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Article History

Received: 18 February 2025

Accepted: 28 April 2025

First Online: 2 July 2025

Acknowledgements

: We thank A. Ahmala, N. Asumaa, J. Ustinov and H. Grym (Medical Faculty, University of Helsinki, Finland) for their expert technical assistance. We thank the Electron Microscopy Unit (Institute of Biotechnology, University of Helsinki, Finland) for providing laboratory facilities. Imaging was performed at the Biomedicum Imaging Unit, University of Helsinki, supported by the Helsinki Institute of Life Science (HiLIFE) and Biocenter Finland. We thank J. Juutila and the MetaStem metabolomics unit (Faculty of Biological and environmental Sciences, University of Helsinki, Finland) for generation of the metabolomics data. We would also like to thank the University of Helsinki laboratory animal centre (LAC) and their animal caretakers for the facilities that allowed for all the animal work in the current study to be conducted. Last but not least, we would like to thank the Nordic Network for Islet Transplantation, the IsletCore (University of Alberta, Canada) and the Center Hospitalier Universitaire de Lille (Lille, France) for supplying human islets for the current study, as well as the islet donors.Some of the data were presented as an abstract at the 59th and 60th Annual Meetings of the EASD in 2023 and 2024.

: All data are available on reasonable request from the corresponding authors.

: Open Access funding provided by University of Helsinki (including Helsinki University Central Hospital). TO and PK acknowledge the funding provided by the Research Council of Finland (grant 297466) and its Center of Excellence (MetaStem, grants 312437, 336195, 353011, 312436, 336194 and 353000). TO acknowledges funding provided by the Sigrid Juselius Foundation and the Novo Nordisk Foundation (NNF22OC0078484). TB acknowledges the funding provided by the Orion Research Foundation. DB acknowledges funding from Research Council of Finland (grant 361593) and Novo Nordisk Foundation (grant NNF24OC0089232). HM acknowledges funding from Doctoral Program in Integrative Life Science at University of Helsinki, Kyllikki and Uolevi Lehikoinen Foundation, the Diabetes Research Foundation and the Maud Kuistila Memorial Foundation.

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

: The study was conceived and planned by EV, JSV, TB and TO, with advice on the experimental work given by HM, VL, SE, HI, EK, DB and PK. SC-islet differentiations were done by EV, JSV, TB, HM and VL. Implantations, blood glucose follow-up measurements and IPGTTs were done by JSV and HM, with assistance from EV. Samples for the dynamic insulin secretion assays were prepared by EV and the assays run by SE, with experiments being planned jointly by EV, TB and SE. ELISAs for C-peptide and insulin were run by SE. Metabolomics sample preparation as well as analysis was done by TB, with assistance from EV. Expert advice on the analysis and interpretation of the metabolomics results was provided by EK. All immunocytochemistry staining was done by EV with help from HM and HI, and quantifications were done by EV with help from HI, using a pipeline originally created by VL. Imaging and analysis of electron micrographs were done by EV. Reanalysis of single-cell data was done by DB. The original manuscript was written by EV. The manuscript was revised and the final version approved by all coauthors. TO is responsible for the integrity of the work as a whole.