scholarly journals Glutamine Metabolism and Its Role in Immunity, a Comprehensive Review

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 326 ◽  
Author(s):  
Ali Mujtaba Shah ◽  
Zhisheng Wang ◽  
Jian Ma
Keyword(s):  
Amino Acid ◽  
Skeletal Muscles ◽  
Vital Role ◽  
The Body ◽  
Glutamine Metabolism ◽  
Glutamine Supplementation ◽  
Beneficial Effects ◽  
Glutamine Consumption

In the body of an animal, glutamine is a plentiful and very useful amino acid. Glutamine consumption in the body of animals in normal or disease conditions is the same or higher than the glucose. Many in vivo as well as in vitro experiments have been conducted to evaluate the importance of glutamine. Glutamine is a valuable nutrient for the proliferation of the lymphocytes. It also plays a crucial role in the production of cytokines, macrophages, phagocytic, and neutrophil to kill the bacteria. Most of the metabolic organs like the liver, gut, and skeletal muscles control the circulation and availability secretion of glutamine. In catabolic and hypercatabolic conditions, glutamine can turn out to be essential and plays a vital role in metabolism; however, availability may be compromised due to the impairment of homeostasis in the inter-tissue metabolism of amino acids. This is why the supplementation of glutamine is commonly used in clinical nutrition and is especially recommended to immune-suppressed persons. Despite this, in catabolic and hyper-catabolic conditions, it is challenging due to the amino acid concentration in plasma/bloodstream and glutamine should be provided via either the oral, enteral or parenteral route. However, the effect of glutamine as an immune-based supplement has been previously recognized as many research studies conducted in vivo and in-vitro evaluated the beneficial effects of glutamine. Hence, the present study delivers a combined review of glutamine metabolism in essential organs of the cell immune system. In this review, we have also reviewed the metabolism and action of glutamine and crucial problems due to glutamine supplementation in catabolic conditions.

scholarly journals Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation

2018 ◽  
Author(s):  
Vinicius Cruzat ◽  
Marcelo Macedo Rogero ◽  
Kevin Noel Keane ◽  
Rui Curi ◽  
Philip Newsholme
Keyword(s):  
Amino Acid ◽  
The Body ◽  
Glutamine Metabolism ◽  
In Vivo Studies ◽  
Glutamine Supplementation ◽  
Bacterial Killing ◽  
Nutrition Supplementation ◽  
Wide Range

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

scholarly journals Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1564 ◽  
Author(s):  
Vinicius Cruzat ◽  
Marcelo Macedo Rogero ◽  
Kevin Noel Keane ◽  
Rui Curi ◽  
Philip Newsholme
Keyword(s):  
Amino Acid ◽  
The Body ◽  
Glutamine Metabolism ◽  
In Vivo Studies ◽  
Glutamine Supplementation ◽  
Bacterial Killing ◽  
Nutrition Supplementation ◽  
Wide Range

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities, and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver, and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to the impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g., ill/critically ill, post-trauma, sepsis, exhausted athletes), it is currently difficult to determine whether glutamine supplementation (oral/enteral or parenteral) should be recommended based on the amino acid plasma/bloodstream concentration (also known as glutaminemia). Although the beneficial immune-based effects of glutamine supplementation are already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review of how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism and action, and important issues related to the effects of glutamine supplementation in catabolic situations.

Glutamine Metabolism in Skeletal Muscle of Glucocorticoid-Treated Rats

1990 ◽  
Vol 79 (2) ◽  
pp. 139-147 ◽  
Author(s):  
M. Salleh M. Ardawi ◽  
Yasir S. Jamal
Keyword(s):  
Skeletal Muscle ◽  
Exchange Rates ◽  
Skeletal Muscles ◽  
Plasma Concentrations ◽  
Maximal Activity ◽  
Glutamine Metabolism ◽  
Dexamethasone Treatment ◽  
Concentration Difference

