L-glutamine Supplementation Research Articles

Effects of l-glutamine supplementation alone or with antioxidants on hydrogen peroxide-induced injury in human intestinal epithelial cells

Background and aims In situations of oxidative stress, l-glutamine (Gln) exhibits protective effects which may be potentiated by its combination with antioxidants. The aim of this study was to compare the effects of a Gln-antioxidants formula vs Gln alone in intestinal epithelial cell lines Caco-2 and HCT-8 submitted to hydrogen peroxide-induced oxidative injury. Methods Cells were cultured during 24 h with 0, 1, 2, 4, 8 or 16 mM Gln or isomolar Gln combined to cysteine, vitamine C, vitamine E, β-carotene, Zn and Se (Gln-AOX). After 24 h, membrane integrity was assessed by means of LDH leakage, the level of oxidative stress by analysis of 8-isoprostane concentration and cell viability by colorimetric-MTT assay. Results LDH activity decreased ( P < 0,05) with a dose-dependent manner in both cell types with Gln-AOX whereas Gln decreased LDH release only in the Caco-2 line at 1 mM. For both cell lines, release of 8-isoprostane was not blunted by any treatment and increased paradoxically with 16 mM Gln ( P < 0.05). Cell viability was higher ( P < 0.05) using Gln-AOX vs Gln at 4, 8 and 16 mM in both cell lines. Conclusions These results suggest that Gln-AOX is more efficient than Gln alone to preserve cell membrane integrity and viability in intestinal cell lines submitted to oxidative injury.

L-Glutamine Supplementation Prevents Myenteric Neuron Loss and Has Gliatrophic Effects in the Ileum of Diabetic Rats

Peripheral neuropathy caused chronically by diabetes mellitus is related to exacerbation of oxidative stress and a significant reduction in important endogenous antioxidants. L: -Glutamine is an amino acid involved in defense mechanisms and is a substrate for the formation of glutathione, the major endogenous cellular antioxidant. This study investigated the effects of 2% L: -glutamine supplementation on peripheral diabetic neuropathy and enteric glia in the ileum in rats. Male Wistar rats were divided into four groups: normoglycemics (N), normoglycemics supplemented with L: -glutamine (NG), diabetics (D), and diabetics supplemented with L: -glutamine (DG). After 120days, the ileums were processed for HuC/D and S100 immunohistochemistry. Quantitative and morphometric analysis was performed. Diabetes significantly reduced the number of HuC/D-immunoreactive myenteric neurons per unit area and per ganglion in group D compared with normoglycemic animals (group N). L: -Glutamine (2%) prevented neuronal death induced by diabetes (group DG) compared with group D. The glial density per unit area did not change with diabetes (group D) but was significantly reduced after L: -glutamine supplementation (groups NG and DG). Ganglionic glial density was similar among the four groups. The neuronal area was not altered in groups D and DG. Glial size was reduced in group D; this was reversed by L: -glutamine supplementation (group DG). We concluded that 2% L: -glutamine had neuroprotective effects directly on myenteric neurons and indirectly through glial cells, which had gliatrophic effects.

Effects of L-glutamine supplementation on the myenteric neurons from the duodenum and cecum of diabetic rats

Peripheral neuropathy is one of the chronic complications of diabetes mellitus and is directly related to gastrointestinal consequences of the disease. Myenteric neurons are affected in some pathological conditions such as diabetic neuropathy. The imbalance between cellular antioxidants and free radicals, leading to an increase in oxidative stress, is considered one of the main factors responsible for neuronal damages in diabetes. Drugs that reduce the oxidative stress may play a significant role in the treatment of neurological complications of diabetes mellitus. To evaluate the effect of L-glutamine supplementation on the myenteric neurons from the cecum and duodenum of Wistar rats with streptozotocin-induced diabetes mellitus. The animals were divided in four groups (n = 5): non-treated normoglycemics, normoglycemics treated with L-glutamine, non-treated diabetics and diabetics treated with L-glutamine from the 4th day of diabetes induction on. The amino acid L-glutamine was added to their diet at 1%. Giemsa's technique was employed to stain the myenteric neurons. We determined the cell body area of 500 neurons in each group studied. The quantitative analysis was performed by sampling in an area of 16.6 mm² in the cecum and 3.6 mm² in the duodenum of each animal. After the supplementation with L-glutamine in the duodenum, we observed a preservation of neuronal density in groups normoglycemic and diabetic (P<0.05). We also observed a preservation of the cell bodies area in diabetic animals (group treated with L-glutamine) (P<0.05). In the cecum, that preservation was not evident. Supplementation with L-glutamine (1%) promoted a neuroprotective effect on the myenteric neurons from the duodenum of rats, both in terms of natural aging and of diabetes mellitus.

