Mechanisms of Glucose-Induced Expression of Pancreatic-Derived Factor in Pancreatic β-Cells

摘要: Pancreatic-derived factor (PANDER) is a cytokine-like peptide highly expressed in pancreatic beta-cells. PANDER was reported to promote apoptosis of beta-cells and secrete response glucose. Here we explored the effects glucose on expression, underlying mechanisms murine beta-cell line MIN6 primary islets. Our results showed that up-regulated mRNA protein levels time- dose-dependent manner cells In expressing cAMP element-binding (CREB) dominant-negative construct, failed induce gene expression promoter activation. Treatment with calcium chelator [EGTA, 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA/AM)], voltage-dependent Ca(2+) channel inhibitor (nifedipine), kinase A (PKA) (H89), C (PKC) (Go6976), or MAPK 1/2 (PD98059), all significantly inhibited glucose-induced Further studies induced CREB phosphorylation through Ca(2+)-PKA-ERK1/2 Ca(2+)-PKC pathways. Thus, Ca(2+)-PKA-ERK1/2-CREB Ca(2+)-PKC-CREB signaling pathways are involved expression. Wortmannin (phosphatidylinositol 3-kinase inhibitor), ammonium pyrrolidinedithiocarbamate (nuclear factor-kappaB nonspecific antioxidant), N-acetylcysteine (antioxidant) were also found inhibit activation Because there no nuclear binding site region gene, these suggest phosphatidylinositol reactive oxygen species be conclusion, induces multiple by similar way those insulin, may homeostasis.