Peptide YY ameliorates cerulein-induced pancreatic injury in the rat

Abstract

Peptide YY (PYY), a known inhibitor of both pancreatic secretion and the release of cholecystokinin (CCK), may play a role in the pathophysiology of acute pancreatitis (AP). Supramaximal stimulation of the pancreas with CCK, or its analogue cerulein, induces edematous AP. We previously documented significant decreases in plasma PYY in sodium taurocholate-induced AP in the anesthetized pig, with exogenous PYY suppressing plasma amylase activity. We hypothesized that PYY may ameliorate cerulein-induced pancreatic injury in a conscious animal model. Thirty-two male Sprague-Dawley rats underwent chronic cannulation of the jugular vein and carotid artery for drug infusion and blood sampling. The animals were allowed to recover from anesthesia for a minimum of 16 hours, after which they were randomized to one of four (n = 8) treatment groups (cerulein 10 micrograms/kg/h, PYY 400 pmol/kg/h, cerulein+PYY, and control-saline 2 mL/kg/h). All treatments were administered by intravenous infusion over the first 6 hours of the experiment. Blood samples were taken prior to infusion and at 1, 3, 6, 9, and 24 hours into the study; the rats were then killed and the pancreata removed for weighing and histologic examination. All pancreatic specimens were graded in a blinded fashion for vacuolization, edema, inflammation, and necrosis. The mean basal plasma amylase level for all animals was 1,171 +/- 100 U/L and was not significantly different between groups. Infusion of cerulein resulted in significant increases in plasma amylase levels at 3, 6, 9, and 24 hours (4,827 +/- 1,022 U/L at 24 hours). In the group receiving both cerulein and PYY, the hyperamylasemia was attenuated with a return to basal values at 24 hours (1,206 +/- 103 U/L). There was significant pancreatic weight gain (1.99 +/- 0.07 g versus 1.03 +/- 0.07 g) and a worsened histologic picture in cerulein-treated animals compared with control animals (worsened edema, necrosis, and vacuolization). The addition of PYY to cerulein resulted in significantly lower pancreatic weight (1.27 +/- 0.11 g) than in the non-PYY-treated rats receiving cerulein. Pancreatic weight was not significantly different in this group compared with the control group. In addition, pancreatic histologic findings were significantly improved in those rats receiving PYY (decreased vacuolization and necrosis). Amylase levels, pancreatic weight, and morphologic findings were not significantly changed compared with basal values in the control or PYY alone treated groups. e conclude that as an inhibitor of pancreatic exocrine secretion, PYY ameliorates cerulein-induced pancreatic injury in the conscious rat.