Hepatic sugar phosphate levels reflect gluconeogenesis in lung cancer: simultaneous turnover measurements and 31P magnetic resonance spectroscopy in vivo.
Stable-isotope tracers were used to assess whether levels of phosphomonoesters (PME) and phosphodiesters (PDE) in the livers of lung cancer patients, as observed by (31)P 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; weight loss 0-24%) and healthy control subjects (n=13) were studied after an overnight fast. (31)P MR spectra of the liver in vivo were obtained, and glucose turnover and gluconeogenesis from alanine were determined simultaneously using primed-constant infusions of [6, 6-(2)H(2)]glucose and [3-(13)C]alanine. Liver PME concentrations were 6% higher in lung cancer patients compared with controls (not significant); PME levels in patients with >/=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) compared with healthy subjects; turnover rates in lung cancer patients with >/=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 gluconeogenesis from alanine in lung cancer patients (r=0.48 and r=0.48 respectively; P<0.05). In conclusion, elevated PME levels in lung cancer patients 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.
Leij-Halfwerk
S
S
Institute of Internal Medicine II, University Hospital Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Dagnelie
P C
PC
Van Den Berg
J W
JW
Wilson
J H
JH
Sijens
P E
PE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D016022:Case-Control Studies; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D010755:Organophosphates / Q000378:metabolism*; D010758:Phosphorus
D001786:Blood Glucose; D010755:Organophosphates; D010758:Phosphorus