Fig 1.
Metabolic fate of each carbon atoms provided by glucose.
Carbons 3 (C3) and 4 (C4) (carbon 1 in pyruvate) are released as CO2 when pyruvate is decarboxylated into acetate. Carbons 2 (C2) and 5 (C5) entering the TCA cycle in position 1 on acetate provide CO2 at the second turn of the cycle: 50% before + 50% after α-ketoglutarate. Carbons 1 (C1) and 6 (C6) entering the TCA cycle in position 2 in acetate provide CO2 beginning at the third turn of the cycle: 25% before + 25% after α-ketoglutarate at the third turn; 12.5% + 12.5% at the fourth turn, and subsequent turns.
Fig 2.
Changes in the body weight of rats used during the study period.
Body weight differed significantly between the two groups (two-way repeated-measures ANOVA: rat × time F(24,408) = 33.57, P < 0.01; time F(24,408) = 1431.45, P < 0.01; rat F(1,17) = 209.58, P < 0.01). LETO, n = 8; OLETF, n = 8 Data are represented as mean ± SD.
Fig 3.
Changes in food intake per day.
Dietary intake differed significantly between the two groups (two-way repeated-measures ANOVA: rat × time F(23,391) = 5.56, P < 0.01; time F(23,391) = 106.22, P < 0.01; rat F(1,17) = 276.72, P < 0.01). LETO, n = 8; OLETF, n = 8. Data are represented as mean ± SD.
Fig 4.
Fasting plasma glucose levels when breath tests were performed.
Blood glucose level was significantly higher in OLETF rats than in LETO rats at every stage. (P < 0.01, Student’s t-test was performed on each diabetic stage.) Data are represented as mean ± SD.
Fig 5.
Results of [1-13C]glucose breath tests.
(A) Changes in expired 13CO2 levels after the oral administration of 100 mg/kg of [1-13C]glucose in OLETF rats at 5–11weeks, 14–17 weeks, and 20–23 weeks of age. (B) Changes in expired 13CO2 levels after the oral administration of 100 mg/kg of [1-13C]glucose in LETO rats at 5–11 weeks, 14–17 weeks, and 20–23 weeks of age. Data are represented as mean ± SD.
Fig 6.
Results of [2-13C]glucose breath tests.
(A) Changes in expired 13CO2 levels after the oral administration of 100 mg/kg of [2-13C]glucose in OLETF rats at 6–12 weeks, 15–18 weeks, and 21–24 weeks of age. (B) Changes in expired 13CO2 levels after the oral administration of 100 mg/kg of [2-13C]glucose in LETO rats at 6–12 weeks, 15–18 weeks, and 21–24 weeks of age. Data are represented as mean ± SD.
Fig 7.
Results of [3-13C]glucose breath tests.
(A) Changes in expired 13CO2 levels after the oral administration of 100 mg/kg of [3-13C]glucose in OLETF rats at 7–13 weeks, 16–19 weeks, and 22–25 weeks of age. (B) Changes in the expired 13CO2 levels after the oral administration of 100 mg/kg of [3-13C]glucose in LETO rats at 7–13 weeks, 16–19 weeks, and 22–25 weeks of age. Data are represented as mean ± SD.
Table 1.
Tmax obtained from the three types of 13C-glucose breath tests for each age group.
Table 2.
Peak values obtained from the three types of 13C-glucose breath tests for each age group.
Table 3.
Values of AUC180 obtained from the three 13C-glucose breath tests for each age group.
Table 4.
Values of AUC90 obtained from the three 13C-glucose breath tests for each age group.
Fig 8.
[1-13C]glucose breath test between OLETF and LETO rats.
Comparison of 13CO2 excretion curves after the oral administration of 100 mg/kg of [1-13C]glucose between OLETF and LETO rats at 5–11 weeks (A), 14–17 weeks (B), and 20–23 weeks (C) of age. Data are represented as mean ± SD.
Fig 9.
[2-13C]glucose breath test between OLETF and LETO rats.
Comparison of 13CO2 excretion curves after the oral administration of 100 mg/kg of [2-13C]glucose between OLETF and LETO rats at 6–12 weeks (A), 15–18 weeks (B), and 21–24 weeks (C) of age. Data are represented as mean ± SD.
Fig 10.
[3-13C]glucose breath test between OLETF and LETO rats.
Comparison of 13CO2 excretion curves after the oral administration of 100 mg/kg of [3-13C]glucose between OLETF and LETO rats at 7–13 weeks (A), 16–19 weeks (B), and 22–25 weeks (C) of age. Data are represented as mean ± SD.