Increased Hsp70 expression attenuates cytokine-induced cell death in islets of Langerhans from Shb knockout mice

Type 1 diabetes may depend on cytokine-induced β-cell death and therefore the current investigation was performed in order to elucidate this response in Shb-deficient islets.A combination of interleukin-1β and interferon-γ caused a diminished β-cell death response in Shb null islets. Furthermore, the induction of an unfolded protein response (UPR) by adding cyclopiazonic acid did not increase cell death in Shb-deficient islets, despite simultaneous expression of UPR markers. The heat-shock protein Hsp70 was more efficiently induced in Shb knockout islets, providing an explanation for the decreased susceptibility of Shb-deficient islets to cytokines.It is concluded that islets deficient in the Shb protein are less susceptible to cytotoxic conditions, and that this partly depends on their increased ability to induce Hsp70 under such circumstances. Interference with Shb signaling may provide means to improve β-cell viability under conditions of β-cell stress.