Glutamine Dipeptide Research Articles

Oral glutamine dipeptide or oral glutamine free amino acid reduces burned injury progression in rats.

This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.

Hydrolyzed whey protein enriched with glutamine dipeptide attenuates skeletal muscle damage and improves physical exhaustion test performance in triathletes.

To investigate the effects of hydrolyzed whey protein enriched with glutamine dipeptide on the percentage of oxygen consumption, second ventilatory threshold, duration and total distance covered, and skeletal muscle damage during an exhaustion test in elite triathletes. The study was a randomized, double-blinded, placebo-controlled, crossover trial. Nine male triathletes performed a progressive incremental test on a treadmill ergometer (1.4 km h-1·3 min-1) 30 min after ingesting either 50 g of maltodextrin plus four tablets of 700 mg hydrolyzed whey protein enriched with 175 mg of glutamine dipeptide diluted in 250 ml of water (MGln) or four tablets of 700 mg maltodextrin plus 50 g maltodextrin diluted in 250 ml of water (M). Each athlete was submitted to the two dietary treatments and two corresponding exhaustive physical tests with an interval of one week between the interventions. The effects of the two treatments were then compared within the same athlete. Maximal oxygen consumption, percentage of maximal oxygen consumption, second ventilatory threshold, and duration and total distance covered were measured during the exhaustion test. Blood was collected before and immediately after the test for the determination of plasma lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration (also measured 6, 10, and 15 min after the test). Plasma cytokines (IL-6, IL-1β, TNF-α, IL-8, IL-10, and IL-1ra) and C-reactive protein levels were also measured. A single dose of MGln increased the percentage of maximal oxygen consumption, second ventilatory threshold duration, and total distance covered during the exhaustion test and augmented plasma lactate levels 6 and 15 min after the test. MGln also decreased plasma LDH and CK activities indicating muscle damage protection. Plasma cytokine and C-reactive protein levels did not change across the study periods. Conditions including overnight fasting and a single dose of MGln supplementation resulted in exercising at a higher percentage of maximal oxygen consumption, a higher second ventilatory threshold, blood lactate levels, and reductions in plasma markers of muscle damage during an exhaustion test in elite triathletes. These findings support oral glutamine supplementation's efficacy in triathletes, but further studies require.

Amino acid dipeptide formation induced by experimental irradiance of a solar flare power

AbstractThe experimental study aimed to select the spectrometric results of the solar flare that meet the mathematical conditions for integration, to measure the power of this integrated flux, and to test the integrated power, whether it is able to form a peptide bond between two molecules of selected amino acids on the Earth's surface. Results show that the radiation power of the X17 solar flare scanned by the SOLSTICE and SIM spectrometers aboard the NASA SORCE spacecraft, when used for experimental irradiance of the same parameters, is sufficient to form methionine, alanine, glutamine and proline dipeptides in aqueous solution with pyrophosphate or carbonyl sulphide at laboratory temperature. The experiments, with their successful outcome, provide insight into the biological significance of the narrowband solar flare anchored in the broadband UV solar radiation.

Insulin degludec and glutamine dipeptide modify glucose homeostasis and liver metabolism in diabetic mice undergoing insulin-induced hypoglycemia.

This study investigated whether a 30-day co-treatment with 1 g/kg glutamine dipeptide (GdiP) and 1 U/kg regular (rapid acting) or 5 U/kg degludec (long acting) insulins modifies glucose homeostasis and liver metabolism of alloxan-induced type 1 diabetic (T1D) male Swiss mice undergoing insulin-induced hypoglycemia (IIH). Glycemic curves were measured in fasted mice after IIH with 1 U/kg regular insulin. One hour after IIH, the lipid profile and AST and ALT activities were assayed in the serum. Morphometric analysis was assessed in the liver sections stained with hematoxylin-eosin and glycolysis, glycogenolysis, gluconeogenesis and ureagenesis were evaluated in perfused livers. T1D mice receiving GdiP or the insulins had a smaller blood glucose drop at 60 minutes after IIH, which was not sustained during the subsequent period up to 300 minutes. The 30-day treatment of T1D mice with insulin degludec, but not with regular insulin, improved fasting glycemia, body weight gain and serum activity of AST and ALT. Treatments with insulin degludec, GdiP and insulin degludec + GdiP decreased the liver capacity in synthesizing glucose from alanine. GdiP, in combination with both insulins, was associated with increases in the serum triglycerides and, in addition, regular insulin and GdiP increased AST and ALT activities, which could be the consequence of hepatic glycogen overload. GdiP and the insulins improved the IIH, although to a small extent. Caution is recommended, however, with respect to the use of GdiP because of its increasing effects on serum triglycerides and AST plus ALT activities.

