https://orcid.org/0000-0001-8509-2036
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Andreas H Lange, Nina L Hansen, Miriam G Pedersen, Henriette H Nerild, Jens F Rehfeld, Bolette Hartmann, Jens J Holst, Anne-Marie Ellegaard, Filip K Knop, Exogenous Glucagon-like Peptide 2 Counteracts Exogenous Cholecystokinin-induced Gallbladder Contraction in Healthy Men, The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 1, January 2025, Pages 123–129, https://doi.org/10.1210/clinem/dgae421
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Abstract
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).
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.
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.
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.
NCT04651868
