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This study aimed to investigate the intracellular mechanism of GLP-1 synthesis in L cells from the perspective of microRNA (miRNA). In the present study, we found that GLP-1 level was down-regulated in the plasma and ileum tissues of obese mice, while the ileac miR-194 expression was up-regulated. In vitro experiments indicated that miR-194 overexpression down-regulated GLP-1 level, mRNA levels of proglucagon gene (\n                    <jats:italic>gcg<\/jats:italic>\n                    ) and prohormone convertase 1\/3 gene (\n                    <jats:italic>pcsk1<\/jats:italic>\n                    ), and the nuclear protein level of beta-catenin (\u03b2-catenin). Further investigation confirmed that \u03b2-catenin could promote\n                    <jats:italic>gcg<\/jats:italic>\n                    transcription through binding to transcription factor 7-like 2 (TCF7L2). miR-194 suppressed\n                    <jats:italic>gcg<\/jats:italic>\n                    mRNA level via negatively regulating TCF7L2 expression. What\u2019s more, forkhead box a1 (Foxa1) could bind to the promoter of\n                    <jats:italic>pcsk1<\/jats:italic>\n                    and enhanced its transcription. miR-194 suppressed\n                    <jats:italic>pcsk1<\/jats:italic>\n                    transcription through targeting\n                    <jats:italic>Foxa1<\/jats:italic>\n                    . Besides, the interference of miR-194 reduced palmitate (PA)-induced cell apoptosis and the anti-apoptosis effect of miR-194 inhibitor was abolished by TCF7L2 knockdown. Finally, in HFD-induced obese mice, the silence of miR-194 significantly elevated GLP-1 level and improved the metabolic symptoms caused by GLP-1 deficiency. To sum up, our study found that miR-194 suppressed GLP-1 synthesis in L cells via inhibiting TCF7L2-mediated\n                    <jats:italic>gcg<\/jats:italic>\n                    transcription and Foxa1-mediated\n                    <jats:italic>pcsk1<\/jats:italic>\n                    transcription. Meanwhile, miR-194 took part in the PA-induced apoptosis of L cells.\n                  <\/jats:p>","DOI":"10.1038\/s41419-020-03366-0","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T05:03:18Z","timestamp":1611205398000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["MicroRNA-194: a novel regulator of glucagon-like peptide-1 synthesis in intestinal L cells"],"prefix":"10.1038","volume":"12","author":[{"given":"Jiao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Zhi","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Na","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Jiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Ling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shui-Ying","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Nan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Fei","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Rui","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,21]]},"reference":[{"key":"3366_CR1","doi-asserted-by":"crossref","unstructured":"Seidell, J. 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