[1‐¹³C]Glucose Metabolism in the Tumoral and Nontumoral Cerebral Tissue of a Glioma‐Bearing Rat

Abstract

C6 cells were used to establish a glioma-bearing rat model by stereotaxic injection in the left caudate nucleus. The tumor status was evaluated by magnetic resonance imaging and conventional histology. The glioma-bearing rats were infused for 1 h with a [1-13 C]glucose solution. Perchloric acid extracts of the tumor and the ipsilateral and contralateral hemispheres were analyzed by 13 C-NMR spectroscopy. The 13 C-labeling patterns in compounds, mainly amino acids, indicated no drastic modification of carbon metabolism in both ipsilateral and contralateral hemispheres, as compared with control rats, whereas profound metabolic differences between brain tissue and tumor were observed. Glutamine C4 enrichment was lower in the glioma than in the brain [mean Ϯ SD values, 5.4 Ϯ 2.3 (n ϭ 5) and 15.0 Ϯ 0.8% (n ϭ 10), respectively] and also lower than the glutamate C4 enrichment in the glioma (mean Ϯ SD value, 22.6 Ϯ 4.2%; n ϭ 5), indicating that tumor glutamine was neither synthesized inside the glioma nor taken up from the surrounding brain. The glutamine C4 enrichment in the serum (6.7 Ϯ 0.5%; n ϭ 10) suggested that the glioma imported glutamine from the blood, a process probably connected with angiogenesis.

Involvement of brain lactate in neuronal metabolism

“…As reported in Table 1, after 20 min infusion, blood glucose concentration under chloralose was slightly lower than under pentobarbital or morphine, and lactate concentration was about 2-fold higher under morphine than pentobarbital or chloralose. As reported in Table 2, glucose C1 enrichment was slightly higher than natural abundance (1.1%) under glucose þ [3-13 C]lactate infusion, whereas it remained at a high level (68%) under [1][2][3][4][5][6][7][8][9][10][11][12][13] C]glucose þ lactate infusion, whatever the used drug. The occurrence of labeled glucose after glucose þ [3-…”

“…Around 15 min after drug administration, the rats were infused in a tail vein for 20 min with a saline solution containing either 750 mM, 99%-enriched [1][2][3][4][5][6][7][8][9][10][11][12][13] C]glucose and 500 mM lactate or 750 mM glucose and 500 mM, 99%-enriched [3][4][5][6][7][8][9][10][11][12][13] C]lactate. The infusate flow was monitored to follow a time-decreasing exponential as previously described.…”

“…For a given compound, correction for partial saturation and nuclear Overhauser enhancement were carried out from the resonance peak areas in metabolite standard solution spectra acquired under the same conditions. 12 The specific enrichment of blood glucose C1 was determined from the satellite peaks of the C-edited spectra as the ratios between homologous peak areas in the 13 C-edited and spin echo spectra, respectively. Each determination was made by superposition of a given resonance peak in the two spectra using the Dual routine from Bruker, after careful line width, phase and base line adjustment.…”

“…Indeed, as the basic point in the model is that lactate is the available energy substrate for activated neurons, a crucial requirement in the experimental approach is to discriminate between the metabolism of glucose and that of brain lactate, when the second compound derives from the first. In the context of ANLS studies, lactate metabolism in brain has been investigated after intravenous administration of either [3][4][5][6][7][8][9][10][11][12][13] C]lactate 7,8 or [U- 13 C]lactate 9 in rodents. The aim of these studies was (i) to examine whether blood lactate could fuel cerebral metabolism and (ii) to characterize its metabolism.…”

“…However, to obtain relevant information relative to ANLS also requires analysis of the competition between endogenous and exogenous lactate under different conditions of brain activity. We chose therefore to analyze metabolite labeling in the brain of rats infused with a solution of glucose and lactate labeled as either [3][4][5][6][7][8][9][10][11][12][13] C]lactate or [1][2][3][4][5][6][7][8][9][10][11][12][13] C]glucose, when their cerebral activity was more or less depressed under the influence of different drugs, as previously used. 2 Comparing the amino acids, lactate and acetyl-CoA C]lactate to glutamate labeling were dependent on the drug used.…”