title: 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.
authors: Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University Health Centre, Montreal, Canada.
authors: Bing
authors: B
authors: Li
authors: Chen
authors: C
authors: Luo
authors: Subrata
authors: S
authors: Chowdhury
authors: Zu-Hua
authors: ZH
authors: Gao
authors: Jun-Li
authors: JL
authors: Liu
mesh_terms: D000818:Animals; D002108:Ceruletide; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000201:enzymology*; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D051847:Lithostathine / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency* / Q000235:genetics; D013311:Streptozocin; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D051273:Glucose Transporter Type 2; D051847:Lithostathine; C495682:Slc2a2 protein, mouse; D013311:Streptozocin; D002108:Ceruletide; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
keywords: Acute pancreatitis; Diabetes; Pancreatic acini; Pancreatic islets; Parp1; Reg proteins