Glutamine depletion and increased gut permeability in nonanorectic, non-weight-losing tumor-bearing rats.
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BACKGROUND & AIMS: Glutamine is an essential amino acid for rapidly dividing cells such as enterocytes. The progress of cancer is associated with a decrease of arterial and muscle glutamine concentrations. The aim of this study was to test whether increasing tumor loads affect gut intracellular glutamine handling, protein turnover, and gut absorptive and barrier function. METHODS: Methylcholantrene-induced tumor-bearing rats were studied with a subcutaneous tumor load of 5%-15% or 15%-30% of body weight. Portal drained visceral net uptake or release of energy substrates, amino acids, and intestinal protein turnover were studied. Gut absorptive capacity and permeability was assessed by the urinary recovery of 3-O-methyl-D-glucose or lactulose-rhamnose ratio after an oral gavage. RESULTS: In tumor-bearing rats, the net uptake of energy substrates (ketones and glutamine) and net protein synthesis increased across the portal drained viscera, whereas mucosal glutamine concentrations decreased. Absorptive capacity remained unchanged in both tumor-bearing groups. However, the lactulose-rhamnose ratio increased with increasing tumor load, indicating loss of gut barrier function. This was not related to changes in villus height, crypt depth, or changes in mucosal cell populations but to decreased intracellular polyamine concentrations. CONCLUSIONS: The presence of a methylcholantrene tumor leads to altered mucosal glutamine metabolism and loss of gut barrier function possibly related to disturbed proliferation or differentiation of enterocytes.