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Here, we characterized NMU as an enteropeptide and determined how it impacts glucose excursion. NMU was expressed predominantly in the proximal small intestine, and its secretion was triggered by ingestion of a mixed meal. Although a single peripheral injection of NMU in C57BL\/6NRj mice prevented the rise of glycemia upon an oral but not an intraperitoneal load of glucose, it unexpectedly prevented insulin secretion, only slightly improved peripheral insulin sensitivity, and barely reduced intestinal glucose absorption. Interestingly, peripheral administration of NMU abrogated gastric emptying. NMU receptors 1 and 2 were detected in pyloric muscles and NMU was able to directly induce pyloric contraction in a dose\u2010dependent manner\n                    <jats:italic>ex vivo<\/jats:italic>\n                    in isometric chambers. Using a modified glucose tolerance test, we demonstrate that improvement of oral glucose tolerance by NMU was essentially, if not exclusively, because of its impact on gastric emptying. Part of this effect was abolished in vagotomized (VagoX) mice, suggesting implication of the vagus tone. Accordingly, peripheral injection of NMU was associated with increased number of c\u2010FOS\u2013positive neurons in the nucleus of the solitary tract, which was partly prevented in VagoX mice. Finally, NMU kept its ability to improve oral glucose tolerance in obese and diabetic murine models. Together, these data demonstrate that NMU is an enteropeptide that prevents gastric emptying directly by triggering pylorus contraction and indirectly through vagal afferent neurons. This blockade consequently reduces intestinal nutrient absorption and thereby results in an apparent improved tolerance to oral glucose challenge.\u2014Jarry, A.\u2010C., Merah, N., Cisse, F., Cayetanot, F., Fiamma, M.\u2010N., Willemetz, A., Gueddouri, D., Barka, B., Valet, P., Guilmeau, S., Bado, A., Le Beyec, J., Bodineau, L., Le Gall, M. Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying\n                    <jats:italic>via<\/jats:italic>\n                    direct contraction of the pylorus and vagal\u2010dependent mechanisms. FASEB J. 33, 5377\u20135388 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801718r","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T16:36:58Z","timestamp":1549989418000},"page":"5377-5388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying\n                    <i>via<\/i>\n                    direct contraction of the pylorus and vagal\u2010dependent mechanisms"],"prefix":"10.1096","volume":"33","author":[{"given":"Anne\u2010Charlotte","family":"Jarry","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR) 1149 Assistance Publique\u2013H\u00f4pitaux de Paris (AP\u2013HP) Universit\u00e9 Paris Diderot  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadir","family":"Merah","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR) 1149 Assistance Publique\u2013H\u00f4pitaux de Paris (AP\u2013HP) Universit\u00e9 Paris Diderot  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanta","family":"Cisse","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR) 1149 Assistance Publique\u2013H\u00f4pitaux de Paris (AP\u2013HP) Universit\u00e9 Paris Diderot  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Cayetanot","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9 INSERM 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Descartes  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Besma","family":"Barka","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9 INSERM UMR\u2010S1158 Neurophysiologie Respiratoire Exp\u00e9rimentale et Clinique  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Valet","sequence":"additional","affiliation":[{"name":"INSERM Unit\u00e9 1048 Institut des Maladies M\u00e9taboliques et Cardiovasculaires (I2MC) Universit\u00e9 Toulouse III\u2013Paul Sabatier  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Guilmeau","sequence":"additional","affiliation":[{"name":"INSERM Unit\u00e9 1016 Centre National de la Recherche Scientifique (CNRS) UMR 8104 Institut Cochin Universit\u00e9 Paris Descartes  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Bado","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR) 1149 Assistance Publique\u2013H\u00f4pitaux de Paris (AP\u2013HP) Universit\u00e9 Paris Diderot  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanne","family":"Le Beyec","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR) 1149 Assistance Publique\u2013H\u00f4pitaux de Paris (AP\u2013HP) Universit\u00e9 Paris Diderot  Paris France"},{"name":"Sorbonne Universit\u00e9 Assistance Publique\u2013H\u00f4pitaux de Paris (AP\u2010HP) Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Department of Endocrine and Oncological Biochemistry  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Bodineau","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9 INSERM UMR\u2010S1158 Neurophysiologie Respiratoire Exp\u00e9rimentale et Clinique  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maude","family":"Le Gall","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR) 1149 Assistance Publique\u2013H\u00f4pitaux de Paris (AP\u2013HP) Universit\u00e9 Paris Diderot  Paris 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