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Isolated islets obtained from donors with type 1 diabetes have a reduced glucagon secretion during low glucose levels, but adding a somatostatin receptor inhibitor increases the glucagon secretion. Despite this, information regarding the delta-cell architecture during diabetes is sparse. The aim of the current study was to determine intra-islet and extra-islet delta-cell architecture in the pancreas during long-standing type 1 diabetes or type 2 diabetes. Pancreatic tissue from nine donors with long-standing type 1 diabetes, six donors with type 2 diabetes, and 13 donors without diabetes were obtained. Sections co-stained for somatostatin, glucagon, and insulin were manually examined. There was an approximately two-fold higher number of alpha cells directly adherent to delta cells in subjects with type 1 diabetes compared with non-diabetic subjects. The delta cells were more peripherally located within the islets of donors with type 1 diabetes. The density of extra-islet single delta cells in the acinar region was more than three-fold higher in type 1 diabetes compared with non-diabetic subjects. No differences in delta-cell architecture could be determined in type 2 diabetes compared to non-diabetic subjects. In conclusion, the islet delta-cell architecture in human type 1 diabetes is remodelled. The higher number of alpha cells directly adherent to delta cells in type 1 diabetes likely increases the alpha cells\u2019 exposure to somatostatin. This finding may be a link partly explaining the reduced glucagon response to hypoglycemia in type 1 diabetes.<\/jats:p>","DOI":"10.1038\/s41598-025-04471-w","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:32:03Z","timestamp":1749101523000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Islet delta-cell architecture is remodelled in the human pancreas during type 1 diabetes"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5489-6688","authenticated-orcid":false,"given":"Angie","family":"Tegehall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8524-9547","authenticated-orcid":false,"given":"Olle","family":"Korsgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie","family":"Ingvast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajana","family":"Gasparyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2888-486X","authenticated-orcid":false,"given":"Louise","family":"Granlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-2237","authenticated-orcid":false,"given":"Marcus","family":"Lundberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"issue":"8","key":"4471_CR1","doi-asserted-by":"publisher","first-page":"2968","DOI":"10.2337\/db13-0164","volume":"62","author":"N Karimian","year":"2013","unstructured":"Karimian, N. et al. 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