Biomedical subjects

C P Fischer

Publications and source records attributed to C P Fischer.

At least 19 recordsLinked to original sources

PubMed2007

Plasma levels of interleukin-6 and C-reactive protein are associated with physical inactivity independent of obesity.

It is recognized that the path from physical inactivity and obesity to lifestyle-related diseases involves low-grade inflammation, indicated by elevated plasma levels of inflammatory markers. Interestingly, contracting skeletal muscle is a major source of circulating interleukin-6 (IL-6) in response to acute exercise, but with a markedly lower response in trained subjects. As C-reactive protein (CRP) is induced by IL-6, we hypothesized that basal levels of IL-6 and CRP reflect the degree of regular physical activity when compared with other markers of inflammation associated with lifestyle-related morbidity. Fasting plasma/serum levels of IL-6, IL-18, CRP, tumur necrosis factor-alpha (TNF-alpha), soluble TNF receptor II (sTNF-RII), and adiponectin were measured in healthy non-diabetic men and women (n=84). The amount of leisure-time physical activity (LTPA) was assessed by interview. Obesity was associated with elevated insulin, C-peptide, triglycerides, low-density lipoprotein, IL-6, CRP, and adiponectin (all P<0.05). Importantly, physical inactivity was associated with elevated C-peptide (P=0.036), IL-6 (P=0.014), and CRP (P=0.007) independent of obesity, age, gender, and smoking. Furthermore, the LTPA score was inversely associated with IL-6 (P=0.017) and CRP (P=0.005), but with neither of the other markers. The results indicate that low levels of IL-6 and CRP - not IL-18, TNF-alpha, sTNF-RII, or adiponectin - reflect regular physical activity.

Adiponectin↗

PubMed2006

Brain-derived neurotrophic factor (BDNF) and type 2 diabetes.

AIMS/HYPOTHESIS: Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of Alzheimer's disease and depression. These disorders are associated with type 2 diabetes, and animal models suggest that BDNF plays a role in insulin resistance. We therefore explored whether BDNF plays a role in human glucose metabolism. SUBJECTS AND METHODS: We included (Study 1) 233 humans divided into four groups depending on presence or absence of type 2 diabetes and presence or absence of obesity; and (Study 2) seven healthy volunteers who underwent both a hyperglycaemic and a hyperinsulinaemic-euglycaemic clamp. RESULTS: Plasma levels of BDNF in Study 1 were decreased in humans with type 2 diabetes independently of obesity. Plasma BDNF was inversely associated with fasting plasma glucose, but not with insulin. No association was found between the BDNF G196A (Val66Met) polymorphism and diabetes or obesity. In Study 2 an output of BDNF from the human brain was detected at basal conditions. This output was inhibited when blood glucose levels were elevated. In contrast, when plasma insulin was increased while maintaining normal blood glucose, the cerebral output of BDNF was not inhibited, indicating that high levels of glucose, but not insulin, inhibit the output of BDNF from the human brain. CONCLUSIONS/INTERPRETATION: Low levels of BDNF accompany impaired glucose metabolism. Decreased BDNF may be a pathogenetic factor involved not only in dementia and depression, but also in type 2 diabetes, potentially explaining the clustering of these conditions in epidemiological studies.

Adult↗

PubMed2005

Recombinant human interleukin-6 infusion during low-intensity exercise does not enhance whole body lipolysis or fat oxidation in humans.