L-Arginine and l-glutamine as immunonutrients and modulating agents for oxidative stress and toxicity induced by sodium nitrite in rats

Sodium nitrite (NaNO 2) is a flavoring, coloring and preservative agent in meat and fish products. The study aimed to evaluate the efficacy of l-arginine and l-glutamine supplementation as a potentially novel and useful strategy for the modulation of oxidative stress and toxicity induced by NaNO 2 in male rats. Rats were divided into six groups each of 10 rats and treated for 6 weeks: group 1 as normal control; group 2 fed standard diet containing 0.2% NaNO 2; group 3 and 4 fed the previous diet supplemented with 1% and 2% arginine, respectively; group 5 and 6 fed NaNO 2 diet supplemented with 1% and 2% glutamine, respectively. NaNO 2 treatment induced a significant increase in serum malondialdehyde, nitric oxide, arginase, glutathione-S-transferase activities, urea and creatinine as well as differential leucocytes%. However, a significant decrease was recorded in reduced glutathione, catalase activity, total protein, albumin and some hematological parameters as well as immunoglobulin G. On the other hand, arginine or glutamine showed a remarkable modulation of these abnormalities as indicated by reduction of malondialdehyde and improvement of the investigated antioxidant and hematological parameters. It can be concluded that arginine or glutamine supplementation may reduce oxidative stress and improve the hazard effects of NaNO 2.

Assessment of the effect of L-glutamine supplementation on DOMS

Glutamine is an amino acid and is not considered one of the eight essential aminos. Amino acid supplementation outspreaded to enhancing athletic performance, preparation, removal fatigue and minimising risk of...

Immunohistochemical study of vasoactive intestinal peptide (VIP) enteric neurons in diabetic rats supplemented with L-glutamine

The purpose of this work was to study the area of the varicosities of nerve fibers of myenteric neurons immunoreactive to vasoactive intestinal peptide (VIP-IR) and of the cell bodies of VIP-IR submucosal neurons of the jejunum of diabetic rats supplemented with 2% L-glutamine. Twenty male rats were divided into the following groups: normoglycemic (N), normoglycemic supplemented with L-glutamine (NG), diabetic (D) and diabetic supplemented with L-glutamine (DG). Whole-mounts of the muscle tunica and the submucosal layer were subjected to the immunohistochemical technique for neurotransmitter VIP identification. Morphometric analyses were carried out in 500 VIP-IR cell bodies of submucosal neurons and 2000 VIP-IR varicosities from each group. L-Glutamine supplementation to the normoglycemic animals caused an increase in the areas of the cell bodies (8.49%) and varicosities (21.3%) relative to the controls (P < 0.05). On the other hand, there was a decrease in the areas of the cell bodies (4.55%) and varicosities (28.9%) of group DG compared to those of group D (P < 0.05). It is concluded that L-glutamine supplementation was positive both to normoglycemic and diabetic animals.

Glutamina: aspectos bioquímicos, metabólicos, moleculares e suplementação

A glutamina é o aminoácido livre mais abundante no plasma e no tecido muscular. Nutricionalmente é classificada como um aminoácido não essencial, uma vez que pode ser sintetizada pelo organismo a partir de outros aminoácidos. A glutamina está envolvida em diferentes funções, tais como a proliferação e desenvolvimento de células, o balanço acidobásico, o transporte da amônia entre os tecidos, a doação de esqueletos de carbono para a gliconeogênese, a participação no sistema antioxidante e outras. Por meio de técnicas de biologia molecular, estudos demonstram que a glutamina pode também influenciar diversas vias de sinalização celular, em especial a expressão de proteínas de choque térmico (HSPs). As HSPs contribuem para a manutenção da homeostasia da célula na presença de agentes estressores, tais como as espécies reativas de oxigênio (ERO). Em situações de elevado catabolismo muscular, como após exercícios físicos intensos e prolongados, a concentração de glutamina pode tornar-se reduzida. A menor disponibilidade desse aminoácido pode diminuir a resistência da célula a lesões, levando a processos de apoptose celular. Por essas razões, a suplementação com L-glutamina, tanto na forma livre, quanto como dipeptídeo, tem sido investigada. Alguns aspectos bioquímicos, metabólicos e mecanismos moleculares da glutamina, bem como os efeitos de sua suplementação, são abordados no presente trabalho.

