GLP-2 and GIP exert separate effects on bone turnover: A randomized, placebo-controlled, crossover study in healthy young men.
Adult
Animals
Blood Glucose
/ drug effects
Bone Remodeling
/ drug effects
COS Cells
Chlorocebus aethiops
Cross-Over Studies
Cyclic AMP
/ metabolism
Gastric Inhibitory Polypeptide
/ pharmacology
Glucagon-Like Peptide 2
/ pharmacology
Humans
Male
Receptors, Gastrointestinal Hormone
/ metabolism
Young Adult
Bone formation
Bone resorption
CTX
P1NP
PTH
Journal
Bone
ISSN: 1873-2763
Titre abrégé: Bone
Pays: United States
ID NLM: 8504048
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
22
01
2019
revised:
15
04
2019
accepted:
11
05
2019
pubmed:
18
5
2019
medline:
4
8
2020
entrez:
18
5
2019
Statut:
ppublish
Résumé
Glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) both inhibit bone resorption in humans but the underlying mechanisms are poorly understood. In vitro, GLP-2 activates the GIP-receptor (GIPR). Based on in vitro studies, we hypothesized that the antiresorptive effect of GLP-2 was mediated through the GIPR. This was tested using the selective GIPR-antagonist GIP(3-30)NH The study was a randomized, single-blinded, placebo-controlled, crossover study conducted at Hvidovre University Hospital, Denmark. Eight healthy young men were included and studied on four study days: GIP (200 μg), GLP-2 (800 μg), GIP(3-30)NH CTX (mean ± SEM) significantly decreased after both GIP (to 55.3 ± 6.3% of baseline at t = 90 min) and GLP-2 (to 60.5 ± 5.0% of baseline at t = 180 min). The maximal reduction in CTX after GIP(3-30)NH GIPR antagonism did not inhibit the GLP-2-induced reduction in bone resorption (CTX) in healthy young men. In contrast to GLP-2, GIP increased P1NP despite decreasing CTX indicating an uncoupling of bone resorption from formation. Thus, GLP-2 and GIP seem to exert separate effects on bone turnover in humans. ClinicalTrials.gov (NCT03159741).
Sections du résumé
BACKGROUND
Glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) both inhibit bone resorption in humans but the underlying mechanisms are poorly understood. In vitro, GLP-2 activates the GIP-receptor (GIPR).
OBJECTIVE
Based on in vitro studies, we hypothesized that the antiresorptive effect of GLP-2 was mediated through the GIPR. This was tested using the selective GIPR-antagonist GIP(3-30)NH
METHODS
The study was a randomized, single-blinded, placebo-controlled, crossover study conducted at Hvidovre University Hospital, Denmark. Eight healthy young men were included and studied on four study days: GIP (200 μg), GLP-2 (800 μg), GIP(3-30)NH
RESULTS
CTX (mean ± SEM) significantly decreased after both GIP (to 55.3 ± 6.3% of baseline at t = 90 min) and GLP-2 (to 60.5 ± 5.0% of baseline at t = 180 min). The maximal reduction in CTX after GIP(3-30)NH
CONCLUSIONS
GIPR antagonism did not inhibit the GLP-2-induced reduction in bone resorption (CTX) in healthy young men. In contrast to GLP-2, GIP increased P1NP despite decreasing CTX indicating an uncoupling of bone resorption from formation. Thus, GLP-2 and GIP seem to exert separate effects on bone turnover in humans.
CLINICAL TRIALS INFORMATION
ClinicalTrials.gov (NCT03159741).
Identifiants
pubmed: 31100534
pii: S8756-3282(19)30189-9
doi: 10.1016/j.bone.2019.05.014
pii:
doi:
Substances chimiques
Blood Glucose
0
Glucagon-Like Peptide 2
0
Receptors, Gastrointestinal Hormone
0
Gastric Inhibitory Polypeptide
59392-49-3
gastric inhibitory polypeptide receptor
D6H00MV7K8
Cyclic AMP
E0399OZS9N
Banques de données
ClinicalTrials.gov
['NCT03159741']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
178-185Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.