Increased Expression Of Glucose Transporters Research Articles

Brain targeted peptide-functionalized chitosan nanoparticles for resveratrol delivery: Impact on insulin resistance and gut microbiota in obesity-related Alzheimer's disease

The pathology of Alzheimer's disease (AD) is highly correlated with obesity-induced insulin resistance. Resveratrol (Res) is a natural phenol that demonstrates a neuroprotective effect, but the bioactivity of Res is low in vivo. Here, chitosan (CS) was cross-linked with sodium tripolyphosphate (TPP) to encapsulate low water solubility Res. Next, a brain-targeted peptide (TG: TGNYKALHPHNG) was modified on the surface of Res-loaded CS/TPP nanoparticles (TG-Res-CS/TPP-NPs) to specifically deliver Res to the brain. Morris water maze results indicated that cognitive impairments were ameliorated by TG-Res-CS/TPP-NPs in obesity-related AD mice. Obesity-related insulin resistance promotes Tau phosphorylation and Aβ aggregation in the brain. Administration of TG-Res-CS/TPP-NPs alleviated lipid deposition-induced insulin resistance and decreased the level of phosphorylated Tau and Aβ aggregation via the JNK/AKT/GSK3β pathway. Additionally, TG-Res-CS/TPP-NPs transported across blood-brain barrier which in turn increased glucose transporter expression levels, antioxidant enzyme activity and inhibited microglial cell activation. Thus, TG-Res-CS/TPP-NPs were more effective than Res-CS/TPP-NPs at regulating glucose homeostasis, oxidative stress and neuroinflammation in the brain. Moreover, inflammatory, lipid metabolism and oxidative stress-related gut microbiota including Helicobacter, Colidextribacter, Anaerotruncus, Parasutterella, Allobaculum, Alloprevotella, Alistipes, Bifidobacterium and Candidatus_Saccharimonas were also regulated by TG-Res-CS/TPP-NPs. This work indicates the potential use of TG-Res-CS/TPP-NPs for the delivery of Res.

DDDR-18. COMPREHENSIVE PROTEOMIC PROFILING OF BRAFV600E GLIOMA CELLS SHOWS UPREGULATION OF GLYCOLYSIS AND TCA CYCLE PROTEINS AFTER COMBINED MTOR AND MAP KINASE PATHWAY BLOCKADE

Abstract Low-grade gliomas (LGG) are slow-growing tumors that affect neurologic function by pressing on the surrounding parts of the brain. Pediatric low-grade glioma (pLGG) is the most common childhood brain tumors. Patients with pLGG often have a significant life-long disabilities. The most common mutations in pLGG are in the mitogen-activated protein kinase (MAPK) pathway including tumor suppressor neurofibromin (NF1), and the oncogene BRAF. BRAF activates MEK1/2, which activates of ERK1/2, leading to tumorigenesis. BRAFV600E mutation results in the activation segment of the kinase “monomeric form of BRAF”, leading to constitutive activation of MAP kinase and mTOR pathways Combination treatment of TAK228 (mTOR inhibitor) and trametinib (MEK1/2 inhibitor), suppressed both mTOR and MAP kinase pathways and inhibited BRAFV600E glioma tumor growth. To further investigate and understand the molecular mechanism of TAK228 and trametinib combinatorial efficacy, we performed comprehensive proteomic analysis of BRAFV600E glioma tumors treated with TAK228 and trametinib. We found increased levels of many proteins in the glycolysis and TCA cycle. Specifically we found increases at the protein level in citrate synthase, aconitase and malate dehydrogenase in the TCA cycle. In glycolysis, we observed increased glucose transporter expression (SLC2A1), increased hexokinase 2, and increased GAPDH. Upregualtion of these proteins may represent attempts to bypass the effects of mTOR and MAP kinase blockade on the activity of these pathways. We are currently performing flux metabolic profiling using uniformly labeled glucose to assess the activity of the pathways after combined mTOR and MAP kinase blockade. Our results may increase our understanding of how glioma cells use glucose and how mTOR and MAP kinase pathway inhibition affects basic metabolic pathways in glioma cells.

