A DNA binding defective mutant XBP1s (ΔDBD) improves glucose homeostasis in ob/ob mice. (a) Nuclear protein levels of XBP1s and ΔDBD in MEFs infected with the same dose of Ad-XBP1s or Ad-ΔDBD. (b) ERSE-luciferase activity and Hspa5 mRNA levels in MEFs infected with Ad-XBP1s or Ad-ΔDBD. (B) Immunoblotting of FoxO1 and ΔDBD in ΔDBD–immunoprecipitates from MEFs expressing FoxO1 and ΔDBD. Total FoxO1 protein levels were determined in whole cell lysates (WCL). (d) FoxO1 protein levels and (e) Foxo1 mRNA levels in MEFs expressing FoxO1 and increasing levels of ΔDBD. (f–j) Seven-week-old, male, ob/ob mice were injected with Ad-LacZ (n = 6), Ad-XBP1s (n = 6) or Ad-ΔDBD (n = 6) (4 × 107 PFU g−1) through tail vein. (f) 6-h fasted blood glucose levels on day 3 and (g) GTT on day 5 after the adenovirus injections. (h) Phospho-AktSer473, total Akt, FoxO1, XBP1s and ΔDBD protein levels in the liver of Ad-LacZ- or Ad-XBP1s- or Ad-ΔDBD-injected ob/ob mice on day 7 after the injections. Graph depicts total FoxO1/tubulin protein ratio. Relative mRNA levels of (i) Hspa5, (j) Igfbp1, G6pc, and Pck1 in the liver of the liver of Ad-LacZ- or Ad-XBP1s- or Ad-ΔDBD-injected ob/ob mice. Error bars are ± s.e.m.; P values were determined by Student’s t-test (* P < 0.05, ** P < 0.01, *** P < 0.001).