Low-Dose Doxycycline Treatment Normalizes Levels of Some Salivary Metabolites Associated with Oral Microbiota in Patients with Primary Sjögren's Syndrome.

Saliva is a complex oral fluid, and plays a major role in oral health. Primary Sjögren’s syndrome (pSS), as an autoimmune disease that typically causes hyposalivation. In the present study, salivary metabolites were studied from stimulated saliva samples (n = 15) of female patients with pSS in a group treated with low-dose doxycycline (LDD), saliva samples (n = 10) of non-treated female patients with pSS, and saliva samples (n = 14) of healthy age-matched females as controls. Saliva samples were analyzed with liquid chromatography mass spectrometry (LC-MS) based on the non-targeted metabolomics method. The saliva metabolite profile differed between pSS patients and the healthy control (HC). In the pSS patients, the LDD treatment normalized saliva levels of several metabolites, including tyrosine glutamine dipeptide, phenylalanine isoleucine dipeptide, valine leucine dipeptide, phenylalanine, pantothenic acid (vitamin B5), urocanic acid, and salivary lipid cholesteryl palmitic acid (CE 16:0), to levels seen in the saliva samples of the HC. In conclusion, the data showed that pSS is associated with an altered saliva metabolite profile compared to the HC and that the LLD treatment normalized levels of several metabolites associated with dysbiosis of oral microbiota in pSS patients. The role of the saliva metabolome in pSS pathology needs to be further studied to clarify if saliva metabolite levels can be used to predict or monitor the progress and treatment of pSS.

Effects of dietary glutamine dipeptide on growth performance, intestinal digestive enzyme activity, and gene expression of related factors in Penaeus vannamei

Effects of dietary glutamine dipeptide on growth performance, intestinal digestive enzyme activity, and gene expression of related factors in Penaeus vannamei

Glutamine as a component of nutritional and metabolic therapy for surgical patients in ICU

Glutamine is the most abundant amino acid in the human body that is involved in various metabolic processes. The development of hypermetabolic and hypercatabolic syndrome that accompanies critical conditions of ICU patients is associated with a decrease in the concentration of glutamine, especially in the blood plasma and muscles. This process may last for quite a long time and lead to a number of complications up to a fatal outcome. This review was aimed to analyze clinical studies conducted over the past 20 years that demonstrate the effect of intravenous infusion of glutamine dipeptide as part of balanced parenteral nutrition on the perioperative period: the severity of inflammatory response; the state of the intestinal mucosa; the incidence and severity of complications; mortality; the duration of stay in the ICU and hospital in general, etc. The analysis was performed using systematic reviews and meta-analyses based on randomized double-blind, placebo-controlled trials in different countries selected in the main databases (PubMed, EMBASE, Web of Science, The Cochrane Library, etc.). Most of the reports state that the inclusion of glutamine dipeptide in nutritional and metabolic therapy (NMT) in surgical patients reduces the frequency and severity of infectious complications and mortality, reduces the length of stay in ICU and in hospital in general, improves the biochemical parameters that reflect the condition of patients, and reduces the treatment costs. Thus, the conducted systematic reviews and meta-analyses confirm that the use of the parenteral form of glutamine dipeptide (Dipeptiven 20%) as part of balanced standard parenteral nutrition (PN) is a clinically and pharmacoeconomically justified strategy of NMT in surgical ICU patients.

