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Sample records for cell glucose metabolism

  1. Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

    Jianhui Liu

    Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

  2. Metabolism Kinetics of Glucose in Anchorage-dependent Cell Cultures

    孙祥明; 张元兴

    2001-01-01

    The kinetic model of glucose metabolism was established and successfully applied to batchcultures of rCHO and rBHK cells. It was found that a large amount of glucose was utilized for cellmaintenance, and the overwhelming majority of maintenance energy from glucose was by its anaerobicmetabolism in both rBHK and rCHO cell cultures. The overall maintenance coefficients from aerobicmetabolism were 1.9×10-13 mmol/(cell.h) for rCHO cells and 7×10-13 mmol/(cell.h) for rBHK cells. Inaddition, all Go/T and Eo/T gradually increased with the same trend as the cell growth in the culture ofboth rCHO and rBHK cells. The overall molecule yield coefficients of lactate to glucose were 1.61 for rCHO cells and 1.38 for rBHK cells. The yield coefficients of cell to glucose were 4.5×108 cells/mmol for rCHO cells and 1.9 × 108 cells/mmol for rBHK cells, respectively.

  3. Specific inactivation of glucose metabolism from eucaryotic cells by pentalenolactone.

    Duszenko, M; Balla, H; Mecke, D

    1982-02-01

    Pentalenolactone, an antibiotic related to the class of the sesquiterpene-lactones and produced by the strain Streptomyces arenae Tü-469, inhibits specifically the glucose metabolism by inactivation of the enzyme glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD oxidoreductase (phosphorylating) ED 1.2.1.1.2). The sensitivity of several eucaryotic cell-systems for pentalenolactone was shown under in vivo conditions. The glycolytic as well as the gluconeogenetic pathway of mammalian cells can be completely inhibited with low concentrations of the antibiotic. In all cases, the minimum inhibitory concentration is dependent on cell density. The inhibitory effect in vivo and in vitro does not seem to be species-specific. In erythrocytes from rats, in Ehrlich-ascites tumor cells and in Plasmodium vinckei infected erythrocytes from mice glycolysis can be inhibited with concentrations of 18--90 micrometers pentalenolactone. In hepatocytes, glycolysis as well as gluconeogenesis in prevented by the same concentrations. In contrast to these results, in yeast the inhibition depends on growth conditions. The inhibition in glucose medium is cancelled by precultivation on acetate-containing medium. PMID:7034785

  4. Effects of turtle oil on insulin sensitivity and glucose metabolism in insulin resistant cell model

    To evaluate the effects of turtle oil on insulin sensitivity and glucose metabolism in an insulin-resistant (IR) cell model which was established by the way of high concentration of insulin induction with HepG2 cell in vitro culture. The IR cells were treated by turtle oil, the glucose consumption and 3H-D-glucose incorporation rate in IR cells were detected by the way of glucose oxidase and 3H-D-glucose incorporation assay respectively. The state of cell proliferation was tested by MTT method. The results showed that the incorporation rate of 3H-D-glucose in IR cells was significantly lower than that in the control cells(P3H-D-glucose incorporation rate in either IR cells or control cells was increased with the increase of insulin concentration. Moreover, the 3H-D-glucose incorporation rate of IR cells increased slower than that of control cells. The MTT assay showed that turtle oil can promote the proliferation of IR cell and control cell. The glucose uptake and glucose consumption in IR cell which treated with turtle oil was significantly increase than that in the control cells (P<0.05). Turtle oil can improve the insulin sensitivity and glucose metabolism in the IR cell model. (authors)

  5. Hepatocyte Growth Factor Is a Novel Stimulator of Glucose Uptake and Metabolism in Skeletal Muscle Cells*

    Perdomo, German; Martinez-Brocca, Maria A.; Bhatt, Bankim A.; Brown, Nicholas F.; O'Doherty, Robert M.; Garcia-Ocaña, Adolfo

    2008-01-01

    Skeletal muscle plays a major role in glucose and lipid metabolism. Active hepatocyte growth factor (HGF) is present in the extracellular matrix in skeletal muscle. However, the effects of HGF on glucose and lipid metabolism in skeletal muscle are completely unknown. We therefore examined the effects of HGF on deoxyglucose uptake (DOGU), glucose utilization, and fatty acid oxidation (FAO) in skeletal muscle cells. HGF significantly enhanced DOGU in mouse soleus muscles in vitro. Furthermore, ...

  6. Characterization of glucose-related metabolic pathways in differentiated rat oligodendrocyte lineage cells.

    Amaral, Ana I; Hadera, Mussie G; Tavares, Joana M; Kotter, Mark R N; Sonnewald, Ursula

    2016-01-01

    Although oligodendrocytes constitute a significant proportion of cells in the central nervous system (CNS), little is known about their intermediary metabolism. We have, therefore, characterized metabolic functions of primary oligodendrocyte precursor cell cultures at late stages of differentiation using isotope-labelled metabolites. We report that differentiated oligodendrocyte lineage cells avidly metabolize glucose in the cytosol and pyruvate derived from glucose in the mitochondria. The labelling patterns of metabolites obtained after incubation with [1,2-(13)C]glucose demonstrated that the pentose phosphate pathway (PPP) is highly active in oligodendrocytes (approximately 10% of glucose is metabolized via the PPP as indicated by labelling patterns in phosphoenolpyruvate). Mass spectrometry and magnetic resonance spectroscopy analyses of metabolites after incubation of cells with [1-(13)C]lactate or [1,2-(13)C]glucose, respectively, demonstrated that anaplerotic pyruvate carboxylation, which was thought to be exclusive to astrocytes, is also active in oligodendrocytes. Using [1,2-(13)C]acetate, we show that oligodendrocytes convert acetate into acetyl CoA which is metabolized in the tricarboxylic acid cycle. Analysis of labelling patterns of alanine after incubation of cells with [1,2-(13)C]acetate and [1,2-(13)C]glucose showed catabolic oxidation of malate or oxaloacetate. In conclusion, we report that oligodendrocyte lineage cells at late differentiation stages are metabolically highly active cells that are likely to contribute considerably to the metabolic activity of the CNS. PMID:26352325

  7. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B-cells

    Le, Anne; Lane, Andrew N.; Hamaker, Max; Bose, Sminu; Gouw, Arvin; Barbi, Joseph; Tsukamoto, Takashi; Rojas, Camilio J.; Slusher, Barbara S.; Zhang, Haixia; Zimmerman, Lisa J.; Liebler, Daniel C.; Slebos, Robbert J. C.; Lorkiewicz, Pawel K.; Higashi, Richard M

    2012-01-01

    Because MYC plays a causal role in many human cancers, including those with hypoxic and nutrient-poor tumor microenvironments, we have determined the metabolic responses of a MYC-inducible human Burkitt lymphoma model P493 cell line to aerobic and hypoxic conditions, and to glucose deprivation, using Stable Isotope Resolved Metabolomics. Using [U-13C]-glucose as the tracer, both glucose consumption and lactate production were increased by MYC expression and hypoxia. Using [U-13C,15N]-glutamin...

  8. Effect of epinephrine and insulin on glucose metabolism in isolated fat cells

    Since epinephrine and insulin are known to counteract each other in several metabolic respects, it was found of interest to evaluate the interaction of these hormones on glucose metabolism in isolated fat cells. Results indicate that in spite of reduced lipolysis, insulin potentiates the conversion of glucose to glyceride-glycerol. This means that a certain degree of esterification of fatty acids must take place. So the low rate of lipolysis is sufficient to provide fatty acids for this esterification. (author)

  9. Effect of epinephrine and insulin on glucose metabolism in isolated fat cells

    Zewail, M.A. (National Research Centre, Cairo (Egypt)); Fahmy, N.M. (National Organisation for Drug Control and Research, Cairo (Egypt)); Nielsen, J.H. (Gentofte Hospital, Copenhagen (Denmark))

    1984-08-01

    Since epinephrine and insulin are known to counteract each other in several metabolic respects, it was found of interest to evaluate the interaction of these hormones on glucose metabolism in isolated fat cells. Results indicate that in spite of reduced lipolysis, insulin potentiates the conversion of glucose to glyceride-glycerol. This means that a certain degree of esterification of fatty acids must take place. So the low rate of lipolysis is sufficient to provide fatty acids for this esterification.

  10. Honeybee retinal glial cells transform glucose and supply the neurons with metabolic substrate

    The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy[3H]glucose convert this glucose analogue to 2-deoxy[3H]glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O2 and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system

  11. Ascorbic acid recycling by cultured beta cells: effects of increased glucose metabolism.

    Steffner, Robert J; Wu, Lan; Powers, Alvin C; May, James M

    2004-11-15

    Ascorbic acid is necessary for optimal insulin secretion from pancreatic islets. We evaluated ascorbate recycling and whether it is impaired by increased glucose metabolism in the rat beta-cell line INS-1. INS-1 cells, engineered with the potential for overexpression of glucokinase under the control of a tetracycline-inducible gene expression system, took up and reduced dehydroascorbic acid to ascorbate in a concentration-dependent manner that was optimal in the presence of physiologic D-glucose concentrations. Ascorbate uptake did not affect intracellular GSH concentrations. Whereas depletion of GSH in culture to levels about 25% of normal also did not affect the ability of the cells to reduce dehydroascorbic acid, more severe acute GSH depletion to less than 10% of normal levels did impair dehydroascorbic acid reduction. Culture of inducible cells in 11.8 mM D-glucose and doxycycline for 48 h enhanced glucokinase activity, increased glucose utilization, abolished D-glucose-dependent insulin secretion, and increased generation of reactive oxygen species. The latter may have contributed to subsequent decreases in the ability of the cells both to maintain intracellular ascorbate and to recycle it from dehydroascorbic acid. Cultured beta cells have a high capacity to recycle ascorbate, but this is sensitive to oxidant stress generated by increased glucose metabolism due to culture in high glucose concentrations and increased glucokinase expression. Impaired ascorbate recycling as a result of increased glucose metabolism may have implications for the role of ascorbate in insulin secretion in diabetes mellitus and may partially explain glucose toxicity in beta cells. PMID:15477012

  12. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B-cells

    Le, Anne; Lane, Andrew N.; Hamaker, Max; Bose, Sminu; Gouw, Arvin; Barbi, Joseph; Tsukamoto, Takashi; Rojas, Camilio J.; Slusher, Barbara S.; Zhang, Haixia; Zimmerman, Lisa J.; Liebler, Daniel C.; Slebos, Robbert J.C.; Lorkiewicz, Pawel K.; Higashi, Richard M.; Fan, Teresa W. M.; Dang, Chi V.

    2012-01-01

    Summary Because MYC plays a causal role in many human cancers, including those with hypoxic and nutrient-poor tumor microenvironments, we have determined the metabolic responses of a MYC-inducible human Burkitt lymphoma model P493 cell line to aerobic and hypoxic conditions, and to glucose deprivation, using Stable Isotope Resolved Metabolomics. Using [U-13C]-glucose as the tracer, both glucose consumption and lactate production were increased by MYC expression and hypoxia. Using [U-13C,15N]-glutamine as the tracer, glutamine import and metabolism through the TCA cycle persisted under hypoxia, and glutamine contributed significantly to citrate carbons. Under glucose deprivation, glutamine-derived fumarate, malate, and citrate were significantly increased. Their 13C labeling patterns demonstrate an alternative energy-generating glutaminolysis pathway involving a glucose-independent TCA cycle. The essential role of glutamine metabolism in cell survival and proliferation under hypoxia and glucose deficiency, makes them susceptible to the glutaminase inhibitor BPTES, and hence could be targeted for cancer therapy. PMID:22225880

  13. Phosphorus-31 and carbon-13 nuclear magnetic resonance studies of glucose and xylose metabolism in Candida tropicalis cell suspensions.