Development of Functional Fermented Dairy Products Containing Taiwan Djulis (Chenopodium formosanum Koidz.) in Regulating Glucose Utilization

Taiwan djulis (Chenopodium formosanum Koidz.) is a plant native to Taiwan and is a grain rich in nutrients, vitamins, and minerals with antioxidant properties. This paper aimed to use appropriate processing technology and incorporate probiotics, thus combining Taiwan’s high-quality milk sources to develop Taiwan djulis fermented dairy products. Later, FL83B cells have used to evaluate the glucose utilization ability after the administration of djulis. We first screened Lactiplantibacillus plantarum and combined it with the traditional yogurt strains Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus for cultivation. Further, the fermentation process was optimized where 7.5% djulis and an inoculum of 107 colony forming unit/mL were fermented at 40 °C for 18 h. Compared to fermented milk without djulis, the analysis of various nutrients and active ingredients showed that free radical scavenging abilities of DPPH and ABTS reached 2.3 and 2.0 times (752.35 ± 29.29 µg and 771.52 ± 3.79 µg TE/g, respectively). The free phenol content increased 2.5 times (169.90 ± 14.59 mg gallic acid/g); the total flavonoid content enhanced 4.8 times (3.05 ± 0.03 mg quercetin/g), and the gamma-aminobutyric acid content was 3.07 ± 0.94 mg/g. In a co-culture of mouse liver cells with fermented products, 100 ppm ethanol extract of fermented products effectively improved glucose utilization with increased glucose transporter expression. This functional fermented dairy product can be developed into the high value added local agricultural products and enhance multiple applications including medical and therapeutic fields.

A Simple Flow Cytometric Method to Measure Glucose Uptake and Glucose Transporter Expression for Monocyte Subpopulations in Whole Blood.

Monocytes are innate immune cells that can be activated by pathogens and inflammation associated with certain chronic inflammatory diseases. Activation of monocytes induces effector functions and a concomitant shift from oxidative to glycolytic metabolism that is accompanied by increased glucose transporter expression. This increased glycolytic metabolism is also observed for trained immunity of monocytes, a form of innate immunological memory. Although in vitro protocols examining glucose transporter expression and glucose uptake by monocytes have been described, none have been examined by multi-parametric flow cytometry in whole blood. We describe a multi-parametric flow cytometric protocol for the measurement of fluorescent glucose analog 2-NBDG uptake in whole blood by total monocytes and the classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)) and non-classical (CD14(+)CD16(++)) monocyte subpopulations. This method can be used to examine glucose transporter expression and glucose uptake for total monocytes and monocyte subpopulations during homeostasis and inflammatory disease, and can be easily modified to examine glucose uptake for other leukocytes and leukocyte subpopulations within blood.

Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression

Both aging and physical inactivity are associated with increased development of insulin resistance whereas physical activity has been shown to promote increased insulin sensitivity. Here we investigated the effects of physical activity level on aging-associated insulin resistance in myotubes derived from human skeletal muscle satellite cells. Satellite cells were obtained from young (22 yrs) normally active or middle-aged (56.6 yrs) individuals who were either lifelong sedentary or lifelong active. Both middle-aged sedentary and middle-aged active myotubes had increased p21 and myosin heavy chain protein expression. Interestingly MHCIIa was increased only in myotubes from middle-aged active individuals. Middle-aged sedentary cells had intact insulin-stimulated Akt phosphorylation however, the same cell showed ablated insulin-stimulated glucose uptake and GLUT4 translocation to the plasma membrane. On the other hand, middle-aged active cells retained both insulin-stimulated increases in glucose uptake and GLUT4 translocation to the plasma membrane. Middle-aged active cells also had significantly higher mRNA expression of GLUT1 and GLUT4 compared to middle-aged sedentary cells, and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact on the metabolism of human myotubes during aging and may contribute to aging-associated insulin resistance through impaired GLUT4 localization.

