Department of Physiology (Phycell), Veterinary Faculty, University of Extremadura, Cáceres, Spain.
Animal House of University of Extremadura, University of Extremadura, Cáceres, Spain.
J Cell Mol Med. 2018 Jan;22(1):684-694. doi: 10.1111/jcmm.13355. Epub 2017 Oct 9.
Stanniocalcins are expressed in the pancreas tissue, and it was suggested a direct correlation between circulating insulin and STC2 concentrations in human. Here, we show a significant correlation between STC1 and both glycaemia and glycosylated haemoglobin among DM2 patients, while DM2 patients who present the greatest glycosylated haemoglobin values exhibited the lowest STC2 expression. However, treatment of patients with antiglycaemic drugs does not significantly modify the expression of both STCs. On the other hand, STC2 mice that exhibited neonatal and adult overweight further presented deregulated glycaemia when they were feed with a hypercaloric diet (breeding pellet, BP). This alteration is more evident at the early stages of the animal life. Deregulated glycaemia in these mice was confirmed using glucose oral test. In addition, STC2 mice present enhanced pancreas size; thus, the histological analysis reveals that WT mice respond to BP diet by increasing the size of the pancreatic islets through inducing cell division, and STC2 mice lack this compensatory mechanism. Contrary, BP fed STC2 mice show enhanced number of islets but of similar size than those fed with regular pellet. Histopathological analysis demonstrates tissue structure disruption and erythrocytes infiltrations in STC2 mice, possibly due to the stress evoked by the BP diet. Finally, enhanced glucagon immunostaining was observed in the islet of STC2 mice, and the glucagon ELISA assay confirmed the increase in the circulating glucagon. Summarizing, we present evidence of the role of STCs, mainly STC2, as a possible early marker during development of diabetes mellitus.
斯坦尼钙素在胰腺组织中表达，有人提出循环胰岛素和人类 STC2 浓度之间存在直接相关性。在这里，我们显示 STC1 与 2 型糖尿病患者的血糖和糖化血红蛋白之间存在显著相关性，而糖化血红蛋白值最高的 2 型糖尿病患者表现出最低的 STC2 表达。然而，用抗血糖药物治疗患者并不能显著改变两种 STC 的表达。另一方面，表现出新生儿和成年超重的 STC2 小鼠在用高热量饮食（繁殖颗粒，BP）喂养时进一步表现出血糖失调。这种改变在动物生命的早期阶段更为明显。使用葡萄糖口服试验证实了这些小鼠的血糖失调。此外，STC2 小鼠的胰腺体积增大；因此，组织学分析表明，WT 小鼠通过诱导细胞分裂来增加胰岛的大小来应对 BP 饮食，而 STC2 小鼠缺乏这种代偿机制。相反，用 BP 喂养的 STC2 小鼠显示胰岛数量增加，但大小与用常规颗粒喂养的相似。组织病理学分析表明 STC2 小鼠存在组织结构破坏和红细胞浸润，可能是由于 BP 饮食引起的应激。最后，在 STC2 小鼠的胰岛中观察到胰高血糖素免疫染色增强，并且胰高血糖素 ELISA 测定证实循环胰高血糖素增加。总之，我们提出了 STCs（主要是 STC2）作为糖尿病发展过程中早期标志物的作用的证据。