1. The effect of dexamethasone (30 μg day−-1 100 g−-1 body weight) on the regulation of glutamine metabolism was studied in skeletal muscles of rats after 9 days of treatment. 2. Dexamethasone resulted in negative nitrogen balance, and produced increases in the plasma concentrations of alanine (23.4%) and insulin (158%) but a decrease in the plasma concentration of glutamine (28.7%). 3. Dexamethasone treatment increased the rate of glutamine production in muscle, skin and adipose tissue preparations, with muscle production accounting for over 90% of total glutamine produced by the hindlimb. 4. Blood flow and arteriovenous concentration difference measurements across the hindlimb showed an increase in the net exchange rates of glutamine (25.3%) and alanine (90.5%) in dexamethasone-treated rats compared with corresponding controls. 5. Dexamethasone treatment produced significant decreases in the concentrations of skeletal muscle glutamine (51.8%) and 2-oxoglutarate (50.8%). The concentrations of alanine (16.2%), pyruvate (45.9%), ammonia (43.3%) and inosine 5′-phosphate (141.8%) were increased. 6. The maximal activity of glutamine synthetase was increased (21–34%), but there was no change in that of glutaminase, in muscles of dexamethasone-treated rats. 7. It is concluded that glucocorticoid administration enhances the rates of release of both glutamine and alanine from skeletal muscle of rats (both in vitro and in vivo). This may be due to changes in efflux and/or increased intracellular formation of glutamine and alanine.

scholarly journals FSMP-18. COMPREHENSIVE METABOLIC PROFILING OF HIGH MYC MEDULLOBLASTOMA REVEALS KEY DIFFERENCES BETWEEN IN VITRO AND IN VIVO GLUCOSE AND GLUTAMINE USAGE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. i19-i19
Author(s):  
Khoa Pham ◽  
Brad Poore ◽  
Allison Hanaford ◽  
Micah J Maxwell ◽  
Heather Sweeney ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Amino Acid ◽  
Principal Component ◽  
Glutamine Metabolism ◽  
Metabolic Profiles ◽  
Normal Brain ◽  
Genomic Amplification ◽  
Nucleotide Synthesis

Abstract Reprograming of cellular metabolism is a hallmark of cancer. Altered metabolism can overcome unfavorable conditions, allowing cancer cells to proliferate and invade in different tumor microenvironments. Medulloblastoma is the most common malignant brain tumor of children. Genomic amplification of MYC is a hallmark of a subset of poor-prognosis medulloblastoma. However, the metabolism of high MYC amplified medulloblastoma subgroup remains underexplored. We performed comprehensive metabolic studies of human MYC-amplified medulloblastoma by comparing the metabolic profiles of tumor cells in different environments – in vitro, in flank xenografts and in orthotopic xenografts. Principal component analysis showed that the metabolic profiles of brain and flank high-MYC medulloblastoma tumors clustered closely together and separated away from normal brain and the high-MYC medulloblastoma cells in culture. Compared to normal brain, MYC-amplified medulloblastoma orthotopic brain tumor xenografts showed upregulation of nucleotide, amino acid and glutathione pathways. Glucose was the main carbon source for the nucleotide synthesis and the TCA cycle in vivo. The glutaminase ii pathway was the main pathway utilizing glutamine in MYC-amplified medulloblastoma. In brain and flank xenografts, glutathione was the most abundant upregulated metabolite. Glutamine derived glutathione was synthesized through glutamine transaminase K (GTK) enzyme in vivo. The glutamine analog 6-diazo-5-oxo-l-norleucine (DON) significantly inhibited glutathione, amino acid, and nucleotide synthesis. In conclusion, we found that MYC-amplified medulloblastoma relied on glutamine metabolism in synthesizing glutathione in vivo. Glutamine antagonists may have therapeutic applications in human patients.

Factors Controlling Movement of Skeletal Muscles

Leonardo ◽  
2015 ◽  
Vol 48 (3) ◽  
pp. 270-271
Author(s):  
Miranda D. Grounds
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Cell Membrane ◽  
Skeletal Muscles ◽  
Muscle Cells ◽  
The Body ◽  
Skeletal Muscle Cells ◽  
3 Dimensional

The contraction of specialized skeletal muscle cells results in classic movements of bones and other parts of the body that are vital for life. There is exquisite control over the movement of diverse types of muscles. This paper indicates the way in which skeletal muscles (myofibres) are formed; then factors that contribute to generating the movement are outlined: these include the nerve, sarcomeres, cytoskeleton, cell membrane and the extracellular matrix. The factors controlling the movement of mature myofibres in 3-dimensional tissues in vivo are vastly more complex than for tissue cultured immature muscle cells in an artificial in vitro environment.

