Expression ofreg/PSP, a Pancreatic Exocrine Gene: Relationship to Changes in Islet β-Cell Mass

Abstract

A cDNA termed reg was recently isolated by differential screening of a library prepared from regenerating islets isolated from pancreatic remnants of rats subjected to 90% pancreatectomy and nicotinamide treatment. This led to speculation that this gene may be involved in expansion of beta-cell mass. In the current study we have measured reg expression after implantation and resection of a solid insulinoma tumor into rats, maneuvers known, respectively, to reduce and reexpand the volume of beta-cells in the islet. Animals with an implanted insulinoma tumor became profoundly hypoglycemic. Islet beta-cells declined from the normal 75% of total islet volume to less than 30%, in concert with a marked reduction in the reg mRNA level. Removal of the tumor resulted in a sharp increase in beta-cell replication, as measured by [3H]thymidine incorporation and a return to normal beta-cell volume within 4 days of tumor resection. This was associated with a transient induction in reg expression compared to that in tumor-bearing animals, effectively returning the amount of reg mRNA to the levels found in normal animals within 48 h; at later time points after tumor removal (3-7 days) reg expression declined, but then rose toward normal. In situ hybridization analysis localized the initial induction in reg mRNA expression to the exocrine pancreas. Continuous infusion of insulin into normal rats for 4 days, a maneuver that does not significantly reduce beta-cell mass, resulted in dramatically reduced insulin mRNA in islets, but no change in the levels of reg mRNA. We conclude that the diminution in pancreatic beta-cell mass caused by subcutaneous implantation of an insulinoma is associated with reduced reg gene expression and that the increase in beta-cell replication after resection of the tumor is preceded by return of reg gene expression toward normal.

Insights into the Mechanisms of Gastric Adaptation to Aspirin-Induced Injury: A Role for Regenerating Protein but Not Trefoil Peptides

“…*p Ͻ 0.05 compared with both the control and single-dose groups. for RegI in cellular proliferation is well demonstrated in pancreas (Francis et al, 1992;Miyaura et al, 1991;Watanabe et al, 1994), and RegI has also been implicated as exerting trophic effects on the gastric epithelium (Asahara et al, 1996;Fukui et al, 1998;Higham et al, 1999;Kawanami et al, 1997;Kazumori et al, 2000). Moreover, our results show clear evidence of concordantly increased expression of RegI and PCNA in both damaged and healing gastric epithelium.…”

Expression of Reg and cytokeratin 20 during ductal cell differentiation and proliferation in a mouse model of autoimmune diabetes

“…Reg gene expression was observed in regenerating pancreatic islets from depancreatized rats, but not in normal ones. Subsequent studies have demonstrated that enhanced reg gene expression is linked to DNA synthesis in pancreatic islets (9,10). Immunocytochemistry has revealed that Reg protein is synthesized in and secreted from the regenerating beta cells and that its expression is closely associated with the regeneration of beta cells (11).…”

Serum reg protein level is not related to the beta cell destruction/regeneration process during early phases of diabetogenesis in type I diabetes

“…Another possible explanation for the discrepancies between human and animal data could be the fact that reg gene overexpression could be a very transient phenomenon. In various animal models of islet regeneration, reg gene overexpression occurs very early in pancreas (1-2 days) and lasts only a few days (less than 1 week) (8)(9)(10)(11). In our series, it is noteworthy that three patients in both prediabetic and diabetic groups exhibited transient high serum reg levels.…”

“…Indeed, measurement of reg protein might be a good candidate for this purpose. The reg protein is normally secreted by exocrine pancreatic cells and reg gene overexpression has previously been shown to be associated with regeneration of pancreatic islets (8)(9)(10)(11). In animal models of autoimmune diabetes, pancreatic overexpression of reg mRNA has been reported (12)(13)(14) during active phases of diabetogenesis and reg gene proposed to play a role in the destruction/regeneration process during autoimmune aggression of beta cells (reviewed in ref.…”