Fig. 2

Sirt2 knockdown impedes NAD+-dependent hepatocyte glucose uptake. a, b Uptake of 2-deoxyglucose (2-DG) in primary hepatocytes treated with siSirt1–7 (a) and nicotinamide (NAM), Ex-527, or AGK2 (b) (n = 3). c Effect of adenovirus-mediated overexpression of Sirt2 on 2-DG uptake in primary hepatocytes derived from db/db mice in the presence or absence of NAM (n = 3). d Effect of Sirt2 and Sirt1 knockdown on 2-DG uptake in primary hepatocytes derived from db/db mice in the presence or absence of NMN (n = 4). e Glucose tolerance testing (1 g/kg) and the area under the curve (AUC) of the glucose tolerance test in HFD mice treated with NMN in the presence or absence of hepatic Sirt2 knockdown or Sirt2 and Sirt1 double knockdown during continuous dosing with somatostatin (n = 5). f Uptake of 2-DG in primary hepatocytes treated with siSirt1, siSirt2 or siSirt1 and siSirt2 (n = 3). g–j Effect of hepatic Sirt2 knockdown on hepatic protein expression of Sirt2 and glucokinase (GK) (g) and levels of blood glucose (n = 6) (h) and plasma insulin (n = 6) (i) and hepatic 2-DG uptake (n = 4) (j) after glucose administration (2 g/kg) in lean mice. k–n Effect of adenovirus-mediated hepatic Sirt2 overexpression on immunoblot analysis of Sirt2 and GK in the liver (k) and levels of blood glucose (n = 7) (l) and plasma insulin (n = 7) (m) and hepatic 2-DG uptake (n = 5) (n) after glucose administration (1 g/kg) in HFD mice. *P < 0.05; one-way ANOVA with the Fisher’s PLSD post-hoc test (a–d, e right, f) and Student’s t-test (h–j, l–n) *P < 0.05, compared with HFD, #P < 0.05, HFD+NMN vs. HFD+NMN with hepatic Sirt2 knockdown or Sirt2 and Sirt1 double knockdown in e left; one-way ANOVA with the Fisher’s PLSD post-hoc test. Data in g, k are representative of at least three independent experiments. Error bars show s.e.m