Pancreatic beta cells synthesize neuropeptide Y and can rapidly release peptide co-transmitters.
Pancreatic beta cells synthesize neuropeptide Y and can rapidly release peptide co-transmitters.
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DOI：
10.1371/journal.pone.0019478
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发表时间：
2011-04-29
期刊：
影响因子：
3.7
通讯作者：
Whim MD
中科院分区：
文献类型：
--
作者：
Whim MD
除了多肽激素，胰腺内分泌细胞还合成包括经典递质和神经肽在内的多种生物活性分子。虽然这些共递质被认为在调节激素释放中起作用，但对它们的分泌是如何调节的知之甚少。在这里，我调查的合成和释放的神经肽Y从胰腺β细胞。NPY似乎是新生儿β细胞而不是成人β细胞中的真正的共递质，因为（1）在小鼠出生后发育的早期，许多β细胞是NPY免疫反应性的，而在来自NPY敲除小鼠的β细胞中没有观察到染色;（2）来自NPY（GFP）转基因小鼠的表达GFP的胰岛细胞是胰岛素免疫反应性的;（3）单细胞RT-PCR实验证实NPY（GFP）细胞含有β细胞的标志物胰岛素mRNA。因此，先前在α和δ细胞中报道的NPY免疫反应性可能是由于NPY相关肽的存在。INS-1细胞是一种β细胞系，也是NPY免疫阳性细胞，含有NPY mRNA。使用FMRFamide标记技术，以高时间分辨率监测INS-1 β细胞的NPY分泌。肽释放由短暂的去极化引起，并由腺苷酸环化酶和蛋白激酶A的激活剂增强。在短暂的去极化后，含有NPY的致密核心颗粒与细胞膜融合，并在几毫秒内排出其内容物。这些结果表明，出生后，NPY在胰岛中的表达仅限于新生儿β细胞。NPY的存在表明肽类共递质可以介导内分泌胰腺内的快速旁分泌或自分泌信号。FMRFamide标记技术可用于研究其他推定的胰岛共递质的释放在真实的时间。
In addition to polypeptide hormones, pancreatic endocrine cells synthesize a variety of bioactive molecules including classical transmitters and neuropeptides. While these co-transmitters are thought to play a role in regulating hormone release little is known about how their secretion is regulated. Here I investigate the synthesis and release of neuropeptide Y from pancreatic beta cells. NPY appears to be an authentic co-transmitter in neonatal, but not adult, beta cells because (1) early in mouse post-natal development, many beta cells are NPY-immunoreactive whereas no staining is observed in beta cells from NPY knockout mice; (2) GFP-expressing islet cells from an NPY(GFP) transgenic mouse are insulin-ir; (3) single cell RT-PCR experiments confirm that the NPY(GFP) cells contain insulin mRNA, a marker of beta cells. The NPY-immunoreactivity previously reported in alpha and delta cells is therefore likely to be due to the presence of NPY-related peptides. INS-1 cells, a beta cell line, are also NPY-ir and contain NPY mRNA. Using the FMRFamide tagging technique, NPY secretion was monitored from INS-1 beta cells with high temporal resolution. Peptide release was evoked by brief depolarizations and was potentiated by activators of adenylate cyclase and protein kinase A. Following a transient depolarization, NPY-containing dense core granules fused with the cell membrane and discharged their contents within a few milliseconds. These results indicate that after birth, NPY expression in pancreatic islets is restricted to neonatal beta cells. The presence of NPY suggests that peptide co-transmitters could mediate rapid paracrine or autocrine signaling within the endocrine pancreas. The FMRFamide tagging technique may be useful in studying the release of other putative islet co-transmitters in real time.
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