Cholecystokinin fails to promote pancreatic regeneration in diabetic rats following the induction of experimental pancreatitis

Pharmacol Res. 2001 Nov;44(5):363-72. doi: 10.1006/phrs.2001.0843.

Abstract

The aim of the present study was to investigate the spontaneous and cholecystokinin-octapeptide (CCK-8)-promoted laboratory changes and morphological alterations in rats with arginine (Arg)-induced pancreatitis in which diabetes had been induced with streptozotocin (STZ). Male Wistar rats were used in our experiments. Pancreatitis was induced by arginine, diabetes by STZ and regeneration was promoted by CCK-8. The serum amylase, glucose and insulin levels, the pancreatic contents of protein, DNA, amylase, trypsinogen and lipase, the pancreatic weight/body- weight ratio (pw/bw) and the plasma glucagon level were examined 1, 3, 7, 14 and 28 days after pancreatitis induction. Pancreatic tissue samples were examined by light microscopy and immunostaining on paraffin-embedded sections. The insulin and glucagon-containing cells were visualized by using monoclonal antibodies. The administration of low doses of CCK-8 accelerated the processes of regeneration following Arg-induced pancreatitis, but in rats that were also diabetic, pancreatic regeneration was not observed. The administration of low doses of CCK-8 seems to reduce the pancreatic beta -cell number and function in diabetic rats. The pancreatic endocrine function was further deteriorated by simultaneous Arg-induced pancreatitis. The diabetic state appeared to shift the normal pancreatic enzyme content (decreased amylase and increased trypsinogen) in this study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholecystokinin / pharmacology*
  • Cholecystokinin / therapeutic use*
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / enzymology
  • Male
  • Pancreas / drug effects*
  • Pancreas / pathology
  • Pancreas / physiology
  • Pancreatitis / chemically induced
  • Pancreatitis / drug therapy*
  • Pancreatitis / enzymology
  • Pancreatitis / pathology
  • Rats
  • Rats, Wistar
  • Regeneration / drug effects*
  • Regeneration / physiology
  • Sincalide / pharmacology
  • Sincalide / therapeutic use

Substances

  • Cholecystokinin
  • Sincalide