The present study examined the role of the cytokine IL-6 in the regulation of fatty acid metabolism during exercise in humans. Six well-trained males completed three trials of 120 min of cycle ergometry at 70% peak O(2) consumption (Vo(2 peak); MOD) and 40% Vo(2 peak) with (LOW + IL-6) and without (LOW) infusion of recombinant human (rh)IL-6. The dose of rhIL-6 during LOW + IL-6 elicited IL-6 concentration similar to those during MOD but without altering the circulating hormonal milieu seen in MOD. Palmitate rate of appearance (R(a)), rate of disappearance (R(d)), and oxidation were measured by means of a constant infusion of [U-(13)C]palmitate (0.015 micromol.kg(-1).min(-1), prime NaHCO(3), 1 micromol/kg). Palmitate R(a), R(d), and oxidation were not affected by rhIL-6 infusion, remaining similar to LOW at all times. Palmitate R(a) and oxidation were significantly greater in the MOD trial (P < 0.05) compared with the LOW + IL-6 and LOW trials. Our data show that a low dose of rhIL-6, administered during low-intensity exercise without altering the hormonal milieu, does not alter fatty acid metabolism. These data suggest that the increase in fatty acid utilization seen during exercise at moderate compared with low intensity is not mediated via alterations in plasma IL-6.

Adult↗

PubMed2005

Interleukin-6 infusion during human endotoxaemia inhibits in vitro release of the urokinase receptor from peripheral blood mononuclear cells.

Leucocyte expression of the urokinase receptor [urokinase-type plasminogen activator receptor (uPAR)] is regulated by inflammatory mediators. This study investigated the in vivo effect of endotoxin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha on uPAR-release in vivo and in vitro in humans. Healthy subjects received intravenous endotoxin injection [high-dose, 2 ng/kg (n=8) and low-dose, 0.06 ng/kg (n=7)], coadministration of 0.06 ng/kg endotoxin and 3 h recombinant human (rh)IL-6 infusion (n=7) or 3 h infusion of rhIL-6 (n=6), rhTNF-alpha (n=6) or NaCl (n=5). Soluble uPAR (suPAR) was measured by enzyme-linked immunosorbent assay in plasma and supernatants from unstimulated and phytohaemagglutinin and lipopolysaccharide-stimulated peripheral blood mononuclear cell (PBMC) cultures incubated for 24 h. The spontaneous and stimulated uPAR-release from PBMC cultures was enhanced 5 h after low-dose endotoxin (both P <0.05), but coadministration of rhIL-6 during low-dose endotoxaemia abolished this enhanced uPAR release. High-dose endotoxin increased plasma suPAR levels (P <0.001) whereas low-dose endotoxin, rhIL-6 or TNF-alpha did not influence uPAR release in vivo to such degree that a systemic effect on the plasma suPAR level was detectable. Even subclinical doses of endotoxin in vivo enhance the capacity of PBMC to release uPAR after incubation in vitro. The inhibitory effect of IL-6 on endotoxin-mediated uPAR-release in vitro suggests that IL-6 has anti-inflammatory effects on endotoxin-mediated inflammation.

Adult↗

PubMed2003

Vascular endothelial growth factor mRNA expression and arteriovenous balance in response to prolonged, submaximal exercise in humans.

Angiogenesis, the growth of new blood vessels from existing ones, occurs in the skeletal muscle as an adaptive response to exercise that satisfies the increased requirement of this tissue for oxygen delivery and metabolic processes. Of the factors that have been identified to regulate this process, the endothelial cell mitogen vascular endothelial growth factor (VEGF) has been proposed to play a key role. The aim of this study was to measure the skeletal muscle VEGF mRNA content and arteriovenous protein balance across the working leg in response to a single bout of prolonged, submaximal exercise. Seven physically active males completed 3 h of two-legged kicking ergometry. Muscle biopsies were collected from the vastus lateralis muscle from both working legs, and blood samples were collected from one femoral artery and femoral vein before, during, and in recovery from exercise. We show that the exercise stimulus elicited a decrease in VEGF protein arteriovenous balance across the exercising leg (P = 0.007), and a ninefold elevation in skeletal muscle VEGF mRNA expression (P < 0.001). The changes in VEGF protein balance and mRNA content were most pronounced 1 h after the cessation of exercise. In conclusion, these findings demonstrate that submaximal exercise, suitable for humans with low CV fitness, induces a decrease in VEGF arteriovenous balance that is likely to be of clinical significance in promoting angiogenic effects.