Media optimization to promote rat embryonic development to the blastocyst stage in vitro

Efficient model production in rats that incorporates newly developed genetic editing and embryo transfer tools, such as CRISPR/Cas9 technology and non-surgical embryo transfer, requires availability of an optimal embryo culture system. However, current technologies for in vitro manipulation of rat gametes, including embryo culture techniques, are less advanced compared to those in mice. In this study, we (1) identified a culture medium that was able to support optimal rat embryonic development by comparing two rat culture media: mR1ECM (modified rat 1-cell embryo culture medium) and KSOM-R (modified potassium simplex optimized medium for rats), and (2) evaluated the effect of glutamine dipeptides: alanyl-l-glutamine and glycyl-l-glutamine, on rat embryonic development. We also investigated the possibility of simplifying the KSOM-R culture procedure by increasing the volume of culture medium, reducing the need for daily medium changes. The results showed that rat embryos cultured in KSOM-R developed faster than those cultured in mR1ECM. Both alanyl-l-glutamine and glycyl-l-glutamine showed detrimental effects on rat embryonic development when supplemented in KSOM-R at the same concentration as glutamine. By increasing the volume of KSOM-R, rat zygotes were able to develop without daily medium refreshment at a similar rate and developmental competence as those in smaller volumes with daily medium changes. These results represent important improvements to rat embryo culture methods and will assist in more efficient production of rat models.

Akt activation by insulin treatment attenuates cachexia in Walker-256 tumor-bearing rats.

Cancer-bearing often exhibits hypoinsulinemia, insulin (INS) resistance and glutamine depletion associated with cachexia. However, INS and glutamine effects on cachexia metabolic abnormalities, particularly on tumor-affected proteins related to INS resistance, are poorly known. The main purpose of this study was to investigate the effects of INS and glutamine dipeptide (GDP) treatments on phospho-protein kinase B (p-Akt), and phospho-hormone sensitive lipase (p-HSL) in Walker-256 tumor-bearing rats. INS (NPH, 40 UI/kg, subcutaneous), GDP (1.5 g/kg, oral), INS+GDP or vehicle (control rats) were administered for 13 days, once a day, starting at the day of inoculation of tumor cells. The experiments were performed 4 hours after the last treatment to evaluate acute effects of INS and GDP, besides the chronic effects. INS and/or INS+GDP treatments, which markedly increased the insulinemia, increased the p-Akt: total Akt ratio and prevented the increased p-HSLSer552 : total HSL ratio in the retroperitoneal fat of tumor-bearing rats, without changing the INS resistance and increased expression of factor tumor necrosis-α (TNF-α) in this tissue. INS and INS+GDP also increased the p-Akt: total Akt ratio, whereas GDP and INS+GDP increased the GLUT4 glucose transporter gene expression, in the gastrocnemius muscle of the tumor-bearing rats. Accordingly, treatments with INS and INS+GDP markedly reduced glycemia, increased retroperitoneal fat and attenuated the body mass loss of tumor-bearing rats. In conclusion, hyperinsulinemia induced by high-dose INS treatments increased Akt phosphorylation and prevented increased p-HSLSer552 : total HSL ratio, overlapping INS resistance. These effects are consistent with increased fat mass gain and weight loss (cachexia) attenuation of tumor-bearing rats, evidencing that Akt activation is a potential strategy to prevent loss of fat mass in cancer cachexia.

Role of heat shock protein and cytokine expression as markers of clinical outcomes with glutamine-supplemented parenteral nutrition in surgical ICU patients

