(A) Enrichment of fully labeled glucose (M+6) in plasma from the indicated mice following a 4 hr U-13C-glucose infusion at a rate of 30 mg/kg/min. Non-tumor bearing C57Bl6/J (WT) mice were used to assess metabolite labeling in normal pancreas. WT, n = 3; KP-/-C, n = 4. Differences in plasma glucose enrichment were not significant between WT and KP-/-C tumor-bearing mice (p=0.7600) based on an unpaired student’s t test. Mean +/- SEM is shown. (B) Plasma glucose levels over time in tumor-bearing KP-/-C mice infused with U-13C-glucose at a rate of 30 mg/kg/min. n = 4. Mean +/- SEM is shown. (C–N) The fractional labeling of pyruvate (C), lactate (D), alanine (E), serine (F), citrate (M+2 p=0.0008, M+3 p=0.0155) (G), α-ketoglutarate (αKG) (M+2 p=0.0038, M+3 p=0.0398) (H), succinate (M+2 p=0.0098, M+3 p=0.0334) (I), fumarate (M+2 p=0.0018, M+3 p=0.0138) (J), malate (M+2 p=0.0208) (K), aspartate (M+2 p=0.0097) (L), glutamate (M+2 p=0.0058, M+3 p=0.0115) (M), and proline (N) in WT normal pancreas (black) and autochthonous pancreatic tumors (grey) from LSL-KrasG12D/+; Trp53fl/fl ; Pdx1-Cre (KP-/-C) mice following a 4 hr U-13C-glucose infusion at a rate of 30 mg/kg/min. Non-tumor bearing C57Bl6/J (WT) mice were used to assess metabolite labeling in normal pancreas. The M+2 and M+3 isotopomers are shown for each metabolite: pancreas, n = 3; tumor, n = 4. Significance was based on unpaired, Students t-test. Mean +/- SEM is shown. (O) Relative abundance of tumor metabolites in WT normal pancreas (black) and autochthonous pancreatic tumors (grey) from LSL-KrasG12D/+; Trp53fl/fl; Pdx1-Cre (KP-/-C) mice following a 4 hr U-13C-glucose infusion at a rate of 30 mg/kg/min. Total ion counts were first normalized to tissue weight and norvaline abundance as an internal control, and then WT pancreas values were set to 1. Differences were significant based on unpaired, Students t-test for aspartate (p=0.0171). pancreas, n = 3; tumor, n = 4. Mean +/- SEM is shown.
Figure 1—figure supplement 2—source data 1. Isotope labeling of tumors in U-13C- glucose-infused mice with autochthonous PDAC tumors presented in Figure 1—figure supplement 2.