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Article History

Received: 29 November 2024

Accepted: 3 July 2025

First Online: 26 September 2025

Acknowledgements

: We thank C. Wollheim (Excellence of Diabetes Research in Sweden, Lund University, Sweden) for providing us the INS-1E cells. We also thank J. Feng (Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore) for helping with the experiments involving the overexpression constructs and gene expression.

: Volcano plots of significant KEGG pathways listed in Fig. b can be found in the ESM. All other datasets are available from the corresponding author on request.

: YA is supported by the Ministry of Education Singapore (MOE-T2EP30221-0003, 2019-T1-001-059, RG30/23) and the National Research Foundation (NRF2020-THE003-0006). This work was also partly supported by the LKCMedicine Healthcare Research Fund (Diabetes Research), established through the generous support of alumni of Nanyang Technological University, Singapore. DK is supported by the NUS Research Scholarship for his PhD. AKKT is supported by IMCB, A*STAR, HLTRP/2022/NUS-IMCB-02, OFIRG21jun-0097, CSASI21jun-0006, MTCIRG21-0071, H22G0a0005, I22D1AG053, HLCA23Feb-0031, SC36/19-000801-A044, H24G1a0015 and M24N2K0087. GAR is supported by a Wellcome Trust Investigator Award (WT212625/Z/18/Z), MRC Programme grant (MR/R022259/1), Diabetes UK (BDA 16/0005485) and NIH-NIDDK (R01DK135268) project grants, a CIHR-Breakthrough T1D (formerly known as JDRF) Team grant (CIHR-IRSC TDP-186358 and JDRF 4-SRA-2023-1182-S-N), CRCHUM start-up funds and an Innovation Canada John R. Evans Leader Award (CFI 42649).

: AKKT is a co-founder and shareholder of BetaLife Pte Ltd but is not employed by BetaLife Pte Ltd. GAR has received grant funding from, and is a consultant for, Sun Pharmaceuticals Inc. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.

: QWCH and YA designed the study and wrote the manuscript. GAR and AKKT provided input on the study design. QWHC, DG, RC, HJB, XYC, SD, VST, DK, XW and DYT performed the experiments. JAM and BL analysed and generated figures for the RNA-seq data. All authors reviewed and approved the final version of the manuscript. YA supervised the project and is the guarantor of this work.