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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Main Authors: Angie Tegehall, Olle Korsgren, Sofie Ingvast, Gajana Gasparyan, Louise Granlund, Marcus Lundberg
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-04471-w
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Summary: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.
ISSN:2045-2322