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Mouse islets express lower levels of reactive oxygen species (ROS) clearing enzymes, such as glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase than several other tissues. It remains unclear if human beta cells show a similar deficiency during T1D or exhibit a higher degree of intrinsic resistance to oxidative stress. We compared islet cell distributions and determined graded intensities of glutathione peroxidase1 (GPX1), a key enzymatic mediator involved in detoxifying hydrogen peroxide, by applying combined immunohistochemistry for GPX1, insulin and glucagon, in pancreatic sections from new-onset T1D (group 1), non-diabetic autoantibody-negative (group 2), non-diabetic autoantibody-positive (group 3) and long-term diabetic (group 4) donors. Islets from all study groups demonstrated either uniform but graded staining intensities for GPX1 in almost all islet cells or strong staining in selective islet cells with weaker intensities in the remaining cells. GPX1 was present in selective glucagon cells and insulin cells, including in cells negative for both hormones, with stronger intensities in a higher percentage of glucagon than insulin cells. It was absent in a higher percentage of beta cells than glucagon cells independent of disease or autoantibody positivity. We conclude that a proportion of human beta cells and glucagon cells express GPX1 but show heterogeneity in its distribution and intensities, independent of disease or autoantibody status. Our studies highlight important differences in the expression of GPX1 in islet cell-types between mice and humans.<\/jats:p>","DOI":"10.1007\/s00441-025-03955-5","type":"journal-article","created":{"date-parts":[[2025,3,9]],"date-time":"2025-03-09T22:27:25Z","timestamp":1741559245000},"page":"255-271","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Distribution of glutathione peroxidase-1 immunoreactive cells in pancreatic islets from type 1 diabetic donors and non-diabetic donors with and without islet cell autoantibodies is variable and independent of disease"],"prefix":"10.1007","volume":"400","author":[{"given":"Kaaj","family":"Pala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Xueying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Krogvold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Dahl-J\u00f8rgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"3955_CR1","doi-asserted-by":"publisher","first-page":"2534","DOI":"10.1007\/s00125-021-05530-3","volume":"64","author":"NS Amirruddin","year":"2021","unstructured":"Amirruddin NS, Tan WX, Tan YS, Gardner DS, Bee YM, Verma CS, Hoon S, Lee KO, Teo AKK (2021) Progressive endoplasmic reticulum stress over time due to human insulin gene mutation contributes to pancreatic beta cell dysfunction. 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Peptides 100:54\u201360","journal-title":"Peptides"}],"container-title":["Cell and Tissue Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-025-03955-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00441-025-03955-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-025-03955-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T01:02:06Z","timestamp":1748566926000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00441-025-03955-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,10]]},"references-count":61,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["3955"],"URL":"https:\/\/doi.org\/10.1007\/s00441-025-03955-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-5369709\/v1","asserted-by":"object"}]},"ISSN":["0302-766X","1432-0878"],"issn-type":[{"value":"0302-766X","type":"print"},{"value":"1432-0878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,10]]},"assertion":[{"value":"1 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval for conducting this study was granted by the New Zealand Ministry of Health and Disability Ethics Committee (Ethics reference: 2023 PR 2121). Harbin Medical University (China), Auckland Tissue Bank and the Department of Anatomy of this faculty provided control tissue sections from the breast, liver and lung and were also covered by the above New Zealand ethics committee approval. Approval for biopsy procurement from new-onset type 1 diabetes donors was granted by the Norwegian Government\u2019s Regional Ethics Committee following informed consent. Ethical approval for the analysis of pancreatic sections from deceased nPOD donors was granted to nPOD. Ethical approval for the analysis of sections from post-mortem pancreas for EADB (\n                      \n                      ) was granted by the West of Scotland Research Committee 4 ((WoSREC4; 15\/\/WS\/0258) to Professors S Richardson and N Morgan, University of Exeter. Therefore, all procedures performed involving human tissue donors were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent for donation and analysis of pancreatic biopsies from DiViD donors was obtained by the DiViD Study Group from the Norwegian Government\u2019s Regional Ethics Committee.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The content and views expressed in this publication are the responsibility of the authors and do not reflect an official view of nPOD, DiViD and EADB.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclaimer"}}]}}