Glucagon ameliorates pancreatic subcellular redistribution of lysosomal enzyme in rats with acute pancreatitis of closed duodenal loop.

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.