Insulin is necessary for the hypertrophic effect of cholecystokinin-octapeptide following acute necrotizing experimental pancreatitis

• Published in: World journal of gastroenterology : WJG Vol. 10; no. 15; pp. 2275 - 2277
• Main Authors: Hegyi, Peter, Rakonczay, Jr, Zoltan, Sari, Reka, Czako, Laszlo, Farkas, Norbert, Gog, Csaba, Nemeth, Jozsef, Lonovics, Janos, Takacs, Tamas
• Format: Journal Article
• Language: English
• Published: United States First Department of Medicine, Faculty of Medicine,University of Szeged Szeged H6722, Hungary 01-08-2004; School of Cell and Molecular Biosciences, Medical School, University of Newcastle, Newcastle upon Tyne, NE2 4HH, United Kingdom%First Department of Medicine, Faculty of Medicine,University of Szeged Szeged H6722, Hungary; Baishideng Publishing Group Inc
• Subjects: Animals; Brief Reports; Diabetes Mellitus, Experimental - complications; Hypoglycemic Agents - pharmacology; Insulin - pharmacology; Male; Pancreatitis, Acute Necrotizing - complications; Pancreatitis, Acute Necrotizing - physiopathology; Rats; Rats, Wistar; Regeneration - drug effects; Sincalide - pharmacology
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v10.i15.2275

In previous experiments we have demonstrated that by administering low doses of cholecystokinin-octapeptide (CCK-8), the process of regeneration following L-arginine (Arg)-induced pancreatitis is accelerated. In rats that were also diabetic (induced by streptozotocin, STZ), pancreatic regeneration was not observed. The aim of this study was to deduce whether the administration of exogenous insulin could in fact restore the hypertrophic effect of CCK-8 in diabetic-pancreatitic rats.
Male Wistar rats were used for the experiments. Diabetes mellitus was induced by administering 60 mg/kg body mass of STZ intraperitoneally (i.p.), then, on d 8, pancreatitis was induced by 200 mg/100 g body mass Arg i.p. twice at an interval of 1 h. The animals were injected subcutaneously twice daily (at 7 a.m. and 7 p.m.) with 1 ?g/kg of CCK-8 and/or 2 IU mixed insulin (300 g/L short-action and 700 g/L intermediate-action insulin) for 14 d after pancreatitis induction. Following this the animals were killed and the serum amylase, glucose and insulin levels as well as the plasma glucagon levels, the pancreatic mass/body mass ratio (pm/bm), the pancreatic contents of DNA, protein, amylase, lipase and trypsinogen were measured. Pancreatic tissue samples were examined by light microscopy on paraffin-embedded sections.
In the diabetic-pancreatitic rats treatment with insulin and CCK-8 significantly elevated pw/bm and the pancreatic contents of protein, amylase and lipase vs the rats receiving only CCK-8 treatment. CCK-8 administered in combination with insulin also elevated the number of acinar cells with mitotic activities, whereas CCK-8 alone had no effect on laboratory parameters or the mitotic activities in diabetic-pancreatitic rats.
Despite the hypertrophic effect of CCK-8 being absent following acute pancreatitis in diabetic-rats, the simultaneous administration of exogenous insulin restored this effect. Our results clearly demonstrate that insulin is necessary for the hypertrophic effect of low-doses of CCK-8 following acute pancreatitis.