Experimental Acute Pancreatitis in Mice

Abstract

Abstract The effects of glucagon on pancreatitis induced by feeding mice a choline-deficient ethionine-supplemented (CDE) diet for 1 day were studied. Glucagon pretreatment (a) decreased the mortality rate of pancreatitis; (b) lessened the rise in serum amylase; (c) diminished the rise in pancreatic digestive enzyme (a-amylase, trypsinogen, and chymotrypsinogen) content and both digestive enzyme and protein in vitro secretion; and (d) decreased the severity of pancreatitis noted microscopically, In contrast, when glucagon was given concomitant with the administration of the CDE diet (treatment group), the mortality rate of pancreatitis was not lowered, and a significant reduction in serum amylase elevation was not observed. Although the effects of glucagon treatment and pretreatment on pancreatic digestive enzyme content and digestive enzyme and protein in vitro secretion were qualitatively similar, the changes noted after pretreatment were of greater magnitude. The effects of glucagon on the pancreas of mice fed a regular diet were also studied. Pretreatment with glucagon lowered amylase content as well as in vitro protein nnd amylase secretion, while treatment with glucagon lowered only pancreatic amylase content. In both cases, the percent amylase output was increased. These studies indicate that glucagon alters the mortality rate, serum amylase elevation, microscopic appearance, and in vitro function of the pancreas during diet-induced experimental pancreatitis. The effects of glucagon are greatest when its administration precedes exposure to the CDE diet. If this model is representative of clinical acute pancreatitis, it is unlikely that glucagon will be of therapeutic value in the treatment of clinically established acute pancreatitis.