Decreased energy and phosphorylation status in the liver of lung cancer patients with weight loss
Section snippets
Subjects
The study was approved by the Medical Ethical Committee of the Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands. Patients with non-small cell lung cancer stage IIIA/B or IV (WHO grading system) attending the outpatient department of the University Hospital Rotterdam, The Netherlands, were recruited. Patients who were in remission or apparently cured were excluded. Additional exclusion criteria were: liver metastases (as checked for by CT/ultrasound); metabolic disease;
Results
Fasting blood glucose levels were similar in lung cancer patients and did not change during L-alanine infusion. Baseline plasma alanine concentrations were similar between lung cancer patients and healthy controls (0.35–0.37 mM) and increased significantly during L-alanine infusion to 5.4±0.1 mM in CaWL, 6.7±0.5 mM in CaWS, and 8.5±0.9 mM in C (change from baseline and difference between all groups: p<0.001).
Discussion
In the present study, bioenergetics in the tumour-free liver of lung cancer patients during an i.v. L-alanine challenge were monitored using 31P MR spectroscopy. Alanine infusion is known to stimulate gluconeogenesis 21., 22., 23., and a standardised dose can be used to investigate gluconeogenic and energy metabolism within the liver by 31P MRS directly and non-invasively (24). In the present study, primed-constant infusion of 1.4–2.8 mmol · kg−1 L-alanine + 2.8 mmol · kg−1 · h−1 induced a
Acknowledgements
We are grateful to C. H. K. Hordijk-Luijk for performing biochemical analyses, and H. J. Agteresch, C. C. M. Bartels, M. Heijsteeg, F. Lagerwaard, A. S. T. Planting, M. J. M. van Mierlo, S. Senan, R. Slingerland, G. Stoter, M. M. A. Tilanus-Linthorst, J. Verweij, and A. G. Zwanenburg for their co-operation in the patient recruitment. We are grateful to W. Schneijderberg and C. Onna for their assistance during the experiments.
This project was supported by a grant from the Dutch Cancer Society
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