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Glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs), such as liraglutide, have shown promising anti\u2010inflammatory effects beyond glucose lowering and weight loss, but the underlying mechanism remains to be elucidated. We hypothesised that GLP\u20101RAs improve the intestinal barrier function and overall inflammatory status by direct gene activation in mucus\u2010secreting Brunner's glands in the mouse duodenum, known for their high density of glucagon\u2010like peptide\u20101 receptors (GLP\u20101Rs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using bulk RNA sequencing, in situ hybridisation, and immunohistochemistry, we analysed the change in the genetic phenotype of mouse Brunner's gland cells following GLP\u20101R activation by liraglutide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We show that liraglutide induces a novel and robust upregulation of the gene for the Cystic fibrosis transmembrane conductance regulator,\n                      <jats:italic>Cftr<\/jats:italic>\n                      , in Brunner's glands as a part of an overall genetic phenotype involved in ion channel activity, mucus secretion, and hydration via GLP\u20101R activation. Additionally, we found a robust upregulation of the genes\n                      <jats:italic>Muc5b<\/jats:italic>\n                      ,\n                      <jats:italic>Il33<\/jats:italic>\n                      ,\n                      <jats:italic>Ren1<\/jats:italic>\n                      , and\n                      <jats:italic>Vldlr<\/jats:italic>\n                      in Brunner's glands.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, our results imply an enhanced mucus response from Brunner's glands following GLP\u20101R activation, which might play a role in the effect of GLP\u20101.<\/jats:p>\n                  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