Effect of LAT2 on glutamine-dependent mTOR activation to promote glycolysis and chemoresistance in pancreatic cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15759-e15759
Author(s):  
Jiangdong Qiu ◽  
Mengyu Feng ◽  
Zhe Cao ◽  
Gang Yang ◽  
Yueze Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Amino Acid ◽  
Cancer Cells ◽  
Amino Acid Transporter ◽  
Glutamine Metabolism ◽  
Clinical Value ◽  
Pancreatic Cancer Cells ◽  
Acid Transporter

e15759 Background: Reprogrammed energy metabolism has become the characteristic of cancer recently. Transporters act as amino acid sensors involved in mTOR recruitment and activation, which is crucial for the growth of both normal and tumor cells. L-type amino acid transporter 2 (LAT2), a Na+ -independent neutral amino acid transporter, is encoded by the SLC7A8 gene and responsible for transporting neutral amino acids, including a mTOR activator, glutamine. LAT2 was reported to be overexpressed in gemcitabine-resistant pancreatic cancer cells. However, the role of LAT2 in chemoresistance in pancreatic cancer remains unclear. Methods: The effects of LAT2 on biological behaviors of pancreatic cancer cells were analyzed. LAT2 and LDHB levels in tissues were detected, and the clinical value was evaluated. Results: We demonstrated that LAT2 played an oncogenic role and decreased the gemcitabine sensitivity of pancreatic cancer cells in vitro and in vivo. Survival analysis indicated that high expression of both LAT2 and LDHB was related to a poor prognosis in patients with pancreatic cancer. Furthermore, we found that LAT2 could promote proliferation, inhibit apoptosis, activate glycolysis and alter glutamine metabolism to activate mTOR in vitro and in vivo. Next, the combination of gemcitabine with an mTOR inhibitor (RAD001) could reverse the decrease in chemosensitivity caused by LAT2 overexpression in pancreatic cancer cells. Mechanistically, LAT2 promoted glycolysis and decreased gemcitabine sensitivity via regulating two glutamine-dependent positive feedback loops (the LAT2/p-mTORSer2448 loop and the glutamine/p-mTORSer2448/glutamine synthetase loop) in pancreatic cancer. Conclusions: Our data indicates that LAT2 functions as an oncogenic protein and could regulate glutamine-dependent mTOR activation to promote glycolysis and decrease gemcitabine sensitivity in pancreatic cancer. The LAT2-mTOR-LDHB pathway might be a promising therapeutic target in pancreatic cancer.

scholarly journals Plants and Diabetes: Description, Role, Comprehension and Exploitation

2021 ◽  
Vol 22 (8) ◽  
pp. 3938
Author(s):  
Alessandra Durazzo ◽  
Massimo Lucarini ◽  
Antonello Santini
Keyword(s):  
Chronic Diseases ◽  
Diabetes Management ◽  
The Body ◽  
In Vivo Studies ◽  
Beneficial Effects ◽  
Treatment Of Diabetes ◽  
Main Components

Many plants have been known for centuries to have medicinal importance with potential beneficial effects on health. Phytotherapeutic compounds are well known to play a globally significant role, in particular in the management and treatment of various chronic diseases. Among these, diabetes can cause long term damage to the body other than having a relevant economic burden on society being among the costliest chronic diseases. This motivated the focus of the proposed Special Issue, intended to develop and exploit the potential role of plants in the management and treatment of diabetes. The main topics included are: (i) description and use of medicinal plants for diabetes management; (ii) the elucidation and delineation of their main components, properties (anti-hyperglycaemic, hypoglicaemic, anti-infiammatory, apoptotic agents, etc.), (iii) the mechanism of action (in vitro and in vivo studies); (iv) formulation of nutraceuticals, botanicals, and dietary supplements useful as tools as an alternative or support to anti-diabetic pharmacological therapies; (v) development of new markers.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Репрограммированые in vitro на М3 фенотип макрофаги останавливают рост солидной карциномы in vivo

