Journal
PANCREAS
Volume 50, Issue 1, Pages 3-11Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPA.0000000000001706
Keywords
acinar cells; acute pancreatitis; bile acids; Ca2+; gallstone
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG) [AG 203/4-1, SE 2702/2-1, GRK 1947 A3]
- Federal Ministry of Education and Research (BMBF) [GANI-MED 03IS2061A, 0314107, 01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012, 03zz0921E]
- European Union (EU-FP-7: EPC-TM) [V-1-083-VBW-028]
- PePPP center of excellence MV [ESF/14-BM-A55-0045/16]
- EnErGie/P2 Project [ESF/14-BM-A55-0008/18]
- Deutscher Akademischer Austauschdienst
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Bile acids play a role in contributing to the pathogenesis and severity of gallstone-induced acute pancreatitis by inducing intracellular calcium overload, mitochondrial depolarization, and acinar cell necrosis. Understanding the detailed mechanisms through which bile acids act may lead to the development of therapeutic and preventive strategies for this condition.
Acute pancreatitis (AP) is one of the most common gastroenterological disorders leading to hospitalization. It has long been debated whether biliary AP, about 30% to 50% of all cases, is induced by bile acids (BAs) when they reach the pancreas via reflux or via the systemic blood circulation. Besides their classical function in digestion, BAs have become an attractive research target because of their recently discovered property as signaling molecules. The underlying mechanisms of BAs have been investigated in various studies. Bile acids are internalized into acinar cells through specific G-protein-coupled BA receptor 1 and various transporters. They can further act via different receptors: the farnesoid X, ryanodine, and inositol triphosphate receptor. Bile acids induce a sustained Ca2+ influx from the endoplasmic reticulum and release of Ca2+ from acidic stores into the cytosol of acinar cells. The overload of intracellular Ca2+ results in mitochondrial depolarization and subsequent acinar cell necrosis. In addition, BAs have a biphasic effect on pancreatic ductal cells. A more detailed characterization of the mechanisms through which BAs contribute to the disease pathogenesis and severity will greatly improve our understanding of the underlying pathophysiology and may allow for the development of therapeutic and preventive strategies for gallstone-induced AP.
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