title: Dipeptidyl-peptidase 4 inhibition and the vascular effects of glucagon-like peptide-1 and brain natriuretic peptide in the human forearm.
abstract: BACKGROUND
  Dipeptidyl-peptidase 4 (DPP4) inhibitors improve glycemic control in patients with diabetes mellitus by preventing the degradation of glucagon-like peptide-1 (GLP-1). GLP-1 causes vasodilation in animal models but also increases sympathetic activity; the effect of GLP-1 in the human vasculature and how it is altered by DPP4 inhibition is not known. DPP4 also degrades the vasodilator brain natriuretic peptide (BNP) to a less potent metabolite. This study tested the hypothesis that DPP4 inhibition potentiates the vasodilator responses to GLP-1 and BNP in the human forearm.
  
  
  RESULTS
  Seventeen healthy subjects participated in this randomized, double-blinded, placebo-controlled crossover study. On each study day, subjects received DPP4 inhibitor (sitagliptin 200 mg by mouth) or placebo. Sitagliptin increased forearm blood flow and decreased forearm vascular resistance without affecting mean arterial pressure and pulse. GLP-1 and BNP were infused in incremental doses via brachial artery. Venous GLP-1 concentrations were significantly higher during sitagliptin use, yet there was no effect of GLP-1 on forearm blood flow in the presence or absence of sitagliptin. BNP caused dose-dependent vasodilation; however, sitagliptin did not affect this response. GLP-1 and BNP had no effect on net norepinephrine release.
  
  
  CONCLUSIONS
  These data suggest that GLP-1 does not act as a direct vasodilator in humans and does not contribute to sympathetic activation. Sitagliptin does not regulate vascular function in healthy humans by affecting the degradation of GLP-1 and BNP.
  
  
  BACKGROUND
  www.clinicaltrials.gov/ Unique identifier: NCT01413542.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.K.D., N.J.B.).
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Devin
authors.affiliation: Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN (M.P., F.T.B.).
authors.forename: Mias
authors.initials: M
authors.lastname: Pretorius
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN (H.N., C.Y.).
authors.forename: Hui
authors.initials: H
authors.lastname: Nian
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN (H.N., C.Y.).
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN (M.P., F.T.B.).
authors.forename: Frederic T
authors.initials: FT
authors.lastname: Billings
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.K.D., N.J.B.).
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply*; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000187:drug effects*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000187:drug effects*; D011719:Pyrazines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; D014230:Triazoles; D020097:Natriuretic Peptide, Brain; D052216:Glucagon-Like Peptide 1; D000068900:Sitagliptin Phosphate
keywords: diabetes mellitus; dipeptidyl‐peptidase 4; glucagon‐like peptide‐1; natriuretic peptide; vasodilation