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Article History

Received: 16 August 2023

Accepted: 18 October 2023

First Online: 21 December 2023

Acknowledgements

: We thank F. O’Harte (University of Ulster, Coleraine, Northern Ireland, UK) for the gift of the GRAs peptides N and R. We also thank S. Barg (Uppsala University, Uppsala, Sweden) for providing the PPPG-NPY adenovirus and H. Yan (REMD Biotherapeutics, USA) for the gift of REMD2.59.

: All data from this study are presented in the published article and the supplementary material. Additional information is available from the corresponding author upon request.

: Studies in Göteborg were covered by a Wallenberg Scholars Fellowship (PR), an International Recruitment Award (538-2013-7107) and project grants from the (2020-01463 and 2020-02485) from the Swedish Research Council (Vetenskapsrådet). NRG’s work in Göteborg was supported by a grant from the Novo Nordisk Foundation (NRG). Initial stages of the project were supported by Diabetes UK RD Lawrence Fellowship (RR and QZ), a Novo Nordisk University of Oxford postdoctoral fellowship (CG) and a project grant from the Rosetrees Trust (PR). The isolation of human islets was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) (PRVJ and PR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Studies in Cambridge were supported by the Rosetrees foundation (to HYY and GL) and an international scholarship from the Cambridge Trust (HYY). Work in Lausanne (BT) was supported by grants from the Swiss National Science Foundation and the European Research Council.

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

: This manuscript reports studies performed over 15 years and that have involved generations of students and postdoctoral fellows. Authorship is in strict compliance with the recommendations of ICMJE. The project was conceived by RR and PR. GL, RR and PR directed the experimental studies, supervised the analysis of the results and interpreted the findings in their respective laboratories. NRG, RG, LK, AP, CS, SA, AB, MVC, AC, CG, MH, JM, CM, MS, AIT, HYY, IWA and QZ designed and performed the experiments and analysed the data in collaboration with or under the guidance of GL, RR and PR. DB, JGK, PRVJ and BT provided valuable experimental models (knockout mice and human islets) and assisted with testing them. PR wrote the manuscript together with RR and GL. All authors contributed to the discussion and read and approved the final version of the manuscript. PR is the guarantor of the work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.