title: Bile and pancreatic juice exclusion activates acinar stress kinases and exacerbates gallstone pancreatitis.
abstract: Bile and pancreatic juice exclusion from gut activates acinar stress kinases and exacerbates gallstone pancreatitis as evidenced by the ameliorating effects of replacement therapy in an experimental model of duct ligation-induced acute pancreatitis. In the early stages of gallstone pancreatitis, bile-pancreatic juice cannot enter the gut. Enteral exclusion worsens pancreatitis by causing feedback hyperstimulation of the exocrine pancreas that activates acinar cell stress kinases. Investigations using a unique surgical model, the Donor Rat Model, showed that duodenal replacement of bile-pancreatic juice in rats with duct ligation attenuates pancreatic stress kinase activation, reduces pancreatic cytokine production, and ameliorates pancreatic morphologic changes. These findings suggest that exclusion-induced acinar hyperstimulation, in the presence of duct obstruction, exacerbates acute pancreatitis via stress kinase activation. Although acinar hyperstimulation has often been implicated in the pathogenesis of acute pancreatitis, the lack of supporting evidence remains a conspicuous void. The proposed hypothesis draws on fresh evidence to present a new paradigm that reexamines the role of exocrine pancreatic hyperstimulation in gallstone pancreatitis pathogenesis.
authors.affiliation: Department of Surgery, University of Iowa Roy J. and Lucille A. Carver College of Medicine and Veterans Administration Medical Center, Iowa City, Iowa 52242, USA. Isaac-samuel@uiowa.edu
authors.forename: Isaac
authors.initials: I
authors.lastname: Samuel
mesh_terms: D000208:Acute Disease; D000818:Animals; D001646:Bile / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D042882:Gallstones / Q000150:complications*; D006801:Humans; D046790:Pancreas, Exocrine / Q000201:enzymology*; D010189:Pancreatic Juice / Q000378:metabolism*; D010195:Pancreatitis / Q000209:etiology* / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D011494:Protein Kinases