Fig. 6: Aminotransferases including Agxt are crucial effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis.

a, b Pharmacological inhibition of aminotransferase, in vivo, by AOA. Lkb1KO^livad (KO) and WT mice were left untreated (−) or were treated with AOA (10 mg/kg) 2 h before the determination of fasting blood glucose levels (a) or the alanine tolerance test (b). The area under the curve (AUC) of glucose level in the ATT is shown. AOA-treated animals, KO: n = 5, WT: n = 6. Animals not treated with AOA, KO: n = 5, WT: n = 4. Mice were fasted for 22 h before treatment with AOA or were left untreated for the same time period. c Scheme of the dual function of Agxt. d, e Agxt protein and mRNA levels in Lkb1KO^livad (KO) mice. d immunoblot of Agxt in fasted and refed mutant (KO, n = 3) and control (WT, n = 3) mice. Representative blot of two independent experiments. e Agxt gene expression levels, as assessed by RT-qPCR in fasted (KO: n = 10, WT: n = 6) and refed (KO: n = 7, WT: n = 5) mice. f, g Phenotypes of mice lacking both Lkb1 and Agxt in the hepatocytes (DKO), as compared with mice with a single deficiency of Lkb1 in hepatocytes (Lkb1KO^livad, KO) and controls (WT and AgxtKO). e Glycemia in fasting (WT: n = 11, KO: n = 19, DKO: n = 17, AgxtKO: n = 18) and refed (WT: n = 8, KO: n = 6, DKO: n = 10, AgxtKO: n = 12) mice. f Kaplan–Meier survival curves for Lkb1KO^livad mice (n = 18), mice lacking both Lkb1 and Agxt (DKO n = 23) and controls (WT, n = 10). All graphical data are means ± SD. P values were determined by unpaired two-tailed t-test. ns: not significant. *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001. Source data are provided as a Source data file.