Sakata Ichiro, Gong Zhi, Ikenoya Chika, Takemi Shota, Sakai Takafumi
Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
Area of Life-NanoBio, Division of Strategy Research, Graduate School of Science and Engineering, Saitama University, Saitama, Japan.
Endocr J. 2017;64(Suppl.):S27-S29. doi: 10.1507/endocrj.64.S27.
Ghrelin is a peptide hormone with a unique structure comprising a medium chain fatty acid modification. Ghrelin cells are known to be abundantly localized in the gastric mucosa and are released into the blood stream to exert their multifunctional physiological effects. To elucidate the regulatory mechanisms of ghrelin secretion and acyl-modification, we developed novel ghrelin-producing cell lines. Using ghrelinoma cell lines, we focused on the mechanisms of ghrelin secretion and found that several GPCRs were highly expressed in ghrelin cells. Then, we showed that noradrenaline treatment stimulated ghrelin secretion via β1-adrenergic receptor, and fasting-induced ghrelin elevation was completely inhibited by the β1-adrenergic receptor antagonist in mice. In addition, we demonstrated that long chain fatty acids, glucose, and L-glutamate significantly inhibited ghrelin secretion. Furthermore, we recently revealed that the genes involved in fatty acid synthesis and long chain fatty acid metabolism were expressed in ghrelin cells, and that CPT-1 inhibitor treatment dramatically decreased the levels of acyl-modified ghrelin. Here, we introduce the current knowledge of the mechanisms involving ghrelin secretion and its acyl-modification.
胃饥饿素是一种具有独特结构的肽类激素，其结构包含一个中链脂肪酸修饰。已知胃饥饿素细胞大量分布于胃黏膜中，并释放到血流中以发挥其多功能生理作用。为了阐明胃饥饿素分泌和酰基修饰的调控机制，我们建立了新型的胃饥饿素产生细胞系。利用胃饥饿素瘤细胞系，我们聚焦于胃饥饿素分泌的机制，发现几种G蛋白偶联受体（GPCRs）在胃饥饿素细胞中高表达。然后，我们表明去甲肾上腺素处理通过β1-肾上腺素能受体刺激胃饥饿素分泌，并且在小鼠中，β1-肾上腺素能受体拮抗剂完全抑制了禁食诱导的胃饥饿素升高。此外，我们证明长链脂肪酸、葡萄糖和L-谷氨酸显著抑制胃饥饿素分泌。此外，我们最近发现参与脂肪酸合成和长链脂肪酸代谢的基因在胃饥饿素细胞中表达，并且肉碱棕榈酰转移酶-1（CPT-1）抑制剂处理显著降低了酰基修饰的胃饥饿素水平。在此，我们介绍目前关于胃饥饿素分泌及其酰基修饰机制的知识。