    Lohmeier-Vogel, E M; Hahn-Hägerdal, B.; Vogel, H J

    1995-01-01

    The metabolism of glucose and xylose was studied as a function of oxygenation in suspensions of Candida tropicalis by 31P and 13C nuclear magnetic resonance spectroscopy. Both the rate of carbohydrate metabolism and the cytoplasmic pH were independent of the rate of oxygenation in cells metabolizing glucose. However, these two parameters were markedly dependent on the rate of oxygenation in C. tropicalis cells metabolizing xylose. For example, the cytoplasmic pH in fully oxygenated xylose-met...

  14. Computational modeling of glucose transport in pancreatic β-cells identifies metabolic thresholds and therapeutic targets in diabetes.

    Camilla Luni

    Full Text Available Pancreatic β-cell dysfunction is a diagnostic criterion of Type 2 diabetes and includes defects in glucose transport and insulin secretion. In healthy individuals, β-cells maintain plasma glucose concentrations within a narrow range in concert with insulin action among multiple tissues. Postprandial elevations in blood glucose facilitate glucose uptake into β-cells by diffusion through glucose transporters residing at the plasma membrane. Glucose transport is essential for glycolysis and glucose-stimulated insulin secretion. In human Type 2 diabetes and in the mouse model of obesity-associated diabetes, a marked deficiency of β-cell glucose transporters and glucose uptake occurs with the loss of glucose-stimulated insulin secretion. Recent studies have shown that the preservation of glucose transport in β-cells maintains normal insulin secretion and blocks the development of obesity-associated diabetes. To further elucidate the underlying mechanisms, we have constructed a computational model of human β-cell glucose transport in health and in Type 2 diabetes, and present a systems analysis based on experimental results from human and animal studies. Our findings identify a metabolic threshold or "tipping point" whereby diminished glucose transport across the plasma membrane of β-cells limits intracellular glucose-6-phosphate production by glucokinase. This metabolic threshold is crossed in Type 2 diabetes and results in β-cell dysfunction including the loss of glucose stimulated insulin secretion. Our model further discriminates among molecular control points in this pathway wherein maximal therapeutic intervention is achieved.

  15. Non-Classical Gluconeogenesis-Dependent Glucose Metabolism in Rhipicephalus microplus Embryonic Cell Line BME26

    Renato Martins da Silva

    2015-01-01

    Full Text Available In this work we evaluated several genes involved in gluconeogenesis, glycolysis and glycogen metabolism, the major pathways for carbohydrate catabolism and anabolism, in the BME26 Rhipicephalus microplus embryonic cell line. Genetic and catalytic control of the genes and enzymes associated with these pathways are modulated by alterations in energy resource availability (primarily glucose. BME26 cells in media were investigated using three different glucose concentrations, and changes in the transcription levels of target genes in response to carbohydrate utilization were assessed. The results indicate that several genes, such as glycogen synthase (GS, glycogen synthase kinase 3 (GSK3, phosphoenolpyruvate carboxykinase (PEPCK, and glucose-6 phosphatase (GP displayed mutual regulation in response to glucose treatment. Surprisingly, the transcription of gluconeogenic enzymes was found to increase alongside that of glycolytic enzymes, especially pyruvate kinase, with high glucose treatment. In addition, RNAi data from this study revealed that the transcription of gluconeogenic genes in BME26 cells is controlled by GSK-3. Collectively, these results improve our understanding of how glucose metabolism is regulated at the genetic level in tick cells.

  16. End products of glucose and glutamine metabolism by L929 cells.

    Lanks, K W

    1987-07-25

    Products of glucose and glutamine metabolism by L929 cells were detected and quantitated by gas chromatography and mass spectrometry of the oxime-trimethylsilyl derivatives. This method allowed detection and identification of all major carboxylic and amino acids produced in the system. Although lactic acid was expected to be the major product, alanine, citric, glutamic, aspartic, and pyruvic acids were also released into the culture medium at significant rates. Incorporation of labeled carbon from D-[U-13C]glucose showed that the alanine, lactic, and pyruvic acids were derived from glucose as was one-third of the citric acid carbon. The rate of glucose utilization for production of these end products was 29-fold greater than the rate of glucose oxidation to CO2, and calculated ATP production from alanine and pyruvate synthesis exceeded that from lactate synthesis by nearly 2-fold. Utilization of glutamine for synthesis of aspartic, glutamic, and citric acids also exceeded the rate of glutamine oxidation, thereby making end-product synthesis from glucose and glutamine the dominant cellular metabolic activity. In the absence of glucose, synthesis and intracellular levels of aspartic and glutamic acids increased, whereas synthesis and cell content of the other acids decreased markedly. This response is consistent with the metabolic pattern proposed by Moreadith and Lehninger (Moreadith, R.W., and Lehninger, A.L. (1984) J. Biol. Chem. 259, 6215-6221) in which much of the glutamine used by these cells is converted to aspartate in the absence of a pyruvate source and to aspartate or citrate in the presence of pyruvate. PMID:3611053

  17. Glucagon-insulin interaction on fat cell metabolism using c14 glucose

    Glucagon is known to stimulate the lipolysis in isolated fat cells from young rats, but not in fat cells from old heavy rate (Manganiello 1972). Insulin is known to counteract the lipolytic effect and to stimulate the synthesis of fatty acids from glucose. However, little is known about the interaction between the two hormones on the glucose metabolism. Experiments based on the use of various inhibitors of lipolysis have however, clearly shown that glucagon can also stimulate the entry and overall oxidation of glucose by mechanism which is distinct from its lipolysis stimulating mechanism (M. Blecher et al. 1969). Fat cells from old heavy rats are known to be less responsive to both the lipogenic action of insulin and the lipolytic action of glucagon than fat cells from young lean rats (E.G. Hansen, Nielsen and Gliemann, 1974). The aim of the present study was to see how glucagon affects glucose metabolism in fat cells, and whether this effect was dependent on the lipolytic action of glucagon

  18. Glucose Metabolism in T Cells and Monocytes: New Perspectives in HIV Pathogenesis

    Palmer, Clovis S.; Cherry, Catherine L.; Sada-Ovalle, Isabel; Singh, Amit; Crowe, Suzanne M.

    2016-01-01

    Activation of the immune system occurs in response to the recognition of foreign antigens and receipt of optimal stimulatory signals by immune cells, a process that requires energy. Energy is also needed to support cellular growth, differentiation, proliferation, and effector functions of immune cells. In HIV-infected individuals, persistent viral replication, together with inflammatory stimuli contributes to chronic immune activation and oxidative stress. These conditions remain even in subjects with sustained virologic suppression on antiretroviral therapy. Here we highlight recent studies demonstrating the importance of metabolic pathways, particularly those involving glucose metabolism, in differentiation and maintenance of the activation states of T cells and monocytes. We also discuss how changes in the metabolic status of these cells may contribute to ongoing immune activation and inflammation in HIV- infected persons and how this may contribute to disease progression, establishment and persistence of the HIV reservoir, and the development of co-morbidities. We provide evidence that other viruses such as Epstein–Barr and Flu virus also disrupt the metabolic machinery of their host cells. Finally, we discuss how redox signaling mediated by oxidative stress may regulate metabolic responses in T cells and monocytes during HIV infection.

  19. Return of the glucoreceptor: Glucose activates the glucose-sensing receptor T1R3 and facilitates metabolism in pancreatic β-cells.

    Kojima, Itaru; Nakagawa, Yuko; Ohtsu, Yoshiaki; Hamano, Kunihisa; Medina, Johan; Nagasawa, Masahiro

    2015-05-01

    Subunits of the sweet taste receptor, namely T1R2 and T1R3, are expressed in mouse pancreatic islets. Quantitatively, the expression of messenger ribonucleic acid for T1R2 is much lower than that of T1R3, and immunoreactive T1R2 is in fact undetectable. Presumably, a homodimer of T1R3 could function as a signaling receptor. Activation of this receptor by adding an artificial sweetener, sucralose, leads to an increase in intracellular adenosine triphosphate ([ATP]c). This increase in [ATP]c is observed in the absence of ambient glucose. Sucralose also augments elevation of [ATP]c induced by methylsuccinate, a substrate for mitochondria. Consequently, activation of T1R3 promotes metabolism in mitochondria and increases [ATP]c. 3-O-Methylglucose, a non-metabolizable analog of glucose, also increases [ATP]c. Conversely, knockdown of T1R3 attenuates elevation of [ATP]c induced by glucose. Hence, glucose promotes its own metabolism by activating T1R3 and augmenting ATP production. Collectively, a homodimer of T1R3 functions as a cell surface glucose-sensing receptor and participates in the action of glucose on insulin secretion. The glucose-sensing receptor T1R3 might be the putative glucoreceptor proposed decades ago by Niki et al. The glucose-sensing receptor is involved in the action of glucose and modulates glucose metabolism in pancreatic β-cells. PMID:25969708

  20. Proliferation-dependent changes in amino acid transport and glucose metabolism in glioma cell lines

    Amino acid imaging is increasingly being used for assessment of brain tumor malignancy, extent of disease, and prognosis. This study explores the relationship between proliferative activity, amino acid transport, and glucose metabolism in three glioma cell lines (U87, Hs683, C6) at different phases of growth in culture. Growth phase was characterized by direct cell counting, proliferation index determined by flow cytometry, and [3H]thymidine (TdR) accumulation, and was compared with the uptake of two non-metabolized amino acids ([14C]aminocyclopentane carboxylic acid (ACPC) and [14C]aminoisobutyric acid (AIB)), and [18F]fluorodeoxyglucose (FDG). Highly significant relationships between cell number (density), proliferation index, and TdR accumulation rate were observed in all cell lines (r>0.99). Influx (K1) of both ACPC and AIB was directly related to cell density, and inversely related to the proliferation index and TdR accumulation in all cell lines. The volume of distribution (Vd) for ACPC and AIB was lowest during rapid growth and highest during the near-plateau growth phase in all cell lines. FDG accumulation in Hs683 and C6 cells was unaffected by proliferation rate, growth phase, and cell density, whereas FDG accumulation was correlated with TdR accumulation, growth phase, and cell density in U87 cells. This study demonstrates that proliferation rate and glucose metabolism are not necessarily co-related in all glioma cell lines. The values of K1 and Vd for ACPC and AIB under different growth conditions suggest that these tumor cell lines can up-regulate amino acid transporters in their cell membranes when their growth conditions become adverse and less than optimal. (orig.)

  1. Metabolic labeling with (14C)-glucose of bloodstream and cell culture trypanosoma cruzi trypomastigotes:

    Trypomastigote forms of Trypanosoma cruzi from infected mouse blood and from cell culture were metabolically labeled by incubation with D-(14C)-glucose. Analysis by polyacrylamide gel electrophoresis of lysates from parasites of two strains (RA and CA1) showed a significantly different pattern. The difference was mainly quantitative when the blood and cell culture trypomastigotes of the RA strain were compared. Analysis of the culture medium by paper electrophoresis showed an anionic exometabolite only in the blood forms of both strains. (Author)

  2. Glycated albumin suppresses glucose-induced insulin secretion by impairing glucose metabolism in rat pancreatic β-cells

    Muto Takashi

    2011-04-01

    Full Text Available Abstract Background Glycated albumin (GA is an Amadori product used as a marker of hyperglycemia. In this study, we investigated the effect of GA on insulin secretion from pancreatic β cells. Methods Islets were collected from male Wistar rats by collagenase digestion. Insulin secretion in the presence of non-glycated human albumin (HA and GA was measured under three different glucose concentrations, 3 mM (G3, 7 mM (G7, and 15 mM (G15, with various stimulators. Insulin secretion was measured with antagonists of inducible nitric oxide synthetase (iNOS, and the expression of iNOS-mRNA was investigated by real-time PCR. Results Insulin secretion in the presence of HA and GA was 20.9 ± 3.9 and 21.6 ± 5.5 μU/3 islets/h for G3 (P = 0.920, and 154 ± 9.3 and 126.1 ± 7.3 μU/3 islets/h (P = 0.046, for G15, respectively. High extracellular potassium and 10 mM tolbutamide abrogated the inhibition of insulin secretion by GA. Glyceraldehyde, dihydroxyacetone, methylpyruvate, GLP-1, and forskolin, an activator of adenylate cyclase, did not abrogate the inhibition. Real-time PCR showed that GA did not induce iNOS-mRNA expression. Furthermore, an inhibitor of nitric oxide synthetase, aminoguanidine, and NG-nitro-L-arginine methyl ester did not abrogate the inhibition of insulin secretion. Conclusion GA suppresses glucose-induced insulin secretion from rat pancreatic β-cells through impairment of intracellular glucose metabolism.

