Figure 3. Bsg deficiency impairs hepatic availability of lactate and pyruvate in vivo.
(A) Schematic illustrating impaired gluconeogenesis resulting from decreased substrate import due to Bsg deficiency. OAA, oxaloacetate. (B) Blood glucose levels in Bsg+/+ and Bsg–/– mice under fasting conditions. White columns and circles, Bsg+/+ mice; gray columns and black circles, Bsg–/– mice (n = 10–12/genotype). Scatter plots display the data for individual mice. (C) Differences in blood lactate values between feeding and fasting states in Bsg+/+ or Bsg–/– female mice (n = 5–6/genotype). (D) Differences in serum pyruvate values between feeding and fasting states in Bsg+/+ or Bsg–/– female mice (n = 5–6/genotype). (E) G6P and F6P with incorporation of 13C3-labeled carbon in isolated Bsg+/+ or Bsg–/– hepatocytes. White columns, Bsg+/+ hepatocytes; gray columns, Bsg–/– hepatocytes. n = 5 for independent experiments. N.D., no detection. (F) Blood glucose excursions and the AUC scores in fasting Bsg+/+ and Bsg–/– female mice during lactate tolerance tests (n = 7–11/genotype). (G) Blood glucose excursions and AUC scores during pyruvate tolerance tests in female mice (n = 8–10/genotype). (H) Endogenous glucose production in isolated hepatocytes of Bsg+/+ and Bsg–/– female mice cultured in medium supplemented with 20 mM sodium lactate and 2 mM sodium pyruvate in the absence or presence of 100 nM AZD3965 (an inhibitor of MCT1 activity). n = 6 for independent experiments. For all relevant panels, data are presented as means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, for the comparison of Bsg+/+ and Bsg–/– at the indicated time point (2-tailed unpaired Student’s t test).
