Role of pancreatic beta-cells in the process of beta-cell death

Studies on the pathogenesis of type 1 diabetes have mainly focused on the r ole of the immune system in the destruction of pancreatic beta -cells. Lack of data on the cellular and molecular events at the beta -cell level is ca used by the inaccessibility of these cells during development of the diseas e. Indirect information has been collected from isolated rodent and human i slet cell preparations that were exposed to cytotoxic conditions. This arti cle reviews in vitro experiments that investigated the role of beta -cells in the process of beta -cell death. beta -Cells rapidly die in necrosis bec ause of toxic levels of oxidizing radicals or of nitric oxide; they progres sively become apoptotic after prolonged culture at low glucose or with proi nflammatory cytokines. Their susceptibility to necrosis or apoptosis varies with their functional state and thus with the environmental conditions. A change in cellular phenotype can alter its recognition of potentially cytot oxic agents and its defense mechanisms against cell death. These observatio ns support the view that beta -cells are not necessarily passive victims of a cytotoxic process but can actively participate in a process of beta -cel l death. Their role will be influenced by neighboring non-beta -cells, whic h can make the islet internal milieu more protective or toxic for the beta -cells. We consider duct cells as potentially important contributors to thi s local process.