High-salt diet advances molecular circadian rhythms in mouse peripheral tissues

Dietary compounds influence the expression of various genes and play a major role in changing physiological and metabolic states. However, little is known about the role of food ingredients in the regulation of circadian gene expression. Here, we show that feeding mice with a high-salt (HS) diet ad libitum for over 2 weeks advanced the phase of clock gene expression by about 3 h in the liver, kidney, and lung, but did not change circadian feeding, drinking, and locomotor rhythms. Focused DNA microarray analysis showed that the expression phase of many genes related to metabolism in the liver was also advanced. Immediately before phase advancement in peripheral tissues, the mRNA expression of sodium–glucose cotransporter 1 ( Sglt1) and glucose transporter 2 ( Glut2), that are responsible for glucose absorption, was increased in the jejunum. Furthermore, blood glucose uptake increased more rapidly after consuming the HS diet than the control diet. Moreover, phloridzin, a specific inhibitor of SGLT1, prevented the increased glucose transporter expression in the jejunum and phase advancement in the livers of mice on the HS diet. These results suggest that increased glucose absorption induced by dietary HS alters the food entrainment of peripheral molecular circadian rhythms.

Effect of chronic hypoglycaemia on glucose concentration and glycogen content in rat brain: a localized 13C NMR study

While chronic hypoglycaemia has been reported to increase unidirectional glucose transport across the blood-brain barrier (BBB) and to increase GLUT1 expression at the endothelium, the effect on steady-state brain d-glucose and brain glycogen content is currently unknown. Brain glucose and glycogen concentrations were directly measured in vivo using localized 13C magnetic resonance spectroscopy (MRS) following 12-14 days of hypoglycaemia. Brain glucose content was significantly increased by 48%, which is consistent with an increase in the maximal glucose transport rate, Tmax, by 58% compared with the sham-treated animals. The localized 13C NMR measurements of brain glucose were directly validated by comparison with biochemically determined brain glucose content after rapid focused microwave fixation (1.4 s at 4 kW). Both in vivo MRS and biochemical measurements implied that brain glycogen content was not affected by chronic hypoglycaemia, consistent with brain glucose being a major factor controlling brain glycogen content. We conclude that the increased glucose transporter expression in chronic hypoglycaemia leads to increased brain glucose content at a given level of glycaemia. Such increased brain glucose concentrations can result in a lowered glycaemic threshold of counter-regulation observed in chronic hypoglycaemia.

Repeated prolonged whole-body low-intensity exercise: effects on insulin sensitivity and limb muscle adaptations

This study investigates the effect of prolonged whole-body low-intensity exercise on insulin sensitivity and the limb muscle adaptive response. Seven male subjects (weight, 90.2 ± 3.2 kg; age, 35 ± 3 years) completed a 32-day unsupported crossing of the Greenland icecap on cross-country skies pulling sleighs. The subjects were studied before and 3 to 4 days after the crossing of the icecap. Subjects came in overnight fasted, and an intravenous glucose tolerance test (IVGTT) was done. A biopsy was obtained from the vastus lateralis and deltoid muscle. On a separate day, a progressive test was performed to establish maximal oxygen uptake. During the crossing, subjects skied for 342 ± 41 min/d. Peak oxygen uptake (4.6 ± 0.2 L/min) was decreased ( P < .05) by 7% after the crossing and body mass decreased ( P < .05) by 7.1 ± 0.2 kg, of which 4.4 ± 0.5 kg was fat mass and 2.7 ± 0.2 kg lean body mass. Glycosylated hemoglobin (5.6% ± 0.01%) was not affected by the crossing. The IVGTT data revealed that insulin sensitivity (7.3 ± 0.6 mU · L −1 · min −1) and glucose effectiveness (0.024 ± 0.002 min −1) were not changed after the crossing. Similarly, the IVGTT data, when expressed per kilogram of lean body mass or body mass, were not affected by the crossing. Citrate synthase activity was higher ( P < .05) in the leg (29 ± 1 μmol · g −1 · min −1) than in the arm muscle (16 ± 2 μmol · g −1 · min −1) and was unchanged after the crossing. Muscle GLUT4 protein concentration was higher ( P < .05) in the leg (104 ± 10 arbitrary units) than in the arm (54 ± 9 arbitrary units) and was not changed in the leg, but was increased ( P < .05) by 70% to 91 ± 9 arbitrary units in the arm after the crossing. In conclusion, the increased glucose transporter expression in arm muscle may compensate for the loss of lean body mass and the decrease in aerobic fitness and thereby contribute to the maintenance of whole-body insulin sensitivity after prolonged low-intensity exercise training.

