Kothegala, L and Miranda, C and Singh, M and Krieger, J-P and Gandasi, NR (2023) Somatostatin Containing δ-Cell Number Is Reduced in Type-2 Diabetes. In: International Journal of Molecular Sciences, 24 (4).
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Abstract
Recent developments suggest that increased glucagon and decreased somatostatin secretion from the pancreas contribute to hyperglycaemia in type-2 diabetes (T2D) patients. There is a huge need to understand changes in glucagon and somatostatin secretion to develop potential anti-diabetic drugs. To further describe the role of somatostatin in the pathogenesis of T2D, reliable means to detect islet δ-cells and somatostatin secretion are necessary. In this study, we first tested currently available anti-somatostatin antibodies against a mouse model that fluorescently labels δ-cells. We found that these antibodies only label 10–15% of the fluorescently labelled δ-cells in pancreatic islets. We further tested six antibodies (newly developed) that can label both somatostatin 14 (SST14) and 28 (SST28) and found that four of them were able to detect above 70% of the fluorescent cells in the transgenic islets. This is quite efficient compared to the commercially available antibodies. Using one of these antibodies (SST10G5), we compared the cytoarchitecture of mouse and human pancreatic islets and found fewer δ-cells in the periphery of human islets. Interestingly, the δ-cell number was also reduced in islets from T2D donors compared to non-diabetic donors. Finally, with the aim to measure SST secretion from pancreatic islets, one of the candidate antibodies was used to develop a direct-ELISA-based SST assay. Using this novel assay, we could detect SST secretion under low and high glucose conditions from the pancreatic islets, both in mice and humans. Overall, using antibody-based tools provided by Mercodia AB, our study indicates reduced δ-cell numbers and SST secretion in diabetic islets. © 2023 by the authors.
| Item Type: | Journal Article |
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| Publication: | International Journal of Molecular Sciences |
| Publisher: | MDPI |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | glucagon; insulin; somatostatin, cell count; human; non insulin dependent diabetes mellitus; pancreas islet, Cell Count; Diabetes Mellitus, Type 2; Glucagon; Humans; Insulin; Islets of Langerhans; Somatostatin |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology Division of Biological Sciences > Molecular Reproduction, Development & Genetics Others |
| Date Deposited: | 15 Mar 2023 06:00 |
| Last Modified: | 15 Mar 2023 06:00 |
| URI: | https://eprints.iisc.ac.in/id/eprint/80981 |
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