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During type 1 diabetes (T1D) and its preceding phase, it is unclear whether syntaxin-4 levels decline in residual beta cells, thereby contributing to impaired insulin release. The level of syntaxin-4 in insulin-positive regions of islets was determined following immunofluorescence staining of human pancreatic sections, with co-immunofluorescence staining for insulin and for glucagon by immunoperoxidase. Random islets from non-diabetic autoantibody-negative (Group 1;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097), non-diabetic autoantibody-positive (Group 2;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096), new-onset T1D (Group 3;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094) and long-term T1D (Group 4;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910) donors were quantified for syntaxin-4 levels. In groups 1 and 2, inter-islet staining intensities for syntaxin-4, although variable across individual donors, were similar overall between the groups, with lower intensities in group 3. In group 4, 3 donors with 0.58\u20131.5 years of T1D showed mean intensities comparable to groups 1 and 2, whereas donors with 4\u20137 years of T1D showed declining intensities. In general, the average syntaxin-4 intensities in the two diabetic groups were lower than those in the non-diabetic groups. The expression of syntaxin-4 in insulin-positive islet cells showed marked differences in intensity among most diabetic donors and autoantibody-positive and -negative non-diabetic donors. In some long-term diabetic donors, syntaxin-4 was also present in insulin- and glucagon-negative cells. During protracted T1D, reduced syntaxin-4 in islets may impair insulin release.\n                  <\/jats:p>","DOI":"10.1007\/s10735-026-10901-4","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T03:30:28Z","timestamp":1785382228000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Syntaxin-4, a key exocytosis mediating protein, shows heterogeneous expression in insulin-positive cells of human donors with new-onset and longer duration of type 1 diabetes: comparison with non-diabetic autoantibody-positive and -negative donors"],"prefix":"10.1007","volume":"57","author":[{"given":"Joshua","family":"Potman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Xueying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaaj","family":"Pala","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":[[2026,7,30]]},"reference":[{"key":"10901_CR1","doi-asserted-by":"publisher","first-page":"6121","DOI":"10.1038\/s41467-025-61534-2","volume":"16","author":"S \u00c1lvarez-Cubela","year":"2025","unstructured":"\u00c1lvarez-Cubela S, Altilio ID, Doke M, Klein D, Tamayo A, Alc\u00e1zar \u00d3, Santana CG, Qadir MMF, Alver CG, Cruz F, Biggs O, Tovar Castro JD, Navarro-Rubio B, Ricordi C, Caicedo A, Buchwald P, Agarwal A, Oltra E, Pastori RL, Dom\u00ednguez-Bendala J (2025) Pancreatic \u03b2-cell regeneration in situ by the ALK3 agonist THR-123. 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J Clin Investig 129:3252\u20133263","journal-title":"J Clin Investig"}],"container-title":["Journal of Molecular Histology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-026-10901-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10735-026-10901-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-026-10901-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:48:41Z","timestamp":1786949321000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10735-026-10901-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10901"],"URL":"https:\/\/doi.org\/10.1007\/s10735-026-10901-4","relation":{},"ISSN":["1567-2379","1567-2387"],"issn-type":[{"value":"1567-2379","type":"print"},{"value":"1567-2387","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]},"assertion":[{"value":"11 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","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). 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. 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","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"252"}}