  3. Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

    Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity

  4. Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

    Bolado-Carrancio, A. [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain); Riancho, J.A. [Department of Internal Medicine, Hospital U.M. Valdecilla-IDIVAL, University of Cantabria, RETICEF, Santander (Spain); Sainz, J. [Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC-University of Cantabria, Santander (Spain); Rodríguez-Rey, J.C., E-mail: rodriguj@unican.es [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain)

    2014-04-04

    Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity.

  5. Cell walls of Saccharomyces cerevisiae differentially modulated innate immunity and glucose metabolism during late systemic inflammation.

    Bushansingh Baurhoo

    Full Text Available BACKGROUND: Salmonella causes acute systemic inflammation by using its virulence factors to invade the intestinal epithelium. But, prolonged inflammation may provoke severe body catabolism and immunological diseases. Salmonella has become more life-threatening due to emergence of multiple-antibiotic resistant strains. Mannose-rich oligosaccharides (MOS from cells walls of Saccharomyces cerevisiae have shown to bind mannose-specific lectin of Gram-negative bacteria including Salmonella, and prevent their adherence to intestinal epithelial cells. However, whether MOS may potentially mitigate systemic inflammation is not investigated yet. Moreover, molecular events underlying innate immune responses and metabolic activities during late inflammation, in presence or absence of MOS, are unknown. METHODS AND PRINCIPAL FINDINGS: Using a Salmonella LPS-induced systemic inflammation chicken model and microarray analysis, we investigated the effects of MOS and virginiamycin (VIRG, a sub-therapeutic antibiotic on innate immunity and glucose metabolism during late inflammation. Here, we demonstrate that MOS and VIRG modulated innate immunity and metabolic genes differently. Innate immune responses were principally mediated by intestinal IL-3, but not TNF-α, IL-1 or IL-6, whereas glucose mobilization occurred through intestinal gluconeogenesis only. MOS inherently induced IL-3 expression in control hosts. Consequent to LPS challenge, IL-3 induction in VIRG hosts but not differentially expressed in MOS hosts revealed that MOS counteracted LPS's detrimental inflammatory effects. Metabolic pathways are built to elucidate the mechanisms by which VIRG host's higher energy requirements were met: including gene up-regulations for intestinal gluconeogenesis (PEPCK and liver glycolysis (ENO2, and intriguingly liver fatty acid synthesis through ATP citrate synthase (CS down-regulation and ATP citrate lyase (ACLY and malic enzyme (ME up-regulations. However, MOS host

  6. Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation

    Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian;

    2015-01-01

    Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in the biopharmaceutical industry. Amino acid and glucose consumption, cell growth, metabolism, antibody titer, and N-glycosylation patterns are always the major concerns during upstream proces...

  7. Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release.

    Huber, Heinrich J

    2011-03-01

    Many anticancer drugs activate caspases via the mitochondrial apoptosis pathway. Activation of this pathway triggers a concomitant bioenergetic crisis caused by the release of cytochrome-c (cyt-c). Cancer cells are able to evade these processes by altering metabolic and caspase activation pathways. In this study, we provide the first integrated system study of mitochondrial bioenergetics and apoptosis signalling and examine the role of mitochondrial cyt-c release in these events. In accordance with single-cell experiments, our model showed that loss of cyt-c decreased mitochondrial respiration by 95% and depolarised mitochondrial membrane potential ΔΨ(m) from -142 to -88 mV, with active caspase-3 potentiating this decrease. ATP synthase was reversed under such conditions, consuming ATP and stabilising ΔΨ(m). However, the direction and level of ATP synthase activity showed significant heterogeneity in individual cancer cells, which the model explained by variations in (i) accessible cyt-c after release and (ii) the cell\\'s glycolytic capacity. Our results provide a quantitative and mechanistic explanation for the protective role of enhanced glucose utilisation for cancer cells to avert the otherwise lethal bioenergetic crisis associated with apoptosis initiation.

  8. Quercetin and epigallocatechin gallate inhibit glucose uptake and metabolism by breast cancer cells by an estrogen receptor-independent mechanism

    In this study we characterized 3H-2-deoxy-D-glucose (3H -DG) uptake by the estrogen receptor (ER)-positive MCF7 and the ER-negative MDA-MB-231 human breast cancer cell lines and investigated the effect of quercetin (QUE) and epigallocatechin gallate (EGCG) upon 3H-DG uptake, glucose metabolism and cell viability and proliferation. In both MCF7 and MDA-MB-231 cells 3H-DG uptake was (a) time-dependent, (b) saturable with similar capacity (Vmax) and affinity (Km), (c) potently inhibited by cytochalasin B, an inhibitor of the facilitative glucose transporters (GLUT), (d) sodium-independent and (e) slightly insulin-stimulated. This suggests that 3H-DG uptake by both cell types is mediated by members of the GLUT family, including the insulin-responsive GLUT4 or GLUT12, while being independent of the sodium-dependent glucose transporter (SGLT1). QUE and EGCG markedly and concentration-dependently inhibited 3H-DG uptake by MCF7 and by MDA-MB-231 cells, and both compounds blocked lactate production by MCF7 cells. Additionally, a 4 h-treatment with QUE or EGCG decreased MCF7 cell viability and proliferation, an effect that was more potent when glucose was available in the extracellular medium. Our results implicate QUE and EGCG as metabolic antagonists in breast cancer cells, independently of estrogen signalling, and suggest that these flavonoids could serve as therapeutic agents/adjuvants even for ER-negative breast tumors. -- Highlights: • Glucose uptake by MCF7 and MDA-MB-231 cells is mainly mediated by GLUT1. • QUE and EGCG inhibit cellular glucose uptake thus abolishing the Warburg effect. • This process induces cytotoxicity and proliferation arrest in MCF7 cells. • The flavonoids’ effects are independent of estrogen receptor signalling

  9. Quercetin and epigallocatechin gallate inhibit glucose uptake and metabolism by breast cancer cells by an estrogen receptor-independent mechanism

    Moreira, Liliana, E-mail: lilianam87@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Araújo, Isabel, E-mail: isa.araujo013@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Costa, Tito, E-mail: tito.fmup16@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Correia-Branco, Ana, E-mail: ana.clmc.branco@gmail.com [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Faria, Ana, E-mail: anafaria@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Chemistry Investigation Centre (CIQ), Faculty of Sciences of University of Porto, Rua Campo Alegre, 4169-007 Porto (Portugal); Faculty of Nutrition and Food Sciences of University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Martel, Fátima, E-mail: fmartel@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal); Keating, Elisa, E-mail: keating@med.up.pt [Department of Biochemistry (U38-FCT), Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto (Portugal)

    2013-07-15

    In this study we characterized {sup 3}H-2-deoxy-D-glucose ({sup 3}H -DG) uptake by the estrogen receptor (ER)-positive MCF7 and the ER-negative MDA-MB-231 human breast cancer cell lines and investigated the effect of quercetin (QUE) and epigallocatechin gallate (EGCG) upon {sup 3}H-DG uptake, glucose metabolism and cell viability and proliferation. In both MCF7 and MDA-MB-231 cells {sup 3}H-DG uptake was (a) time-dependent, (b) saturable with similar capacity (V{sub max}) and affinity (K{sub m}), (c) potently inhibited by cytochalasin B, an inhibitor of the facilitative glucose transporters (GLUT), (d) sodium-independent and (e) slightly insulin-stimulated. This suggests that {sup 3}H-DG uptake by both cell types is mediated by members of the GLUT family, including the insulin-responsive GLUT4 or GLUT12, while being independent of the sodium-dependent glucose transporter (SGLT1). QUE and EGCG markedly and concentration-dependently inhibited {sup 3}H-DG uptake by MCF7 and by MDA-MB-231 cells, and both compounds blocked lactate production by MCF7 cells. Additionally, a 4 h-treatment with QUE or EGCG decreased MCF7 cell viability and proliferation, an effect that was more potent when glucose was available in the extracellular medium. Our results implicate QUE and EGCG as metabolic antagonists in breast cancer cells, independently of estrogen signalling, and suggest that these flavonoids could serve as therapeutic agents/adjuvants even for ER-negative breast tumors. -- Highlights: • Glucose uptake by MCF7 and MDA-MB-231 cells is mainly mediated by GLUT1. • QUE and EGCG inhibit cellular glucose uptake thus abolishing the Warburg effect. • This process induces cytotoxicity and proliferation arrest in MCF7 cells. • The flavonoids’ effects are independent of estrogen receptor signalling.

  10. Formaldehyde Metabolism and Formaldehyde-induced Alterations in Glucose and Glutathione Metabolism of Cultured Brain Cells

    Tulpule, Ketki

    2013-01-01

    Formaldehyde is an environmental pollutant that is also generated in the body during normal metabolic processes. Interestingly, several pathological conditions are associated with an increase in formaldehyde-generating enzymes in the body. The level of formaldehyde in the brain is elevated with increasing age and in neurodegenerative conditions which may contribute to lowered cognitive functions. Although the neurotoxic potential of formaldehyde is well established, the molecular mechanisms i...

  11. Effects of lindane on the glucose metabolism in rat brain cortex cells

    The influence of 0.5 mM γ-hexachlorocyclohexane (γ-HCH, lindane) on glucose transport has been investigated using the analog 3-O-methyl-D(U-14C) glucose. The glucose uptake was lineal for at least 10 sec. Preincubation of dissociated brain cortex cells with lindane decreased the transport of glucose with respect to the controls. The treatment of brain cortex cells with other organochlorine compounds indicated that the α-, δ-HCH isomers and dieldrin reproduced the same inhibitory pattern, while β-HCH and endrin were inactive. The total radioactivity incorporated into CO2 from (U-14C) glucose in the cerebral cortex is also inhibited by lindane in a time dependent manner

  12. Effects of lindane on the glucose metabolism in rat brain cortex cells

    Pulido, J.A.; del Hoyo, N.; Perez-Albarsanz, M.A. (Univ. of Alcala, Madrid (Spain))

    1990-01-01

    The influence of 0.5 mM {gamma}-hexachlorocyclohexane ({gamma}-HCH, lindane) on glucose transport has been investigated using the analog 3-O-methyl-D(U-{sup 14}C) glucose. The glucose uptake was lineal for at least 10 sec. Preincubation of dissociated brain cortex cells with lindane decreased the transport of glucose with respect to the controls. The treatment of brain cortex cells with other organochlorine compounds indicated that the {alpha}-, {delta}-HCH isomers and dieldrin reproduced the same inhibitory pattern, while {beta}-HCH and endrin were inactive. The total radioactivity incorporated into CO{sub 2} from (U-{sup 14}C) glucose in the cerebral cortex is also inhibited by lindane in a time dependent manner.

  13. Antihypertensive drugs and glucose metabolism

    Christos; V; Rizos; Moses; S; Elisaf

    2014-01-01

    Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.

  14. ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells.

