1982-P: Glucagon-Like Peptide-2 Inhibits Postprandial Gallbladder Emptying in Healthy Male Individuals—A Randomized, Double-Blinded, Placebo-Controlled Study

Abstract

A recent study in mice has demonstrated that the gut-derived hormone glucagon-like peptide-2 (GLP-2) may be involved in the regulation of gallbladder motility and induces gallbladder refilling. This study evaluated the effect of exogenous GLP-2 on postprandial gallbladder motility in humans. On three experimental days, 15 young healthy males ([mean±SEM] age 24.3±1.9 years, BMI 22.5±0.9 kg×m-2, HbA1c 4.8±0.1% (29.3±1.5 mmol/mol)) were subjected to a 3.5-hour 300 kcal mixed liquid meal-test. Continuous 4-hour intravenous infusions of placebo (saline), low-dose GLP-2 (1 pmol×kg-1×min-1) or high-dose GLP-2 (10 pmol×kg-1×min-1) were initiated 30 min before meal ingestion. Gallbladder volume was determined by ultrasonography, and gallbladder ejection fraction was calculated. Postprandial maximum gallbladder ejection fraction during saline infusion (76.3±2.8%) was significantly reduced by low-dose GLP-2 (65.5±3.5%, P=0.026) and completely abolished during high-dose GLP-2 infusion (4.0±3.7%, P<0.0001) (Figure). Postprandial peak plasma glucose was lower during high-dose GLP-2 infusion (6.4±0.2 mmol/l) compared to low-dose GLP-2 (6.9±0.2mmol/l, P=0.0004) and placebo infusion (7.2±0.2 mmol/l, P=0.008). In conclusion, exogenous GLP-2 dose-dependently inhibits postprandial gallbladder emptying in healthy male subjects. Disclosure N.L. Hansen: None. C.C. Nexøe-Larsen: None. A. Brønden: Other Relationship; Self; AstraZeneca. A.S. Christensen: None. D.P. Sonne: None. B. Hartmann: None. T. Vilsbøll: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S.