Glucagon-Like Peptide 2 Inhibits Postprandial Gallbladder Emptying in Man: A Randomized, Double-Blinded, Crossover Study

INTRODUCTION: A recent study in mice points to the gut-derived hormone glucagon-like peptide 2 (GLP-2) as an important regulator of gallbladder motility inducing gallbladder relaxation and refilling. In this study, we evaluated the effect of exogenous GLP-2 on postprandial gallbladder motility in healthy men. METHODS: In a randomized, double-blinded, placebo-controlled, crossover study, we evaluated the effect of 4-hour intravenous infusions of high-dose GLP-2 (10 pmol × kg(−1) × min(−1)), low-dose GLP-2 (1 pmol × kg(−1) × min(−1)), and placebo (saline) on postprandial gallbladder motility. A 300-kcal liquid-mixed meal (added 1.5 g of acetaminophen for indirect measurement of gastric emptying) was served 30 minutes after start of intravenous infusions. Gallbladder volume was assessed by ultrasonography. RESULTS: Fifteen healthy men, age 24.3 (22.4–26.1) years (mean [95% confidence interval]) and body mass index 22.5 (21.7–23.4) kg × m(−2), were included. Basal plasma GLP-2 concentration was 14 (11–17) pmol/L. During low-dose and high-dose GLP-2 infusions, steady-state postprandial plasma GLP-2 concentrations amounted to 201 (188–214) and 2,658 (2,443–2,873) pmol/L, respectively, compared with maximum postprandial plasma GLP-2 concentration of 34 (25–44) pmol/L during placebo. Gallbladder emptying (assessed as baseline-subtracted area under the curve for gallbladder volume) was reduced by low-dose GLP-2 (−0.8 [0.7–1.9] L × min, P < 0.0001) and nearly abolished by high-dose GLP-2 (1.3 [−1.7 to 0.01] L × min, P = 0.029) compared to placebo (−2.0 [−2.8 to −1.1] L × min). Compared to placebo, gastric emptying was reduced by high-dose GLP-2 (P = 0.0060 and 0.019), whereas low-dose GLP-2 did not affect gastric emptying (P = 0.13 and 0.85). DISCUSSION: Exogenous GLP-2 exerts a dose-dependent inhibitory effect on postprandial gallbladder emptying in healthy men.