    Yoshihara, Eiji; Wei, Zong; Lin, Chun Shi; Fang, Sungsoon; Ahmadian, Maryam; Kida, Yasuyuki; Tseng, Tiffany; Dai, Yang; Yu, Ruth T; Liddle, Christopher; Atkins, Annette R; Downes, Michael; Evans, Ronald M

    2016-04-12

    Pancreatic β cells undergo postnatal maturation to achieve maximal glucose-responsive insulin secretion, an energy intensive process. We identify estrogen-related receptor γ (ERRγ) expression as a hallmark of adult, but not neonatal β cells. Postnatal induction of ERRγ drives a transcriptional network activating mitochondrial oxidative phosphorylation, the electron transport chain, and ATP production needed to drive glucose-responsive insulin secretion. Mice deficient in β cell-specific ERRγ expression are glucose intolerant and fail to secrete insulin in response to a glucose challenge. Notably, forced expression of ERRγ in iPSC-derived β-like cells enables glucose-responsive secretion of human insulin in vitro, obviating in vivo maturation to achieve functionality. Moreover, these cells rapidly rescue diabetes when transplanted into β cell-deficient mice. These results identify a key role for ERRγ in β cell metabolic maturation, and offer a reproducible, quantifiable, and scalable approach for in vitro generation of functional human β cell therapeutics. PMID:27076077

  15. High Glucose-Induced PC12 Cell Death by Increasing Glutamate Production and Decreasing Methyl Group Metabolism

    Minjiang Chen

    2016-01-01

    Full Text Available Objective. High glucose- (HG- induced neuronal cell death is responsible for the development of diabetic neuropathy. However, the effect of HG on metabolism in neuronal cells is still unclear. Materials and Methods. The neural-crest derived PC12 cells were cultured for 72 h in the HG (75 mM or control (25 mM groups. We used NMR-based metabolomics to examine both intracellular and extracellular metabolic changes in HG-treated PC12 cells. Results. We found that the reduction in intracellular lactate may be due to excreting more lactate into the extracellular medium under HG condition. HG also induced the changes of other energy-related metabolites, such as an increased succinate and creatine phosphate. Our results also reveal that the synthesis of glutamate from the branched-chain amino acids (isoleucine and valine may be enhanced under HG. Increased levels of intracellular alanine, phenylalanine, myoinositol, and choline were observed in HG-treated PC12 cells. In addition, HG-induced decreases in intracellular dimethylamine, dimethylglycine, and 3-methylhistidine may indicate a downregulation of methyl group metabolism. Conclusions. Our metabolomic results suggest that HG-induced neuronal cell death may be attributed to a series of metabolic changes, involving energy metabolism, amino acids metabolism, osmoregulation and membrane metabolism, and methyl group metabolism.

  16. Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.

    Charlotte J Green

    Full Text Available BACKGROUND: Glucagon like peptide-1 (GLP-1 stimulates insulin secretion from the pancreas but also has extra-pancreatic effects. GLP-1 may stimulate glucose uptake in cultured muscle cells but the mechanism is not clearly defined. Furthermore, while the pancreatic effects of GLP-1 are glucose-dependent, the glucose-dependency of its extra-pancreatic effects has not been examined. METHODS: Skeletal muscle satellite cells isolated from young (22.5 ± 0.97 yr, lean (BMI 22.5 ± 0.6 kg/m(2, healthy males were differentiated in media containing either 22.5 mM (high or 5 mM (normal glucose for 7 days in the absence or presence of insulin and/or various GLP-1 concentrations. Myocellular effects of GLP-1, insulin and glucose were assessed by western-blot, glucose uptake and glycogen synthesis. RESULTS: We firstly show that the GLP-1 receptor protein is expressed in differentiated human muscle satellite cells (myocytes. Secondly, we show that in 5 mM glucose media, exposure of myocytes to GLP-1 results in a dose dependent increase in glucose uptake, GLUT4 amount and subsequently glycogen synthesis in a PI3K dependent manner, independent of the insulin signaling cascade. Importantly, we provide evidence that differentiation of human satellite cells in hyperglycemic (22.5 mM glucose conditions increases GLUT1 expression, and renders the cells insulin resistant and interestingly GLP-1 resistant in terms of glucose uptake and glycogen synthesis. Hyperglycemic conditions did not affect the ability of insulin to phosphorylate downstream targets, PKB or GSK3. Interestingly we show that at 5 mM glucose, GLP-1 increases GLUT4 protein levels and that this effect is abolished by hyperglycemia. CONCLUSIONS: GLP-1 increases glucose uptake and glycogen synthesis into fully-differentiated human satellite cells in a PI3-K dependent mechanism potentially through increased GLUT4 protein levels. The latter occurs independently of the insulin signaling pathway. Attenuation

  17. SIRT3 participates in glucose metabolism interruption and apoptosis induced by BH3 mimetic S1 in ovarian cancer cells.

    Xiang, Xi-Yan; Kang, Jin-Song; Yang, Xiao-Chun; Su, Jing; Wu, Yao; Yan, Xiao-Yu; Xue, Ya-Nan; Xu, Ye; Liu, Yu-He; Yu, Chun-Yan; Zhang, Zhi-Chao; Sun, Lian-Kun

    2016-08-01

    The Bcl-2 antiapoptotic proteins are important cancer therapy targets; however, their role in cancer cell metabolism remains unclear. We found that the BH3-only protein mimetic S1, a novel pan Bcl-2 inhibitor, simultaneously interrupted glucose metabolism and induced apoptosis in human SKOV3 ovarian cancer cells, which was related to the activation of SIRT3, a stress-responsive deacetylase. S1 interrupted the cellular glucose metabolism mainly through causing damage to mitochondrial respiration and inhibiting glycolysis. Moreover, S1 upregulated the gene and protein expression of SIRT3, and induced the translocation of SIRT3 from the nucleus to mitochondria. SIRT3 silencing reversed the effects of S1 on glucose metabolism and apoptosis through increasing the level of HK-II localized to the mitochondria, while a combination of the glycolysis inhibitor 2-DG and S1 intensified the cytotoxicity through further upregulation of SIRT3 expression. This study underscores an essential role of SIRT3 in the antitumor effect of Bcl-2 inhibitors in human ovarian cancer through regulating both metabolism and apoptosis. The manipulation of Bcl-2 inhibitors combined with the use of classic glycolysis inhibitors may be rational strategies to improve ovarian cancer therapy. PMID:27277143

  18. Glucose metabolism in ischemic myocardium

    We determined the myocardial metabolic rate for glucose (MMRGlc) in the ischemic or infarcted myocardium using 18-F-fluorodeoxyglucose (18-FDG) with positron emission tomography (PET), and studied energy metabolism in the ischemic myocardium. In some cases, we compared glucose metabolism images by 18-FDG with myocardial blood flow images using 15-oxygen water. Two normal subjects, seven patients with myocardial infarction and four patients with angina pectoris were studied. Coronary angiography was performed within two weeks before or after the PET study to detect ischemic areas. PET studies were performed for patients who did not eat for 5 to 6 hours after breakfast. Cannulation was performed in the pedal artery to measure free fatty acid, blood sugar, and insulin. After recording the transmission scan for subsequent correction of photon attenuation, blood pool images were recorded for two min. after the inhalation of carbon monoxide (oxygen-15) which labeled the red blood cells in vivo. After 20 min., oxygen-15 water (15 to 20 mCi) was injected for dynamic scans, and flow images were obtained. Thirty min. after this procedure, 18-FDG (5 to 6 mCi) was injected, and 60 min later, a static scan was performed and glucose metabolism images were obtained. Arterial blood sampling for the time activity curve of the tracer was performed at the same time. According to the method of Phelps et al, MMRGlc was calculated in each of the region of interest (ROI) which was located in the left ventricular wall. MMRGlc obtained from each ROI was 0 to 17 mg/100 ml/min. In normal subjects MMRGlc was 0.4 to 7.3 mg/100 ml/min. In patients with myocardial infarction, it ranged from 3 to 5 mg/100 ml/min in the infarcted lesion. In patients with angina pectoris and subendocardial infarction, MMRGlc was 7 to 17 mg/100 ml/min in the ischemic lesion. In this lesion, myocardial blood flow was relatively low by oxygen-15 imagings (so-called mismatch). (J.P.N.)

  19. Glucose and lipid metabolism in insulin resistance : an experimental study in fat cells

    Burén, Jonas

    2003-01-01

    Type 2 diabetes is usually caused by a combination of pancreatic β-cell failure and insulin resistance in target tissues like liver, muscle and fat. Insulin resistance is characterised by an impaired effect of insulin to reduce hepatic glucose production and to promote glucose uptake in peripheral tissues. The focus of this study was to further elucidate cellular mechanisms for insulin resistance that may be of relevance for type 2 diabetes in humans. We used rat and human adipocytes as an es...

  20. AMP-activated protein kinase plays an important evolutionary conserved role in the regulation of glucose metabolism in fish skeletal muscle cells

    Leonardo J Magnoni; Yoryia Vraskou; Palstra, Arjan P.; Planas, Josep V.

    2012-01-01

    AMPK, a master metabolic switch, mediates the observed increase of glucose uptake in locomotory muscle of mammals during exercise. AMPK is activated by changes in the intracellular AMP∶ATP ratio when ATP consumption is stimulated by contractile activity but also by AICAR and metformin, compounds that increase glucose transport in mammalian muscle cells. However, the possible role of AMPK in the regulation of glucose metabolism in skeletal muscle has not been investigated in other vertebrates,...

  1. The RUNX2 Transcription Factor Negatively Regulates SIRT6 Expression to Alter Glucose Metabolism in Breast Cancer Cells.

    Choe, Moran; Brusgard, Jessica L; Chumsri, Saranya; Bhandary, Lekhana; Zhao, Xianfeng Frank; Lu, Song; Goloubeva, Olga G; Polster, Brian M; Fiskum, Gary M; Girnun, Geoffrey D; Kim, Myoung Sook; Passaniti, Antonino

    2015-10-01

    Activation of genes promoting aerobic glycolysis and suppression of mitochondrial oxidative phosphorylation is one of the hallmarks of cancer. The RUNX2 transcription factor mediates breast cancer (BC) metastasis to bone and is regulated by glucose availability. But, the mechanisms by which it regulates glucose metabolism and promotes an oncogenic phenotype are not known. RUNX2 expression in luminal BC cells correlated with lower estrogen receptor-α (ERα) levels, anchorage-independent growth, expression of glycolytic genes, increased glucose uptake, and sensitivity to glucose starvation, but not to inhibitors of oxidative phosphorylation. Conversely, RUNX2 knockdown in triple-negative BC cells inhibited mammosphere formation and glucose dependence. RUNX2 knockdown resulted in lower LDHA, HK2, and GLUT1 glycolytic gene expression, but upregulation of pyruvate dehydrogenase-A1 (PDHA1) mRNA and enzymatic activity, which was consistent with lower glycolytic potential. The NAD-dependent histone deacetylase, SIRT6, a known tumor suppressor, was a critical regulator of these RUNX2-mediated metabolic changes. RUNX2 expression resulted in elevated pAkt, HK2, and PDHK1 glycolytic protein levels that were reduced by ectopic expression of SIRT6. RUNX2 also repressed mitochondrial oxygen consumption rates (OCR), a measure of oxidative phosphorylation (respiration). Overexpression of SIRT6 increased respiration in RUNX2-positive cells, but knockdown of SIRT6 in cells expressing low RUNX2 decreased respiration. RUNX2 repressed SIRT6 expression at both the transcriptional and post-translational levels and endogenous SIRT6 expression was lower in malignant BC tissues or cell lines that expressed high levels of RUNX2. These results support a hypothesis whereby RUNX2-mediated repression of the SIRT6 tumor suppressor regulates metabolic pathways that promote BC progression. PMID:25808624

  2. Glucose metabolism is altered after loss of L cells and α-cells but not influenced by loss of K cells

    Pedersen, J; Ugleholdt, Randi Kjærsgaard; Jørgensen, Signe Marie;

    2013-01-01

    glucagon is associated with impaired regulation of metabolism. This study evaluates the consequences of acute removal of Gip- or Gcg-expressing cells on glucose metabolism. Generation of the two diphtheria toxin receptor cellular knockout mice, TgN(GIP.DTR) and TgN(GCG.DTR), allowed us to study effects of...... acute ablation of K and L cells and α-cells. Diphtheria toxin administration reduced the expression of Gip and content of GIP in the proximal jejunum in TgN(GIP.DTR) and expression of Gcg and content of proglucagon-derived peptides in both proximal jejunum and terminal ileum as well as content of...

