The protective effects of glucagon on the exocrine pancreas were investigated in rats with a closed duodenal loop (CDL). A CDL in rats caused marked hyperamylasemia, pancreatic edema and pancreatic histological damage such as acinar cell vacuolization and interstitial edema. A CDL also caused redistribution of the lysosomal enzyme, cathepsin B, from the lysosomal fraction to the zymogen fraction as well as the activation of trypsinogen in pancreatic tissue. Moreover, a CDL caused a marked motality rate (40% at 48 h). However, treatment with glucagon at a dose of 1.0 mg/kg (subcutaneous injection) every 8 h (3 times) significantly inhibited these pancreatic injuries, improving the survival rate (95% at 48 h). These results indicate the important role of lysosomal enzymes in the pathogenesis of severe acute pancreatitis, and also suggest the possible usefulness of glucagon in the treatment of clinical pancreatitis.

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