L-Glutamine supplementation during the lactation period facilitates cortical spreading depression in well-nourished and early-malnourished rats

Aims Glutamine (Gln) participates in the so-called “brain glutamine–glutamate cycle” and therefore it is likely to influence brain excitability. Here we investigated, in weaned well-nourished and early-malnourished rats, the effects of previous Gln oral supplementation, during the brain development period, on cortical spreading depression (CSD), an excitability-related brain phenomenon. Main methods Male Wistar (W) suckling rat pups, well-nourished (litters with 6 pups) and malnourished (M) during lactation (by increasing the litters to 12 pups), received Gln (500 mg/kg/day) by gavage during postnatal days 7 to 27. At 30–40 days of life, they were submitted to a cortical spreading depression (CSD) recording session during 4 h, on 2 cortical parietal points of the right hemisphere. CSD velocity propagation was calculated from the time required for a CSD wave to cross the inter-electrode distance. Key findings In both nutritional condition, Gln rats presented higher ( p < 0.05) CSD propagation velocities (W-Gln, 4.22 ± 0.23; M-Gln, 4.51 ± 0.27 mm/min), as compared to water-treated controls (W-Wa, 3.77 ± 0.21; M-Wa, 4.15 ± 0.18 mm/min). This water control group did not differ from a naïve control group that was not submitted to the gavage procedure. A fourth group, treated with a “placebo amino acid” (glycine), also displayed CSD velocities in the control range. Significance The results indicate that Gln supplementation during brain development facilitates cortical spreading depression propagation, as judged by the higher CSD velocities, and this effect is not abolished by malnutrition. Data support the idea of Gln-related changes in brain excitability, during neural development.

Role of l-glutamine and glycine supplementation on irradiated colonic wall

Radiotherapy is frequently used for cancer treatment, but it may be associated with several complications. Thus, this study aimed to evaluate the role of L-glutamine and/or glycine supplementation on the colonic wall in rats submitted to abdominal radiation. Sixty adult Wistar rats were randomly divided into six groups: I-healthy, II (control)-irradiated rats without amino acid supplementation, III-irradiated rats with glycine supplementation, IV-irradiated rats with L-glutamine supplementation, V-irradiated rats with glycine supplementation 7 days before irradiation and with L-glutamine supplementation 7 days after irradiation, and VI-irradiated rats with L-glutamine supplementation 7 days before irradiation and with glycine supplementation 7 days after irradiation. Abdominal irradiation was employed with a dose of 1,000 cGy on the eighth day of the experiment. All animals underwent laparotomy on the 15th day for resection of a colonic segment for stereologic analysis. Parametric and nonparametric tests were used for statistical analysis, with the level of significance set at p<or=0.05. Control animals (group II) presented a significantly smaller total volume of colonic wall when compared to animals of groups I, III, IV, V, and VI. There was a significant increase in mucosal layer volume in the animals of group IV compared to animals of groups I, II, and III. Our findings suggest that L-glutamine and/or glycine supplementation is beneficial for the repair of the colonic wall of rats, but L-glutamine, with its trophic effects on the colonic mucosa, seems to exhibit better results.

GADD153 expression does not necessarily correlate with changes in culture behavior of hybridoma cells

BackgroundThe acute sensitivity of some hybridoma cell lines to culture-related stresses severely limits their productivity. Recent developments in the characterization of the stress signals modulating the cellular phenotype revealed that the pro-apoptotic transcription factor Gadd153 could be used as a marker to facilitate the optimization of mammalian cell cultures. In this report, we analyzed the expression of Gadd153 in Sp2/0-Ag14 murine hybridoma cells grown in stationary batch culture and subjected to two different culture optimization paradigms: L-glutamine supplementation and ectopic expression of Bcl-xL, an anti-apoptotic gene.ResultsThe expression of Gadd153 was found to increase in Sp2/0-Ag14 cells in a manner which coincided with the decline in cell viability. L-glutamine supplementation prolonged Sp2/0-Ag14 cell survival and greatly suppressed Gadd153 expression both at the mRNA and protein level. However, Gadd153 levels remained low after L-glutamine supplementation even as cell viability declined. Bcl-xL overexpression also extended Sp2/0-Ag14 cell viability, initially delayed the induction of Gadd153, but did not prevent the increase in Gadd153 protein levels during the later phase of the culture, when cell viability was declining. Interestingly, L-glutamine supplementation prevented Gadd153 up-regulation in cells ectopically expressing Bcl-xL, but had no effect on cell viability.ConclusionThis study highlights important limitations to the use of Gadd153 as an indicator of cell stress in hybridoma cells.