Nutrients, such as glutamine (GLN), have been shown to effect levels of a family of protective proteins termed heat shock proteins (HSPs) in experimental and clinical critical illness. HSPs are believed to serve as extracellular inflammatory messengers and intracellular cytoprotective molecules. Extracellular HSP70 (eHSP70) has been termed a chaperokine due to ability to modulate the immune response. Altered levels of eHSP70 are associated with various disease states. Larger clinical trial data on GLN effect on eHSP expression and eHSP70's association with inflammatory mediators and clinical outcomes in critical illness are limited. Explore effect of longitudinal change in serum eHSP70, eHSP27 and inflammatory cytokine levels on clinical outcomes such as pneumonia and mortality in adult surgical intensive care unit (SICU) patients. Further, evaluate effect of parenteral nutrition (PN) supplemented with GLN (GLN-PN) versus GLN-free, standard PN (STD-PN) on serum eHSP70 and eHSP27 concentrations. Secondary observational analysis of a multicenter clinical trial in 150 adults after cardiac, vascular, or gastrointestinal surgery requiring PN support and SICU care conducted at five academic medical centers. Patients received isocaloric, isonitrogenous PN, with or without GLN dipeptide. Serum eHSP70 and eHSP27, interleukin-6 (IL-6), and 8 (IL-8) concentrations were analyzed in patient serum at baseline (prior to study PN) and over 28 days of follow up. eHSP70 declined over time in survivors during 28 days follow-up, but non-survivors had significantly higher eHSP70 concentrations compared to survivors. In patients developing pneumonia, eHSP70, eHSP27, IL-8, and IL-6 were significantly elevated. Adjusted relative risk for hospital mortality was reduced 75% (RR=0.25, p=0.001) for SICU patients with a faster decline in eHSP70. The area under the receiver operating characteristic curve was 0.85 (95% CI: 0.76 to 0.94) for the final model suggesting excellent discrimination between SICU survivors and non-survivors. GLN-PN did not alter eHSP70 or eHSP27 serum concentrations over time compared to STD-PN. Our results suggest that serum HSP70 concentration may be an important marker for severity of illness and likelihood of recovery in the SICU. GLN-supplemented-PN did not increase eHSP70.

Farmaconutrición: ¿El fin de una era?

Pharmaconutrition has been an interesting area of research in critical care. Initially, trials with high dose glutamine and/or selenium reported promising outcomes but were often underpowered. Notwithstanding, systematic reviews and meta-analyses conducted up to 2015 found significant reductions in infection and/ or mortality rates in the critically ill. However, later meta- analyses have not shown improvement in clinical outcomes. Consequently, current guidelines do not make any recommendations for high dose nutrient therapy. Is this the end of the pharmaconutrition era? Not necessarily! It is time to return to basics and adopt a more pharmaceutical approach by categorising pharmaconutrients as drugs; better establish their in vitro and in vivo stability, pharmacology, toxicology and safety, then determine any drug-drug or drug-nutrient interactions before proceeding to pharmacokinetics and pharmacodynamics studies. We must additionally investigate the true nature of nutrient deficiency in the critically ill. How different is a deficiency in a naturally low Selenium population versus a ‘normal’ population? What happens to a high dose of a synthetic glutamine dipeptide in a nutrient deficient patient, orone with organ failure, and what happens to the excess pharmaconutrient that is not utilised by a nutritionally replete patient?These basic questions were inadequately investigated in the past, where fixed supraphysiological doses were administered to all patients, a significant proportion of whom were not nutrient deficient. When quality data have been generated on these preclinical parameters, we can more accurately determine indications, optimum posology and better guidelines for new clinical investigations and begin a new era of Pharmaceutical Nutrition.

Dietary alanyl-glutamine improves growth performance of weaned piglets through maintaining intestinal morphology and digestion–absorption function

Alanyl-glutamine (Ala-Gln), a highly soluble and stable glutamine dipeptide, is known to improve gut integrity and function. The aim of this study was to evaluate whether dietary Ala-Gln supplementation could improve growth performance, intestinal development and digestive-absorption function in weaned piglets. A total of 100 purebred Yorkshire piglets weaned at 21 days of age were assigned randomly to four dietary treatment groups and fed a basal diet (control group) or a basal diet containing 0.15%, 0.30% and 0.45% Ala-Gln, respectively. Compared with the control group, piglets fed the Ala-Gln diets had higher average daily gain and lower feed : gain and diarrhea rate (P < 0.05). Moreover, dietary Ala-Gln supplementation increased villous height and villous height : crypt depth ratio in duodenum and jejunum (P < 0.05), as well as the activities of maltase and lysozyme in jejunum mucosa (P < 0.05). In addition, a decrease in serum diamine oxidase activity and crypt depth in duodenum and jejunum was observed in piglets fed the Ala-Gln diets (P < 0.05). Serum cytosolic phospholipase A2 (cPLA2) concentration and gene expression of cPLA2, Na+-dependent glucose transporter 1, glucose transporter 2 and peptide transporter 1 in jejunum were increased by feeding Ala-Gln diets relative to control diet (P < 0.05). These results indicated that feeding Ala-Gln diet has beneficial effects on the growth performance of weaned piglets, which associated with maintaining intestinal morphology and digestive-absorption function.

