Ramesh Naresh, Mortazavi Sima, Unniappan Suraj
Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada.
Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4, Canada.
Biochem Biophys Res Commun. 2016 Mar 25;472(1):201-8. doi: 10.1016/j.bbrc.2016.02.095. Epub 2016 Feb 23.
Nesfatin-1 is an 82 amino acid secreted peptide encoded in the precursor, nucleobindin-2 (NUCB2). It is an insulinotropic anorexigen abundantly expressed in the stomach and hypothalamus. Post-prandial insulin secretion is predominantly regulated by incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Nesfatin-1 was previously reported to modulate GLP-1 and GIP secretion in vitro in an enteroendocrine (STC-1) cell line. Intestine is a source of additional hormones including cholecystokinin (CCK) and peptide YY (PYY) that regulate metabolism. We hypothesized that nesfatin-1 modulates CCK and PYY secretion. Immunofluorescence histochemistry showed NUCB2/nesfatin-1 co-localizing CCK and PYY in the intestinal mucosa of mice. Static incubation of STC-1 cells with nesfatin-1 upregulated both CCK mRNA expression (1 and 10 nM) and secretion (0.1, 1 and 10 nM) at 1 h post-incubation. In contrast, nesfatin-1 treatment for 1 h downregulated PYY mRNA expression (all doses tested) and secretion (0.01 and 0.1 nM) in STC-1 cells. Continuous infusion of nesfatin-1 using osmotic mini-pumps for 12 h upregulated CCK mRNA expression in large intestine, and downregulated PYY mRNA expression in both large and small intestines of male C57BL/6J mice. In these tissues, Western blot analysis found a corresponding increase in CCK and a decrease in PYY content. Collectively, we provide new information on the cell specific localization of NUCB2/nesfatin-1 in the intestinal mucosa, and a novel function for nesfatin-1 in modulating intestinal CCK and PYY expression and secretion in mice.
Nesfatin-1是一种由82个氨基酸组成的分泌肽，由前体核结合蛋白-2（NUCB2）编码。它是一种促胰岛素分泌的食欲抑制因子，在胃和下丘脑大量表达。餐后胰岛素分泌主要受肠促胰岛素胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性促胰岛素多肽（GIP）调节。先前有报道称，Nesfatin-1在体外可调节肠内分泌（STC-1）细胞系中GLP-1和GIP的分泌。肠道是包括胆囊收缩素（CCK）和肽YY（PYY）在内的其他调节代谢的激素的来源。我们推测Nesfatin-1可调节CCK和PYY的分泌。免疫荧光组织化学显示，在小鼠肠黏膜中，NUCB2/Nesfatin-1与CCK和PYY共定位。用Nesfatin-1对STC-1细胞进行静态孵育，在孵育1小时后，上调了CCK mRNA表达（1和10 nM）和分泌（0.1、1和10 nM）。相反，用Nesfatin-1处理1小时可下调STC-1细胞中PYY mRNA表达（所有测试剂量）和分泌（0.01和0.1 nM）。使用渗透微型泵连续输注Nesfatin-1 12小时，可上调雄性C57BL/6J小鼠大肠中CCK mRNA表达，并下调其大肠和小肠中PYY mRNA表达。在这些组织中，蛋白质印迹分析发现CCK含量相应增加，PYY含量减少。总体而言，我们提供了关于NUCB2/Nesfatin-1在肠黏膜中细胞特异性定位的新信息，以及Nesfatin-1在调节小鼠肠道CCK和PYY表达及分泌方面的新功能。
