Recombinant Reg3α Protein Protects Against Streptozotocin-Induced β-cell Damage and Diabetes

Abstract

Regenerating (Reg) proteins have been identified as putative trophic factors, which are involved in pancreatic tissue regeneration and neogenesis. Our recent research found that recombinant Reg3α protein (rReg3α) protects against experimental, acute pancreatitis by alleviating pancreatic acinar cell necrosis and apoptosis. In order to further investigate the potential role of rReg3α in promoting islet β-cell survival against streptozotocin(STZ)-triggered cell death, rReg3α was directly administrated in MIN6 insulinoma cells and STZ-induced type 1 diabetes. Our results demonstrate that rReg3α stimulated MIN6 cell proliferation through Erk1/2 phosphorylation and cyclinD1/CDK4 upregulation mediated by Akt/ATF-2 signaling. Furthermore, it ameliorated STZ-induced cell death via enhanced Bcl-2 and Bcl-xL expression caused by Akt activation and reduced Caspase-3 cleavage. The administration of exogenous rReg3α partially prevented STZ-induced hyperglycemia and weight loss, and totally prevented animal death. The superiority of rReg3α in preserving insulin content and islet β- cell mass, and putatively promoting the regeneration of insulin positive cell clusters suggested its therapeutic potential against diabetes mellitus.