L-Glutamine supplementation optimizes the repair of the colonic mucosa in rats subjected to abdominal irradiation

Radiotherapy plays an important role in cancer treatment but may be associated with several gastrointestinal complications. The present study investigated the role of l -glutamine supplementation in the repair of the colonic mucosa of rats subjected to abdominal irradiation (AI). Sixty adult male Wistar rats were divided into 6 study groups: healthy—animals not subjected to abdominal radiation; control—irradiated rats without amino acid supplementation; Gly-Gly—irradiated rats with glycine supplementation throughout the study; Gln-Gln—irradiated rats with l -glutamine supplementation throughout the study; Gly-Gln—irradiated rats with glycine supplementation 7 days before irradiation and with l -glutamine supplementation 7 days after irradiation; and Gln-Gly—irradiated rats with l -glutamine supplementation 7 days before irradiation and with glycine supplementation 7 days after irradiation. Animals belonging to the control, Gly-Gly, Gln-Gln, Gly-Gln, and Gln-Gly groups were subjected to AI on the eighth day of experimentation. All animals underwent laparotomy on the 15th day for resection of a circumferential colonic segment for stereological analysis. Partial volume of the epithelium and epithelial surface of groups Gln-Gln and Gly-Gln were similar to those of healthy animals but significantly increased compared with control animals ( P < .05 for both groups regarding partial epithelium volume; P < .001 and P < .05, respectively, regarding epithelial surface). The present findings suggest that dietary supplementation with l -glutamine before and after AI or only after irradiation is beneficial for the repair of the colonic mucosa of rats, optimizing its recovery.

RETRACTED ARTICLE:l-glutamine supplementation induces insulin resistance in adipose tissue and improves insulin signalling in liver and muscle of rats with diet-induced obesity

Diet-induced obesity (DIO) is associated with insulin resistance in liver and muscle, but not in adipose tissue. Mice with fat-specific disruption of the gene encoding the insulin receptor are protected against DIO and glucose intolerance. In cell culture, glutamine induces insulin resistance in adipocytes, but has no effect in muscle cells. We investigated whether supplementation of a high-fat diet with glutamine induces insulin resistance in adipose tissue in the rat, improving insulin sensitivity in the whole animal. Male Wistar rats received standard rodent chow or a high-fat diet (HF) or an HF supplemented with alanine or glutamine (HFGln) for 2 months. Light microscopy and morphometry, oxygen consumption, hyperinsulinaemic-euglycaemic clamp and immunoprecipitation/immunoblotting were performed. HFGln rats showed reductions in adipose mass and adipocyte size, a decrease in the activity of the insulin-induced IRS-phosphatidylinositol 3-kinase (PI3-K)-protein kinase B-forkhead transcription factor box 01 pathway in adipose tissue, and an increase in adiponectin levels. These results were associated with increases in insulin-stimulated glucose uptake in skeletal muscle and insulin-induced suppression of hepatic glucose output, and were accompanied by an increase in the activity of the insulin-induced IRS-PI3-K-Akt pathway in these tissues. In parallel, there were decreases in TNFalpha and IL-6 levels and reductions in c-jun N-terminal kinase (JNK), IkappaB kinase subunit beta (IKKbeta) and mammalian target of rapamycin (mTOR) activity in the liver, muscle and adipose tissue. There was also an increase in oxygen consumption and a decrease in the respiratory exchange rate in HFGln rats. Glutamine supplementation induces insulin resistance in adipose tissue, and this is accompanied by an increase in the activity of the hexosamine pathway. It also reduces adipose mass, consequently attenuating insulin resistance and activation of JNK and IKKbeta, while improving insulin signalling in liver and muscle.

Short time L-glutamine supplementation of malnourished rats

OBJETIVE: Considering that in malnourished patients supplemented with L-glutamine the negativity of the nitrogen balance tends to decrease, the present study aimed to determine whether malnourished Wistar rats supplemented with L-glutamine would show lower urinary nitrogen excretion, a greater deposition of nitrogen content in different tissues, and/or an alteration in the plasma amino acid levels. METHODS: The rats were divided into groups: 1) protein-energy malnutrition, 2) protein malnutrition and 3) normally nourished group. The urinary and tissue nitrogen contents were determined by the Kjeldahl method and plasma amino acids by liquid chromatography. RESULTS: Weight, urinary and tissue nitrogen accumulation were significantly reduced in the group with protein-energy malnutrition, but did not improve with L-glutamine supplementation supplied for a short time. The plasma amino acid concentrations showed no special pattern with L-glutamine supplementation. CONCLUSION: It was concluded that it was not possible to detect any positive effect of L-glutamine supplementation on the tissue and urinary nitrogen metabolism in malnourished rats.

