Nesfatin-1 stimulates glucagon and insulin secretion and beta cell NUCB2 is reduced in human type 2 diabetic subjects
Nesfatin-1 stimulates glucagon and insulin secretion and beta cell NUCB2 is reduced in human type 2 diabetic subjects
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DOI：
10.1007/s00441-011-1268-5
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发表时间：
2011-12-01
影响因子：
3.6
通讯作者：
Wierup, Nils
中科院分区：
文献类型：
--
作者：
Riva, Matteo;Nitert, Marloes Dekker;Wierup, Nils
Nesfatin-1是一种新型的厌氧性调节肽。该肽是核结合蛋白2 （NUCB2）的n端部分，在调节摄食的脑区表达。在脑外，nesfatin-1在脂肪细胞、胃内分泌细胞和胰岛细胞中也有表达。我们采用免疫细胞化学、原位杂交和western blot技术研究了NUCB2在人和啮齿动物胰岛中的表达。此外，我们还研究了nesfatin-1对体外、体内小鼠和INS-1（832/13）细胞分泌胰岛素和胰高血糖素的潜在影响。采用芯片技术研究了2型糖尿病（T2D）和糖脂毒性对人胰岛NUCB2基因表达的影响及其与胰岛素分泌能力和胰岛基因表达的关系。Nesfatin-1免疫反应性（IR）在人和啮齿动物β细胞中丰富，但在α、δ、PP和ghrelin细胞中缺乏。重要的是，原位杂交显示NUCB2 mRNA在人和大鼠胰岛中表达。Western blot分析显示，nesfatin-1 IR在啮齿动物胰岛中代表全长NUCB2。人胰岛NUCB2 mRNA在T2D受试者中减少，但在糖脂中毒条件下培养后上调。此外，NUCB2与胰高血糖素和胰岛素基因表达以及胰岛素分泌能力呈正相关。Nesfatin-1增强胰高血糖素分泌，但对小鼠胰岛或INS-1（832/13）细胞的胰岛素分泌无影响。另一方面，在IVGTT期间，nesfatin-1引起小鼠胰岛素分泌的少量增加和葡萄糖的降低。我们得出结论，nesfatin-1是一种在β细胞中表达的新型胰高血糖素刺激肽，其表达在T2D胰岛中降低。
Nesfatin-1 is a novel anorexigenic regulatory peptide. The peptide is the N-terminal part of nucleobindin 2 (NUCB2) and is expressed in brain areas regulating feeding. Outside the brain, nesfatin-1 expression has been reported in adipocytes, gastric endocrine cells and islet cells. We studied NUCB2 expression in human and rodent islets using immunocytochemistry, in situ hybridization and western blot. Furthermore, we investigated the potential influence of nesfatin-1 on secretion of insulin and glucagon in vitro and in vivo in mice and in INS-1 (832/13) cells. The impact of type 2 diabetes (T2D) and glucolipotoxicity on NUCB2 gene expression in human islets and its relationship to insulin secretory capacity and islet gene expression was studied using microarray. Nesfatin-1 immunoreactivity (IR) was abundant in human and rodent beta cells but absent in alpha, delta, PP and ghrelin cells. Importantly, in situ hybridization showed that NUCB2 mRNA is expressed in human and rat islets. Western blot analysis showed that nesfatin-1 IR represented full length NUCB2 in rodent islets. Human islet NUCB2 mRNA was reduced in T2D subjects but upregulated after culture in glucolipotoxic conditions. Furthermore, a positive correlation between NUCB2 and glucagon and insulin gene expression, as well as insulin secretory capacity, was evident. Nesfatin-1 enhanced glucagon secretion but had no effect on insulin secretion from mouse islets or INS-1 (832/13) cells. On the other hand, nesfatin-1 caused a small increase in insulin secretion and reduced glucose during IVGTT in mice. We conclude that nesfatin-1 is a novel glucagon-stimulatory peptide expressed in the beta cell and that its expression is decreased in T2D islets.