ABSTRACT. Background: Amino acids are an integral part of parenteral nutrition because of their anabolic action helping to conserve body protein after surgical stress. At the gastrointestinal tract, an adequate supply of amino acids may be particularly important because of the gut's high rate of protein turnover, cell division, and proliferation. However, no information is available about the effects of amino acids on human intestinal protein metabolism after surgery. Methods: Studies were performed in postabsorptive patients 8 -10 days after major abdominal surgery. Mass spectrometry techniques (capillary gas chromatography/ combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[13 C]-leucine into colon mucosal protein. All subjects had a colostomy, which allowed easy access to the colon mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 mol/kg min). Isotopic enrichments were determined at baseline and after a 4-hour infusion of amino acids or after infusion of saline (control group). Results: Compared with baseline, infusion of amino acids reduced fractional colon protein synthesis significantly by Ϫ29.2 Ϯ 8.3%. This decrease was also significantly different from the corresponding (insignificant) change during saline infusion (ϩ19.4 Ϯ 26.9%, p Ͻ .05 vs amino acid group). Conclusions: After surgery, an amino acid infusion acutely reduces postoperative colon protein synthesis. This effect possibly may be attributed to interactions of specific amino acids (glutamine) with an altered intestinal immune system and enterocyte activity. Amino acid supply has gained its firm place during parenteral nutrition in a wide range of patients who cannot tolerate enteral feeding. Amino acids are usually considered necessary to reduce protein loss after surgical stress. An optimal conservation of body protein will be obtained with daily administration of 1.2-1.5 g amino acids per kg body weight.1 Potential anabolic actions of amino acids are known to occur in muscle and in splanchnic tissues.2 At the intestinal tract, amino acid metabolism and protein turnover are particularly important because an efficient formation of new protein is essential for maintaining a high rate of cell division and proliferation and for the production of cellular structure compounds and secreted enzymes.3,4 Unfortunately, in humans effects of specific substrates have almost exclusively been studied in the whole splanchnic bed, not allowing a differentiation between hepatic and intestinal changes.5-7 Virtually nothing is known on the effects of amino acids on human intestinal protein metabolism in situ.We sought in the present study to examine the effects of a standard amino acid infusion on colon protein synthesis using stable isotopes (1-[ 13 C]-leucine) and advanced mass spectrometry techniques. Studies were performed in patients after major abdominal surgery whose mucosal function may be altered and who are frequent candidates for parenteral...

Hyperglycemic hyperinsulinemia cannot stimulate intestinal protein synthesis in healthy individuals but does so in conditions characterized by an altered somatotropic axis such as diabetes. Only in a state of growth hormone resistance (high growth hormone but low insulin like growth factor [IGF‐1] concentrations), extra insulin may acutely reverse the impaired, growth‐hormone‐induced IGF‐1 release, thereby exerting anabolic actions at the intestinal tract. Growth hormone resistance can be also found in patients after surgical stress. Therefore, we wanted to test the hypothesis whether hyperglycemic hyperinsulinemia would stimulate ileal protein synthesis in the latter condition. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1‐[13C]‐leucine into ileal mucosal protein. All subjects had an ileostomy, which allowed easy access to the ileal mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 μmol/kg min). Isotopic enrichments and fractional protein synthesis were determined at baseline (period I) and after a 4‐hour glucose infusion (170 mg/kg/h) or after infusion of saline (control group) (period II). In controls, ileal protein synthesis declined significantly during prolonged isotope infusion (period I: 1.11± 0.14%/h, period II: 0.39 ± 0.13%/h, p < .01). In contrast, ileal protein synthesis remained constant during glucose infusion (period I: 1.32 ± 0.35%/h, period II: 1.33 ± 0.21%/h, n.s. vs period I, but p < .005 vs the corresponding value at the end of period II in the control group). Using the continuous tracer infusion technique, ileal protein synthesis seemingly declines over a short time in control subjects. We found evidence that this artificial decline was due to mass effects of a rapidly turning over mucosa protein pool in which an isotopic plateau was reached during the experiment and of which the size amounted to approximately 4% of the total mixed protein pool. Maintenance of ileal protein synthesis during glucose infusion therefore indicates a rise of ileal protein synthesis in a slowly turning over protein pool. This effect in postsurgical patients would be compatible with the concept of intestinal insulin action to depend on the specific clinical state (eg, growth hormone resistance).