GLUTAMINE DEPLETION AND INCREASED GUT PERMEABILITY IN NONANORECTIC, NON-WEIGHT-LOSING TUMOR-BEARING RATS

Background & Aims: Glutamine is an essential amino acid for rapidly di viding 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 gu t intracellular glutamine handling, protein turnover, and gut absorpti ve and barrier function, Methods: Methylcholantrene-induced tumor-bear ing 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 e nergy substrates, amino acids, and intestinal protein turnover were st udied. Gut absorptive capacity and permeability was assessed by the ur inary recovery of 3-O-methyl-D-glucose or lactulose-rhamnose ratio aft er an oral gavage, Results: In tumor-bearing rats, the net uptake of e nergy substrates (ketones and glutamine) and net protein synthesis inc reased across the portal drained viscera, whereas mucosal glutamine co ncentrations 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, oh chan ges in mucosal cell populations but to decreased intracellular polyami ne concentrations. Conclusions: The presence of a methylcholantrene tu mor leads to altered mucosal glutamine metabolism and loss of gut barr ier function possibly related to disturbed proliferation or differenti ation of enterocytes.