title: Insulin is necessary for the hypertrophic effect of cholecystokinin-octapeptide following acute necrotizing experimental pancreatitis.
abstract: 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.
authors.affiliation: University of Szeged, Faculty of Medicine, First Department of Medicine, PO Box 469, H-6701 Szeged, Hungary. hep@in1st.szote.u-szeged.hu
authors.forename: Peter
authors.initials: P
authors.lastname: Hegyi
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Rakonczay
authors.forename: Reka
authors.initials: R
authors.lastname: Sari
authors.forename: Laszlo
authors.initials: L
authors.lastname: Czako
authors.forename: Norbert
authors.initials: N
authors.lastname: Farkas
authors.forename: Csaba
authors.initials: C
authors.lastname: Gog
authors.forename: Jozsef
authors.initials: J
authors.lastname: Nemeth
authors.forename: Janos
authors.initials: J
authors.lastname: Lonovics
authors.forename: Tamas
authors.initials: T
authors.lastname: Takacs
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*; D012844:Sincalide / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D012844:Sincalide