Mohan Haneesha, Unniappan Suraj
Laboratory of Integrative Neuroendocrinology, Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3.
Regul Pept. 2012 Apr 10;175(1-3):61-9. doi: 10.1016/j.regpep.2012.02.006. Epub 2012 Feb 28.
Nesfatin-1 is a novel metabolic hormone that has glucose-responsive insulinotropic actions. Islet β-cells and gastrointestinal tissues have been reported as abundant sources of nesfatin-1 and its precursor hormone nucleobindin-2 (NUCB2). While nesfatin-1 is emerging as a multifunctional hormone, there are no reports on the developmental expression of NUCB2/nesfatin-1. The main objective of this study was to examine the ontogenic expression of NUCB2 mRNA, and NUCB2/nesfatin-1 immunoreactivity in the pancreas, stomach and duodenum, and the circulating levels NUCB2/nesfatin-1 in Sprague Dawley rats. In addition, we also determined the co-localization of NUCB2/nesfatin-1 and insulin immunoreactivity during development. NUCB2/nesfatin-1 immunoreactivity was found in the rat stomach from postnatal days 13-27. Furthermore, NUCB2/nesfatin-1 immunoreactivity was also detected in the enteroendocrine cells of the duodenum at postnatal days 13 and 27. Duodenal NUCB2 mRNA expression at postnatal day 27 was highest. Serum NUCB2/nesfatin-1 levels on embryonic day 21 and postnatal day 1 were lower than serum NUCB2/nesfatin-1 levels of adults and neonates at postnatal days 13, 20 and 27, gradually increasing with growth, suggesting an increase in its production and secretion from tissues including the gastrointestinal tract and pancreas. Our findings indicate that NUCB2/nesfatin-1 colocalizes with insulin in the islet β-cells at all developmental stages, but the percentage of colocalization varies in an age-dependent manner. These findings suggest that NUCB2/nesfatin-1 has potential age- and tissue-specific role in the developmental physiology of rats during growth.
Nesfatin-1是一种具有葡萄糖反应性促胰岛素分泌作用的新型代谢激素。胰岛β细胞和胃肠道组织已被报道为nesfatin-1及其前体激素核结合蛋白-2（NUCB2）的丰富来源。虽然nesfatin-1正逐渐成为一种多功能激素，但关于NUCB2/nesfatin-1的发育表达尚无报道。本研究的主要目的是检测Sprague Dawley大鼠胰腺、胃和十二指肠中NUCB2 mRNA的个体发生表达、NUCB2/nesfatin-1免疫反应性，以及循环中NUCB2/nesfatin-1的水平。此外，我们还确定了发育过程中NUCB2/nesfatin-1与胰岛素免疫反应性的共定位情况。在出生后第13 - 27天的大鼠胃中发现了NUCB2/nesfatin-1免疫反应性。此外，在出生后第13天和第27天的十二指肠肠内分泌细胞中也检测到了NUCB2/nesfatin-1免疫反应性。出生后第27天十二指肠中NUCB2 mRNA表达最高。胚胎第21天和出生后第1天的血清NUCB2/nesfatin-1水平低于出生后第13、20和27天的成年大鼠和新生大鼠的血清NUCB2/nesfatin-1水平，并随生长逐渐升高，这表明其从包括胃肠道和胰腺在内的组织中的产生和分泌增加。我们的研究结果表明，在所有发育阶段，NUCB2/nesfatin-1在胰岛β细胞中与胰岛素共定位，但共定位的百分比以年龄依赖性方式变化。这些发现表明，NUCB2/nesfatin-1在大鼠生长发育生理过程中具有潜在的年龄和组织特异性作用。