Akt and Bcl-xL Promote Growth Factor-independent Survival through Distinct Effects on Mitochondrial Physiology

A comparison of Akt- and Bcl-x(L)-dependent cell survival was undertaken using interleukin-3-dependent FL5.12 cells. Expression of constitutively active Akt allows cells to survive for prolonged periods following growth factor withdrawal. This survival correlates with the expression level of activated Akt and is comparable in magnitude to the protection provided by the anti-apoptotic gene Bcl-x(L). Although both genes prevent cell death, Akt-protected cells can be distinguished from Bcl-x(L)-protected cells on the basis of increased glucose transporter expression, glycolytic activity, mitochondrial potential, and cell size. In addition, Akt-expressing cells require high levels of extracellular nutrients to support cell survival. In contrast, Bcl-x(L)-expressing cells deprived of interleukin-3 survive in a more vegetative state, in which the cells are smaller, have lower mitochondrial potential, reduced glycolytic activity, and are less dependent on extracellular nutrients. Thus, Akt and Bcl-x(L) suppress mitochondrion-initiated apoptosis by distinct mechanisms. Akt-mediated survival is dependent on promoting glycolysis and maintaining a physiologic mitochondrial potential. In contrast, Bcl-x(L) maintains mitochondrial integrity in the face of a reduced mitochondrial membrane potential, which develops as a result of the low glycolytic rate in growth factor-deprived cells.

Effect of Troglitazone on Blood Pressure, Glut Expression, Glucose Uptake and Reactivity of Vascular Smooth Muscle in Doca/Salt Hypertension.

P73 We previously demonstrated that glucose transporter (GLUT4) expression was reduced in aorta and carotid arteries of DOCA/salt hypertensive rats. Although this model of hypertension is not insulin resistant, we hypothesized that the insulin sensitizer, troglitazone (TG), stabilizes GLUT expression possibly through maintenance of the differentiated phenotype. DOCA/salt rats and shams were fed either standard chow or ground chow with TG at the rate of 100 mg/rat/day for 4 weeks post-surgery. While there was no difference in blood pressure between the two sham groups, there was a significant (p≤0.009), decrease in systolic BP in the DOCA/TG (157.2±5.66 mmHg) compared to the DOCA/salt (202.2±10.34 mmHg) treated rats. Immunoblotting of extracts of carotid arteries demonstrated that GLUT4 expression was significantly decreased with DOCA/salt and that this was reversed by TG. Decreased GLUT4 with DOCA/salt is specific to vascular tissue since there was no effect in heart. Both the expression and activity (phospho-specific antibody) of Akt/PKB were increased in DOCA/TG carotid arteries compared to DOCA/salt. There was decreased 2-deoxyglucose (2-DOG) uptake in aorta of DOCA/salt rats and this returned to control level in DOCA/TG aorta. We previously showed that DOCA/salt carotid strips exhibited increased agonist stimulated contractility. 2-DOG increased the contractility of sham strips, but had no further effect on DOCA/salt strips. Contractility of DOCA/TG strips is now being compared to DOCA/salt strips. TG (5μM), IGFI (2ng/mL) or the combined treatment of a human fetal-derived vascular smooth muscle cell line for 48-144h demonstrated an increased glucose transporter expression and a parallel increase in Akt expression. Since Akt/PKB is associated with a differentiated phenotype these combined data suggest that the effect of TG on GLUT levels partially may be mediated via increased Akt expression/activity and may explain the salutary effects of TG on BP.

Effect of Troglitazone on Blood Pressure, Glut Expression, Glucose Uptake and Reactivity of Vascular Smooth Muscle in Doca/Salt Hypertension.

