Islet delta-cell architecture is remodelled in the human pancreas during type 1 diabetes

• Published in: Scientific reports Vol. 15; no. 1; pp. 19776 - 8
• Main Authors: Tegehall, Angie, Korsgren, Olle, Ingvast, Sofie, Gasparyan, Gajana, Granlund, Louise, Lundberg, Marcus
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.06.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 692/163/2743/137/1418; 692/163/2743/137/773; 692/420; 692/699/249/1313/1418; Adult; Alpha cell; Beta cells; Delta cell; Delta cells; Diabetes; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Female; Glucagon; Glucagon - metabolism; Glucagon-Secreting Cells - metabolism; Glucagon-Secreting Cells - pathology; Humanities and Social Sciences; Humans; Hypoglycemia; Insulin - metabolism; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Male; Middle Aged; multidisciplinary; Pancreas; Pancreas - metabolism; Pancreas - pathology; Science; Science (multidisciplinary); Secretion; Somatostatin; Somatostatin - metabolism; Somatostatin-Secreting Cells - metabolism; Somatostatin-Secreting Cells - pathology; Type 1 diabetes; Type 2 diabetes; Type 2 diabetes; Delta cell; Alpha cell; Somatostatin; Hypoglycemia; Type 1 diabetes
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-04471-w

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.