  3. Effect of sera from cystic fibrosis homozygotes and heterozygotes on glucose metabolism in vero cells

    The effect on intracellular production of carbon dioxide from glucose of sera from cystic fibrosis (C.F.) homozygotes and heterozygotes was determined in an established cell line (Vero cell) by a double-blind assay. CO2 production was reduced when cells were incubated with an ammonium-sulphate-precipitated fraction of sera from C.F. homozygotes and heterozygotes but not by a similar fraction from sera of healthy donors. (author)

  4. Paclitaxel Combined with Inhibitors of Glucose and Hydroperoxide Metabolism Enhances Breast Cancer Cell Killing Via H2O2-Mediated Oxidative Stress

    Hadzic, Tanja; Aykin-Burns, Nükhet; Zhu, Yueming; Coleman, Mitchell C.; Leick, Katie; Jacobson, Geraldine M.; Douglas R Spitz

    2010-01-01

    Cancer cells (relative to normal cells) demonstrate alterations in oxidative metabolism characterized by increased steady-state levels of reactive oxygen species [i.e. hydrogen peroxide, H2O2] that may be compensated for by increased glucose metabolism but the therapeutic significance of these observations is unknown. In the current study, inhibitors of glucose [i.e., 2-deoxy-D-glucose, 2DG] and hydroperoxide [i.e., L-buthionine-S, R-sulfoximine, BSO] metabolism were utilized in combination w...

  5. Sepsis does not alter red blood cell glucose metabolism or Na+ concentration: A 2H-, 23Na-NMR study

    The effects of sepsis on intracellular Na+ concentration ([Na+]i) and glucose metabolism were examined in rat red blood cells (RBCs) by using 23Na- and 2H-nuclear magnetic resonance (NMR) spectroscopy. Sepsis was induced in 15 halothane-anesthetized female Sprague-Dawley rats by using the cecal ligation and perforation technique; 14 control rats underwent cecal manipulation without ligation. The animals were fasted for 36 h, but allowed free access to water. At 36 h postsurgery, RBCs were examined by 23Na-NMR by using dysprosium tripolyphosphate as a chemical shift reagent. Human RBCs from 17 critically ill nonseptic patients and from 7 patients who were diagnosed as septic were also examined for [Na+]i. Five rat RBC specimens had [Na+]i determined by both 23Na-NMR and inductively coupled plasma-atomic emission spectroscopy (ICP-AES). For glucose metabolism studies, RBCs from septic and control rats were suspended in modified Krebs-Henseleit buffer containing [6,6-2H2]glucose and examined by 2H-NMR. No significant differences in [Na+]i or glucose utilization were found in RBCs from control or septic rats. There were no differences in [Na+]i in the two groups of patients. The [Na+]i determined by NMR spectroscopy agreed closely with measurements using ICP-AES and establish that 100% of the [Na+]i of the RBC is visible by NMR. Glucose measurements determined by 2H-NMR correlated closely (correlation coefficient = 0.93) with enzymatic analysis. These studies showed no evidence that sepsis disturbed RBC membrane function or metabolism

  6. Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic beta-cells

    Haugaard, Steen B; Andersen, Ove; Dela, Flemming; Holst, Jens Juul; Storgaard, Heidi; Fenger, Mogens; Iversen, Johan; Madsbad, Sten

    2005-01-01

    glucose metabolism, lipid metabolism and beta-cell function in lipodystrophic HIV-infected patients. METHODS: [3-3H]glucose was applied during euglycaemic hyperinsulinaemic clamps in association with indirect calorimetry in 43 normoglycaemic HIV-infected patients (18 lipodystrophic patients on HAART (LIPO......), 18 patients without lipodystrophy on HAART (NONLIPO) and seven patients who were naive to antiretroviral therapy (NAIVE) respectively). beta-cell function was evaluated by an intravenous glucose tolerance test. RESULTS: Compared with NONLIPO and NAIVE separately, LIPO displayed markedly reduced ratio...... of limb to trunk fat (RLF; > 34%, P < 0.001), hepatic insulin sensitivity (> 40%, P < 0.03), incremental glucose disposal (>50%, P < 0.001) and incremental exogenous glucose storage (>50%, P < 0.05). Furthermore, LIPO displayed reduced incremental glucose oxidation (P < 0.01), increased clamp free...

  7. Effect of endotoxin-induced monokines on glucose metabolism in the muscle cell line L6

    Exposure of fully differentiated L6 myotubes to a crude monokine preparation from endotoxin-stimulated RAW 264.7 cells resulted in a rapid and substantial (70%) increase in fructose 2,6-bisphosphate concentration coincident with a depletion of cellular glycogen and an increased lactate production. During the time required for glycogen depletion (3 hr), stimulation of 3-O-methyl-D-glucose and 2-deoxy-D-glucose uptake was initiated and observed to reach a maximum enhancement of 200% 12-15 hr later. The monokine had no effect on the K/sub m/ value for 2-deoxy-D-glucose uptake (1.1 mM), while V/sub max/ was increased from 912 to 2400 pmol/min per mg of protein. The increase was cytochalasin B inhibitable and was dependent on protein synthesis. Photoaffinity labeling and equilibrium binding studies with [3H]cytochalasin B support the hypothesis that this increase in hexose transport was due to an increase in hexose transporters present in the plasma membrane. Purified recombinant interleukin-1α had no effect on hexose transport, whereas purified recombinant cachectin/tumor necrosis factor did stimulate hexose uptake, with half-maximal stimulation occurring at 36 nM. Although cachectin accounts for most of the biological activity associated with the crude monokine preparation, it is not the only monokine capable of inducing glucose transport in L6 cells. Specific immunoabsorption of cachectin/tumor necrosis factor from the crude monokine preparation revealed a monokine that had a similar bioactivity at extremely low concentrations on L6 cells

  8. Testosterone deficiency induced by progressive stages of diabetes mellitus impairs glucose metabolism and favors glycogenesis in mature rat Sertoli cells.

    Rato, Luís; Alves, Marco G; Duarte, Ana I; Santos, Maria S; Moreira, Paula I; Cavaco, José E; Oliveira, Pedro F

    2015-09-01

    The incidence of type 2 diabetes mellitus and its prodromal stage, pre-diabetes, is rapidly increasing among young men, leading to disturbances in testosterone synthesis. However, the impact of testosterone deficiency induced by these progressive stages of diabetes on the metabolic behavior of Sertoli cells remains unknown. We evaluated the effects of testosterone deficiency associated with pre-diabetes and type 2 diabetes on Sertoli cells metabolism, by measuring (1) the expression and/or activities of glycolysis and glycogen metabolism-related proteins and (2) the metabolite secretion/consumption in Sertoli cells obtained from rat models of different development stages of the disease, to unveil the mechanisms by which testosterone deregulation may affect spermatogenesis. Glucose and pyruvate uptake were decreased in cells exposed to the testosterone concentration found in pre-diabetic rats (600nM), whereas the decreased testosterone concentrations found in type 2 diabetic rats (7nM) reversed this profile. Lactate production was not altered, although the expression and/or activity of lactate dehydrogenase and monocarboxylate transporter 4 were affected by progressive testosterone-deficiency. Sertoli cells exposed to type 2 diabetic conditions exhibited intracellular glycogen accumulation. These results illustrate that gradually reduced levels of testosterone, induced by progressive stages of diabetes mellitus, favor a metabolic reprogramming toward glycogen synthesis. Our data highlights a pivotal role for testosterone in the regulation of spermatogenesis metabolic support by Sertoli cells, particularly in individuals suffering from metabolic diseases. Such alterations may be in the basis of male subfertility/infertility associated with the progression of diabetes mellitus. PMID:26148570

  9. Glucosamine metabolism of herpes simplex virus infected cells. Inhibition of glycosylation by tunicamycin and 2-deoxy-D-glucose

    The formation of glucosamine-containing cell surface glycoproteins of herpes simplex virus (HSV) infected BMK cells was studied. Tunicamycin (TM) and 2-deoxy-D-glucose (DG) were used as inhibitors. With both inhibitors the multiplication of HSV was inhibited. DG markedly reduced cellular uptake of radioactively labelled glucosamine while TM interfered with the processing of glucosamine into TCA-insoluble material. Gel filtration chromatography on Sephadex G50 gel of cell surface material released by trypsin and further prepared by digestion with pronase indicated that TM and DG reduced the apparent high molecular weights of virus induced surface glycoproteins. In presence of DG the accumulation of a class of glucosamine-containing heterosaccharides (MW less than 3000) not present on DG-free HSV infected cells was observed. IN TM treated cells virtually all surface heterosaccharides with molecular weights exceeding 3000 and containing glucosamine disappeared. Moreover, a component compatible with a lipid-linked oligosaccharide present in DG treated cells was not observed in HSV infected TM treated cells. The results exemplifies some different steps in glucosamine metabolism of virus-induced cell surface glycoproteins differently affected by tunicamycin and 2-deoxy-D-glucose. (author)

  10. Protective properties of radio-chemoresistant glioblastoma stem cell clones are associated with metabolic adaptation to reduced glucose dependence.

    Fei Ye

    Full Text Available Glioblastoma stem cells (GSC are a significant cell model for explaining brain tumor recurrence. However, mechanisms underlying their radiochemoresistance remain obscure. Here we show that most clonogenic cells in GSC cultures are sensitive to radiation treatment (RT with or without temozolomide (TMZ. Only a few single cells survive treatment and regain their self-repopulating capacity. Cells re-populated from treatment-resistant GSC clones contain more clonogenic cells compared to those grown from treatment-sensitive GSC clones, and repeated treatment cycles rapidly enriched clonogenic survival. When compared to sensitive clones, resistant clones exhibited slower tumor development in animals. Upregulated genes identified in resistant clones via comparative expression microarray analysis characterized cells under metabolic stress, including blocked glucose uptake, impaired insulin/Akt signaling, enhanced lipid catabolism and oxidative stress, and suppressed growth and inflammation. Moreover, many upregulated genes highlighted maintenance and repair activities, including detoxifying lipid peroxidation products, activating lysosomal autophagy/ubiquitin-proteasome pathways, and enhancing telomere maintenance and DNA repair, closely resembling the anti-aging effects of caloric/glucose restriction (CR/GR, a nutritional intervention that is known to increase lifespan and stress resistance in model organisms. Although treatment-introduced genetic mutations were detected in resistant clones, all resistant and sensitive clones were subclassified to either proneural (PN or mesenchymal (MES glioblastoma subtype based on their expression profiles. Functional assays demonstrated the association of treatment resistance with energy stress, including reduced glucose uptake, fatty acid oxidation (FAO-dependent ATP maintenance, elevated reactive oxygen species (ROS production and autophagic activity, and increased AMPK activity and NAD(+ levels accompanied by

  11. Arginine deiminase resistance in melanoma cells is associated with metabolic reprogramming, glucose dependence, and glutamine addiction.