P73 We previously demonstrated that glucose transporter (GLUT4) expression was reduced in aorta and carotid arteries of DOCA/salt hypertensive rats. Although this model of hypertension is not insulin resistant, we hypothesized that the insulin sensitizer, troglitazone (TG), stabilizes GLUT expression possibly through maintenance of the differentiated phenotype. DOCA/salt rats and shams were fed either standard chow or ground chow with TG at the rate of 100 mg/rat/day for 4 weeks post-surgery. While there was no difference in blood pressure between the two sham groups, there was a significant (p≤0.009), decrease in systolic BP in the DOCA/TG (157.2±5.66 mmHg) compared to the DOCA/salt (202.2±10.34 mmHg) treated rats. Immunoblotting of extracts of carotid arteries demonstrated that GLUT4 expression was significantly decreased with DOCA/salt and that this was reversed by TG. Decreased GLUT4 with DOCA/salt is specific to vascular tissue since there was no effect in heart. Both the expression and activity (phospho-specific antibody) of Akt/PKB were increased in DOCA/TG carotid arteries compared to DOCA/salt. There was decreased 2-deoxyglucose (2-DOG) uptake in aorta of DOCA/salt rats and this returned to control level in DOCA/TG aorta. We previously showed that DOCA/salt carotid strips exhibited increased agonist stimulated contractility. 2-DOG increased the contractility of sham strips, but had no further effect on DOCA/salt strips. Contractility of DOCA/TG strips is now being compared to DOCA/salt strips. TG (5μM), IGFI (2ng/mL) or the combined treatment of a human fetal-derived vascular smooth muscle cell line for 48-144h demonstrated an increased glucose transporter expression and a parallel increase in Akt expression. Since Akt/PKB is associated with a differentiated phenotype these combined data suggest that the effect of TG on GLUT levels partially may be mediated via increased Akt expression/activity and may explain the salutary effects of TG on BP.

Regulation of glucose transport by interleukin-3 in growth factor-dependent and oncogene-transformed bone marrow-derived cell lines

Growth factors maintain cell viability and promote cell growth by stimulating glucose transport into cells and by progressing cells through the cell cycle. In the short term, effects on glucose transport involve transporter activation, while in the longer term increased gene expression is involved. This study aimed to investigate growth factor regulation of glucose transport in an interleukin (IL)-3-dependent bone marrow-derived cell line and its oncogene-transformed counterparts. 32D clone 3 (32Dcl3) cells and cells transfected with temperature-sensitive (ts) ras and abl oncogenes, were treated with and without IL-3 and their ability to take up 2-deoxy- d-glucose compared. Transformed cells, which are not dependent on IL-3 for growth at the permissive temperature of 32 °C, exhibited a two- to six-fold higher proliferative response, enhanced tyrosine kinase activity and c- myc expression than control cells optimally stimulated with IL-3. Compared with control 32Dcl3 cells, 2-deoxy- d-glucose uptake was also 36–76% higher in transformed cells. The increased glucose uptake in transformed cells was consistent with 2.5-fold higher affinity of the glucose transporters for glucose. IL-3 stimulated glucose uptake in both control and oncogene-transformed cells. With control and ras-transformed cells, enhanced glucose uptake in response to IL-3 was associated with increased affinity of glucose transporters for glucose but with abl-transformed cells, no significant affinity changes were observed. IL-3 also increased glucose transporter expression in both control and oncogene-transformed cells, suggesting that increased transporter expression as well as changes in transporter affinity for glucose can affect glucose uptake.

The hemopoietic growth factor, interleukin-3, promotes glucose transport by increasing the specific activity and maintaining the affinity for glucose of plasma membrane glucose transporters.

Most mammalian cells rely on an external supply of glucose for survival, proliferation, and function. Glucose enters cells through specific transporter molecules at the plasma membrane by a facilitative process that does not expend energy. Regulation of glucose transport into cells is thought to occur largely through transporter expression at the cell surface, but the extent to which the intrinsic properties of glucose transporters are regulated is at present controversial. Using a bone marrow-derived cell line that responds to the hemopoietic growth factor, interleukin-3 (IL-3), we investigated IL-3 regulation of glucose transport. IL-3 significantly increased 2-deoxyglucose (2-DOG) uptake within 1 h (26 +/- 8.0%, n = 11) with a maximum 73% increase after 6 h. Withdrawal of IL-3 resulted in decreased uptake within 1 h and this continued to decline to 43% of initial uptake by 16 h. To determine whether these changes in 2-DOG uptake were associated with corresponding changes in glucose transporter expression, subtype-specific antisera against Glut-1 and Glut-3 were used. Little change in membrane expression of these transporters was observed prior to 16 h. Fractionation of cell membranes on Nycodenz gradients showed that the majority of each transporter subtype was associated with the plasma membrane (63-93%) and that transporter distribution did not change markedly in response to addition or withdrawal of IL-3. These results demonstrate that IL-3 regulates glucose uptake by modulating the intrinsic transporting ability of glucose transporters. Decreased transporter affinity for 2-DOG and 3-O-methylglucose was observed following IL-3 withdrawal. Similar affinity changes were observed with 2-DOG following exposure of IL-3-stimulated cells to the protein kinase inhibitors, genistein and staurosporine. In contrast, the tyrosine phosphatase inhibitor, vanadate, acted like IL-3 to increase transporter affinity for glucose. Together these results demonstrate that IL-3 acts to maintain the intrinsic transport properties of glucose transporters without markedly affecting their expression or translocation.

