Endocrine Abstracts

Within the exocrine pancreas, p8 expression is induced by pancreatitis and protects exocrine tissue from inflammatory damage via inhibition of NFκB. In previous work, we investigated the role of p8 within the endocrine pancreas and characterised p8 as a glucose-dependent mediator of beta cell proliferation. Here we investigate the hypothesis that p8 protects beta cells from cell damage by the diabetogenic drug STZ. We investigated native and transiently transfected INS-1E and beta-TC3 beta cells. For transfections, we used a CMV-driven p8 expression plasmid or an empty plasmid control (mock). STZ-induced p8 gene expression and viability of cells were established with a MTS assay and qPCR using commercially bench-tested primers, respectively. Initially we characterised time and dose response of cell lines to 6, 12, and 24 h STZ. Mouse beta-TC3 (24 h LD50, 5 mM) were substantially more resistant to STZ than rat INS-1E (24 h LD50, 0.7 mM). In both cell lines, 6 h exposure to STZ dose-dependently enhances endogenous p8 gene expression to a maximum of about 4-fold at 24 h LD50 concentrations. Further increase of STZ dosages continuously reduces p8 gene expression indicating that endogenous p8 cannot be induced in lethally damaged beta cells. Furthermore, transient p8 overexpression enhances cell viability after 24 h exposure to STZ below 24 h LD50 dosages in both INS-1E and beta-TC3 about 20% despite only low efficiency of liposomal gene transfer (INS-1E, 30–50%; beta-TC3, 10–30%). The protective effect of ectopic p8 expression is abolished at dosages higher than 24 h LD50 indicating that enhanced p8 levels cannot protect lethally damaged cells. In conclusion, these results demonstrate that, in beta cells, p8 is a stress-induced factor, which exerts protection against STZ-induced cell death. Whether p8 mediates its protective effects only via stimulation of cell proliferation or also via inhibition of apoptosis is under current research.