Exocrine AR42J acinar cells enhance viability of cocultured endocrine INS-1E beta cells

 

REG3beta is acutely upregulated in acinar cells during pancreatitis and has been shown to reduce tissue inflammation via induction of the anti-inflammatory protein NUPR1. Own previous data demonstrated that transgenic mice with beta cell-specific overexpression of NUPR1 are protected against inflammatory and obesity-related beta cell stress. Therefore, this study evaluated whether acinar cells affect viability of beta cells and whether this involves REG3beta and NUPR1.

Rat pancreatic AR42J acinar cells and INS-1E beta cells were cocultured using inserts. Cellular stress in INS-1E was induced by ALX and STZ at LD50 concentrations. Viability was measured by MTS assay and gene expression of Reg3beta and Nupr1 was evaluated by qPCR.

The inflammatory cytokines IL-1beta, TNF and IL-6 induce Reg3beta gene expression in AR42J acinar cells but not in INS-1E, beta-TC3 and MIN6 beta cells or primary mouse islets. Reg3beta gene expression in AR42J acinar cells was significantly induced by untreated cocultured INS-1E beta cells after 24h and further increased by STZ- or IL-1beta-injured INS-1E beta cells. AR42J significantly enhanced viability of cocultured INS-1E after 32h. This was not associated with induction of Nupr1 gene expression in INS-1E. ALX and STZ-induced loss of viability was not affected by AR42J.

The results indicate a local interaction between exo- and endocrine pancreatic tissue which is associated with of Reg3beta gene expression in acinar cells but not with induction of Nupr1 in INS-1E beta cells. The underlying molecular mechanisms of acinar cell-induced viability in beta cells need further characterization.