Fig 1.
Faster plasma glucose clearance and fewer ketone body plasma levels in the Liver-PtenKO mouse model.
(A) Plasma glucose clearance was faster in the Liver-PtenKO mice and (B) plasma ketone body levels were significantly lower than in the Liver-PtenKO mice. Statistical significance calculated using student t-test (*P ≤ 0.05; n = 5 per group). Error bars indicate ± SD.
Fig 2.
Dynamic [18F]-FDG-PET imaging of CTL and Liver-PtenKO mouse brains.
Standard uptake value (SUV) was calculated after [18F]-FDG injection followed by dynamic PET and CT scanning. (A) Representative combined images from PET-CT scanning of CTL and Liver-PtenKO at 180 and 3300 s into [18F]- PET scan. (B) Average rates of uptake of glucose by brains of CTL and Liver-PtenKO mice reveal significantly faster rates of glucose uptake in the Liver-PtenKO brains, with error bars indicating ± SEM. (C) Total glucose uptake at the end of Dynamic [18F]-FDG scan duration show Liver-PtenKO brains taking up glucose in larger quantities than CTL mice brains (n = 4 per group). Error bars indicate ± SD.
Table 1.
Concentrations of different isotopomers of 13C Glu, Gln, Asp, NAA, GABA, and MI in mouse brains after 150-min infusion of [1-13C]glucose and [1,2-13C]acetate quantified by 13C-NMR spectroscopy.
Fig 3.
Increased percentage enrichment of 13C labeled isotopomers in Liver-PtenKO mouse brains.
Overall, an increase in the enrichment of 13-C labeled isotopomers of (A) Glutamate, (B) Glutamine, (C) Aspartate, and (D) GABA after [1-13C] glucose + [1,2-13C] acetate infusion observed the brains of the Liver-PtenKO mice suggests a possible hypermetabolic state in the brain. Metabolic ratios, calculated as described in the materials and methods section, after [1-13C]glucose + [1,2-13C]acetate infusion for 150 min are shown in the Graphs E-G. (E) % Glycolytic activity based on the levels of [3-13C]alanine. (F) TCA cycle activity. (G) Glucose versus acetate utilization for formation of Glu, Gln and GABA. Statistical significance calculated using paired student t-test (*P ≤ 0.05; n = 4 per group). Error bars indicate ± SD.
Table 2.
Total concentrations of [12C + 13C] of glutamate, glutamine, GABA, and aspartate; n = 4 per group.
Fig 4.
Improved hippocampal synaptic plasticity in Liver-PtenKO mouse model.
Input/Output (I/O) and LTP changes were measured in both groups. (A) Representative I/O curves for both groups at increasing stimulus intensities, and I/O slope values at increasing stimulus intensities. (B) Average I/O curve slopes for both groups at 400 μA. (C) LTP induced at baseline intensity using theta burst stimulation (TBS) consisting of ten trains of five 100 Hz stimulation repeated at 5 Hz. Slope of EPSPs was measured and results normalized to the average value measured during the 10 min baseline period. (D) Average of the last 5 min of recordings post-TBS, which is considered as LTP. Total n = 20 slices; n = 10 slices/group and at n = 4 animals/group. Statistical significance calculated using paired student t-test (*P ≤ 0.05; **P ≤ 0.01). Error bars indicate ± SD.
Fig 5.
Insulin stimulation of brain slices from CTL and Liver-PtenKO mice.
Levels of p-AKT (Ser473) and total AKT were measured using a plate assay in whole brain protein extracts with or without 10 nM insulin treatment. pAKT/AKT ratios indicate significant changes after insulin treatment within groups, but no significant differences in ratios between CTL (gray) and Liver-PtenKO (black) groups. Error bars indicate ± SD (*P ≤ 0.05) (n = 4 per group).