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While central GLP\u20101 pathways are well studied, the distribution and functional role of GLP\u20101R within the human enteric nervous system (ENS) remain unclear. We characterised GLP\u20101R expression across the human GI tract, examining its anatomical localisation among distinct enteric neuronal subtypes. Non\u2010inflamed, full\u2010thickness human GI tissues (antrum, ileum, ascending, descending and sigmoid colon;\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200930, 5 different human samples per region) were obtained from surgical resections and analysed using immunohistochemistry, epifluorescence and confocal microscopy. Mean number of positive pixels of GLP\u20101R and PGP9.5 was quantified in mucosal varicosities, muscle, submucosal and myenteric plexuses. GLP\u20101R co\u2010localisation with neuronal markers (PGP9.5, nNOS, ChAT, Substance P, CGRP, Calretinin, HuC\/D) was assessed. Quantification used Mander's coefficient, and statistical analysis used one\u2010way ANOVA with Tukey's post hoc test. GLP\u20101R was expressed abundantly in ENS structures, including mucosal varicosities, muscle, submucosal plexus and myenteric neurons throughout the lower GI tract, with significantly higher expression in the colon compared to the stomach and ileum (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Co\u2010localisation analyses revealed preferential GLP\u20101R expression in nNOS\u2010expressing inhibitory neurons and CGRP\u2010expressing varicosities, moderate expression in calretinin\u2010expressing neurons, and sparse expression in ChAT\u2010expressing and substance P\u2010immunoreactive excitatory neurons. Whole\u2010mount confocal imaging confirmed GLP\u20101R localisation to HuC\/D\u2010immunoreactive neuronal cell bodies with punctate, membrane\u2010associated staining. GLP\u20101R is differentially expressed across the human ENS, with increased expression in inhibitory neurons and putative extrinsic sensory afferents, particularly in the distal colon. This suggests that peripherally released GLP\u20101 acts locally within the ENS to regulate motility and sensory signalling, underpinning both its physiological functions and the gastrointestinal side effects of GLP\u20101\u2010based therapies.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70461-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70461","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:11:21Z","timestamp":1778850681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic Characterisation of\n                    <scp>GLP<\/scp>\n                    \u2010\n                    <scp>1R<\/scp>\n                    in Human Enteric Nervous System: Implications for\n                    <scp>GLP<\/scp>\n                    \u20101 as a Key Regulator of Colonic Activity"],"prefix":"10.1111","volume":"170","author":[{"given":"Kiran Devi","family":"Dontamsetti","sequence":"first","affiliation":[{"name":"Wingate Institute of Neurogastroenterology, Blizard Institute, The Faculty of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubina","family":"Aktar","sequence":"additional","affiliation":[{"name":"Wingate Institute of Neurogastroenterology, Blizard Institute, The Faculty of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madusha","family":"Peiris","sequence":"additional","affiliation":[{"name":"Wingate Institute of Neurogastroenterology, Blizard Institute, The Faculty of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-13-0525"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2010.01476.x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0198024"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13041271"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2024.167489"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.034"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00499155"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.07.011"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-010-9302-6"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241813979"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155413497586"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.10.046"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.7.8584"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.28095"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-74000-8"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2023.06.010"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2021.101794"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.14309\/crj.0000000000001789"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804106105"},{"key":"e_1_2_12_21_1","first-page":"9","article-title":"Luminal Sensing in the Gut: An Overview","volume":"54","author":"Dockray G. 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