Influence of glutamine-supplemented parenteral nutrition on intestinal amino acid metabolism in rats after small bowel resection

Abstract

Glutamine (Gln)-supplemented total parenteral nutrition (TPN) has been shown to improve mucosal adaptation after massive small bowel resection (SBR); however, its influences on intestinal amino acid metabolism remain unknown. In this study, intestinal amino acid flux, circulating plasma aminogram, mucosal glutaminase activity and protein, and DNA content were measured 7 days after massive SBR in rats receiving either standard (Std) or Gln-supplemented TPN. Sham-operated rats and rats fed chow after enterectomy served as controls. The uptake of Gln and the release of citrulline (Cit) by the remaining intestine was significantly decreased, with reduced mucosal glutaminase activity after SBR in the Chow and Std-TPN groups. Glutamine supplementation resulted in significantly increased gut Gln uptake compared with Std-TPN (P < 0.01). Mucosal glutaminase activity, mucosal protein, and DNA content was also increased by Gln; however, the gut release of Cit remained unchanged (P > 0.05). The subsequent decrease in circulating arginine (Arg) in the Gln-TPN group compared with the Std-TPN group (P < 0.05) was attributed to an insufficient exogenous supply. These findings show that Gln-supplemented TPN improves mucosal growth and gut Gln uptake after SBR. However, the intestinal production of Cit, which remained low in both TPN groups, may lead to an insufficiency of endogenous Arg synthesis. Thus, both Gln and Arg may be essential amino acids after SBR.

Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model

“…Recently, several reports have demonstrated that citrulline can be used as a quantitative marker for radiation-induced small bowel injury. 35,41,42 Reduction of small bowel epithelial cell mass through surgery or ionizing radiation is associated with diminished plasma citrulline levels, as demonstrated in rodents 35,43,44 and patients. 45 In the present study, we demonstrated that plasma citrulline levels decreased by almost 75% 1 week after allogeneic transplantation and that KGF treatment was able to diminish this effect.…”

Biomarkers for radiation-induced small bowel epithelial damage: An emerging role for plasma Citrulline

“…Hence, although the small intestinal mucosa contains a metabolically significant urea cycle, the liver is without doubt the major organ for urea synthesis in mammals [106,112] . Furthermore, citrulline can be effectively regarded as an endproduct of glutamine/glutamate metabolism of intestinal enterocytes as sug gested by Windmueller and Spaeth [80,98] and confirmed in many studies since then [66,69,83,[86][87][88]90,104,111,[113][114][115] .…”

“…Hence, despite the results obser ved with the organ exclusion experiments performed by Windmueller and Spaeth, no other site but the intestine has been identified so far that releases significant amounts of citrulline under physiological conditions. The role of the small intestine as the major source for circulating citrulline is demonstrated by experiments in which the plasma citrulline concentration is reduced by means of small bowel targeted interventions such as specific inhibitors of OAT [116] or OCT [132] , yielding a similar decrease of plasma citrulline concentration as observed after small bowel resection [83,86,113,114] . Furthermore, strong lines of evidence have been obtained since then through clinical observations which are in agreement with this concept [66,69,71,73,87,90,133,134] .…”

“…In this respect cumulative data indicate an important role for glucose metabolism [140,141,150] . A major determinant, however, under steady state conditions for the rate of citrulline released into the portal and subsequently the systemic circulation is the actual number of functional enterocytes [65][66][67][68][69]83,86,87,90,113,114,134,151] . This was further demonstrated by clinical data on small bowel transplantation [70][71][72][73][74][75]152] .…”

“…small intestinal enterocytes. Thus under steady state conditions, citrulline can be considered a marker for the functional epithelial cell mass of the small bowel, a concept amply demonstrated in experimental and clinical studies [65][66][67][68][69][70][71][72][73][74][75]80,83,[86][87][88]90,104,111,[113][114][115][116][132][133][134]152] . Of notice, the lower plasma citrulline level observed in short bowel patients was sustained up to one year after treatment [66] emphasizing its strict dependence on the epithelial cell mass.…”