Fig. 4.

Model of the role of TOSO in protecting the β-cell from Fas/FasL induced apoptosis. Elevated glucose levels and IL-1β, which is consequently secreted by β-cells or by infiltrating macrophages in diabetes, induce apoptosis and impair function through activation of the Fas receptor. Binding of the receptor to FasL, which is constitutively expressed by β-cells, leads to recruitment of the Fas associated death domain (FADD) to the receptor complex followed by cleavage of caspases and apoptosis. Direct binding of TOSO to FADD via its C-terminal tail at the cell membrane leads to increased levels of cFLIP which binds to FADD and inhibits further cleavage of Caspases. FLIP is also able to induce β-cell proliferation and thus may lead to the restoration of β-cell mass and function.