2018 ◽  
pp. 41-46
Author(s):  
А.А. Раецкая ◽  
С.В. Калиш ◽  
С.В. Лямина ◽  
Е.В. Малышева ◽  
О.П. Буданова ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Antitumor Effect ◽  
Tumor Development ◽  
Significant Inhibition ◽  
The Body ◽  
Ehrlich Carcinoma ◽  
Solid Carcinoma ◽  
Ec Cells

Цель исследования. Доказательство гипотезы, что репрограммированные in vitro на М3 фенотип макрофаги при введении в организм будут существенно ограничивать развитие солидной карциномы in vivo . Методика. Рост солидной опухоли инициировали у мышей in vivo путем подкожной инъекции клеток карциномы Эрлиха (КЭ). Инъекцию макрофагов с нативным М0 фенотипом и с репрограммированным M3 фенотипом проводили в область формирования солидной КЭ. Репрограммирование проводили с помощью низких доз сыворотки, блокаторов факторов транскрипции STAT3/6 и SMAD3 и липополисахарида. Использовали две схемы введения макрофагов: раннее и позднее. При раннем введении макрофаги вводили на 1-е, 5-е, 10-е и 15-е сут. после инъекции клеток КЭ путем обкалывания макрофагами с четырех сторон область развития опухоли. При позднем введении, макрофаги вводили на 10-е, 15-е, 20-е и 25-е сут. Через 15 и 30 сут. после введения клеток КЭ солидную опухоль иссекали и измеряли ее объем. Эффект введения макрофагов оценивали качественно по визуальной и пальпаторной характеристикам солидной опухоли и количественно по изменению ее объема по сравнению с группой без введения макрофагов (контроль). Результаты. Установлено, что M3 макрофаги при раннем введении от начала развития опухоли оказывают выраженный антиопухолевый эффект in vivo , который был существенно более выражен, чем при позднем введении макрофагов. Заключение. Установлено, что введение репрограммированных макрофагов M3 ограничивает развитие солидной карциномы в экспериментах in vivo . Противоопухолевый эффект более выражен при раннем введении М3 макрофагов. Обнаруженные в работе факты делают перспективным разработку клинической версии биотехнологии ограничения роста опухоли, путем предварительного программирования антиопухолевого врожденного иммунного ответа «в пробирке». Aim. To verify a hypothesis that macrophages reprogrammed in vitro to the M3 phenotype and injected into the body substantially restrict the development of solid carcinoma in vivo . Methods. Growth of a solid tumor was initiated in mice in vivo with a subcutaneous injection of Ehrlich carcinoma (EC) cells. Macrophages with a native M0 phenotype or reprogrammed towards the M3 phenotype were injected into the region of developing solid EC. Reprogramming was performed using low doses of serum, STAT3/6 and SMAD3 transcription factor blockers, and lipopolysaccharide. Two schemes of macrophage administration were used: early and late. With the early administration, macrophages were injected on days 1, 5, 10, and 15 following the injection of EC cells at four sides of the tumor development area. With the late administration, macrophages were injected on days 10, 15, 20, and 25. At 15 and 30 days after the EC cell injection, the solid tumor was excised and its volume was measured. The effect of macrophage administration was assessed both qualitatively by visual and palpation characteristics of solid tumor and quantitatively by changes in the tumor volume compared with the group without the macrophage treatment. Results. M3 macrophages administered early after the onset of tumor development exerted a pronounced antitumor effect in vivo , which was significantly greater than the antitumor effect of the late administration of M3 macrophages. Conclusion. The observed significant inhibition of in vivo growth of solid carcinoma by M3 macrophages makes promising the development of a clinical version of the biotechnology for restriction of tumor growth by in vitro pre-programming of the antitumor, innate immune response.

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