    Long, Yan; Tsai, Wen-Bin; Wangpaichitr, Medhi; Tsukamoto, Takashi; Savaraj, Niramol; Feun, Lynn G; Kuo, Macus Tien

    2013-11-01

    Many malignant human tumors, including melanomas, are auxotrophic for arginine due to reduced expression of argininosuccinate synthetase-1 (ASS1), the rate-limiting enzyme for arginine biosynthesis. Pegylated arginine deiminase (ADI-PEG20), which degrades extracellular arginine, resulting in arginine deprivation, has shown favorable results in clinical trials for treating arginine-auxotrophic tumors. Drug resistance is the major obstacle for effective ADI-PEG20 usage. To elucidate mechanisms of resistance, we established several ADI-PEG20-resistant (ADI(R)) variants from A2058 and SK-Mel-2 melanoma cells. Compared with the parental lines, these ADI(R) variants showed the following characteristics: (i) all ADI(R) cell lines showed elevated ASS1 expression, resulting from the constitutive binding of the transcription factor c-Myc on the ASS1 promoter, suggesting that elevated ASS1 is the major mechanism of resistance; (ii) the ADI(R) cell lines exhibited enhanced AKT signaling and were preferentially sensitive to PI3K/AKT inhibitors, but reduced mTOR signaling, and were preferentially resistant to mTOR inhibitor; (iii) these variants showed enhanced expression of glucose transporter-1 and lactate dehydrogenase-A, reduced expression of pyruvate dehydrogenase, and elevated sensitivity to the glycolytic inhibitors 2-deoxy-glucose and 3-bromopyruvate, consistent with the enhanced glycolytic pathway (the Warburg effect); (iv) the resistant cells showed higher glutamine dehydrogenase and glutaminase expression and were preferentially vulnerable to glutamine inhibitors. We showed that c-Myc, not elevated ASS1 expression, is involved in upregulation of many of these enzymes because knockdown of c-Myc reduced their expression, whereas overexpressed ASS1 by transfection reduced their expression. This study identified multiple targets for overcoming ADI-PEG resistance in cancer chemotherapy using recombinant arginine-degrading enzymes. PMID:23979920

  12. Glucose deprivation-induced metabolic oxidative stress and cancer therapy

    Simons Andrean; Mattson David; Dornfeld Ken; Spitz Douglas

    2009-01-01

    Cancer cells (vs. normal cells) demonstrate evidence of oxidative stress, increased glycolysis, and increased pentose cycle activity. The oxidative stress in cancer cells has been hypothesized to arise from mitochondrial dysfunction leading to increased levels of hydroperoxides, and cancer cells have been proposed to compensate for this defect by increasing glucose metabolism. Glucose metabolism has also been shown to play a role in hydroperoxide detoxification via the formation of pyruvate (...

  13. Design of a selective insulin receptor tyrosine kinase inhibitor and its effect on glucose uptake and metabolism in intact cells

    An inhibitor of the insulin receptor tyrosine kinase (IRTK), (hydroxy-2-napthalenylmethyl)phosphonic acid, was designed and synthesized and was shown to be an inhibitor of the biological effects of insulin in vitro. With a wheat germ purified human placental insulin receptor preparation, this compound inhibited the insulin-stimulated autophosphorylation of the 95-kDa β-subunit of the insulin receptor. The ability of the kinase to phosphorylate an exogenous peptide substrate, angiotensin II, was also inhibited. Half-maximal inhibition of basal and insulin-stimulated human placental IRTK activity was found at concentrations of 150 and 100 μM, respectively, with 2 mM angiotensin II as the peptide substrate. The inhibitor was found to be specific for tyrosine kinases over serine kinases and noncompetitive with ATP. The inhibitor was converted into various (acyloxy)methyl prodrugs in order to achieve permeability through cell membranes. These prodrugs inhibited insulin-stimulated autophosphorylation of the insulin receptor 95-kDa β-subunit in intact CHO cells transfected with human insulin receptor. Inhibition of insulin-stimulated glucose oxidation in isolated rat adipocytes and 2-deoxyglucose uptake into CHO cells was observed with these prodrugs. The data provide additional evidence for the involvement of the insulin receptor tyrosine kinase in the regulation of glucose uptake and metabolism. These results and additional data reported herein suggest that this class of prodrugs and inhibitors will be useful for modulating the activity of a variety of tyrosine kinases

  14. Elevated White Blood Cell Count Is Associated with Higher Risk of Glucose Metabolism Disorders in Middle-Aged and Elderly Chinese People

    Hua Jiang

    2014-05-01

    Full Text Available White blood cell (WBC count has been associated with diabetic risk, but whether the correlation is independent of other risk factors has hardly been studied. Moreover, very few such studies with large sample sizes have been conducted in Chinese. Therefore, we investigated the relationship between WBC count and glucose metabolism in china. We also examined the relevant variables of WBC count. A total of 9,697 subjects (mean age, 58.0 ± 9.1 years were recruited. The subjects were classified into four groups, including subjects with normal glucose tolerance, isolated impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus (T2DM. We found that WBC count increased as glucose metabolism disorders exacerbated. WBC count was also positively correlated with waist hip ratio, body mass index, smoking, triglycerides, glycosylated haemoglobin A1c (HbA1c and 2-h postprandial glucose. In addition, high density lipoprotein and the female gender were inversely correlated with WBC count. In patients with previously diagnosed T2DM, the course of T2DM was not correlated with WBC count. Our findings indicate that elevated WBC count is independently associated with worsening of glucose metabolism in middle-aged and elderly Chinese. In addition, loss of weight, smoking cessation, lipid-modifying therapies, and control of postprandial plasma glucose and HbA1c may ameliorate the chronic low-grade inflammation.

  15. Metabolism of 18F-FDG (2-fluoro-2-deoxy-D-glucose) in tumor cells

    Tumor cell components obtained at 5 min, 1 hr and 3 hr after 18F-FDG injections were analyzed by radio-thin-layer chromatography (TLC). Major metabolites were 18F-FDG-phosphate and 18F-FDM-phosphate. 18F-FDM and three unidentified compounds were found as minor metabolites. Time course of the composition of metabolites are as follows; 18F-FDG-phosphate was 88% at 5 mm after injection, but decreased to 53% at 3 hr after. 18F-FDM-phosphate was increased to 38% at 3 hr after injection. In conclusion, 18F-FDG is promptly phosphorylated after transportation into cell, and then exists as FDG-phosphate or 18F-FDM-phosphate. These results support known FDG distribution and metabolism, and it is possible that we use the information accumulated until now employing FDG manufactured by commercial supply system. (author)

  16. Correlation of glucose metabolism in brain cells and brain morphological changes with clinical typing in children with cerebral palsy

    Qiongxiang Zhai; Huixian Qiao; Jiqing Liu

    2006-01-01

    BACKGROUND:It is widely known that fluorino-18-fluorodeoxyglucose positron emission tomography(18F-FDG PET)is commonly used to evaluate and diagnose epilepsy;however,whether it is beneficial to understand functional metabolism of bra in cells so as to reflect injured site and degree of brain cells or not should be studied further.OBJECTIVE:To evaluate the correlation between glucose metabolism and clinical typling as well as the conelation between active function of brain cells and degree of brain injury among children with cerbral palsy with 18F-FDG PET and MRI and compare the results of them.DESIGN:Case analysis.SETTING:Department of Pediatrics,People's Hospital of Guangdong Province.PARTICIPANTS:A total of 31 children with cerebral palsy were selected from Out-patient Clinic and In-patient Department of People's Hospital of Guangdong Province from July 2001 to August 2004.Based on clinical criteria of cerebral palsy,patients were classified into spasm(n=10),gradual movement(n=4),mixed type(n =13)and ataxia(n=4).There were 18 boys and 13 girls aged from 10 months to 4 years.All of them were met the diagnostic criteria of cerebral palsy and all parents of them were told the facts.Exclusion cdteria:Patients who had cerebral palsy caused by genetic metabolism disease were excluded.METHODS:①All children accepted MRI examination after hospitalization with Philips Acs NT 15T superconductling magnetic resonance scanner.②All children were fasted for 4 hours.And then,PET image of brain was collected based on T+EID type.If obvious hypermetabolism or hypometabolism region successively occurred on two layers, the image was regarded as abnormality. ③Different correlations of various abnormal greups of MRI and vadous types of cerebral palsy with PET image were compared and analyzed with Erusal-Willas rank sum test.MAIN OUTCOME MEASURES:①Results of 18F-FDG PET;②Results of MRI examination;③Correlation of variously abnormal groups of MRI and various types of cerebral

  17. AMPK, a metabolic sensor, is involved in isoeugenol-induced glucose uptake in muscle cells

    Kim, Nami; Lee, Jung Ok; Lee, Hye Jeong; Lee, Yong Woo; Kim, Hyung Ip; Kim, Su Jin; Park, Sun Hwa; Lee, Chul Su; Ryoo, Sun Woo; Hwang, Geum-Sook; Kim, Hyeon Soo

    2016-01-01

    Isoeugenol exerts various beneficial effects on human health. However, the mechanisms underlying these effects are poorly understood. In this study, we observed that isoeugenol activated AMP-activated protein kinase (AMPK) and increased glucose uptake in rat L6 myotubes. Isoeugenol-induced increase in intracellular calcium concentration and glucose uptake was inhibited by STO-609, an inhibitor of calcium/calmodulin-dependent protein kinase kinase (CaMKK). Isoeugenol also increased the phospho...

  18. Repressing malic enzyme 1 redirects glucose metabolism, unbalances the redox state, and attenuates migratory and invasive abilities in nasopharyngeal carcinoma cell lines

    Chao-Nan Qian

    2012-11-01

    Full Text Available A large amount of nicotinamide adenine dinucleotide phosphate (NADPH is required for fatty acid synthesis and maintenance of the redox state in cancer cells. Malic enzyme 1(ME1-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool. ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis. In the present study, we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC cells. High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells. However, there were no obvious changes in the other two pathways for glucose metabolism: glycolysis and oxidative phosphorylation. Interestingly, NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells, whereas no significant difference was observed under high-glucose condition. ME1-repressed cells had significantly decreased tolerance to low-glucose condition. Moreover, NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress. Furthermore, diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein. Collectively, these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.

  19. Gis1 and Rph1 regulate glycerol and acetate metabolism in glucose depleted yeast cells.

    Jakub Orzechowski Westholm

    Full Text Available Aging in organisms as diverse as yeast, nematodes, and mammals is delayed by caloric restriction, an effect mediated by the nutrient sensing TOR, RAS/cAMP, and AKT/Sch9 pathways. The transcription factor Gis1 functions downstream of these pathways in extending the lifespan of nutrient restricted yeast cells, but the mechanisms involved are still poorly understood. We have used gene expression microarrays to study the targets of Gis1 and the related protein Rph1 in different growth phases. Our results show that Gis1 and Rph1 act both as repressors and activators, on overlapping sets of genes as well as on distinct targets. Interestingly, both the activities and the target specificities of Gis1 and Rph1 depend on the growth phase. Thus, both proteins are associated with repression during exponential growth, targeting genes with STRE or PDS motifs in their promoters. After the diauxic shift, both become involved in activation, with Gis1 acting primarily on genes with PDS motifs, and Rph1 on genes with STRE motifs. Significantly, Gis1 and Rph1 control a number of genes involved in acetate and glycerol formation, metabolites that have been implicated in aging. Furthermore, several genes involved in acetyl-CoA metabolism are downregulated by Gis1.

  20. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

    Cheng, Xiaofei; Ni, Bin; Zhang, Feng; Hu, Ying

    2016-01-01

    Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

  1. Twist promotes reprogramming of glucose metabolism in breast cancer cells through PI3K/AKT and p53 signaling pathways.