Adult↗

PubMed2002

Laparoscopic appendectomy: indications and controversies.

The introduction of laparoscopic appendectomy has been more controversial than that of laparoscopic cholecystectomy. Randomized trials have been performed, as well as meta-analysis, with equivocal results regarding effectiveness. The further expansion of the technique for interval appendectomy and in cases of complicated appendicitis has introduced new controversies and success stories. We hope to review the current application of laparoscopic appendectomy in adults based on the available literature and discuss some current controversies.

Adult↗

PubMed2002

Laparoscopic approach to small bowel obstruction.

Historically, laparotomy and open adhesiolysis have been the treatment of choice for patients requiring surgery with small bowel obstruction (SBO), although laparotomy itself is an independent risk factor for bowel obstruction. Laparoscopy is known to create fewer intra-abdominal adhesions than open laparotomy. The observation that many patients with SBO have isolated adhesive bands has led to the use of laparoscopy as primary treatment of SBO by some authors. Although the laparoscopic approach to SBO has been described, the outcomes and indications are not well established. We will review the available literature regarding the laparoscopic approach to SBO. Additionally, we will describe the technique and make recommendations regarding which patients may be best suited for a trial of laparoscopy for adhesiolysis.

Humans↗

PubMed2000

Tumor-influenced amino acid transport activities in zonal-enriched hepatocyte populations.

Cancer influences hepatic amino acid metabolism in the host. To further investigate this relationship, the effects of an implanted fibrosarcoma on specific amino acid transport activities were measured in periportal (PP)- and perivenous (PV)-enriched rat hepatocyte populations. Na(+)-dependent glutamate transport rates were eightfold higher in PV than in PP preparations but were relatively unaffected during tumor growth. System N-mediated glutamine uptake was 75% higher in PV than in PP preparations and was stimulated up to twofold in both regions by tumor burdens of 9 +/- 4% of carcass weight compared with hepatocytes from pair-fed control animals. Excessive tumor burdens (26 +/- 7%) resulted in hypophagia, loss of PV-enriched system N activities, and reduced transporter stimulation. Conversely, saturable arginine uptake was enhanced fourfold in PP preparations and was induced twofold only after excessive tumor burden. These data suggest that hepatic amino acid transporters are differentially influenced by cancer in a spatial and temporal manner, and they represent the first report of reciprocal zonal enrichment of system N and saturable arginine uptake in the mammalian liver.

Amino Acids↗

PubMed1999

Preferential loss of large neocortical neurons during HIV infection: a study of the size distribution of neocortical neurons in the human brain.

The infection with human immunodeficiency virus (HIV) is associated with a global and severe loss of neocortical neurons. However, there is limited knowledge concerning whether all neurons are equally susceptible to damage during HIV infection. Other studies have reported low vulnerability of small interneurons and high vulnerability of large motor neurons. Thus, it is natural to suggest that HIV infection, which causes damage to neurons in several ways, may predominantly affect large neurons in the neocortex. In this study we have used three unbiased stereological probes: Cavalieri's principle, the optical dissector and the rotator method, to obtain both total neocortical neuron number and their size distribution in formalin-fixed brains from six male acquired immunodeficiency syndrome (AIDS) patients and six male controls. The material is a selection of a large material choosing the youngest. The number of neurons in neocortex was reduced by 25% from 24.4 x 10(9) in controls to 18.3 x 10(9) in the AIDS patients; the reduction is similar to that of 27% found in the large material. In the normal size distribution of the neocortical neurons most neurons were smaller than 5000 micron3 and no sampled neurons were larger than 28,000 micron3. In addition, the absolute size distribution of neocortical neurons showed a significant decrease of the largest group of neurons by 50% (2p = 0.01) in the AIDS group, while there was no significant difference between controls and AIDS patients in the number of small neurons. The pattern of reduction in the number of large neocortical neurons was found in frontal, temporal, parietal as well as in occipital regions. This suggests that large neurons are more sensitive than small neurons to the destruction caused by the HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Effects of endotoxin challenge on hepatic amino acid transport during cancer.

