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Article History

Received: 7 June 2024

Accepted: 3 December 2024

First Online: 30 April 2025

Acknowledgements

: We thank members of the Johnson and Jan labs for helpful discussions. We thank the Life Sciences Institute Proteomics Core Facility for expert work. Graphical abstract was created in BioRender. 1, J. (2025)

: RNA-seq data are available at . GEO accession GSE166829. The R scripts for RNA-seq, proteomics and pathway enrichment are available on GitHub ().

: This work was supported by a Diabetes Investigator Award from Diabetes Canada to JDJ and CIHR grants to EJ (PJT148761) and CBV (PJ153156). EP, JDJ, SS, GS and CBV were supported by grant #3-COE-2022-1103-M-B- from Breakthrough T1D. EP was supported by postdoctoral fellowships from Breakthrough T1D and UBC.

: CBV is an Advisory Board member of the Diabetologia Editorial Board. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.

: EP designed the experiments, conducted the majority of the experiments, analysed all data and wrote the manuscript. SS, HHC, AR, JAZ, KYC, KM, GS, DAD, LKH-W, JSW, SM, NN and FT conducted experiments, analysed and interpreted data and reviewed the article critically. CBV interpreted data, designed experiments and reviewed the article critically for important intellectual content. EJ co-conceived the project, designed experiments, supervised experiments and edited the manuscript. JDJ co-conceived the project, supervised experiments, edited the manuscript and is the guarantor of this work. All authors approved of the version to be published.