title: GLP-1 Receptor Agonist Exenatide Increases Capillary Perfusion Independent of Nitric Oxide in Healthy Overweight Men.
abstract: OBJECTIVE
  The insulinotropic gut-derived hormone glucagon-like peptide-1 (GLP-1) increases capillary perfusion via a nitric oxide-dependent mechanism in rodents. This improves skeletal muscle glucose use and cardiac function. In humans, the effect of clinically used GLP-1 receptor agonists (GLP-1RAs) on capillary density is unknown. We aimed to assess the effects of the GLP-1RA exenatide on capillary density as well as the involvement of nitric oxide in humans.
  
  
  RESULTS
  We included 10 healthy overweight men (age, 20-27 years; body mass index, 26-31 kg/m(2)). Measurements were performed during intravenous infusion of placebo (saline 0.9%), exenatide, and a combination of exenatide and the nonselective nitric oxide-synthase inhibitor L-N(G)-monomethyl arginine. Capillary videomicroscopy was performed, and baseline and postocclusive (peak) capillary densities were counted. Compared with placebo, exenatide increased baseline and peak capillary density by 20.1% and 8.3%, respectively (both P=0.016). Concomitant L-N(G)-monomethyl arginine infusion did not alter the effects of exenatide. Vasomotion was assessed using laser Doppler fluxmetry. Exenatide nonsignificantly reduced the neurogenic domain of vasomotion measurements (R=-5.6%; P=0.092), which was strongly and inversely associated with capillary perfusion (R=-0.928; P=0.036). Glucose levels were reduced during exenatide infusion, whereas levels of insulin were unchanged.
  
  
  CONCLUSIONS
  Acute exenatide infusion increases capillary perfusion via nitric oxide-independent pathways in healthy overweight men, suggesting direct actions of this GLP-1RA on microvascular perfusion or interaction with vasoactive factors.
authors.affiliation: From the Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands. mm.smits1@vumc.nl.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Smits
authors.affiliation: From the Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marcel H A
authors.initials: MH
authors.lastname: Muskiet
authors.affiliation: From the Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lennart
authors.initials: L
authors.lastname: Tonneijck
authors.affiliation: From the Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mark H H
authors.initials: MH
authors.lastname: Kramer
authors.affiliation: From the Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: From the Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Daniël H
authors.initials: DH
authors.lastname: van Raalte
authors.affiliation: From the Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Erik H
authors.initials: EH
authors.lastname: Serné
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects*; D018592:Cross-Over Studies; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D018715:Microscopy, Video; D009569:Nitric Oxide / Q000378:metabolism*; D050177:Overweight / Q000503:physiopathology*; D010455:Peptides / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply; D014688:Venoms / Q000494:pharmacology*; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010455:Peptides; D014688:Venoms; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide
keywords: capillaries; glucagon-like peptide-1; nitric oxide