Feng Jiangyin, Kang Cuicui, Wang Chao, Ding Liren, Zhu Weiyun, Hang Suqin
National Center for International Research on Animal Gut Nutrition, Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Animals (Basel). 2019 Jul 24;9(8):476. doi: 10.3390/ani9080476.
Luminal amino acids have a pivotal role in gut hormone secretion, and thereby modulate food intake and energy metabolism. However, the mechanisms by which amino acids exert this effect remains unknown. The purpose of this research was to investigate the response of L-phenylalanine (L-Phe) to gut hormone secretion and its underlying mechanisms by perfusing the pig duodenum. Eighty mM L-Phe and extracellular Ca stimulated cholecystokinin (CCK) and glucose-dependent insulinotropic peptide (GIP) release, and upregulated the mRNA expression of the calcium-sensing receptor (CaSR), CCK, and GIP. Western blotting results showed that L-Phe also elevated the protein levels of CaSR, the inositol 1,4,5-triphosphate receptor (IPR), and protein kinase C (PKC). However, the CaSR inhibitor NPS 2143 reduced the mRNA expression of CaSR, CCK, and GIP, and the secretion of CCK and GIP, as well as the protein level of CaSR, IPR, and PKC. These results indicated that Phe stimulated gut secretion through a CaSR-mediated pathway and its downstream signaling molecules, PKC and IPR.
肠腔氨基酸在肠道激素分泌中起关键作用,从而调节食物摄入和能量代谢。然而,氨基酸发挥这种作用的机制尚不清楚。本研究的目的是通过灌注猪十二指肠来研究L-苯丙氨酸(L-Phe)对肠道激素分泌的反应及其潜在机制。80 mM的L-Phe和细胞外钙刺激胆囊收缩素(CCK)和葡萄糖依赖性促胰岛素多肽(GIP)的释放,并上调钙敏感受体(CaSR)、CCK和GIP的mRNA表达。蛋白质印迹结果表明,L-Phe还提高了CaSR、肌醇1,4,5-三磷酸受体(IPR)和蛋白激酶C(PKC)的蛋白水平。然而,CaSR抑制剂NPS 2143降低了CaSR、CCK和GIP的mRNA表达,以及CCK和GIP的分泌,以及CaSR、IPR和PKC的蛋白水平。这些结果表明,苯丙氨酸通过CaSR介导的途径及其下游信号分子PKC和IPR刺激肠道分泌。