Effects of a Glutamine Supplement on the Skeletal Muscle Contractile Force of Mice

L-glutamine is the most abundant amino acid found in human muscle and plays an important role in protein synthesis. It is, therefore, believed that by increasing L-glutamine levels, protein metabolism can be increased, resulting in skeletal muscle growth. The goal of this research was to determine if increased L-glutamine levels enhanced muscle growth in mice. Comparisons between the contractile force of the gastrocnemis muscles of a control group and a group that received the supplement through their water supply were intended to determine if muscle growth occurred. T-tests were used to compare the contractile forces of the experimental and control mice. There was a significant difference between the contractile forces of the experimental and control groups. This suggests that L-glutamine supplementation increased the muscle growth of the experimental mice.

Effect of oral supplement of l-glutamine in colonic wall of rats subjected to abdominal irradiation

To evaluate the structural alterations of the irradiated colonic wall in rats, verifying if L-glutamine supplementation is able to prevent them. We used 30 male adult Wistar rats, divided into three groups: I--control, II--irradiated, and III-irradiated with L-glutamine supplementation during the 14 days of the study. Control group was maintained in laboratory standard conditions while groups II and three were submitted to abdominal radiation with an only dose of 1000 cGy in the 8th day of experimentation. All the animals were submitted to laparotomy in the 15th day for resection of the colonic segment for stereological analysis. Group II presented total volume of colonic wall significantly smaller than control group without altering the partial volumes of each layer. Compared to groups II and III, group II exhibited maintenance of total volume of colonic wall, nearing control group. Compared to control group, animals of group III exhibited maintenance of epithelial partial volume without altering significantly epithelial surface. It is suggested that L-glutamine supplementation can be of benefit in the irradiated colonic wall in rats.

Effects of glutamine isomers on human (Caco-2) intestinal epithelial proliferation, strain-responsiveness, and differentiation

Enteral feeding with small amounts to stimulate bowel motility, and glutamine supplementation, which provides nutrients selectively used by intestinal epithelial cells, might preserve the gut mucosa during fasting. We evaluated the effects of the interaction between mechanical strain and glutamine supplementation in human Caco-2 intestinal epithelial cells, and pursued the finding of equivalent effects of l- and d-glutamine in Caco-2, HT-29, and primary malignant human colonocytes. Caco-2 cells were subjected to repetitive strain in media containing 2 mmol/L of l-glutamine and media supplemented with l- or d-glutamine. Proliferation was determined by automated cell counting. Differentiation and cellular production of l-glutamine were determined spectroscopically. Rhythmic deformation stimulated Caco-2 proliferation in a frequency-dependent manner. Maximal stimulation occurred at 10 cpm, consistent with in vivo frequencies of peristalsis and villous motility. Deformation at 10 cpm and l-glutamine supplementation from 2 to 5 mmol/L concentrations independently stimulated Caco-2 proliferation; the combination further increased proliferation. d-Glutamine supplementation yielded similar results, although with lesser potency. Furthermore, both l- and d-glutamine equivalently reduced Caco-2 dipeptidyl dipeptidase activity. The effects of each isoform were blocked by 1 to 3 mmol/L acivicin, a selective antagonist of glutamine metabolism. Indeed Caco-2 and HT-29 cells and primary malignant colonocytes each metabolized d-glutamine to l-glutamine. Glutamine supplementation in fasting patients might prove synergistic with stimulation of bowel motility by non-nutritive feeding, whereas tissue-specific variations in d-glutamine metabolism might facilitate selective nutripharmaceutical targeting of the gut mucosa.

