Dipeptidyl Peptidase 4 Inhibition Increases Postprandial Norepinephrine via Substance P (NK1 Receptor) During RAAS Inhibition.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_925652F1A63C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dipeptidyl Peptidase 4 Inhibition Increases Postprandial Norepinephrine via Substance P (NK1 Receptor) During RAAS Inhibition.
Journal
Journal of the Endocrine Society
Author(s)
Wilson J.R., Kerman S.J., Hubers S.A., Yu C., Nian H., Grouzmann E., Eugster P.J., Mayfield D.S., Brown N.J.
ISSN
2472-1972 (Electronic)
ISSN-L
2472-1972
Publication state
Published
Issued date
01/10/2019
Peer-reviewed
Oui
Volume
3
Number
10
Pages
1784-1798
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Dipeptidyl peptidase 4 (DPP4) inhibitors may increase the risk of heart failure. Decreased degradation of vasoactive peptides like substance P [also degraded by angiotensin-converting enzyme (ACE)] and Y1 agonists peptide YY (PYY 1-36) and neuropeptide Y (NPY 1-36) could contribute.
This study tested the hypothesis that there is an interactive effect of DPP4 inhibition and ACE inhibition (vs antihypertensive control subjects) on vasoactive peptides after a mixed meal.
Fifty-three patients with type 2 diabetes and hypertension were randomized to double-blind treatment with ramipril, valsartan, or amlodipine for 15 weeks in parallel groups. During the 5th, 10th, and 15th weeks, participants also received placebo + placebo, sitagliptin 100 mg/d + placebo, and sitagliptin + aprepitant 80 mg/d in random order. On the last day of each crossover treatment, participants underwent a mixed-meal study.
Sitagliptin increased postprandial glucagon-like peptide-1 and decreased glucose in all antihypertensive groups. Sitagliptin increased NPY 1-36 and decreased Y2 agonists NPY 3-36 and PYY 3-36 in all groups. During ramipril or valsartan, but not amlodipine, sitagliptin increased postprandial norepinephrine; substance P receptor blockade with aprepitant prevented this effect. Despite increased norepinephrine, sitagliptin decreased postprandial blood pressure during ACE inhibition.
DPP4 inhibition increases postprandial concentrations of the Y1 agonist NPY 1-36. During treatment with an ACE inhibitor or angiotensin receptor blocker, DPP4 inhibition increased postprandial norepinephrine through a substance P receptor-dependent mechanism. Increased NPY 1-36 and norepinephrine could increase risk of heart failure but did not result in higher postprandial blood pressure.
Keywords
DPP4, dipeptidyl peptidase-4 inhibition, hypertension, sitagliptin, substance P, type 2 diabetes mellitus
Pubmed
Open Access
Yes
Create date
20/09/2019 21:33
Last modification date
30/04/2021 6:12
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