Impaired autophagy underlies key pathological responses of acute pancreatitis

The main function of the exocrine pancreas is to produce digestive enzymes, which normally are secreted as inactive zymogens and become activated after reaching the duodenum. Pancreatitis is a relatively common and potentially fatal inflammatory disease of the exocrine pancreas. Its mild forms are self-limited, but severe pancreatitis has 10%-30% mortality. The pathogenesis of pancreatitis remains obscure, and there are no specific treatments. The disease is believed to initiate in acinar cells, the main cell type of the exocrine pancreas. Hallmark responses of acute pancreatitis are the premature, intra-acinar cell activation of trypsinogen (i.e., its conversion from zymogen to active trypsin), vacuole accumulation, inflammation and death of acinar cells through both necrosis and apoptosis.