GENETIC DELETION OF ISLET AMYLOID POLYPPEPTIDE ATTENUATES PANCREATIC INFLAMMATION IN MICE WITH CERULEIN INDUCED PANCREATITIS

Abstract

As a product of pancreatic beta cells, islet amyloid polypeptide (IAPP or amylin) has been found to regulate pancreatic circulation, stimulate amylase output, and modulate inflammatory cytokines. This being the case, IAPP may play a part in acute pancreatitis (AP). In keeping with this hypothesis, circulating IAPP is found increased in severe AP. To investigate the role of IAPP in AP, we in this study compared cerulein-induced AP between IAPP-knockout (IAPPKO) mice and their wild type (wt) littermates. Methods: In wt- or IAPPKO mice, AP was induced by intraperitoneal injection of cerulein (5 ug/kg/h, 9 times). Saline was similarly injected in wt- and IAPPKO mice for controls. All the mice were sacrificed 9 hours after the first injection. Pancreatic lesions were assessed by histology and by serum amylase level. Pancreatic myeloperoxidase (MPO) activity was determined as an index of leukocyte infiltration in the ailing gland. In addition, circulating levels of glucose, alanine aminotransferase (ALT) and insulin were measured as well. Results: Serum amylase and MPO activity were increased in wt- and IAPPKO-mice following cerulein treatment. By histology, the wt- and IAPPKO mice showed similar acinar injury in their pancreas. However, the IAPPKO mice with AP showed a significant reduction in MPO activity (P < 0.01), compared to wt-mice with AP. Circulating glucose levels decreased significantly in both AP groups, compared with saline-treated controls. In addition, the IAPPKO mice with AP mice showed additional reduction in the glucose level compared to wt-mice with AP (P < 0.01). ALT and insulin were unaltered by AP. Conclusion: The output of IAPP from the endocrine islets of pancreas appears to participate in AP by promoting leukocyte infiltration into the ailing gland. IAPP may also be involved in maintenance of glucose homeostasis during acute pancreatitis.