    Yang, Li; Hou, Yixuan; Yuan, Jie; Tang, Shifu; Zhang, Hailong; Zhu, Qing; Du, Yan-e; Zhou, Mingli; Wen, Siyang; Xu, Liyun; Tang, Xi; Cui, Xiaojiang; Liu, Manran

    2015-09-22

    Twist, a key regulator of epithelial-mesenchymal transition (EMT), plays an important role in the development of a tumorigenic phenotype. Energy metabolism reprogramming (EMR), a newly discovered hallmark of cancer cells, potentiates cancer cell proliferation, survival, and invasion. Currently little is known about the effects of Twist on tumor EMR. In this study, we found that glucose consumption and lactate production were increased and mitochondrial mass was decreased in Twist-overexpressing MCF10A mammary epithelial cells compared with vector-expressing MCF10A cells. Moreover, these Twist-induced phenotypic changes were augmented by hypoxia. The expression of some glucose metabolism-related genes such as PKM2, LDHA, and G6PD was also found to be upregulated. Mechanistically, activated β1-integrin/FAK/PI3K/AKT/mTOR and suppressed P53 signaling were responsible for the observed EMR. Knockdown of Twist reversed the effects of Twist on EMR in Twist-overexpressing MCF10A cells and Twist-positive breast cancer cells. Furthermore, blockage of the β1-integrin/FAK/PI3K/AKT/mTOR pathway by siRNA or specific chemical inhibitors, or rescue of p53 activation can partially reverse the switch of glucose metabolism and inhibit the migration of Twist-overexpressing MCF10A cells and Twist-positive breast cancer cells. Thus, our data suggest that Twist promotes reprogramming of glucose metabolism in MCF10A-Twist cells and Twist-positive breast cancer cells via activation of the β1-integrin/FAK/PI3K/AKT/mTOR pathway and inhibition of the p53 pathway. Our study provides new insight into EMR. PMID:26342198

  2. Effects of myostatin propeptide gene tranfection on glucose metabolism in cultured C2C12 cells

    张莎莎

    2014-01-01

    Objective To investigate the effects of recombinant adeno-associated virus-mediated myostatin propeptide(MPRO)on uptake and oxidation of glucose,and glycogen synthesis in C2C12 myotubes,as well as the associated molecular mechanism.Methods Mature C2C12myotubes were assigned to the following 6 groups:control,insulin,green fluorescent protein(GFP),insulin+

  3. Keratin 8/18 regulation of glucose metabolism in normal versus cancerous hepatic cells through differential modulation of hexokinase status and insulin signaling

    Mathew, Jasmin; Loranger, Anne; Gilbert, Stéphane [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada); Faure, Robert [Département de Pédiatrie, Université Laval and Centre de recherche du CHUQ (Centre Mère-Enfant), Québec, Qc, Canada G1V 4G2 (Canada); Marceau, Normand, E-mail: normand.marceau@crhdq.ulaval.ca [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada)

    2013-02-15

    As differentiated cells, hepatocytes primarily metabolize glucose for ATP production through oxidative phosphorylation of glycolytic pyruvate, whereas proliferative hepatocellular carcinoma (HCC) cells undergo a metabolic shift to aerobic glycolysis despite oxygen availability. Keratins, the intermediate filament (IF) proteins of epithelial cells, are expressed as pairs in a lineage/differentiation manner. Hepatocyte and HCC (hepatoma) cell IFs are made solely of keratins 8/18 (K8/K18), thus providing models of choice to address K8/K18 IF functions in normal and cancerous epithelial cells. Here, we demonstrate distinctive increases in glucose uptake, glucose-6-phosphate formation, lactate release, and glycogen formation in K8/K18 IF-lacking hepatocytes and/or hepatoma cells versus their respective IF-containing counterparts. We also show that the K8/K18-dependent glucose uptake/G6P formation is linked to alterations in hexokinase I/II/IV content and localization at mitochondria, with little effect on GLUT1 status. In addition, we find that the insulin-stimulated glycogen formation in normal hepatocytes involves the main PI-3 kinase-dependent signaling pathway and that the K8/K18 IF loss makes them more efficient glycogen producers. In comparison, the higher insulin-dependent glycogen formation in K8/K18 IF-lacking hepatoma cells is associated with a signaling occurring through a mTOR-dependent pathway, along with an augmentation in cell proliferative activity. Together, the results uncover a key K8/K18 regulation of glucose metabolism in normal and cancerous hepatic cells through differential modulations of mitochondrial HK status and insulin-mediated signaling.

  4. Evidence for Central Regulation of Glucose Metabolism*

    Carey, Michelle; Kehlenbrink, Sylvia; Hawkins, Meredith

    2013-01-01

    Evidence for central regulation of glucose homeostasis is accumulating from both animal and human studies. Central nutrient and hormone sensing in the hypothalamus appears to coordinate regulation of whole body metabolism. Central signals activate ATP-sensitive potassium (KATP) channels, thereby down-regulating glucose production, likely through vagal efferent signals. Recent human studies are consistent with this hypothesis. The contributions of direct and central inputs to metabolic regulat...

  5. Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults.

    Emmanuel Maganga

    Full Text Available Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART, yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher's exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7% vs.11/153 (7.2%, p<0.001 and frank diabetes mellitus (27/150 (18.0% vs. 8/153 (5.2%, p = 0.001 than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78-11.77, p<0.001. Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%.HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.

  6. Glucose metabolism of lactobacillus divergens

    The aim of this study was to compile an optimal growth and selective medium for Lactobacillus divergens and to determine the pathway by which it metabolised glucose. The optimum growth temperature is 25oC which is lower than that of most other lactobacilli. Citrate stimulates growth up to a concentration of 1% while acetate inhibits the organism at neutral pH, but it stimulates growth at pH 8.5 up to a concentration of 0.8%. MRS medium was therefore modified in order to obtain maximum growth of the organism. The acetate was omitted, sucrose was substituted for glucose and the pH was adjusted to 8.5. Sucrose was used, since a neutral pH is obtained after sterilisation of glucose in alkaline (pH ≥ 7.5) solution due to the degradation of glucose by the Maillard reaction. Various inhibitors and dyes were tested in order to formulate a selective medium. In the present study differently labelled glucose precursors were fermented by L. divergens and the fermentation products isolated by HPLC. The concentrations of acetate and formate were determined by comparison to a standard while the concentration of lactate and glucose was determined by enzymic assay. The radioactivity was determined by liquid scintillation counting and the positional labelling in lactate and acetate by chemical degradation. Fermentation of D-[U-14C]-glucose was included to correct for endogenous product dilution

  7. Glucose Metabolism in Mentally Retarded Children

    Glucose metabolism has been studied in normal, mentally retarded and hypothyroid children who exhibited subnormal I.Q. in spite of an adequate thyroxine dose. Two parameters, the breath and the blood, were examined. Continuous breath analysis following intravenous glucose-U-14C was carried out to examine its end product 14CO2. Blood was analysed half-hourly for the specific activity of glucose in this pool. Data are presented in terms of stable carbon dioxide expiration rate, the maximum specific activity of carbon dioxide attained, the glucose pool of the body and its turnover rate. (author)

  8. Centrosomal Protein of 55 Regulates Glucose Metabolism, Proliferation and Apoptosis of Glioma Cells via the Akt/mTOR Signaling Pathway

    Wang, Guangzhi; Liu, Mingna; Wang, Hongjun; Yu, Shan; Jiang, Zhenfeng; Sun, Jiahang; Han, Ke; Shen, Jia; Zhu, Minwei; Lin, Zhiguo; Jiang, Chuanlu; Guo, Mian

    2016-01-01

    Introduction: Glioma is one of the most common and most aggressive brain tumors in humans. The molecular and cellular mechanisms responsible for the onset and the progression of glioma are elusive and controversial. Centrosomal protein of 55 (CEP55) was initially described as a highly coiled-coil protein that plays critical roles in cell division, but was recently identified as being overexpressed in many human cancers. The function of CEP55 has not previously been characterized in glioma. We aim to discover the effect and mechanism of CEP55 in glioma development. Method: qRT-PCR and immunohistochemistry were used to analyze CEP55 expression. Glucose uptake, western blot, MTS, CCK-8, Caspase-3 activity and TUNEL staining assays were performed to investigate the role and mechanism of CEP55 on glioma cell process. Results: We found that the levels of CEP55 expression were upregulated in glioma. In addition, CEP55 appeared to regulate glucose metabolism of glioma cells. Furthermore, knockdown of CEP55 inhibited cell proliferation and induced cell apoptosis in glioma. Finally, we provided preliminary evidence that knockdown of CEP55 inhibited glioma development via suppressing the activity of Akt/mTOR signaling. Conclusions: Our results demonstrated that CEP55 regulates glucose metabolism, proliferation and apoptosis of glioma cells via the Akt/mTOR signaling pathway, and its promotive effect on glioma tumorigenesis can be a potential target for glioma therapy in the future. PMID:27471559

  9. Rosemary (Rosmarinus officinalis L.) extract regulates glucose and lipid metabolism by activating AMPK and PPAR pathways in HepG2 cells.

    Tu, Zheng; Moss-Pierce, Tijuana; Ford, Paul; Jiang, T Alan

    2013-03-20

    An epidemic of metabolic disorders such as obesity and diabetes is rising dramatically. Using natural products as potential preventive and therapeutic interventions for these disorders has drawn worldwide attention. Rosemary has been shown to lower blood glucose and cholesterol levels and mitigate weight gain in several in vivo studies. However, the mechanisms are essentially unknown. We investigated the effects of rosemary extract on metabolism and demonstrated that rosemary extract significantly increased glucose consumption in HepG2 cells. The phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC), was increased by rosemary extract. Rosemary extract also transcriptionally regulated the genes involved in metabolism, including SIRT1, PPARγ coactivator 1α (PGC1α), glucose-6-phosphatase (G6Pase), ACC, and low-density lipoprotein receptor (LDLR). Furthermore, the PPARγ-specific antagonist GW9662 diminished rosemary's effects on glucose consumption. Overall, our study suggested that rosemary potentially increases liver glycolysis and fatty acid oxidation by activating AMPK and PPAR pathways. PMID:23432097

  10. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

    Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra, E-mail: sukhmahendrasingh@yahoo.com

    2013-11-15

    Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment.

  11. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

    Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment.

  12. Effects of gamma-rays and glucose analogs on the energy metabolism of a cell line derived from human cerebral glioma

    Effects of gamma-rays and glucose analogs, 2-deoxy-D-glucose (2-DG), 5-thio-D-glucose (5-TG) and 3-O-methyl glucose (3-O-MG) on cellular energy metabolism have been studied in a cell line, derived from a human cerebral glioma, by analysing intermediates of glycolysis and some important nucleotides (ATP, NAD etc.) using the technique of isotachophoresis. Gamma-irradiation induced a transient decrease in the nucleotide levels accompanied by an accumulation of sugar phosphates, the nucleotide levels recovering in a few hours post-irradiation. 2-DG inhibited glycolysis and reduced the nucleotide levels of irradiated as well as unirradiated cells in a concentration-dependent manner both in presence and absence of respiration, whereas 5-TG and 3-OMG did not show significant effects in the presence of respiration. Reduced energy status observed with 2-DG under respiratory proficient conditions was completely reversed in 2 hr following its removal, whereas such a recovery was not observed in the absence of respiration. These results have important implications in the energy-linked modifications of tumor radiation response using glucose analogs. (author). 36 refs., 6 figs., 4 tabs

  13. Improved glucose regulation in type 2 diabetic patients with DPP-4 inhibitors: focus on alpha and beta cell function and lipid metabolism.

