(a) Glucose tolerance test in control or TSC22D4 shRNA adenovirus–injected db/db mice 1 week after injection. Glucose was injected i.p. at a concentration of 1 g glucose kg−1 body weight (means±s.e.m., n≥6). (b) Serum glucose levels in same mice as in a after 16 h fasting and refeeding. (c) Serum insulin levels in same mice as in a. (d) Serum C-Peptide levels in same mice as in a after 16 h fasting and refeeding. (e) Representative western blot of liver extracts from control (NC shRNA) or TSC22D4 (TSC shRNA) shRNA adenovirus–injected db/db mice; same mice as in a using indicated antibodies. Blot representative of 6 similar samples. (f) Glucose tolerance test in control or TSC22D4 shRNA adenovirus–injected NZO mice 1 week after injection. Glucose was i.p. injected at a concentration of 1 g glucose kg−1 body weight (means±s.e.m., n≥6). (g) Serum glucose levels in same mice as in f after 16 h fasting and refeeding. (h) HOMA-IR index in control or TSC22D4 miRNA AAV–injected (at 5 weeks of age) db/db mice 4 weeks after miRNA injection (means±s.e.m., n≥6). (i) Serum insulin levels in same mice as in h 10 weeks after miRNA injection. (j) Glucose tolerance test in the same mice as in h 4 weeks after miRNA injection. Glucose was injected i.p at a concentration of 1 g glucose kg−1 body weight. (k) Weekly serum glucose quantification of same mice as in h. (l–n) Quantitative PCR analysis of phosphoenolpyruvate carboxykinase (Pepck1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1alpha), glucose-6 phosphatase (G6Pase), carnitine palmitoyltransferase I (Cpt1), acyl-CoA synthetase long-chain family member 1 (Acsl1), peroxisome proliferator-activated receptor alpha (PPARalpha), acetyl-CoA carboxylase alpha (Acaca), fatty acid synthase (Fasn), stearoyl-coA desaturase-1 (Scd1), sterol regulatory element-binding protein 1 (Srebp1) in livers of same mice as in h 10 weeks after miRNA injection. Error bars in l−n represent standard deviation (s.d.). Statistical analysis: Student's t-test, *P≤0.05; **P≤0.01; ***P≤0.001.