title: Acute effects of glucagon-like peptide-1, GLP-19-36 amide, and exenatide on mesenteric blood flow, cardiovascular parameters, and biomarkers in healthy volunteers.
abstract: Glucagon-like peptide-1 (GLP-1, GLP-17-36amide) and its sister peptide glucagon-like peptide 2 (GLP-2) influence numerous intestinal functions and GLP-2 greatly increases intestinal blood flow. We hypothesized that GLP-1 also stimulates intestinal blood flow and that this would impact on the overall digestive and cardiovascular effects of the hormone. To investigate the influence of GLP-1 receptor agonism on mesenteric and renal blood flow and cardiovascular parameters, we carried out a double-blinded randomized clinical trial. A total of eight healthy volunteers received high physiological subcutaneous injections of GLP-1, GLP-19-36 amide(bioactive metabolite), exenatide (stable GLP-1 agonist), or saline on four separate days. Blood flow in mesenteric, celiac, and renal arteries was measured by Doppler ultrasound. Blood pressure, heart rate, cardiac output, and stroke volume were measured continuously using an integrated system. Plasma was analyzed for glucose, GLP-1 (intact and total), exenatide and Pancreatic polypeptide (PP), and serum for insulin and C-peptide. Neither GLP-1, GLP-19-36 amide, exenatide nor saline elicited any changes in blood flow parameters in the mesenteric or renal arteries. GLP-1 significantly increased heart rate (two-way ANOVA, injection [P= 0.0162], time [P= 0.0038], and injection × time [P= 0.082]; Tukey post hoc GLP-1 vs. saline and GLP-19-36amide[P< 0.011]), and tended to increase cardiac output and decrease stroke volume compared to GLP-19-36 amideand saline. Blood pressures were not affected. As expected, glucose levels fell and insulin secretion increased after infusion of both GLP-1 and exenatide.
authors.affiliation: Department of Medicine (Gastroenterology Section), Koege Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lasse
authors.initials: L
authors.lastname: Bremholm
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine and PET, Rigshospitalet (Glostrup Section), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulrik B
authors.initials: UB
authors.lastname: Andersen
authors.affiliation: Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Hornum
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Linda
authors.initials: L
authors.lastname: Hilsted
authors.affiliation: Department of Biomedical Sciences & NNF Center for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Simon
authors.identifier: http://orcid.org/0000-0002-0797-3417
authors.initials: S
authors.lastname: Veedfald
authors.affiliation: Department of Biomedical Sciences & NNF Center for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Department of Biomedical Sciences & NNF Center for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark jjholst@sund.ku.dk.
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004311:Double-Blind Method; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D010191:Pancreatic Polypeptide / Q000097:blood; D010455:Peptides / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects*; D013152:Splanchnic Circulation / Q000187:drug effects*; D016896:Treatment Outcome; D014688:Venoms / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D010455:Peptides; D014688:Venoms; C114437:glucagon-like peptide-1 (9-36)-amide; D010191:Pancreatic Polypeptide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide
keywords: Exenatide; glucagon like‐peptide‐1; mesenteric blood flow