BACKGROUND: The hepatic uptake of amino acids is increased in both sepsis and cancer, and this response appears to be both global and essential in the catabolic host. Because immunocompromised cancer patients are susceptible to episodes of gram-negative sepsis, we examined the capacity of hepatocytes from normal and tumor-influenced livers to respond to the additional challenge of endotoxemia via increases in the Na+-dependent uptake of glutamine and zwitterionic amino acids by System N and System A, respectively. MATERIALS AND METHODS: Fischer 344 rats were implanted with methylcholanthrene-induced fibrosarcomas. Control rats were sham-operated and pair-fed. Animal pairs (tumor burden = 8-32% carcass weight) were injected intraperitoneally with either Escherichia coli endotoxin (10 mg/kg) or PBS, and after 4 h, hepatocytes were isolated from the livers of the animals via collagenase perfusion and placed in primary culture. Three hours later, amino acid transport rates were measured using radiolabeled glutamine for System N and alpha-methylaminoisobutyric acid (MeAIB), a nonmetabolizable substrate specific for System A. RESULTS: Cancer-independent of tumor size-and endotoxin each elicited similar 1.5- to 2-fold inductions of System N activity. When combined, their effects were additive rather than synergistic. In contrast, endotoxin induced an insignificant increase in System A activity, whereas cancer stimulated this carrier 2-fold in either the absence or the presence of endotoxin. CONCLUSIONS: The primary glutamine and alanine carriers in hepatocytes are differentially influenced during catabolic states, and the tumor-influenced liver is competent to further increase glutamine uptake in response to additional catabolic insults.

Amino Acids↗

PubMed1998

Adaptive alterations in cellular metabolism with malignant transformation.

OBJECTIVE: The authors studied the differences between glutamine and glucose utilization in normal fibroblasts and in fibrosarcoma cells to gain insights into the metabolic changes that may occur during malignant transformation. SUMMARY BACKGROUND DATA: The process of malignant transformation requires that cells acquire and use nutrients efficiently for energy, protein synthesis, and cell division. The two major sources of energy for cancer cells are glucose and glutamine. Glutamine is also essential for protein and DNA biosynthesis. We studied glucose and glutamine metabolism in normal and malignant fibroblasts. METHODS: Studies were done in normal rat kidney fibroblasts and in rat fibrosarcoma cells. We measured glutamine transport across the cell membrane, breakdown of glutamine by the enzyme glutaminase (the first step in oxidation), glutamine and glucose oxidation rates to CO2, rates of protein synthesis from glutamine, and glutamine-dependent growth rates. RESULTS: Glutamine transport rates were increased more than sixfold in fibrosarcomas compared to normal fibroblasts. In fibroblasts, glutamine transport was mediated by systems ASC and A. In malignant fibrosarcomas, only system ASC was identifiable, and its Vmax was 15 times higher than that observed in fibroblasts. Despite an increase in transport, glutaminase activity was diminished and glutamine oxidation to CO2 was reduced in fibrosarcomas versus normal fibroblasts. In fibroblasts, glutamine oxidation was 1.8 times higher than glucose oxidation. In contrast, glucose oxidation was 3.5 times greater than glutamine oxidation in fibrosarcomas. Protein synthesis from glutamine transported by fibrosarcomas was threefold greater than that observed in normal fibroblasts. Despite marked increases in glutamine utilization and glucose oxidation in fibrosarcoma cells, growth rates were higher in the normal fibroblasts. CONCLUSIONS: The process of malignant transformation is associated with a marked increase in cellular glutamine transport, which is mediated by a single high-affinity, high-capacity plasma membrane carrier protein. In normal fibroblasts, the transported glutamine is used primarily for energy production via oxidation of glutamine carbons to CO2. In fibrosarcomas, glutamine oxidation falls and glutamine is shunted into protein synthesis; simultaneously, the malignant cell switches to a glucose oxidizer. The increased glutamine transport and glucose oxidation in fibrosarcomas appears to be related to the malignant phenotype and not merely to an increase in cell growth rates.

