Nucleobindin-2/nesfatin in the endocrine pancreas: distribution and relationship to glycaemic state
Nucleobindin-2/nesfatin in the endocrine pancreas: distribution and relationship to glycaemic state
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DOI：
10.1677/joe-09-0254
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发表时间：
2010-03-01
影响因子：
4
通讯作者：
Broberger, Christian
中科院分区：
文献类型：
--
作者：
Foo, Kylie S.;Brauner, Hanna;Broberger, Christian
核结合蛋白-2（NUCB 2，也称为nesfatin）最近被认为是中枢神经系统中厌食症和catastrophic的介质，并被认为是切割和分泌的信使。考虑到大脑和胰腺之间信号分子的重叠，我们探索了胰岛中NUCB 2的存在。我们还对不同代谢状态下胰腺NUCB 2的动态调节进行了研究。通过免疫荧光法在所有人和大鼠胰岛β细胞中检测到NUCB 2样免疫反应性（通过与胰岛素共定位检测），但在其他胰岛细胞或外分泌胰腺中未检测到。通过酶免疫测定法测量的胰岛NUCB 2含量在禁食过夜后没有显著变化，但在从2型糖尿病动物模型Goto-Kakizaki（GK）大鼠分离的胰岛中显著降低（非糖尿病Wistar大鼠对照的48%）。然而，血清水平在Wistar和GK大鼠之间没有差异。在葡萄糖刺激后，NUCB 2从分离的大鼠胰岛的释放显著升高（123%），但这种作用显著低于对胰岛素观察到的作用（816%）。相比之下，NUCB 2的血清水平在腹膜内葡萄糖耐量试验中显示可逆性降低。这些数据表明NUCB 2在β细胞功能中的作用和在糖尿病病理学中的潜在参与。然而，我们的研究结果，加上以前的报告，似乎更符合细胞内的行动，而不是与内分泌/旁分泌通信，并建议NUCB 2在血清中主要来自非胰岛来源。内分泌学杂志（2010）204，255-263
The protein nucleobindin-2 (NUCB2, also known as nesfatin) was recently implicated as a mediator of anorexia and catabolism in the central nervous system, and has been suggested to act as a cleaved and secreted messenger. Given the overlap of signalling molecules between the brain and pancreas, we have explored the presence of NUCB2 in the islets of Langerhans. We also performed an investigation of the dynamic regulation of pancreatic NUCB2 in different metabolic states. NUCB2-like immunoreactivity was detected by immunofluorescence in all human and rat islet beta-cells (as detected by co-localization with insulin), but not in other islet cells or in the exocrine pancreas. Islet NUCB2 content, as measured by enzyme immunoassay, did not change significantly following an overnight fast, but was substantially lower in islets isolated from an animal model of type 2 diabetes, the Goto-Kakizaki (GK) rats (48% of non-diabetic Wistar rat control). Serum levels, however, were not different between Wistar and GK rats. The release of NUCB2 from isolated rat islets was significantly elevated following glucose challenge (123%), but this effect was substantially lower than that observed for insulin (816%). In contrast, serum levels of NUCB2 showed a reversible decrease in an i.p. glucose tolerance test. These data suggest a role for NUCB2 in beta-cell function and a potential involvement in diabetic pathology. However, our findings, together with previous reports, appear more compatible with intracellular actions rather than with endocrine/paracrine communication, and suggest that NUCB2 in serum derives primarily from non-islet sources. Journal of Endocrinology (2010) 204, 255-263