Iida, Hitoshi http://orcid.org/0000-0001-5889-7701
Kono, Tatsuyoshi http://orcid.org/0000-0002-7524-6836
Lee, Chih-Chun http://orcid.org/0000-0003-2802-519X
Krishnan, Preethi http://orcid.org/0000-0001-6957-385X
Arvin, Matthew C. http://orcid.org/0000-0002-1744-2142
Weaver, Staci A. http://orcid.org/0000-0002-2974-2580
Jarvela, Timothy S. http://orcid.org/0000-0001-6364-0900
Branco, Renato C. S. http://orcid.org/0000-0002-6886-7693
McLaughlin, Madeline R. http://orcid.org/0000-0003-0355-591X
Bone, Robert N. http://orcid.org/0000-0003-3222-8918
Tong, Xin http://orcid.org/0000-0003-4408-3832
Arvan, Peter http://orcid.org/0000-0002-4007-8799
Lindberg, Iris http://orcid.org/0000-0002-1188-170X
Evans-Molina, Carmella http://orcid.org/0000-0001-7764-8663
Funding for this research was provided by:
U.S. Department of Veterans Affairs (I01BX001733)
George and Frances Ball Foundation
National Center for Advancing Translational Sciences (TL1 UL1TR002529)
Ball Brothers Foundation
National Institute on Drug Abuse (R01DA042351)
Manpei Suzuki Diabetes Foundation
National Institute of Diabetes and Digestive and Kidney Diseases (F31DK134168, R01DK093954, R01DK127236, R01DK127308, R01DK48280, T32 DK0604466, T32 DK101001, U01DK127747, U01DK127786, UC4DK104166)
Sigma Beta Sorority
Article History
Received: 14 February 2023
Accepted: 13 June 2023
First Online: 4 August 2023
Acknowledgements
: The authors would like to thank E. Anderson-Baucum (freelance science writer, Indianapolis, IN, USA) for her helpful advice and edits. The authors also thank K. Orr and J. Aquino (Indiana University) for their technical assistance. The authors acknowledge the support of the Islet and Physiology, Translation, and Optical Microscopy Cores of the Indiana Diabetes Research Center (P30-DK-097512).
: All data generated or analysed during this study are included in the manuscript and supporting files. Further information and requests for resources and/or reagents should be directed to CE-M (cevansmo@iu.edu). This study did not generate any new unique reagents. RNA-seq data have been deposited in the Gene Expression Omnibus (GEO; accession no.: GSE207498)<u>.</u> This paper does not report original code.
: This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases grants R01DK093954, R01DK127236, U01DK127786, R01DK127308 and UC4DK104166 (to CE-M), R01DK48280 and U01DK127747 (to PA) and R01DA042351 (to IL); Clinical and Translational Sciences grants TL1 UL1TR002529 and F31DK134168 (to SAW), T32 DK0604466 (to MCA) and T32 DK101001 (to MRM); US Department of Veterans Affairs Merit Award I01BX001733 (to CE-M); and gifts from the Sigma Beta Sorority, the Ball Brothers Foundation and the George and Frances Ball Foundation (to CE-M) and the Manpei Suzuki Diabetes Foundation (to HI). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.
: MCA is currently an employee at Cooke Medical. RNB is currently an employee at Cardinal Health. IL received consulting fees from Weil, Gotshal & Manges. CE-M received grants from Astellas Pharmaceuticals and Lilly Pharmaceuticals and also received consulting fees from Dompe Pharmaceuticals. CE-M also has the following patents: ‘A discovery-based proteomics approach identifies protein disulfide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes’ and ‘Extracellular vesicle ribonucleic acid (RNA) cargo as a biomarker of hyperglycaemia and type 1 diabetes’. CE-M previously participated in or actively participates in the Provention Bio Advisory Board, Isla Technologies Advisory Board, Mai Cell Technologies Advisory Board, Avotres Advisory Board, Neurodon Advisory Board and Innodia Advisory Board. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.
: HI designed and conducted the experiments, analysed the data and wrote the manuscript. TK contributed to funding acquisition, conception and design of the study, data analysis and interpretation, collection and assembly of data and manuscript writing/editing. CL, PK, MCA, SAW, TJ, RNB, XT, RCSB and MRM participated in data collection and critical revision of the manuscript. PA and IL contributed to the research design, directed the protein processing analysis experiments, provided critical reagents and participated in critical revision of the manuscript. CE-M directed funding acquisition, study conception and design and manuscript writing. All authors approved of the final version of the manuscript. CE-M is the guarantor of this work, had full access to all of the study data and takes responsibility for the integrity and accuracy of the data.