Adaptation, Physiological↗

PubMed1997

Alterations in oxidative metabolism and glutamine transport support glucose production in the tumor-influenced hepatocyte.

Glutamine is the primary substrate whose hepatic transport is upregulated in the tumor-bearing host; however, the subsequent metabolism of transported glutamine is currently unknown. The purpose of this study was to determine if glutamine is an important oxidative fuel source for hepatocytes in cancer. Specifically we compare rates of glutamine transport and oxidation in hepatocytes from control and tumor-bearing animals. We also compare rates of glucose oxidation and rates of glucose production from glutamine in control hepatocytes versus those from tumor-bearing animals. Hepatocytes from rats bearing the MCA fibrosarcoma were isolated when tumors comprised 5 and 15% of total body weight and compared to sham-implanted and pair-fed control animals. [3H]GLN transport, GLN and glucose oxidation to CO2, and glucose production from glutamine were assayed. Tumor burden of 5% stimulated a 2.52-fold increase in hepatocyte glutamine transport and a 2-fold increase when tumor burden reached 15%. Rates of oxidation of glutamine were suppressed by 1.5-fold when tumors comprised 5% of body weight compared to sham animals and were equivalent to sham animals when tumors comprised 15% of body weight. Significant alterations in glucose oxidation were observed when tumors were both small and large-glucose oxidation was suppressed by 3.6- and 3.7-fold when tumors comprised 5 and 15% of body weight respectively compared to sham-implanted rats. Incubation of hepatocytes from tumor-bearing animals with glutamine as a gluconeogenic substrate induced a 1.84-fold increase in glucose production compared to sham hepatocytes. In conclusion, (i) despite a doubling of GLN transport by the tumor-influenced hepatocyte, GLN oxidation by hepatocytes was not increased. (ii) Glucose oxidation by hepatocytes from tumor-bearing animals was decreased compared to sham hepatocytes and, simultaneously, glucose production by tumor-influenced hepatocytes from glutamine was increased. The augmentation of hepatic glutamine transport and decreased glutamine oxidation seen in tumor-influenced hepatocytes appear to support hepatocyte gluconeogenesis from glutamine.

Animals↗

PubMed1997

Characterization of glutamine and glutamate transport in rat lung plasma membrane vesicles.

Insufficient glutamine for the lungs during sepsis may contribute to an impairment in lung function. Lung glutamine metabolism is supported by both blood glutamine uptake and de novo biosynthesis using circulating glutamate as a precursor. Information regarding the specific plasma membrane carriers involved in this uptake is lacking. Furthermore, the effect of sepsis on amino acid transport in whole lung has not been studied. We isolated lung plasma membrane vesicles (LPMVs) from control and LPS-treated rats and assayed glutamine and glutamate transport activity in LPMVs. Vesicle purity and functionality were confirmed by time-dependent concentrative amino acid uptake in the presence of Na+, impoverishment of microsomal enzymes, and a 25-fold enrichment in the plasma membrane marker 5'-nucleotidase. Eighty percent of glutamine uptake in lung vesicles was mediated via the high affinity Na(+)-dependent carrier System ASC (Vmax = 80 +/- 10 pmole/mg protein/15 sec; Km = 224 +/- 30 microM) while 19% occurred via the Na(+)-independent System ASC (Vmax = 11 +/- 2 pmole/mg/15 sec; Km = 141 +/- 23 microM). Ninety percent of glutamate transport was mediated by the Na(+)-independent System XAG-. Treatment of rats with LPS resulted in a decrease in both glutamine and glutamate transport in LPMVs. LPMVs offer a novel method for characterizing lung amino acid transport and studying the effects of catabolic states on this activity. The effects of endotoxin on System ASC and XAG- activity may contribute to reduced lung glutamine availability during septic states which may impair cellular metabolism and function.

