{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T19:43:09Z","timestamp":1771530189803,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 31501980"],"award-info":[{"award-number":["No. 31501980"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for Central Universities of the Central South University","doi-asserted-by":"publisher","award":["KYDS201808"],"award-info":[{"award-number":["KYDS201808"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Animal Physiology Nutrition"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The objective of this study was to test the hypothesis that aspartame supplementation in starter diet accelerates small intestinal cell cycle by stimulating secretion and expression of glucagon\u2010like peptide \u22122 (GLP\u20102) in pre\u2010weaned lambs using animal and cell culture experiments. In vivo, twelve 14\u2010day\u2010old lambs were selected and allocated randomly to two groups; one was treated with plain starter diet (Con, <jats:italic>n<\/jats:italic>\u00a0=\u00a06) and the other was treated with starter supplemented with 200\u00a0mg of aspartame\/kg starter (APM, <jats:italic>n<\/jats:italic>\u00a0=\u00a06). Results showed that the lambs received APM treatment for 35 d had higher (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) GLP\u20102 concentration in the plasma and greater jejunum weight\/live body weight (BW) and jejunal crypt depth. Furthermore, APM treatment significantly upregulated (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) the mRNA expression of <jats:italic>cyclin D1<\/jats:italic> in duodenum; and <jats:italic>cyclin A2<\/jats:italic>, <jats:italic>cyclin D1<\/jats:italic>, <jats:italic>cyclin\u2010dependent kinases 6<\/jats:italic> (<jats:italic>CDK6<\/jats:italic>) in jejunum; and <jats:italic>cyclin A2<\/jats:italic>, <jats:italic>cyclin D1<\/jats:italic>, <jats:italic>CDK4<\/jats:italic> in ileum. Moreover, APM treatment increased (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) the mRNA expression of glucagon (<jats:italic>GCG<\/jats:italic>), <jats:italic>insulin\u2010like growth factor 1<\/jats:italic> (<jats:italic>IGF\u20101<\/jats:italic>) in the jejunum and ileum and mRNA expression of <jats:italic>GLP\u20102 receptor<\/jats:italic> (<jats:italic>GLP\u20102R<\/jats:italic>) in the jejunum. In vitro, when jejunal cells were treated with GLP\u20102 for 2\u00a0hr, the 3\u2010(4,5\u2010dimethyl\u20102\u2010thiazolyl)\u20102,5\u2010diphenyl\u20102\u2010H\u2010tetrazolium bromide (MTT) OD, IGF\u20101 concentration, and the mRNA expression of <jats:italic>IGF\u20101<\/jats:italic>, <jats:italic>cyclin D1<\/jats:italic> and <jats:italic>CDK6<\/jats:italic> were increased (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05). Furthermore, IGF\u20101 receptor (IGF\u20101R) inhibitor decreased (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) the mRNA expression of <jats:italic>IGF\u20101<\/jats:italic>, <jats:italic>cyclin A2<\/jats:italic>, <jats:italic>cyclin D1<\/jats:italic> and <jats:italic>CDK6<\/jats:italic> in GLP\u20102 treatment jejunal cells. These results suggest that aspartame supplementation in starter accelerates small intestinal cell cycle that may, in part, be related to stimulate secretion and expression of GLP\u20102 in pre\u2010weaning lambs. Furthermore, GLP\u20102 can indirectly promote the proliferation of jejunal cells mainly through the IGF\u20101 pathway. These findings provide new insights into nutritional interventions that promote the development of small intestines in young ruminants.<\/jats:p>","DOI":"10.1111\/jpn.13159","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T09:02:14Z","timestamp":1564045334000},"page":"1338-1350","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Aspartame supplementation in starter accelerates small intestinal epithelial cell cycle and stimulates secretion of glucagon\u2010like peptide\u20102 in pre\u2010weaned lambs"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1989-0448","authenticated-orcid":false,"given":"Daming","family":"Sun","sequence":"first","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology Nanjing Agricultural University Nanjing China"},{"name":"National Centre for International Research on Animal Gut Nutrition Nanjing Agricultural University Nanjing China"},{"name":"National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology Nanjing Agricultural University Nanjing China"},{"name":"National Centre for International Research on Animal Gut Nutrition Nanjing Agricultural University Nanjing China"},{"name":"National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengyong","family":"Mao","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology Nanjing Agricultural University Nanjing China"},{"name":"National Centre for International Research on Animal Gut Nutrition Nanjing Agricultural University Nanjing China"},{"name":"National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology Nanjing Agricultural University Nanjing China"},{"name":"National Centre for International Research on Animal Gut Nutrition Nanjing Agricultural University Nanjing China"},{"name":"National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1028-5586","authenticated-orcid":false,"given":"Junhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology Nanjing Agricultural University Nanjing China"},{"name":"National Centre for International Research on Animal Gut Nutrition Nanjing Agricultural University Nanjing China"},{"name":"National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022879"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2010-3205"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2014-8577"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00031.2012"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021113-170317"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00149.2007"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.05.055"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1242\/jcs.101.1.219","article-title":"The development of a method for the preparation of rat intestinal epithelial cell primary cultures","volume":"101","author":"Evans G. 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