The effect of glutamine supplementation on athletic performance, body composition, and immune function: A systematic review and a meta-analysis of clinical trials

This systematic review and meta-analysis of available evidence was conducted to obtain a conclusive result on the effects of glutamine supplementation on athletes. Systematic review and meta-analysis. Data related to body mass, lean body mass, body fat percentage, Vo2 max, lymphocytes, leukocytes and neutrophil counts were extracted to determine the effects of GLN on performance outcomes. The literature search was conducted across the databases Pubmed, Scopus, ISI Web of Science, SID (Scientific Information Database) and Cochrane Central Register of Controlled Trials, covering a period up to January 2017. Clinical trials evaluating glutamine supplementation outcomes on athletes aged over 18 were included. A total of 47 studies were included in the systematic review, and 25 trials matched the inclusion criteria for the meta-analysis. According to the meta-analysis, glutamine has a significant effect on weight reduction (WMD=-1.36 [95% CI:-2.55 to-0.16], p=0.02). Moreover, neutrophil numbers were reduced following glutamine intake at doses greater than 200mg/kg body weight (WMD=-605.77 [95% CI:-1200.0 to 52.1]; P=0.03). Also, supplementation by glutamine dipeptide resulted in higher blood glucose after exercise (WMD=0.51 [95% CI: 0.18, 0.83] mmol/l; P=0.002). There was no association between glutamine ingestion and other outcomes investigated. According to this meta-analysis, generally, glutamine supplementation has no effect on athletics immune system, aerobic performance, and body composition. However, the current study showed that glutamine resulted in greater weight reduction. In addition, the present study suggests that the efficacy of glutamine supplementation on neutrophil numbers could be affected by supplement type and dose.

The Effect of a Short Period of Supplementation with Glutamine Dipeptide on the Cognitive Responses after a Resistance Training Session of Women with HIV/AIDS: A Randomized Double-Blind Placebo-Controlled Crossover Study.

The aim of the present study was to investigate the effect of a short period of supplementation with glutamine dipeptide (GDP) on the acute responses to resistance training on the executive functions of people with HIV/AIDS. The sample consisted of 10 HIV+ women (45.00 ± 12.77 years old; 65.71 ± 12.04 kg; 1.54 ± 0.05 m) who were submitted to a randomized double-blind crossover procedure according to two experimental conditions: orally supplemented with 20 g/day of GDP or with maltodextrin for seven days. On the seventh day of supplementation all participants did cognitive function tests before and immediately after a resistance training session. Seven days of washout were adopted between conditions. Stroop and N-back tests were used to evaluate the executive functions. The training reduced the response time of each card in isolation and the latency time among them. GDP supplementation increased the magnitude of this effect, thus, reducing the latency time from the first to the last card in the Stroop test by almost 50% (P < 0.01). Considering the N-back test, there were no significant differences. It is suggested that GDP supplementation may increase the magnitude of the effect of an acute resistance training session in cognitive functions, particularly in the inhibitory control of people with HIV/AIDS. This trial is registered with NCT03236532.

Пептиды L-Глутамина как средство ускоренной регидратации при интенсивных физических нагрузках у спортсменов

This review is devoted to the theory and practice of the use of glutamine dipeptides in sports. The pathway of L-Glutamine dipeptides is described from the moment of oral intake and entering the intestine to inclusion in intracellular metabolic processes of organs and tissues. The physico-chemical properties of L-Glutamine dipeptides are considered. Urgent effects of L-Glutamine dipeptides under conditions of physical stress and hydration stress, influence on motor and cognitive functions of athletes, positive influence on physical readiness of athletes for prolonged debilitating exercises, reduction of weight loss (rehydration) are described. Positive results of the study of the effect of oral administration of AH and electrolytes on the concentration of plasma electrolytes, physiological indices and neuromuscular fatigue in the process of endurance training, as well as neuroprotective and analgesic properties of L-Glutamine dipeptides are presented.

