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As the vast majority of endogenous GLP-1 is released from intestinal l-cells following ingestion, it stands to reason that paracrine GLP-1 signaling, activating adjacent GLP-1R expressed on vagal afferent fibers of gastrointestinal origin, contributes to glycemic and food intake control. However, systemic GLP-1R-mediated control of glycemia is currently attributed to endocrine action involving GLP-1R expressed in the hepatoportal bed on terminals of the common hepatic branch of the vagus (CHB). Here, we examine the hypothesis that activation of GLP-1R expressed on the CHB is not required for GLP-1's glycemic and intake suppressive effects, but rather paracrine signaling on non-CHB vagal afferents is required to mediate GLP-1's effects. Selective CHB ablation (CHBX), complete subdiaphragmatic vagal deafferentation (SDA), and surgical control rats received an oral glucose tolerance test (2.0 g glucose\/kg) 10 min after an intraperitoneal injection of the GLP-1R antagonist, exendin-(9\u201339) (Ex-9; 0.5 mg\/kg) or vehicle. CHBX and control rats showed comparable increases in blood glucose following blockade of GLP-1R by Ex-9, whereas SDA rats failed to show a GLP-1R-mediated incretin response. Furthermore, GLP-1(7\u201336) (0.5 mg\/kg ip) produced a comparable suppression of 1-h 25% glucose intake in both CHBX and control rats, whereas intake suppression in SDA rats was blunted. These findings support the hypothesis that systemic GLP-1R mediation of glycemic control and food intake suppression involves paracrine-like signaling on GLP-1R expressed on vagal afferent fibers of gastrointestinal origin but does not require the CHB.<\/jats:p>","DOI":"10.1152\/ajpregu.00356.2011","type":"journal-article","created":{"date-parts":[[2011,8,18]],"date-time":"2011-08-18T02:22:49Z","timestamp":1313634169000},"page":"R1479-R1485","source":"Crossref","is-referenced-by-count":79,"title":["The common hepatic branch of the vagus is not required to mediate the glycemic and food intake suppressive effects of glucagon-like-peptide-1"],"prefix":"10.1152","volume":"301","author":[{"given":"Matthew R.","family":"Hayes","sequence":"first","affiliation":[{"name":"Department of Psychology, School of Arts and Sciences,"},{"name":"Department of Psychiatry, Translational Neuroscience Program, School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott 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