{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T17:01:11Z","timestamp":1768582871393,"version":"3.49.0"},"reference-count":53,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:p> The importance of vagal efferent signaling for the insulinotropic and glucagonostatic effects of glucagon-like peptide-1 (GLP-1) was investigated in a randomized single-blinded study. Healthy male participants ( n = 10) received atropine to block vagal cholinergic transmission or saline infusions on separate occasions. At t = 15 min, plasma glucose was clamped at 6 mmol\/l. GLP-1 was infused at a low dose (0.3 pmol\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>) from t = 45\u201395 min and at a higher dose (1 pmol\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>) from t = 95\u2013145 min. Atropine blocked muscarinic, cholinergic transmission, as evidenced by an increase in heart rate [peak: 70 \u00b1 2 (saline) vs. 90 \u00b1 2 (atropine) beats\/min, P &lt; 0.002] and suppression of pancreatic polypeptide levels [area under the curve during the GLP-1 infusions (AUC<jats:sub>45\u2013145<\/jats:sub>): 492 \u00b1 85 (saline) vs. 247 \u00b1 59 (atropine) pmol\/l \u00d7 min, P &lt; 0.0001]. More glucose was needed to maintain the clamp during the high-dose GLP-1 infusion steady-state period on the atropine day [6.4 \u00b1 0.9 (saline) vs. 8.7 \u00b1 0.8 (atropine) mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>, P &lt; 0.0023]. GLP-1 dose-dependently increased insulin secretion on both days. The insulinotropic effect of GLP-1 was not impaired by atropine [C-peptide AUCs<jats:sub>45\u2013145<\/jats:sub>: 99 \u00b1 8 (saline) vs. 113 \u00b1 13 (atropine) nmol\/l \u00d7 min, P = 0.19]. Atropine suppressed glucagon levels additively with GLP-1 [AUC<jats:sub>45\u2013145<\/jats:sub>: 469 \u00b1 70 (saline) vs. 265 \u00b1 50 (atropine) pmol\/l \u00d7 min, P = 0.018], resulting in hypoglycemia when infusions were suspended [3.6 \u00b1 0.2 (saline) vs. 2.7 \u00b1 0.2 (atropine) mmol\/l, P &lt; 0.0001]. To ascertain whether atropine could independently suppress glucagon levels, control experiments ( n = 5) were carried out without GLP-1 infusions [AUC<jats:sub>45\u2013145<\/jats:sub>: 558 \u00b1 103 (saline) vs. 382 \u00b1 76 (atropine) pmol\/l \u00d7 min, P = 0.06]. Our results suggest that efferent muscarinic activity is not required for the insulinotropic effect of exogenous GLP-1 but that blocking efferent muscarinic activity independently suppresses glucagon secretion. In combination, GLP-1 and muscarinic blockade strongly affect glucose turnover. <\/jats:p>","DOI":"10.1152\/ajpregu.00123.2015","type":"journal-article","created":{"date-parts":[[2015,7,2]],"date-time":"2015-07-02T04:11:00Z","timestamp":1435810260000},"page":"R544-R551","source":"Crossref","is-referenced-by-count":22,"title":["The role of efferent cholinergic transmission for the insulinotropic and glucagonostatic effects of GLP-1"],"prefix":"10.1152","volume":"309","author":[{"given":"Astrid","family":"Plamboeck","sequence":"first","affiliation":[{"name":"Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark;"},{"name":"The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Veedfald","sequence":"additional","affiliation":[{"name":"Center for Diabetes Research, Gentofte 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