Fig. 3: Regulation of AKT/Bim axis protects β cells from TG and TU-induced death.

A, B WT, and GRP94 KD Cells were exposed to LY for 30 min prior to and during the 24 h treatment with TG or 48 h treatment with TU. Cell viability was measured and compared. A ^*p < 0.05 versus con WT, ^#p < 0.05 versus con shGRP94, ^$p < 0.05 versus TG24h WT, ^%p < 0.05 versus TG24h shGRP94, ^{^}p < 0.05 versus TG24h + LY10 μM WT, ^&p < 0.05 versus TG24h + LY10 μM shGRP94, ^@p < 0.05 versus TG24h + LY25 μM WT, one-way ANOVA. B ^*p < 0.05 versus con WT, ^#p < 0.05 versus con shGRP94, ^$p < 0.05 versus TU48h WT, ^%p < 0.05 versus TU48h shGRP94, ^{^}p < 0.05 versus TU48h + LY10 μM WT, ^&p < 0.05 versus TU48h + LY10 μM shGRP94, ^@p < 0.05 versus TU48h + LY25 μM WT, one-way ANOVA, at indicated time after treatment with or without LY. C, D WT, and GRP94 KD cells were exposed to LY (10 µM) for 1 h, and treated with or without TG (1 μM) or TU (10 μg/ml). Immunoblots of GRP94, p-AKT, AKT, Bim, and caspase-3 cleavage. E, F WT and GRP94 KD cells were infected with the indicated adenovirus and then treated with TU or TG. Immunoblots of p-AKT, AKT, and caspase-3 cleavage. G–J WT and GRP94 KD cells were transfected with control siRNA or Bim siRNA, and then treated with TG for 6 h or TU for 48 h. G, H Total cell extracts analyzed by immunoblot of Bim and c-Cas-3. I, J Cell death was determined by trypan blue staining. ^*p < 0.05 versus con WT, ^#p < 0.05 versus con shGRP94, ^$p < 0.05 versus Consi10nM + TG24h or TU48h WT, ^%p < 0.05 versus Consi10nM + TG24h or TU48h shGRP94, ^{^}p < 0.05 versus Bimsi10nM + TG24h or TU48h WT, ^&p < 0.05 versus Bimsi10nM + TG24h or TU48h WT, ^@p < 0.05 versus Bimsi50nM + TG24h or TU48h WT^, one-way ANOVA.