{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:34:18Z","timestamp":1790836458305,"version":"4.1.0"},"reference-count":39,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T00:00:00Z","timestamp":1584662400000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF10CC1016515"],"award-info":[{"award-number":["NNF10CC1016515"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF14OC0016798"],"award-info":[{"award-number":["NNF14OC0016798"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF15OC0013655"],"award-info":[{"award-number":["NNF15OC0013655"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:p>Glucagon-like peptide 1 (GLP-1) mimetics are effective drugs for treatment of type 2 diabetes, and there is consequently extensive interest in increasing endogenous GLP-1 secretion and L-cell abundance. Here we identify G-protein\u2013coupled bile acid receptor 1 (GPBAR1) as a selective regulator of intestinal L-cell differentiation. Lithocholic acid and the synthetic GPBAR1 agonist, L3740, selectively increased L-cell density in mouse and human intestinal organoids and elevated GLP-1 secretory capacity. L3740 induced expression of Gcg and transcription factors Ngn3 and NeuroD1. L3740 also increased the L-cell number and GLP-1 levels and improved glucose tolerance in vivo. Further mechanistic examination revealed that the effect of L3740 on L cells required intact GLP-1 receptor and serotonin 5-hydroxytryptamine receptor 4 (5-HT4) signaling. Importantly, serotonin signaling through 5-HT4 mimicked the effects of L3740, acting downstream of GLP-1. Thus, GPBAR1 agonists and other powerful GLP-1 secretagogues facilitate L-cell differentiation through a paracrine GLP-1\u2013dependent and serotonin-mediated mechanism.<\/jats:p>","DOI":"10.2337\/db19-0764","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T03:45:12Z","timestamp":1581392712000},"page":"614-623","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":81,"title":["L-Cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling"],"prefix":"10.2337","volume":"69","author":[{"given":"Mari Lilith","family":"Lund","sequence":"first","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 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