Figure 2.

Proposed models for ER stress-induced apoptosis in cytokine-treated rat and human beta cells. A: IL-1β + IFN-γ, via NO production and consequent SERCA-2b inhibition, cause severe ER Ca²⁺ depletion in rat beta cells. NO also inhibits XBP1s protein expression, depriving these cells of a relevant adaptive mechanism. B: In human beta cells IL-1β + IFN-γ induce ER stress via mechanisms that are independent of NO production. The nature of these mechanisms remains to be clarified, but they may be related to inhibition of other Ca²⁺ channels, excessive insulin secretion, and over-expression of MHC class I and related proteins. The persistent activation of the IRE1α/JNK and PERK/CHOP pathways contributes to apoptosis in both rat and human beta cells.