Molecular characterization and nutritional regulation of specificity protein 1 (Sp1) in grass carp (Ctenopharyngodon idella )

Specificity protein 1 (Sp1) is a ubiquitous nuclear factor in eukaryotic cells and plays a crucial role in the regulation of di-/tripeptide absorption in the intestine. However, the function of Sp1 in bony fish remains poorly understood. In this study, a fish Sp1 gene (designated CiSp1) was identified from Ctenopharyngodon idella. The deduced CiSp1 protein contains structural features typical of Sp1 family proteins, including a glutamine-rich (Q-rich) region and three typical Cys2His2 zinc fingers. Quantitative real-time PCR analysis revealed ubiquitous expression of CiSp1 in all tested tissues and embryonic developmental stages of grass carp. In addition, CiSp1 expression in the intestine was significantly increased after feeding with fish meal and 270 g/kg dietary protein. Moreover, in vitro and in vivo glutamine dipeptide treatments showed similar stimulatory effects on the expression of the transcription factors CiSp1 and CiCDX2 and their potential target gene CiPepT1 in the intestines of grass carp. Finally, our results demonstrated that the mRNA expression of CiSp1/CiCDX2/CiPepT1 in the intestine was significantly increased after treatment with sodium butyrate in vitro and in vivo. Altogether, these results demonstrate for the first time that grass carp possesses a functional Sp1 and that its expression is regulated by dietary protein and feed additives.

A short-time economic evaluation of various modalities of glutamine dipeptide-enriched parenteral nutrition support in patients undergoing elective surgery for gastrointestinal tumors using decision-tree model

Objective To assess the short-time economics of various glutamine dipeptide-enriched parenteral nutrition (PN) for patients undergoing elective surgery for gastrointestinal tumors, with an attempt to provide evidence for decision makers on clinical nutrition support. Methods A prospective cohort study was designed. From payer/disburser's perspective, a cost-effectiveness decision-tree model was developed to assess the clinical outcomes and short-time economic effects of glutamine dipeptide-enriched PN that used in different time points (early postoperative or perioperative). Cost-effectiveness analysis, cost-utility analysis, and incremental cost-effectiveness analysis were adopted in the decision-tree model. One-way sensitivity analysis was performed to determine the robustness of the results. Results Totally 107 patients were included. There was no significant difference between the perioperative alanine(Ala) glutamine(Gln) nutrition support (group A) and early postoperative Ala-Gln nutrition support (group B) in the ratio of 5% weight declines on the 8th day after surgery and infection-related postoperative complications (72.1% vs. 78.1%, χ2=0.509, P=0.498 and 2.32% vs. 4.69%, χ2=0.060, P=0.806). The levels of prealbumin (PA) and albumin(Alb) and the level of total lymphocyte count(TLC) also the time of recovering gastrointestinal function, length of stay nutritional discharge index(LOSNDI), and direct costs were significantly different [PA: (208.19±56.92)mg/L vs. (187.97±62.05)mg/L, t=2.283, P=0.039; Alb: (33.82±3.91)×109vs. (31.96±4.57)×109,t=2.184, P=0.036; TLC: (1.19±0.55)×109vs. (0.89±0.66)×109,t=2.461, P=0.015; the time of recovering gastrointestinal function(3.06±0.28)d vs. (3.39 ± 0.34)d, t=-3.675, P=0.000; LOSNDI: (16.84±2.92)d vs. (18.52 ±3.47)d, t=-2.613, P=0.011; direct costs: ￥(17 029.05±317.28) vs. ￥(15 610.64±292.56), t=23.764, P=0.000]. When LOSNDI and quality-adjusted life years (QALYs) were estimated as indicators of effectiveness, the incremental cost-effectiveness ratios and incremental cost-utility ratios of group A were ￥844.3 and ￥70 920.5, respectively. Net monetary benefit of group B was more than that of group A. One-way sensitivity analysis showed that parameters had no significant effect on the model. Conclusion When using local per capita gross domestic product as threshold, early postoperative Ala-Gln PN was more economical than perioperative Ala-Gln PN strategy evaluation. Key words: Parenteral nutrition; Decision trees; Glutamine dipeptide; Gastro-intestinal tumors; Health economic evaluation

Cloning, expression, and nutritional regulation of the glutamine synthetase gene in Ctenopharyngodon idellus.

