Islet delta-cell architecture is remodelled in the human pancreas during type 1 diabetes
Abstract Delta cells participate in regulating hormone secretion in adjacent alpha- and beta cells and a general assumption is that cells with a shorter distance to the secreting cell receive a higher concentration of the secretory compounds. Isolated islets obtained from donors with type 1 diabetes...
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Nature Portfolio
2025-06-01
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| Online Access: | https://doi.org/10.1038/s41598-025-04471-w |
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| author | Angie Tegehall Olle Korsgren Sofie Ingvast Gajana Gasparyan Louise Granlund Marcus Lundberg |
| author_facet | Angie Tegehall Olle Korsgren Sofie Ingvast Gajana Gasparyan Louise Granlund Marcus Lundberg |
| author_sort | Angie Tegehall |
| collection | DOAJ |
| description | Abstract Delta cells participate in regulating hormone secretion in adjacent alpha- and beta cells and a general assumption is that cells with a shorter distance to the secreting cell receive a higher concentration of the secretory compounds. 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’ exposure to somatostatin. This finding may be a link partly explaining the reduced glucagon response to hypoglycemia in type 1 diabetes. |
| format | Article |
| id | doaj-art-e96d99db9cd6448ea1ed33f0801576ca |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-e96d99db9cd6448ea1ed33f0801576ca2025-08-20T02:31:04ZengNature PortfolioScientific Reports2045-23222025-06-011511810.1038/s41598-025-04471-wIslet delta-cell architecture is remodelled in the human pancreas during type 1 diabetesAngie Tegehall0Olle Korsgren1Sofie Ingvast2Gajana Gasparyan3Louise Granlund4Marcus Lundberg5Department of Immunology, Genetics and Pathology, Uppsala UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityAbstract Delta cells participate in regulating hormone secretion in adjacent alpha- and beta cells and a general assumption is that cells with a shorter distance to the secreting cell receive a higher concentration of the secretory compounds. 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’ exposure to somatostatin. This finding may be a link partly explaining the reduced glucagon response to hypoglycemia in type 1 diabetes.https://doi.org/10.1038/s41598-025-04471-wDelta cellType 1 diabetesAlpha cellHypoglycemiaType 2 diabetesSomatostatin |
| spellingShingle | Angie Tegehall Olle Korsgren Sofie Ingvast Gajana Gasparyan Louise Granlund Marcus Lundberg Islet delta-cell architecture is remodelled in the human pancreas during type 1 diabetes Scientific Reports Delta cell Type 1 diabetes Alpha cell Hypoglycemia Type 2 diabetes Somatostatin |
| title | Islet delta-cell architecture is remodelled in the human pancreas during type 1 diabetes |
| title_full | Islet delta-cell architecture is remodelled in the human pancreas during type 1 diabetes |
| title_fullStr | Islet delta-cell architecture is remodelled in the human pancreas during type 1 diabetes |
| title_full_unstemmed | Islet delta-cell architecture is remodelled in the human pancreas during type 1 diabetes |
| title_short | Islet delta-cell architecture is remodelled in the human pancreas during type 1 diabetes |
| title_sort | islet delta cell architecture is remodelled in the human pancreas during type 1 diabetes |
| topic | Delta cell Type 1 diabetes Alpha cell Hypoglycemia Type 2 diabetes Somatostatin |
| url | https://doi.org/10.1038/s41598-025-04471-w |
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