Nesfatin-1 exerts a direct, glucose-dependent insulinotropic action on mouse islet β- and MIN6 cells
Nesfatin-1 exerts a direct, glucose-dependent insulinotropic action on mouse islet β- and MIN6 cells
复制标题
DOI：
10.1530/joe-10-0492
复制
发表时间：
2011-03-01
影响因子：
4
通讯作者：
Unniappan, Suraj
中科院分区：
文献类型：
--
作者：
Gonzalez, Ronald;Reingold, Benjamin K.;Unniappan, Suraj
Nesfatin-1是最近发现的一种多功能代谢激素，在胰岛中大量表达。本研究的主要目的是使用从 C57BL/6 小鼠中分离的 MIN6 细胞和胰岛来表征 nesfatin-1 对体外胰岛素分泌的直接影响。我们还检测了正常小鼠胰岛以及链脲佐菌素诱导的 1 型糖尿病小鼠和饮食诱导肥胖 (DIO) 2 型糖尿病小鼠的胰岛中 nesfatin-1 前体蛋白、核结合素 2 (NUCB2) mRNA 和 nesfatin-1 免疫反应性 (ir) 的表达。 Nesfatin-1 在体外以剂量依赖性方式刺激葡萄糖诱导的小鼠胰岛和 MIN6 细胞的胰岛素释放。当 MIN6 细胞/胰岛在低葡萄糖条件下与 nesfatin-1 一起孵育时，没有发现胰岛素分泌的这种刺激。此外，与低葡萄糖 (2 mM) 相比，在高葡萄糖 (16.7 mM) 中孵育后，MIN6 细胞释放的 nesfatin-1 增加了四倍。此外，我们观察到 1 型糖尿病小鼠胰岛中 NUCB2 mRNA 表达和 nesfatin-1-ir 显着减少，而 DIO 小鼠胰岛中却观察到显着增加。总之，我们的研究结果表明，nesfatin-1 是一种新型促胰岛素肽，并且内源性胰岛 NUCB2/nesfatin 在糖尿病和饮食诱导的肥胖中发生改变。内分泌学杂志（2011）208，R9-R16
Nesfatin-1 is a recently discovered multifunctional metabolic hormone abundantly expressed in the pancreatic islets. The main objective of this study is to characterize the direct effects of nesfatin-1 on insulin secretion in vitro using MIN6 cells and islets isolated from C57BL/6 mice. We also examined the expression of the nesfatin-1 precursor protein, nucleobindin 2 (NUCB2) mRNA, and nesfatin-1 immunoreactivity (ir) in the islets of normal mice and in the islets from mice with streptozotocin-induced type 1 diabetes and diet-induced obese (DIO) mice with type 2 diabetes. Nesfatin-1 stimulated glucose-induced insulin release in vitro from mouse islets and MIN6 cells in a dose-dependent manner. No such stimulation in insulin secretion was found when MIN6 cells/islets were incubated with nesfatin-1 in low glucose. In addition, a fourfold increase in nesfatin-1 release from MIN6 cells was observed following incubation in high glucose (16.7 mM) compared to low glucose (2 mM). Furthermore, we observed a significant reduction in both NUCB2 mRNA expression and nesfatin-1-ir in the pancreatic islets of mice with type 1 diabetes, while a significant increase was observed in the islets of DIO mice. Together, our findings indicate that nesfatin-1 is a novel insulinotropic peptide and that the endogenous pancreatic islet NUCB2/nesfatin is altered in diabetes and diet-induced obesity. Journal of Endocrinology (2011) 208, R9-R16