Glutamine synthetase (GS) is considered a master enzyme that catalyzes ATP-dependent biosynthesis of glutamine from glutamate. In the present study, the GS gene was cloned from the intestine of grass carp (Ctenopharyngodon idellus). The full-length cDNA sequence of GS encodes a 371-amino-acid polypetide. Phylogenetic analysis of the C. idellus GS sequence reveals common carp (Cyprinus carpio) as its closest neighbor. GS mRNA was differentially expressed in different tissues, with high to low gradient expression the intestine, brain, muscle, heart, gill, liver, pituitary gland, and spleen. Additionally, GS exhibited a dynamic pattern of expression during embryonic development, reaching maximal and minimal levels in the organ and hatching stages, respectively, and constant low levels from 7 to 28days post-hatching. We also assessed dietary protein levels and feed sources in diet-regulated fish, and the results suggested that low crude protein (CP) and fish meal stimulate GS gene expression. Furthermore, intestinal GS mRNA expression was significantly increased by 0.2, 0.4, 0.6, 0.8mM concentrations of glutamine dipeptide in vitro. This study provides valuable knowledge about the regulation of GS expression in teleosts.

Insulin, not glutamine dipeptide, reduces lipases expression and prevents fat wasting and weight loss in Walker 256 tumor-bearing rats

Cachexia is the main cause of mortality in advanced cancer patients. We investigated the effects of insulin (INS) and glutamine dipeptide (GDP), isolated or associated, on cachexia and metabolic changes induced by Walker 256 tumor in rats. INS (NPH, 40 UI/kg, sc) or GDP (1.5g/kg, oral gavage) was once-daily administered during 11 days after tumor cell inoculation. GDP, INS or INS+GDP treatments did not influence the tumor growth. However, INS and INS+GDP prevented retroperitoneal fat wasting and body weight loss of tumor-bearing rats. In consistency, INS and INS+GDP prevented the increased expression of triacylglycerol lipase (ATGL) and hormone sensitive lipase (HSL), without changing the expression of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in the retroperitoneal adipose tissue of tumor-bearing rats. INS and INS+GDP also prevented anorexia and hyperlactatemia of tumor-bearing rats. However, INS and INS+GDP accentuated the loss of muscle mass (gastrocnemius, soleus and long digital extensor) without affecting the myostatin expression in the gastrocnemius muscle and blood corticosterone. GDP treatment did not promote beneficial effects. It can be concluded that treatment with INS (INS or INS+GDP), not with GDP, prevented fat wasting and weight loss in tumor-bearing rats without reducing tumor growth. These effects might be attributed to the reduction of lipases expression (ATGL and LHS) and increased food intake. The results show the physiological function of INS in the suppression of lipolysis induced by cachexia mediators in tumor-bearing rats.

Glutamine dipeptide and cortisol change the liver glucose metabolism and reduce the severity of insulin-induced hypoglycaemia in untreated T1DM Swiss mice

Context: Glutamine is conditionally essential in type 1 diabetes mellitus, and might be useful to counteract hypoglycaemia. Objective: To investigate the systemic and hepatic effects of counter-regulatory hormones and glutamine dipeptide (GDP) during hypoglycemic episodes. Materials and methods: Diabetic Swiss mice made hypoglycaemic by insulin injection (1 U/kg) were given counter-regulatory hormones and/or GDP. Sixty minutes later, liver histology, liver glucose metabolism and plasma were assessed. Results: Combined, cortisol and GDP improved the hypoglycemic profile. During liver perfusion, gluconeogenesis was possibly the major pathway leading to glucose release. Perfusion with gluconeogenic precursors after glycogen depletion by adrenaline increased liver glucose and urea release. Discussion: The less severe hypoglycaemia could result from cortisol stimulating periportal gluconeogenesis and GDP inhibiting pericentral glycogenolysis, both favouring liver glucose release. Conclusions: At least some benefits of GDP and cortisol during hypoglycaemia came from their hepatic actions, and their use in diabetic patients should be explored.