5'-Nucleotidase↗

PubMed1996

Glucocorticoid-dependent induction of interleukin-6 receptor expression in human hepatocytes facilitates interleukin-6 stimulation of amino acid transport.

OBJECTIVE: The authors studied the effects of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on glutamine and alanine transport in isolated human hepatocytes. They also evaluated the role of dexamethasone in modulating this response and its effects on the expression of the plasma membrane high-affinity IL-6 receptor. SUMMARY BACKGROUND DATA: Animal studies indicate that cytokines are important mediators of the increased hepatic amino acid uptake that occurs during cancer and sepsis, but studies in human tissues are lacking. The control of transport by cytokines and cytokine receptor expression in the liver may provide a mechanism by which hepatocytes can modulate amino acid availability during catabolic disease states. METHODS: Human hepatocytes were isolated from wedge biopsy specimens and plated in 24-well trays. Interleukin-6 and TNF-alpha, in combination with the synthetic glucocorticoid dexamethasone, were added to hepatocytes in culture, and the transport of radiolabeled glutamine and alanine was measured. Fluorescent-activated cell sorter (FACS) analysis was used to study the effects of dexamethasone on IL-6 receptor number in the well-differentiated human hepatoma HepG2. RESULTS: Both IL-6 and TNF-alpha exerted a small stimulatory effect on alanine and glutamine transport. Dexamethasone alone did not alter transport rates, but pretreatment of cells augmented the effects of both cytokines on carrier-mediated amino acid uptake. Dexamethasone pretreatment and a combination of IL-6 and TNF-alpha resulted in a greater than twofold increase in transport activity. Fluorescent-activated cell sorter analysis demonstrated that dexamethasone induced a threefold increase in the expression of high-affinity IL-6 receptors. CONCLUSIONS: Interleukin-6 and TNF-alpha work coordinately with glucocorticoids to stimulate amino acid uptake in human hepatocytes. Dexamethasone exerts a permissive effect on cytokine-mediated increases in transport by increasing IL-6 receptor expression on the cell surface. It is likely that this upregulation of IL-6 receptors "primes" human liver cells for subsequent stimulation by cytokines. The resulting increase in hepatic amino acid transport provides the liver with substrate to support key metabolic pathways during catabolic states.

Amino Acids↗

PubMed1996

A sarcoma-derived protein regulates hepatocyte metabolism via autocrine production of tumor necrosis factor-alpha.

OBJECTIVE: The effects of conditioned media from the methylcholanthrene (MCA) fibrosarcoma on hepatocyte albumin production and amino acid transport were studied. The authors characterized a factor responsible for the observed effects and investigated the role of tumor necrosis factor-alpha (TNF-alpha) in these events. SUMMARY BACKGROUND DATA: Cancer cachexia is mediated in part by TNF-alpha. However, few tumors secrete TNF-alpha, implicating host production of this cytokine in response to as yet uncharacterized tumor-derived factors. Autocrine production of TNF-alpha recently has been described as a potent mechanism for orchestrating hepatic metabolism. METHODS: Conditioned media from the MCA fibrosarcoma was incubated with isolated primary rat hepatocytes. Albumin production and TNF-alpha production by hepatocytes was measured by enzyme-linked immunosorbent assay and amino acid transport assayed by tritium (3H)-labeled amino acid uptake. Dialysis membranes ranging from 3 kD to 100 kD were used to determine the size of the factor/factors responsible for the observed effects. RESULTS: Conditioned media from the MCA fibrosarcoma contained no TNF-alpha, whereas treatment of primary rat hepatocytes with the conditioned media resulted in a 53-fold increase in TNF-alpha production by hepatocytes compared with control. Treatment of hepatocytes with MCA fibrosarcoma-conditioned media resulted in decreases in hepatic albumin production of 46%, 61%, and 42% over 3 days of treatment, and these effects were reversible by the addition of antibody to TNF-alpha. Treatment of hepatocytes with MCA fibrosarcoma conditioned media resulted in increases in hepatocyte amino acid transport via inductions of System N (1.87 fold) and System A (1.93 fold). These effects were partially abrogated by the addition of antibody to TNF-alpha. Dialysis experiments determined the molecular weight of the factor or factors responsible for the observed effects to be greater than 100 kD. The effects of the MCA fibrosarcoma conditioned media were abolished by both trypsin treatment and heat inactivation, indicating the protein nature of the factor being studied. CONCLUSIONS: A tumor-derived protein has been isolated from the MCA fibrosarcoma. The protein inhibits hepatocyte albumin production and increases amino acid transport in vitro via the autocrine production of TNF-alpha.

