307815 for scRNA-seq and GSE307751 for bulk RNA-seq). They are now freely available from the following sites: ; and . GG is the guarantor of the data, and he will fulfil reasonable resource and reagent requests.

: This study is supported by NIH grants (DK125696 and DK128710 for GG, DK103831 and CA274367 for KSL, YX and AJS). The imaging facility used is funded by grants CA68485, DK20593, DK58404, DK59637 and EY08126.

: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

: RH, MY, XT and GG designed and performed human PSI production, GSIS, immunofluorescence assays and imaging. NH performed the type 2 diabetes association studies and beta cell immunofluorescence imaging. RH performed ITT and TD designed and performed PSI transplantation. JL and CH helped with viral production and PSI growth. YW and QL critically analysed scRNA-seq data to help with hypothesis generation. YX, AJS and KSL designed and performed scRNA-seq using InDrop. PD and DJ designed and did Ca 2+ recording. AB performed human islet isolation. RS, IK, AB, QL, KC and GG conceptualised the overall study. All authors participated in manuscript writing/proofing, and approved the submission. GG is the guarantor of this work.