XBP1s can also improve glucose homeostasis in insulin independent manner. (a–d) Eight-week-old, male, STZ-treated mice were injected with Ad-XBP1s (n = 9) or Ad-LacZ (n = 9) (1.5 × 108 PFU g−1) though tail vein. (a) Plasma insulin levels before and after STZ treatment. (b) Fed and 12-h fasted blood glucose levels on indicated days. (c) Total and nuclear FoxO1 protein levels and (d) Liver Igfbp1, G6pc, and Pck1 mRNA levels 10 days after adenovirus injections. (e–g) Eight-week-old, male, LIRKO mice were injected with Ad-LacZ (n = 8) or Ad-XBP1s (n = 8) (4 × 107 PFU g–1) through tail vein. (e) Liver IR protein levels and GTT on day 4 after adenovirus injections. (f) FoxO1, XBP1s, pAktSer473, pAktThr308 and total Akt levels and (g) Igfbp1, G6pc, and Pck1 mRNA levels in the liver of Ad-XBP1s- or Ad-LacZ-injected LIRKO mice 8 days after adenovirus injection. (h–j) Eight-week-old, male DKO mice were injected with Ad-LacZ (n = 8) or Ad-XBP1s (n = 8) (7.5 × 107 PFU g–1) through tail vein. (h) Liver IRS1 and IRS2 protein levels in Irs1Flox/Flox;Irs2Flox/Flox (DF) and DKO mice. GTT was performed on post injection day 4. (i) FoxO1 and XBP1s protein levels and (j) Igfbp1, G6pc, and Pck1 mRNA levels in the liver of adenovirus-injected DKO mice on day 8 after the injections. Error bars are ± s.e.m.; P values were determined by Student’s t-test. (* P < 0.05, ** P < 0.01, *** P < 0.001).