1. New Avenues in the Regulation of Gallbladder Motility-Implications for the Use of Glucagon-Like Peptide-Derived Drugs.
- Author
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Gether IM, Nexøe-Larsen C, and Knop FK
- Subjects
- Bile Acids and Salts metabolism, Cholecystitis chemically induced, Cholecystitis physiopathology, Cholecystokinin metabolism, Cholelithiasis chemically induced, Cholelithiasis physiopathology, Diabetes Mellitus, Type 2 drug therapy, Gallbladder physiopathology, Gallbladder Emptying physiology, Glucagon-Like Peptide 1 metabolism, Glucagon-Like Peptide 2 metabolism, Glucagon-Like Peptide-1 Receptor agonists, Glucagon-Like Peptide-1 Receptor metabolism, Glucagon-Like Peptide-2 Receptor agonists, Glucagon-Like Peptide-2 Receptor metabolism, Humans, Muscle Contraction physiology, Muscle, Smooth drug effects, Muscle, Smooth physiopathology, Obesity drug therapy, Postprandial Period physiology, Gallbladder drug effects, Gallbladder Emptying drug effects, Glucagon-Like Peptides adverse effects, Muscle Contraction drug effects
- Abstract
Context: Several cases of cholelithiasis and cholecystitis have been reported in patients treated with glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) and GLP-2 receptor agonists (GLP-2RAs), respectively. Thus, the effects of GLP-1 and GLP-2 on gallbladder motility have been investigated. We have provided an overview of the mechanisms regulating gallbladder motility and highlight novel findings on the effects of bile acids and glucagon-like peptides on gallbladder motility., Evidence Acquisition: The articles included in the present review were identified using electronic literature searches. The search results were narrowed to data reporting the effects of bile acids and GLPs on gallbladder motility., Evidence Synthesis: Bile acids negate the effect of postprandial cholecystokinin-mediated gallbladder contraction. Two bile acid receptors seem to be involved in this feedback mechanism, the transmembrane Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor. Furthermore, activation of TGR5 in enteroendocrine L cells leads to release of GLP-1 and, possibly, GLP-2. Recent findings have pointed to the existence of a bile acid-TGR5-L cell-GLP-2 axis that serves to terminate meal-induced gallbladder contraction and thereby initiate gallbladder refilling. GLP-2 might play a dominant role in this axis by directly relaxing the gallbladder. Moreover, recent findings have suggested GLP-1RA treatment prolongs the refilling phase of the gallbladder., Conclusions: GLP-2 receptor activation in rodents acutely increases the volume of the gallbladder, which might explain the risk of gallbladder diseases associated with GLP-2RA treatment observed in humans. GLP-1RA-induced prolongation of human gallbladder refilling may explain the gallbladder events observed in GLP-1RA clinical trials., (Copyright © 2019 Endocrine Society.)
- Published
- 2019
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