Positron emission tomography (PET) scanning in breast cancer.

primary diagnosis, more accurate non-invasive Quantitative analysis techniques include dynamic staging, and more effective methods of following studies which generate absolute glucose metabolic therapy and establishing prognosis. A large number rates and simple relative quantitative ratios, known of new or improved imaging techniques have been as standardized uptake values or SUVs [3, 6]. developed in recent years yet most patients still Simple qualitative visual analysis of the images has require multiple examinations of various organs, also shown high accuracy [6, 7]. including ultrasound of the liver, isotope bone Several studies have examined the initial detecscans, mammograms and CT scans. Furthermore, tion and staging of breast cancer using FDG–PET the current sensitivities and/or specificities of these scans. Wahl and colleagues detected 10 out of 10 methods leave much room for improvement. primary breast lesions and, although these were Positron emission tomography (PET) imaging has generally large lesions (3.2–12 cm), 2 of the patients recently shown promise as a single technique that had dense glandular breast tissue with negative might have equivalent or better accuracy than the mammograms [4]. In a series of 28 patients with other current methods combined [1–4]. 35 suspect breast masses, 27 of which were found The greatest developments in PET imaging to be malignant, Adler et al reported a sensitivity during the 1990s have been in oncology. A number of 90% and specificity of 100% with primary of PET radiopharmaceuticals have been utilized lesions as small as 0.9 cm being correctly identified for oncological investigations including labelled as tumour [8]. In their quantitative analysis, the hormones or their analogues, labelled amino acids, malignant lesions had a mean FDG uptake value labelled hypoxia agents and labelled thymidine [2, (SUV) of 12.8, while benign solid lesions averaged 3]. However, the vast majority of the work to date 1.8 and benign cysts 0.2. Furthermore, there was a has centred on the use of fluorodeoxyglucose labsignificant correlation between normalized FDG elled with Fluorine-18 (18FDG). The 2 h half life uptake and the histological nuclear grade of the not only makes whole body imaging practical but primary lesion. Tse et al from the University of allows for multicentre distribution of tracer. The California at Los Angeles also reported 100% high aerobic glycolytic rate of most tumours means specificity but a false negative rate of 16% [9]. that there is a much higher uptake of FDG in One of their false negative studies had diffuse malignant tissues than in normal tissue. These high microscopic foci and the other had a low grade glycolytic rates are most likely the result of tumour with microscopic foci of invasion. Lesions increased glucose transporter expression and less than 1 cm were detected. While mammography increased hexokinase activity in tumours [2, 3, 5]. was less specific, it was complementary in detecting Moderate levels of hypoxia also increase tumour a FDG–PET negative non-palpable lesion. The glucose uptake rates by 30% or more [5]. Most following year, Nieweg et al from the MD modern PET scanners have large fields of view, Anderson Cancer Center reported a series of 20

Human immunodeficiency virus type 1 infection of H9 cells induces increased glucose transporter expression.

A clone obtained from a differential display screen for cellular genes with altered expression during human immunodeficiency virus (HIV) infection matched the sequence for the human GLUT3 facilitative glucose transporter, a high-velocity-high-affinity facilitative transporter commonly expressed in neurons of the central nervous system. Northern (RNA) analysis showed that GLUT3 expression increased during infection. Flow cytometry showed that GLUT3 protein expression increased specifically in the HIV-infected cells; this increase correlated with increased 2-deoxyglucose transport in the HIV-infected culture. HIV infection therefore leads to increased expression of a glucose transporter normally expressed at high levels in other cell types and a corresponding increase in glucose transport activity. If HIV infection places increased metabolic demands on the host cell, changes in the expression of a cellular gene that plays an important role in cellular metabolism might provide a more favorable environment for viral replication.