Figure 3. Effect of diabetes and of SGLT2i on glycolysis and glucose oxidation in liver of WT and Akita mice.

WT and Akita mice were treated with and without dapagliflozin for 1 week, followed by ¹³C-glucose injections and metabolomics and metabolic flux analyses. (A) Unlabeled levels of glycolytic intermediates in liver extracts. Shown are the relative levels of unlabeled (¹²C) glucose and ¹³C-labeled glycolytic intermediates. (B) mRNA expression of glycolytic enzymes in liver. (C) Pyruvate kinase activity in liver homogenate. (D) GAPDH activity in liver homogenate. (E) Relative abundance of ¹³C-labeled tricarboxylic acid (TCA) cycle metabolites in liver. (F) mRNA levels of Pdk1–4 in liver. (G) Western blotting on liver extracts for phosphorylated pyruvate dehydrogenase α1 (pPDHe1α) and GAPDH. (H) mRNA expression of TCA cycle enzymes in liver. Data represent the mean ± SEM, n = 3–6 mice per group. For statistical analysis, we used the sum of all ¹³C isotopologues for each metabolite or the unlabeled + ¹³C-labeled metabolites. Data were analyzed by 2-way ANOVA. *P < 0.05, **P < 0.01.