TY - JOUR
T1 - Glucagon-Like Peptide 2 Inhibits Postprandial Gallbladder Emptying in Man
T2 - A Randomized, Double-Blinded, Crossover Study
AU - Hansen, Nina L.
AU - Bronden, Andreas
AU - Nexoe-Larsen, Christina C.
AU - Christensen, Alexander S.
AU - Sonne, David P.
AU - Rehfeld, Jens F.
AU - Wever Albretchsen, Nicolai J.
AU - Hartmann, Bolette
AU - Vilsbøll, Tina
AU - Holst, Jens J.
AU - Knop, Filip K.
PY - 2020
Y1 - 2020
N2 - 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 x kg(-1) x min(-1)), low-dose GLP-2 (1 pmol x kg(-1) x 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 x 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 x min, P <0.0001) and nearly abolished by high-dose GLP-2 (1.3 [-1.7 to 0.01] L x min, P = 0.029) compared to placebo (-2.0 [-2.8 to -1.1] L x 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.
AB - 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 x kg(-1) x min(-1)), low-dose GLP-2 (1 pmol x kg(-1) x 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 x 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 x min, P <0.0001) and nearly abolished by high-dose GLP-2 (1.3 [-1.7 to 0.01] L x min, P = 0.029) compared to placebo (-2.0 [-2.8 to -1.1] L x 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.
KW - SHORT-BOWEL SYNDROME
KW - SUM-OF-CYLINDERS
KW - SECRETION
KW - VOLUME
KW - CHOLECYSTOKININ
KW - ABSORPTION
KW - DISEASE
U2 - 10.14309/ctg.0000000000000257
DO - 10.14309/ctg.0000000000000257
M3 - Journal article
C2 - 33512799
VL - 11
JO - Clinical and Translational Gastroenterology
JF - Clinical and Translational Gastroenterology
SN - 2155-384X
IS - 12
M1 - e00257
ER -