Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
J Endocrinol. 2010 Mar;204(3):255-63. doi: 10.1677/JOE-09-0254. Epub 2009 Dec 23.
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.
核结合蛋白-2（NUCB2，也称为 nesfatin）最近被认为是中枢神经系统厌食和分解代谢的介质，并被认为是一种被切割和分泌的信使。鉴于大脑和胰腺之间信号分子的重叠，我们已经探索了在胰岛中 NUCB2 的存在。我们还研究了不同代谢状态下胰腺 NUCB2 的动态调节。免疫荧光检测到人类和大鼠胰岛β细胞（通过与胰岛素共定位检测到）中存在 NUCB2 样免疫反应性，但在其他胰岛细胞或外分泌胰腺中不存在。通过酶免疫测定法测量的胰岛 NUCB2 含量在 overnight fast（ overnight fast 是一种禁食实验，通常用于研究代谢和生理过程。在 overnight fast 期间，实验动物会被禁食一段时间，通常为 12-24 小时，以模拟人类在夜间的禁食状态。）后没有显著变化，但在 2 型糖尿病动物模型 Goto-Kakizaki（GK）大鼠的胰岛中显著降低（非糖尿病 Wistar 大鼠对照的 48%）。然而，Wistar 和 GK 大鼠之间的血清水平没有差异。分离的大鼠胰岛释放的 NUCB2 在葡萄糖刺激后显著升高（123%），但这一效应明显低于胰岛素（816%）。相比之下，血清 NUCB2 水平在腹腔内葡萄糖耐量试验中呈可逆性下降。这些数据表明 NUCB2 在β细胞功能中起作用，并可能参与糖尿病病理。然而，我们的发现，连同以前的报告，似乎更与细胞内作用相容，而不是与内分泌/旁分泌通讯相容，并表明血清中的 NUCB2 主要来源于非胰岛来源。
