Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes

Abstract

Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis. Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis. We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition. To test this possibility, Parp1 −/− and wild-type mice were injected with streptozotocin to induce diabetes. Separately, acute pancreatitis was induced with repeated injections of caerulein. Upon streptozotocin administration, Parp1 −/− mice displayed much decreased hyperglycemia and preserved serum insulin level. The treatment induced similar levels of Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1 −/− mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation. In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion. Our results reconfirmed the protective effect of Parp1 gene deletion on islet β-cells but questioned its effect on the acinar cells. In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.