Cell Metabolism Lab (GA-08), Department of Developmental Biology and Genetics (DBG), Indian Institute of Science (IISc), Bengaluru 560012, India.
Department of Metabolic Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Box 430, 40530 Gothenburg, Sweden.
Int J Mol Sci. 2023 Feb 9;24(4):3449. doi: 10.3390/ijms24043449.
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.
最近的研究进展表明，胰腺中胰高血糖素分泌增加和生长抑素分泌减少导致 2 型糖尿病（T2D）患者的高血糖。因此，迫切需要了解胰高血糖素和生长抑素分泌的变化，以开发潜在的抗糖尿病药物。为了进一步描述生长抑素在 T2D 发病机制中的作用，需要可靠的方法来检测胰岛 δ 细胞和生长抑素的分泌。在这项研究中，我们首先用现有的抗生长抑素抗体检测了一种荧光标记 δ 细胞的小鼠模型。我们发现这些抗体只能标记胰岛中荧光标记的 δ 细胞的 10-15%。我们进一步测试了六种（新开发的）可以标记生长抑素 14（SST14）和 28（SST28）的抗体，发现其中四种抗体能够检测到转基因胰岛中超过 70%的荧光细胞。与市售抗体相比，这一效率相当高。使用其中一种抗体（SST10G5），我们比较了小鼠和人胰岛的细胞结构，发现人胰岛的外周 δ 细胞较少。有趣的是，与非糖尿病供体相比，T2D 供体的胰岛中 δ 细胞数量也减少了。最后，为了测量胰岛分泌的 SST，我们使用了候选抗体之一开发了基于直接 ELISA 的 SST 检测方法。使用这种新的检测方法，我们可以在低葡萄糖和高葡萄糖条件下从胰岛中检测到 SST 的分泌，无论是在小鼠还是人类中。总的来说，使用 Mercodia AB 提供的抗体工具，我们的研究表明糖尿病胰岛中 δ 细胞数量和 SST 分泌减少。
