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Exogenous Glucagon-like Peptide 2 Counteracts Exogenous Cholecystokinin-induced Gallbladder Contraction in Healthy Men
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Exogenous Glucagon-like Peptide 2 Counteracts Exogenous Cholecystokinin-induced Gallbladder Contraction in Healthy Men
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Journal Article
Exogenous Glucagon-like Peptide 2 Counteracts Exogenous Cholecystokinin-induced Gallbladder Contraction in Healthy Men
2025
Overview
Abstract
Background and Objective
Studies in humans and mice have demonstrated that the gut hormone glucagon-like peptide 2 (GLP-2) promotes gallbladder relaxation and refilling. Here, we assessed the effect of exogenous GLP-2 on gallbladder motility in the fasted state of healthy men with and without infusion of the potent gallbladder-contracting hormone cholecystokinin (CCK).
Methods
In a randomized, double-blind, placebo-controlled, crossover study, 15 male participants (mean [SD]: age 24.7 [3.6] years; body mass index 22.9 [1.6] kg/m2) underwent 4 experimental days receiving 2 infusions on each day: either CCK (0.4 pmol × kg−1 × min−1, time 0-180 minutes) + GLP-2 (10 pmol × kg−1 × min−1, time 30-240 minutes), CCK + placebo, placebo + GLP-2, or placebo + placebo, respectively. Gallbladder volume was measured at baseline and throughout the 4-hour study day using ultrasonography.
Results
Compared to placebo + placebo, GLP-2 + placebo did not affect gallbladder volume, but when infused in combination with CCK, GLP-2 completely abolished the strong gallbladder-contracting effect seen during CCK + placebo infusion, restoring baseline levels of gallbladder volume.
Conclusion
Exogenous GLP-2 counteracts exogenous CCK-induced gallbladder emptying in healthy men, pointing to a possible therapeutic potential for GLP-2 as a relaxing modulator of gallbladder smooth muscle tone (eg, as a bridge to surgery in biliary colic). The effect may also explain the gallbladder-related adverse events reported for GLP-2 receptor agonists used in the treatment of short bowel syndrome.
Clinical Trial Registration number
NCT04651868
Publisher
Oxford University Press
Subject
/ Cholecystokinin - administration & dosage
/ Cholecystokinin - pharmacology
/ Ethylenediaminetetraacetic acid
/ Gallbladder - diagnostic imaging
/ Gallbladder Emptying - drug effects
/ Gallbladder Emptying - physiology
/ Glucagon
/ Glucagon-Like Peptide 2 - administration & dosage
/ Glucagon-Like Peptide 2 - pharmacology
/ Humans
/ Male
/ Muscle Contraction - drug effects
/ Peptides
/ Placebos
