glutaminase and alanylglutamine

The aim of the present study was to investigate the effects of the alanyl-glutamine dipeptide (Ala-Gln) or the combination supplementation of free alanine and glutamine (Ala+Gln) on the mammalian target of rapamycin (mTOR) and ubiquitin-proteasome proteolysis (UPP) signaling pathways in piglets.. We randomly allocated 180 piglets to three treatments with three replicates of 20 piglets each, fed with diets containing 0.62% Ala, 0.5% Ala-Gln, 0.21% Ala+0.34% Gln, respectively. The duration of the experiment was 28 d.. The results showed that Ala-Gln increased average daily gain of piglets, and decreased the ratio of feed to gain (P < 0.05). Ala-Gln supplementation increased the concentrations of Gln and glutamate and decreased the activity of glutamine synthetase in liver and skeletal muscle (P < 0.05). Ala-Gln increased the expression of glutaminase and glutamate dehydrogenate (P < 0.05). The increased phosphorylation of eIF-4 E binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1) in Ala-Gln treatment were associated with phosphorylation of the mTOR in liver and skeletal muscle. Ala+Gln did not affect the phosphorylation abundances of mTOR, 4E-BP1, or S6K1 (P > 0.05). Ala-Gln supplementation inhibited the mRNA expressions of MAFbx and MuRF1 in skeletal muscle of piglets (P < 0.05).. Taken together, Ala-Gln supplementation improved the growth performance of piglets, enhanced the metabolism of Gln, upregulated protein synthetic signaling in liver and skeletal muscle and decreased protein degradative signaling in muscle of piglets. Moreover, these effects of Ala-Gln were more effective than those of Ala+Gln.

Topics: Alanine; Alanine Transaminase; Animals; Aspartate Aminotransferases; Dietary Supplements; Dipeptides; Glutamate Dehydrogenase; Glutamate-Ammonia Ligase; Glutamic Acid; Glutaminase; Glutamine; Liver; Male; Muscle, Skeletal; Proteasome Endopeptidase Complex; Proteolysis; RNA, Messenger; Signal Transduction; Sus scrofa; TOR Serine-Threonine Kinases; Ubiquitins; Weight Gain

Although parental administration of glutamine promotes intestinal adaptation, it is controversial whether enteral glutamine is effective after small bowel resection. To further evaluate the benefits of enteral supplementation, peptide and amino acid peptide transporter function must be considered. We evaluated the effect of enteral alanyl-glutamine based on the alteration of peptide and amino acid transporter expressions after massive small intestinal resection. Rats underwent 80% proximal intestinal resection. Expression of the glutaminase (GA), amino acid transporter B0 and peptide transporter PepT1 mRNA in the residual intestinal cells was initially examined by Northern blot analysis. Rats with a small bowel received a bolus supplement of glutamine (2.0 g/kg/day) + alanine (1.22 g/kg/day) mixture, alanyl-glutamine (2.972/kg/day) or saline for 3 days from one day before operation. On the 3rd postoperative day (POD) and the 7th POD, residual intestinal tissue was removed, and mucosal parameters were measured. The GA activity and GA mRNA significantly increased on the 1st POD. Although the levels of B0 mRNA gradually decreased, the PepT1 mRNA increased after surgery, and reached 150% of the initial level on the 5th POD. In the rats administered alanyl-glutamine, mucosal wet weight and protein content similarly increased with increasing villus height on the 7th POD. Enteral supplementation with alanyl-glutamine but not glutamine + alanine mixture promotes intestinal adaptation as evidenced by increased peptide transport after intestinal resection.

Topics: Alanine; Animals; Blotting, Northern; Dipeptides; Glutaminase; Glutamine; Intestine, Small; Intestines; Male; Peptides; Rats; Rats, Sprague-Dawley; RNA, Messenger; Time Factors

Following extensive bowel resection, the intestinal tract undergoes a variety of adaptive responses to enhance bowel function. The purpose of this study was to determine the effect of glutamine-supplemented parenteral nutrition on mucosal cellularity and gut function. In addition, enterocyte gene expression of two relevant systems was also characterized and related to the structural and functional changes that occurred. Male Wistar rats underwent a 60% small bowel resection and jugular vein catheterization and were randomized into two groups. The control group (n = 10) received a standard intravenous nutritional solution and the study group (n = 10) received a similar solution but enriched with alanylglutamine dipeptide. After 7 days blood was taken for amino acid analysis, and bowel was harvested to determine mucosal morphology and expression of mucosal cell glutaminase and IGF-I mRNA. Mesentery lymphnodes were cultured to determine the presence of bacteria and thus access bacteria translocation. Serum glutamine concentration and mucosal architecture were maintained in the study group compared to the controls. Seventy percent of lymphnodes were cultured positive in control vs. only 20% in the study group (P < 0.05). Jejunal mucosal glutaminase and ileum mucosal IGF-I mRNA increased twofold and threefold respectively compared to control animals. Parenteral nutrition supplemented with alanyl-glutamine dipeptide supports mucosal cellularity and regional immune function in rodents following intestinal resection, These alterations are associated with enhanced enterocyte expression of glutaminase and IGF-I. These changes may facilitate the structural and functional alterations which were observed in the glutamine treated animals.

Topics: Animals; Dipeptides; Enterocytes; Gene Expression; Glutaminase; Ileum; Insulin-Like Growth Factor I; Intestinal Mucosa; Intestine, Small; Jejunum; Male; Parenteral Nutrition; Rats; Rats, Wistar; RNA, Messenger

Surgical stress and parenteral nutrition (PN) may cause gut mucosal atrophy and alter barrier function. Gene expression of growth factors and enzymes in small intestine may change. The effects of alanyl-glutamine dipeptide (Ala-Gln) on gut barrier and the gene expression of insulin-like factor I (IGF-I) and glutaminase in parenteral infusion rats with massive small intestine resection were investigated. Twenty Wistar rats were catheterized with 60% small bowel resectin. They were divided into two groups. Control group (n = 10) received traditional parenteral nutritional solution, and study group (n = 10) received Ala-Gln enriched nutritional solution (3% Ala-Gln). The rats were maintained with their respective diets for 7 days. The rats in the study group maintained serum glutamine concentration (844.0 +/- 13.2uMol: 640.4 +/- 17.2uMol, P < 0.05), mucosal architecture (mucosal thickness 591 +/- 12uM: 486 +/- 8uM, P < 0.05) and villus height (404 +/- 7uM: 303 +/- 5uM, P < 0.05). Bacterial translocation rate decreased in the study group (70%: 20%, P < 0.05). Ileal mucosal IGF-I mRNA and jejunal mucosal glutaminase mRNA in the study group increased twofold and threefold respectively. The results suggest that Ala-Gln may enhance gut growth and improve gut mucosa integrity and barrier function in part by means of stimulating IGF-I and glutaminase expression in surgical stress.

Topics: Animals; Bacterial Translocation; Dipeptides; Gene Expression; Glutaminase; Insulin-Like Growth Factor I; Intestinal Mucosa; Intestine, Small; Male; Parenteral Nutrition; Rats; Rats, Wistar; RNA, Messenger; Stress, Physiological