The Role of Glutamine in the Aetiology of the Chronic Fatigue Syndrome

AbstractBackground: Recent studies have observed low plasma glutamine concentrations in chronic fatigue syndrome (CFS) subjects. Glutamine has been shown to be essential for immune function and a key substrate in brain neurochemistry. A dysfunctional immune response to infection and/or neurotransmitter dysfunction may be associated with CFS.Objective: To compare the glutamine status of CFS subjects to matched controls and to test the effect of L-glutamine supplementation on the symptoms associated with CFS.Design: A 26-week, randomised, double-blind, placebo-controlled trial.Patients: Sixteen subjects diagnosed with CFS and 16 age- and sex-matched, healthy controls.Intervention: L-glutamine or placebo (2000 mg/day for 26 weeks).Measurements: Plasma and muscle glutamine concentrations, complete haematology counts, lymphocyte surface marker analysis, serum cortisol and testosterone concentrations, and self-reported symptomatic status.Results: Plasma and muscle glutamine concentrations were lower in CFS subj...

Epithelial cell growth and differentiation. II. Intestinal apoptosis.

Epithelial cell growth and differentiation. II. Intestinal apoptosis.

Dietary L-Glutamine Supplementation Reduces the Growth of the Morris Hepatoma 7777 in Exercise-Trained and Sedentary Rats , ,

Dietary glutamine supplementation and exercise have been reported independently to enhance immune function and reduce tumor growth. We study the effect of both of these interventions on the growth of the Morris Hepatoma 7777, implanted in 59 female Sprague-Dawley Buffalo rats. Rats were fed a nutritionally complete, purified diet with or without L-glutamine 20 g/kg diet and randomized to swim 3 h/d or to remain sedentary. After 14 d, the mean tumor weight of glutamine-supplemented rats was lower (P < 0.0001) than that of unsupplemented rats (5.8 ± 0.4 vs. 8.7 ± 0.5 g, respectively). Exercise did not alter tumor growth. Glutamine supplementation increased [3H] thymidine incorporation by splenocytes incubated with Concanavalin A and the proportion of natural killer cells in spleen, but not cytotoxic activity against YAC-1 cells. Glutamine supplementation did not alter glutamine concentrations in plasma (691 ± 12 μmol/L) or soleus muscle (5328 ± 102 pmol/mg) but resulted in higher (P < 0.004) plasma concentrations of leucine, isoleucine and valine, precursors of glutamine. Splenocytes from exercised rats had a higher (P < 0.001) mitogen response than those from sedentary rats. Isolated tumor cells demonstrated high rates of non-oxidative glucose and glutamine metabolism and consumption of glutamine, tryptophan and methionine. However, neither diet nor exercise significantly affected glucose or glutamine metabolism by tumor cells. The precise mechanism of tumor growth suppression by oral glutamine supplementation is not clear but may be related to changes in substrate availability, improved tumor-directed natural killer cytotoxic activity or a faster response to an immune challenge.

Effect of l-glutamine supplementation on impaired glucose regulation during intravenous lipid administration

In contrast to l-glutamine, lipid emulsions are routinely administered to patients receving nutritional support. The provision of fat during intravenous feeding is essential, but the potentially toxic byproducts of fatty acid oxidation may have adverse metabolic consequences. In the present study, we have examined the effect of l-glutamine, an inhibitor of fatty acid oxidation, on the development of defective blood glucose regulation caused by a 48-hour infusion of 10% intralipid in rats. Male Sprague-Dawley rats (200–290g) were anesthetized with sodium pentobarbital, the right femoral vein cannulated, and baseline blood samples were taken. Each rat was placed in a metabolic cage with access to water, in the presence or absence of rodent chow. Two hours after waking, the rats were infused with 10% intralipid with either saline (control), 2% l-glutamine, or 2% l-alanine. After 48 hours, all animals were sacrificed and blood samples were again obtained. The mean ± SEM plasma glucose levels before and after lipid infusion at the rate of 1 mL/hr in control rats fed ad libitum, were 125 ± 13 and 170 ± 5 mg/dL ( p < 0.01, n = 7). Similarly, plasma free fatty acids (FFA) in these animals rose from 0.74 ± 0.11 to 1.34 ± 0.32 mmol/L ( p < 0.05). Plasma insulin levels also increased from 337 ± 44 to 1278 ± 88 pg/mL ( p < 0.01). Reduction of intralipid dose infusion did not prevent insulin resistance characterized by hyperglycemia and hyperinsulinemia. However, addition of l-glutamine to the high-dose lipid infusion with chow feeding prevented changes in plasma glucose, insulin levels, and FFA but not triglyceride levels. Also, glutamine but not alanine supplementation in intralipid infused rats without chow feeding prevented changes in plasma glucose, insulin, and malondialdehyde levels. In conclusion, these data show that glutamine supplementation during intravenous lipid administration in rats prevents the development of impaired glucose regulation associated with hyperlipidemia.