Beta cell destruction in the development of autoimmune diabetes in the non-obese diabetic (NOD) mouse

In the non-obese diabetic (NOD) mouse model of Type 1 (insulin-dependent) d iabetes, evidence suggests that pancreatic beta cells are destroyed in part by apoptotic mechanisms. The precise mechanisms of beta cell destruction l eading to diabetes remain unclear. The NOD mouse has been studied to gain i nsight into the cellular and molecular mediators of beta cell death, which are discussed in this review. Perforin, secreted by CD8(+) T cells, remains one of the only molecules confirmed to be implicated in beta cell death in the NOD mouse. There are many other molecules, including Fas ligand and cy tokines such as interferon-gamma, interleukin-1 and tumor necrosis factor-a , which may lead to beta cell destruction either directly or indirectly via regulation of toxic molecules such as nitric oxide. As beta cell death can occur in the absence of perforin, these other factors, in addition to othe r as yet unidentified factors, may be important in the development of diabe tes. Effective protection of NOD mice from beta cell destruction may theref ore require inhibition of multiple effector mechanisms. Copyright (C) 2000 John Wiley & Sons, Ltd.