{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:45:50Z","timestamp":1788903950918,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T00:00:00Z","timestamp":1563926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Basic Research Program of China","award":["2013CB127301"],"award-info":[{"award-number":["2013CB127301"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>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 Ca2+ 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 (IP3R), 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, IP3R, and PKC. These results indicated that Phe stimulated gut secretion through a CaSR-mediated pathway and its downstream signaling molecules, PKC and IP3R.<\/jats:p>","DOI":"10.3390\/ani9080476","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T10:48:19Z","timestamp":1563965299000},"page":"476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["L-phenylalanine Increased Gut Hormone Secretion through Calcium-Sensing Receptor in the Porcine Duodenum"],"prefix":"10.3390","volume":"9","author":[{"given":"Jiangyin","family":"Feng","sequence":"first","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuicui","family":"Kang","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liren","family":"Ding","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyun","family":"Zhu","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suqin","family":"Hang","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.anifeedsci.2016.01.001","article-title":"Factors involved in the regulation of feed and energy intake of pigs","volume":"233","author":"Li","year":"2017","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.physbeh.2008.01.003","article-title":"Protein-induced satiety: Effects and mechanisms of different proteins","volume":"94","author":"Veldhorst","year":"2008","journal-title":"Physiol. Behav."},{"key":"ref_3","first-page":"117","article-title":"Morphologic study of the effect of phenylalanine and its metabolites on the neuronal differentiation of P19 cell","volume":"18","author":"Qiu","year":"2002","journal-title":"Chin. J. Inorg. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10123","DOI":"10.1021\/acs.jafc.8b02355","article-title":"Intestinal Signaling of Proteins and Digestion-Derived Products Relevant to Satiety","volume":"66","author":"Miralles","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1136\/gut.29.9.1158","article-title":"Cholecystokinin release and biliopancreatic secretion in response to selective perfusion of the duodenal loop with amino acids in man","volume":"29","author":"Colombel","year":"1988","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1113\/jphysiol.2011.223800","article-title":"The regulation of K- and L- cell activity by GLUT2 and the calcium-sensing receptor CasR in rat small intestine","volume":"590","author":"Mace","year":"2012","journal-title":"J. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"G271","DOI":"10.1152\/ajpgi.00074.2012","article-title":"Sensing of amino acids by the gut-expressed taste receptor T1R1-T1R3 stimulates CCK secretion","volume":"304","author":"Daly","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_8","first-page":"1","article-title":"The role of calcium sensing receptors in GLP-1 and PYY secretion after acute intraduodenal administration of L-Tryptophan in rats","volume":"17","author":"Acar","year":"2018","journal-title":"Nutr. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.tem.2012.11.006","article-title":"Nutrient sensing in the gut: New roads to therapeutics?","volume":"24","author":"Janssen","year":"2013","journal-title":"Trends Endocrin. Met."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/366575a0","article-title":"Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid","volume":"366","author":"Brown","year":"1993","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1038\/ijo.2017.164","article-title":"L-phenylalanine modulates gut hormone release and glucose tolerance and suppresses food intake through the calcium-sensing receptor in rodents","volume":"41","author":"Alamshah","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4620","DOI":"10.1111\/j.1742-4658.2008.06604.x","article-title":"Calcium-sensing receptor mediates phenylalanine-induced cholecystokinin secretion in enteroendocrine STC-1 cells","volume":"275","author":"Hira","year":"2008","journal-title":"FEBS J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/sj.ejcn.1601463","article-title":"L-Amino acid sensing by the calcium-sensing receptor: A general mechanism for coupling protein and calcium metabolism?","volume":"56","author":"Conigrave","year":"2002","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_14","first-page":"178","article-title":"Structure and function of inositol 1,4,5-trisphosphate receptor","volume":"707","author":"Yoshida","year":"2010","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s11427-014-4779-y","article-title":"The calcium sensing receptor: From calcium sensing to signaling","volume":"58","author":"Zhang","year":"2015","journal-title":"Sci. China Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.npep.2018.12.004","article-title":"Endothelin-1 enhanced carotid body chemosensory activity in chronic intermittent hypoxia through PLC, PKC and p38MAPK signaling pathways","volume":"74","author":"Li","year":"2019","journal-title":"Neuropeptides"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4714","DOI":"10.1172\/JCI81975","article-title":"GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation","volume":"125","author":"Shigeto","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.4142\/jvs.2018.19.2.179","article-title":"Calcium-sensing receptor-mediated L-tryptophan-induced secretion of cholecystokinin and glucose-dependent insuliotropic peptide in swine duodenum","volume":"19","author":"Zhao","year":"2018","journal-title":"J. Vet. Sci."},{"key":"ref_19","first-page":"72","article-title":"The effect of \u03b2-casomorphin on piglets\u2019 stomach antrum under superfusion","volume":"23","author":"Tan","year":"2000","journal-title":"J. Nanjing Agric. Univ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ygcen.2018.05.022","article-title":"Phenylalanine and tryptophan stimulate gastrin and somatostatin secretion and H+-K+-ATPase activity in pigs through calcium-sensing receptor","volume":"267","author":"Xian","year":"2018","journal-title":"Gen. Comp. Endcor."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1172\/JCI111809","article-title":"Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction","volume":"75","author":"Liddle","year":"1985","journal-title":"J. Clin. Investig"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000201231","article-title":"Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients","volume":"56","author":"Herrmann","year":"1995","journal-title":"Digestion"},{"key":"ref_23","first-page":"G122","article-title":"Identification and localization of extracellular Ca2+-sensing receptor in rat intestine","volume":"274","author":"Chattopadhyay","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1177\/002215540004800503","article-title":"Immunocytochemical localization of the extracellular calcium-sensing receptor in normal and malignant human large intestinal mucosa","volume":"48","author":"Sheinin","year":"2000","journal-title":"J. Histochem. Cytochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1111\/1750-3841.14297","article-title":"Sensing of L-Arginine by gut-expressed calcium sensing receptor stimulates cholecystokinin and glucose-dependent insulinotropic peptide secretion in pig model","volume":"83","author":"Wang","year":"2018","journal-title":"J. Food Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/mnfr.201100666","article-title":"Calcium-sensing receptor mediates dietary peptide-induced CCK secretion in enteroendocrine STC-1 cells","volume":"56","author":"Nakajima","year":"2012","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.carbpol.2016.05.047","article-title":"Effects of abalone (Haliotis discus hannai Ino) gonad polysaccharides on cholecystokinin release in STC-1 cells and its signaling mechanism","volume":"151","author":"Zhao","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/toxsci\/kfv061","article-title":"Deoxynivalenol (vomitoxin)-induced cholecystokinin and glucagon-like peptide-1 release in the STC-1 enteroendocrine cell model is mediated by calcium-sensing receptor and transient receptor potential ankyrin-1 channel","volume":"145","author":"Zhou","year":"2015","journal-title":"Toxicol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.regpep.2009.11.007","article-title":"Soybean \u03b251\u201363 peptide stimulates cholecystokinin secretion via a calcium-sensing receptor in enteroendocrine STC-1 cells","volume":"159","author":"Nakajima","year":"2010","journal-title":"Regul. Pept."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S0007114518002088","article-title":"Calcium-sensing receptor in nutrient sensing: An insight into the modulation of intestinal homoeostasis","volume":"120","author":"Liu","year":"2018","journal-title":"Brit. J. Nutr."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/9\/8\/476\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:09:00Z","timestamp":1760188140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/9\/8\/476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,24]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["ani9080476"],"URL":"https:\/\/doi.org\/10.3390\/ani9080476","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,24]]}}}