Increased glutamine consumption in small intestine epithelial cells during sepsis in rats

Previous reports have emphasized increased intestinal glutamine consumption during sepsis. This may be of clinical significance as glutamine is a (and perhaps the) physiologic fuel for the intestine. A problem remains, however, as glutaminase, the major enzyme for the degradation of glutamine, is decreased rather than increased in sepsis. This implies an alteration in the metabolic fate of glutamine in sepsis, which may be of clinical significance.

We determined the effect of sepsis on glutamine metabolism in mucosa of small intestine. Sepsis was induced in rats by cecal ligation and puncture. Control rats were sham-operated. After 16 hours, glutamine consumption was measured in isolated enterocytes, and glutaminase, glutamine synthetase, and glutamine transaminase activities and DNA synthesis were determined in mucosa.

Glutamine consumption was increased during sepsis in enterocytes from the tips of the villi and was unchanged in enterocytes from the midportions of the villi and the crypts. As previously shown, mucosal glutaminase activity was reduced. However, glutamine synthetase and glutamine transaminase activities were stimulated in septic rats, suggesting an increase in metabolism of glutamine via alternate pathways. DNA synthesis was increased during sepsis, especially in crypt cells.

Increased or unchanged glutamine consumption in enterocytes from septic rats, despite reduced glutaminase activity, appears to reflect increased activity of other enzyme systems and/or increased utilization of the amino acid for DNA and protein synthesis. Since other aspects of glutamine metabolism may also be deranged in sepsis, a continual enteral supply of glutamine to the intestinal lumen during sepsis may be clinically useful.