Hepatic sugar phosphate levels reflect gluconeogenesis in lung cancer: simultaneous turnover measurements and P-31 magnetic resonance spectroscopy invivo

Stable-isotope tracers were used to assess whether levels of phosphomonoest ers (PME) and phosphodiesters (PDE) in the livers of lung cancer patients, as observed by P-31 magnetic resonance (MR) spectroscopy, reflect elevated whole-body glucose turnover and gluconeogenesis from alanine. Patients with advanced non-small-cell lung cancer without liver metastases (n = 24;weigh t loss 0-24%) and healthy control subjects (n = 13) were stud led after an overnight fast. P-31 MR spectra of the liver in vivo were obtained, and glu cose turnover and gluconeogenesis from alanine were determined simultaneous ly using primed-constant infusions of [6,6-H-2(2)]glucose and [3-C-13]alani ne. Liver PME concentrations were 6% higher in lung cancer patients compare d with controls (not significant); PME levels in patients with greater than or equal to 5% weight loss were significantly higher than in patients with < 5% weight loss (P < 0.01). PDE levels did not differ between the groups. In lung cancer patients, whole-body glucose production was 19% higher (not significant) and gluconeogenesis from alanine was 42% higher (P < 0.05) co mpared with healthy subjects; turnover rates in lung cancer patients with g reater than or equal to 5% weight loss were significantly elevated compared with both patients with < 5% weight loss and healthy subjects (P < 0.05). PME levels were significantly correlated with glucose turnover and gluconeo genesis from alanine in lung cancer patients (r = 0.48 and r = 0.48 respect ively; P < 0.05). In conclusion, elevated PME levels in lung cancer patient s appear to reflect increased glucose flux and gluconeogenesis from alanine . These results are consistent with the hypothesis that elevated PME levels are due to contributions from gluconeogenic intermediates.