Why does pancreatic overstimulation cause pancreatitis?

Ashok K. Saluja, Markus M. Lerch, Phoebe A. Phillips, Vikas Dudeja

Research output: Contribution to journalReview article

129 Scopus citations

Abstract

Many animal models are available to investigate the pathogenesis of pancreatitis, an inflammatory disorder of the pancreas. However, the secretogogue hyperstimulation model of pancreatitis is the most commonly used. Animals infused with high doses of cholecystokinin (CCK) exhibit hyperamylasemia, pancreatic edema, and acinar cell injury, which closely mimic pancreatitis in humans. Intra-acinar zymogen activation is an essential early event in the pathogenesis of secretagogue-induced pancreatitis. Early in the course of pancreatitis, lysosomal hydrolases colocalize with digestive zymogens and activate them. These activated zymogens then cause acinar cell injury and necrosis, a characteristic of pancreatitis. Besides being the site of initiation of injury in pancreatitis, acinar cells also synthesize and release cytokines and chemokines very early in the course of pancreatitis, which then attract and activate inflammatory cells and initiate the disease's systemic phase.

Original languageEnglish (US)
Pages (from-to)249-269
Number of pages21
JournalAnnual Review of Physiology
Volume69
DOIs
StatePublished - Mar 27 2007

Keywords

  • Cholecystokinin
  • Cytokine
  • Exocrine pancreas
  • Heat shock protein
  • Lysosome
  • Zymogen

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