Abstract
Two animal models have been employed to examine the role of pancreatic polypeptide, a potent and selective inhibitor of pancreatic exocrine secretion, in the treatment of acute pancreatitis. In one model pancreatitis was induced by feeding young female Swiss Webster mice an ethionine-supplemented, choline-deficient diet for 48 hr. Animals (N=30 per group) were injected subcutaneously every 8 hr for 7 days with pancreatic polypeptide (0, 2, 20, and 200 μg/kg/day). Treatment with 20 and 200 μg/kg/day pancreatic polypeptide significantly (P<0.05) reduced moriality from a control rate of 70% to 42% and 33%, respectively. Treated animals also exhibited significant (P<0.05) decreases in pancreatic content of activated chymotrypsin and an improvement in pancreatic histology. Pancreatic polypeptide was effective whether treatment was started before or at the same time the test diet was introduced. In contrast, pancreatic polypeptide failed to protect dogs with acute pancreatitis induced by retrograde injection of the pancreas with bile, which may reflect the rapid and mechanical nature of pancreatic damage in this animal model.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Trapnell J: The natural history and management of acute pancreatitis. Clin Gastroenterol 1:147–166, 1972
Lankisch PG, Winckler K, Bokermann M, Schmidt H, Creutzfeldt W: The influence of glucagon on acute pancreatitis in the rat. Scand J Gastroenterol 9:725–729, 1974
Schmidt H, Hesch RD, Hüfner M, Paschen K, Creutzfeldt W: Hemmung der exokrinen pankreassekretion des menschen durch calcitonin. Dtsch Med Wochenschr 96:1773–1775, 1971
Lankisch PG, Koop H, Winckler K, Fölsch UR, Creutzfeldt W: Somatostatin therapy of acute experimental pancreatitis. Gut 18:713–716, 1977
Raptis S, Schlegel W, Lehmann E, Dollinger HC, Zoupas CH: Effects of somatostatin on the exocine pancreas and the release of duodenal hormones. Metabolism 27:1321–1328, 1978
Lin TM, Evans DC, Chance RE, Spray GF: Bovine pancreatic polypeptide: Action on gastric and pancreatic secretion in dogs. Am J Physiol 232:E311–315, 1977
Taylor IL, Solomon TE, Walsh JH, Grossman MI: Pancreatic polypeptide: Metabolism and effect on pancreatic secretion in dogs. Gastroenterology 76:524–528, 1979
Greenberg GR, McCloy RF, Adrian TE, Chadwick VS, Baron JH, Bloom SR: Inhibition of pancreas and gallbladder by pancreatic polypeptide. Lancet 2:1280–1282, 1978
de Almeida AL, Grossman MI: Experimental production of pancreatitis with ethionine. Gastroenterology 20:554–577, 1952
Wachstein M, Meisel E: Equal effectiveness ofl-andd-ethionine in producing tissue damage in rats and mice. Proc Soc Exp Biol Med 82:70–72, 1953
Lombardi B, Estes LW, Longnecker DS: Acute hemorrhagic pancreatitis (massive necrosis) with fat necrosis induced in mice byDl-ethionine fed with a choline-deficient diet. Am J Pathol 79:465–480, 1975
Beck IT, Kahn DS, Solymar J, McKenna RD, Zylberszac B: The role of pancreatic enzymes in the pathogenesis of acute pancreatitis III. Comparison of the pathologic and biochemical changes in the canine pancreas, to intraductal injection with bile and with trypsin. Gastroenterology 46:531–542 1964
Rinderknecht H, Renner IG, Carmack C: Activation of human pancreatic juice. Clin Chem Acta 73:369–372, 1976
Lombardi B, Rao NK: Acute hemorrhagic pancreatitis in mice. Influence of the age and sex of the animals and of dietary ethionine, choline, methionine and adenine sulfate. Am J Pathol 81:87–100, 1975
Rao KN, Tuma J, Lombardi B: Acute hemorrhagic pancreatic necrosis in mice. Intraparenchymal activation of zymogens and other enzyme changes in pancreas and serum Gastroenterology 70:720–726, 1976
Rao KN, Zuretti MF, Baccino FM, Lombardi B: Acute hemorrhagic pancreatic necrosis in mice. The activity of lysosomal enzymes in the pancreas and the liver. Am J Pathol 98:45–59, 1980
Gilliland L, Steer ML: Effect of ethionine on digestive enzyme synthesis and discharge by mouse pancreas. Am J Physiol 239:G418–426, 1980
Koike H, Steer ML, Meldolesi J: Pancreatic effects of ethionine: Blockade of exocytosis and appearance of crinophage and autophagy precede cellular necrosis. Am J Physiol 242:G297-G307, 1982
Schlunk FF, Lombardi B: Inhibition of phospholipid synthesis as an early feature of the ethionine fatty liver. Fed Proc 28:365, 1969
Lombardi B: Influence of dietary factors on the pancreatotoxicity of ethionine. Am J Pathol 84:633–648, 1976
Malaisse-Lagae F, Carpentier JL, Patel YC, Malaisse WJ, Orci L: Pancreatic polypeptide, a possible role in the regulation of food intake in the mouse. Hypothesis. Experentia 33:915–917, 1977
Chance RE, Moon NE, Johnson MG: Human pancreatic polypeptide (HPP) and bovine pancreatic polypeptide (BPP).In. Methods of Hormone Radio-immunoassay. BM Jaffe, HR Behram (eds). New York, Academic Press, 1979, pp 657–672
Debas HT, Hancock RJ, Soon-Shiong P, Smythe HA, Cassim MM Glucagon therapy in acute pancreatitis: Prospective randomized double-blinded study. Can J Surg 23:578–580, 1980
Regan PT, Malagelada JR, Go VLW, Wolf AM, DiMagno EP: A prospective study of the antisecretory and therapeutic effect of cimetidine and glucagon in human pancreatitis. Mayo Clin Proc 56:499–503, 1981
Goebell H, Ammann R, Herfarth CH, Horn J, Hotz J, Knolauch M, Schmid M, Jaeger M, Akovbiantz A, Linder E, Abt K, Nuesch E, Barth E: A double-blind trial of synthetic salmon calcitonin in the treatment of acute pancreatitis. Scand J Gastroenterol 4:881–889, 1979
Manabe T, Steer ML: Experimental acute pancreatitis in mice: Protective effects of glucagon. Gastroenterology 76:529–534, 1979
Author information
Authors and Affiliations
Additional information
This study was supported by a grant from the Veterans Administration.
Rights and permissions
About this article
Cite this article
Coelle, E.F., Taylor, I.L., Lewin, K. et al. Beneficial effect of pancreatic polypeptide in experimental pancreatitis. Digest Dis Sci 28, 1083–1088 (1983). https://doi.org/10.1007/BF01295806
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01295806