Albumins↗

PubMed1996

Starvation and endotoxin act independently and synergistically to coordinate hepatic glutamine transport.

OBJECTIVE: Because hepatic glutamine transport is markedly enhanced during critical illness, we tested the hypothesis that nutrient starvation and endotoxemia act coordinately to augment transport activity. DESIGN: Fed or starved (48 hours) rats received Escherichia coli endotoxin (LPS, 10 mg/kg of body weight, intraperitoneally) or saline before hepatocyte isolation for measurement of glutamine transport. MATERIALS AND METHODS: Hepatocytes were isolated from fed or fasted rats 4 hours after LPS treatment. [3H]glutamine uptake was measured and normalized to cellular protein. Data (mean +/- standard deviation, three separate determinations) were analyzed by Student's t test and analysis of variance. MAIN RESULTS: Starvation induced a 1.6-fold increase in glutamine transport, while LPS treatment of fed rats increased transport activity 2.6-fold. Treatment of fasted animals with LPS induced a sixfold increase in glutamine transport. Kinetically, this effect in endotoxemic starved rats was mediated by both an increase in System N Vmax and the induction of a high affinity System A amino acid carrier which transports glutamine. CONCLUSIONS: Starvation and endotoxemia regulate hepatocyte glutamine transport independently and synergistically. This hepatic response provides glutamine and other amino acids to support key metabolic pathways in the liver during critical illness.

Amino Acids↗

PubMed1995

Amino acid metabolism and the vascular endothelium: regulation and disease implications.

Amino acid metabolism by the vascular endothelium is a complex process that often begins with the carrier-mediated uptake of circulating amino acids into the endothelial cytoplasm. Amino acids are essential for maintaining intact endothelial functions, which include cell proliferation, regulation of blood flow and vascular tone, coagulation and fibrinolysis, and metabolism of a variety of macromolecules. The disturbances in endothelial amino acid transport and metabolism that occur during infection and inflammation are due, in part, to changes in substrate availability and to the local and/or systemic elaboration of specific mediators. An improved understanding of endothelial amino acid metabolism will not only provide new knowledge regarding disease mechanisms and regulation, but may also lead to new treatment strategies that may include the clinical use of specific nutritional formulas.

Amino Acid Sequence↗

PubMed1995

Hepatic uptake of glutamine and other amino acids during infection and inflammation.

Catabolic illness such as sepsis and injury induce profound changes in host amino acid metabolism, including increased hepatic amino acid uptake. Because many amino acid-dependent pathways such as gluconeogenesis and acute-phase protein synthesis are activated in the liver during severe infection, this review will focus on the control of hepatic plasma membrane amino acid transport by specific inflammatory mediators. We specifically review the role of cytokines, eicosanoids, and glucorticoids in this response. Collectively, these signaling molecules act in a concerted manner to exert local control of hepatic function including the stimulation of amino acid transport. In particular, we review the role of glutamine and its transport in the liver, as it occupies a unique role in interorgan ammonia metabolism during critical illness.

Acute-Phase Reaction↗