The effects of dipeptidyl-peptidase-IV inhibitor, vildagliptin, on the exocrine pancreas in spontaneously diabetic Goto-Kakizaki rats.

OBJECTIVES: The risk of adverse effects of dipeptidyl peptidase-4 inhibitors on the exocrine pancreas, particularly the high risk of pancreatitis, is controversial. In this study, we examined the exocrine pancreatic function and structure in spontaneously diabetic Goto-Kakizaki (GK) rats treated with a dipeptidyl peptidase-4 inhibitor. METHODS: Male GK rats and normal Wistar rats 4 weeks of age were treated with vildagliptin (VG; 30 mg/kg/d) for 18 weeks. Subsequently, exocrine pancreatic pathology and function in treated animals were compared to those in untreated animals. RESULTS: In GK rats, VG treatment suppressed elevated serum concentrations of amylase and lipase, reduced lymphocytic infiltration around ducts, around vessels, and in acinar areas, and reduced the frequency of apoptotic acinar cells and ductule formation (both of which occurred more frequently in GK rats than Wistar rats). However, VG treatment had no effect on the proliferation rate of pancreatic duct glandular cells (which was low in GK rats) and of cells in the main ducts, peripheral ducts, and acini (which was similar in all groups). CONCLUSIONS: Perturbations of exocrine pancreatic function and structure in GK rats are ameliorated by long-term VG treatment.