    Ahrén, Bo; Foley, James E

    2016-05-01

    Inhibition of dipeptidyl peptidase-4 (DPP-4) is an established glucose-lowering strategy for the management of type 2 diabetes mellitus. DPP-4 inhibitors reduce both fasting and postprandial plasma glucose levels, resulting in reduced HbA1c with low risk for hypoglycaemia and weight gain. They act primarily by preventing inactivation of the incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, thereby prolonging the enhanced endogenous levels of these hormones after meal ingestion. This in turn causes islet and extrapancreatic effects, including increased glucose sensing in islet alpha and beta cells. These effects result in increased insulin secretion and decreased glucagon secretion being more effective in hyperglycaemic states and reduced insulin secretion and increased glucagon secretion being more effective during hypoglycaemia. Other secondary pharmacological actions of DPP-4 inhibitors include mobilisation and burning of fat during meals, decrease in fat extraction from the gut, reduction of fasting lipolysis and liver fat and increase in LDL particle size. These actions contribute to the clinical effects of DPP-4 inhibition, and the reduced demand for insulin could also lead to a durability benefit. This review summarises the current knowledge of the secondary pharmacological actions of DPP-4 inhibitors that lead to improved glucose regulation in patients with type 2 diabetes, focusing on alpha and beta cell function and lipid metabolism. PMID:26894277

  14. Sleep Control, GPCRs, and Glucose Metabolism.

    Tsuneki, Hiroshi; Sasaoka, Toshiyasu; Sakurai, Takeshi

    2016-09-01

    Modern lifestyles prolong daily activities into the nighttime, disrupting circadian rhythms, which may cause sleep disturbances. Sleep disturbances have been implicated in the dysregulation of blood glucose levels and reported to increase the risk of type 2 diabetes (T2D) and diabetic complications. Sleep disorders are treated using anti-insomnia drugs that target ionotropic and G protein-coupled receptors (GPCRs), including γ-aminobutyric acid (GABA) agonists, melatonin agonists, and orexin receptor antagonists. A deeper understanding of the effects of these medications on glucose metabolism and their underlying mechanisms of action is crucial for the treatment of diabetic patients with sleep disorders. In this review we focus on the beneficial impact of sleep on glucose metabolism and suggest a possible strategy for therapeutic intervention against sleep-related metabolic disorders. PMID:27461005

  15. Effect of 2-deoxy-D-glucose on DNA double strand break repair, cell survival and energy metabolism in euoxic Ehrlich ascites tumour cells

    Effects of 2-deoxy-D-glucose (2-DG) on DNA double strand break (dsb) repair, cell survival and on the energy metabolism were investigated in exponentially growing Ehrlich ascites tumour (EAT) cells. Cells in suspension were exposed to 40 Gy of X-rays and allowed to repair (up to 4h) with or without 2-DG at 37oC. DNA dsb rejoining was measured by means of clamped homogeneous electric field (CHEF), a pulsed field gel electrophoresis technique. The fraction of activity released (FAR) during electrophoresis (DNA associated 14C-thymidine) was used as a parameter to determine the number of dsb present in the DNA. Biphasic kinetics for dsb repair were observed. The presence of 2-DG significantly inhibited the slow component of dsb repair. The presence of 2-DG also enhanced radiation-induced cell killing. ATP content of cells was measured by a bioluminescence method. ATP content in exponentially growing cells was about 4 pg per cell. The level of ATP was reduced by 50% in presence of 2-DG (C2-DG/CG = 1.0). (author)

  16. Glucose addiction of TSC-null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply

    Choo, Andrew Y.; Kim, Sang Gyun; Heiden, Matthew G. Vander; Mahoney, Sarah J.; Vu, Hieu; Yoon, Sang-Oh; Cantley, Lewis C.; Blenis, John

    2010-01-01

    Summary The mTORC1 signaling pathway integrates environmental conditions into distinct signals for cell growth by balancing anabolic and catabolic processes. Accordingly, energetic stress inhibits mTORC1 signaling predominantly through AMPK-dependent activation of TSC1/2. Thus, TSC1/2-/- cells are hypersensitive to glucose deprivation and this has been linked to increased p53 translation and activation of apoptosis. Herein, we show that mTORC1 inhibition during glucose deprivation prevented not only the execution of death, but also induction of energetic stress. mTORC1 inhibition during glucose deprivation decreased AMPK activation and allowed ATP to remain high, which was both necessary and sufficient for protection. This effect was not due to increased catabolic activities such as autophagy, but rather exclusively due to decreased anabolic processes, reducing energy consumption. Specifically, TSC1/2-/- cells become highly dependent on glutamate dehydrogenase-dependent glutamine metabolism via the TCA cycle for survival. Therefore, mTORC1 inhibition during energetic stress is primarily to balance metabolic demand with supply. PMID:20513425

  17. Oroxylin A regulates glucose metabolism in response to hypoxic stress with the involvement of Hypoxia-inducible factor-1 in human hepatoma HepG2 cells.

    Dai, Qinsheng; Yin, Qian; Wei, Libin; Zhou, Yuxin; Qiao, Chen; Guo, Yongjian; Wang, Xiaotang; Ma, Shiping; Lu, Na

    2016-08-01

    Metabolic alteration in cancer cells is one of the most conspicuous characteristics that distinguish cancer cells from normal cells. In this study, we investigated the influence and signaling ways of oroxylin A affecting cancer cell energy metabolism under hypoxia. The data showed that oroxylin A remarkably reduced the generation of lactate and glucose uptake under hypoxia in HepG2 cells. Moreover, oroxylin A inhibited HIF-1α expression and its stability. The downstream targets (PDK1, LDHA, and HK II), as well as their mRNA levels were also suppressed by oroxylin A under hypoxia. The silencing or the overexpression of HIF-1α assays suggested that HIF-1α is required for metabolic effect of oroxylin A in HepG2 cells during hypoxia. Furthermore, oroxylin A could reduce the expression of complex III in mitochondrial respiratory chain, and then decrease the accumulation of ROS at moderate concentrations (0-50 µM) under hypoxia, which was benefit for its inhibition on glycolytic activity by decreasing ROS-mediated HIF-1 expression. Besides, oroxylin A didn't cause the loss of MMP under hypoxia and had no obvious effects on the expression of OXPHOS complexes, suggesting that oroxylin A did not affect mitochondrial mass at the moderate stress of oroxylin A. The suppressive effect of oroxylin A on glycolysis led to a significantly repress of ATP generation, for ATP generation mostly depends on glycolysis in HepG2 cells. This study revealed a new aspect of glucose metabolism regulation of oroxylin A under hypoxia, which may contribute to its new anticancer mechanism. © 2015 Wiley Periodicals, Inc. PMID:26259145

  18. Hepatic glucose and lipid metabolism.

    Jones, John G

    2016-06-01

    The liver has a central role in the regulation of systemic glucose and lipid fluxes during feeding and fasting and also relies on these substrates for its own energy needs. These parallel requirements are met by coordinated control of carbohydrate and lipid fluxes into and out of the Krebs cycle, which is highly tuned to nutrient availability and heavily regulated by insulin and glucagon. During progression of type 2 diabetes, hepatic carbohydrate and lipid biosynthesis fluxes become elevated, thus contributing to hyperglycaemia and hypertriacylglycerolaemia. Over this interval there are also significant fluctuations in hepatic energy state. To date, it is not known to what extent abnormal glucose and lipid fluxes are causally linked to altered energy states. Recent evidence that the glucose-lowering effects of metformin appear to be mediated by attenuation of hepatic energy generation places an additional spotlight on the interdependence of hepatic biosynthetic and oxidative fluxes. The transition from fasting to feeding results in a significant re-direction of hepatic glucose and lipid fluxes and may also incur a temporary hepatic energy deficit. At present, it is not known to what extent these variables are additionally modified by type 2 diabetes and/or non-alcoholic fatty liver disease. Thus, there is a compelling need to measure fluxes through oxidative, gluconeogenic and lipogenic pathways and determine their relationship with hepatic energy state in both fasting and fed conditions. New magnetic resonance-based technologies allow these variables to be non-invasively studied in animal models and humans. This review summarises a presentation given at the symposium entitled 'The liver in focus' at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Kenneth Cusi, DOI: 10.1007/s00125-016-3952-1 , and by Hannele Yki-Järvinen, DOI: 10.1007/s00125-016-3944-1 ) and a commentary by the Session Chair, Michael

  19. Short-term high-fat diet alters postprandial glucose metabolism and circulating vascular cell adhesion molecule-1 in healthy males.

    Numao, Shigeharu; Kawano, Hiroshi; Endo, Naoya; Yamada, Yuka; Takahashi, Masaki; Konishi, Masayuki; Sakamoto, Shizuo

    2016-08-01

    Short-term intake of a high-fat diet aggravates postprandial glucose metabolism; however, the dose-response relationship has not been investigated. We hypothesized that short-term intake of a eucaloric low-carbohydrate/high-fat diet (LCHF) would aggravate postprandial glucose metabolism and circulating adhesion molecules in healthy males. Seven healthy young males (mean ± SE; age: 26 ± 1 years) consumed either a eucaloric control diet (C, approximately 25% fats), a eucaloric intermediate-carbohydrate/intermediate-fat diet (ICIF, approximately 50% fats), or an LCHF (approximately 70% fats) for 3 days. An oral meal tolerance test (MTT) was performed after the 3-day dietary intervention. The concentrations of plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1) were determined at rest and during MTT. The incremental area under the curve (iAUC) of plasma glucose concentration during MTT was significantly higher in LCHF than in C (P = 0.009). The first-phase insulin secretion indexes were significantly lower in LCHF than in C (P = 0.04). Moreover, the iAUC of GLP-1 and VCAM-1 concentrations was significantly higher in LCHF than in C (P = 0.014 and P = 0.04, respectively). The metabolites from ICIF and C were not significantly different. In conclusion, short-term intake of eucaloric diet containing a high percentage of fats in healthy males excessively increased postprandial glucose and VCAM-1 concentrations and attenuated first-phase insulin release. PMID:27454856

  20. CMPF does not associate with impaired glucose metabolism in individuals with features of metabolic syndrome.

    Maria A Lankinen

    Full Text Available 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF is a metabolite produced endogenously from dietary sources of furan fatty acids. The richest source of furan fatty acids in human diet is fish. CMPF was recently shown to be elevated in fasting plasma in individuals with gestational diabetes and type 2 diabetes, and mechanistically high level of CMPF was linked to β cell dysfunction. Here we aimed to study the association between plasma CMPF level and glucose metabolism in persons with impaired glucose metabolism.Plasma CMPF concentration was measured from plasma samples of the study participants in an earlier controlled dietary intervention. All of them had impaired glucose metabolism and two other characteristics of the metabolic syndrome. Altogether 106 men and women were randomized into three groups for 12 weeks with different fish consumption (either three fatty fish meals per week, habitual fish consumption or maximum of one fish meal per week. Associations between concentration of CMPF and various glucose metabolism parameters at an oral glucose tolerance test at baseline and at the end of the study were studied.Fasting plasma CMPF concentration was significantly increased after a 12-week consumption of fatty fish three times per week, but the concentration remained much lower compared to concentrations reported in diabetic patients. Increases of plasma CMPF concentrations mostly due to increased fish consumption were not associated with impaired glucose metabolism in this study. Instead, elevated plasma CMPF concentration was associated with decreased 2-hour insulin concentration in OGTT.Moderately elevated concentration of CMPF in plasma resulting from increased intake of fish is not harmful to glucose metabolism. Further studies are needed to fully explore the role of CMPF in the pathogenesis of impaired glucose metabolism.ClinicalTrials.gov NCT00573781.

  1. Preferential Transport and Metabolism of Glucose in Bergmann Glia over Purkinje Cells: A Multiphoton Study of Cerebellar Slices

    L.F.BARROS; R.COURJARET; P.JAKOBY; A.LOAIZA; C.LOHR; J.W.DEITMER

    2009-01-01

    了解不同类型的细胞如何处理葡萄糖有助于解释能量供应是如何是如何根据大脑能量需求来进行调整的.荧光追踪结合共聚焦显微镜技术已用于研究培养的脑细胞摄取葡萄糖的实时动态过程.本文采用这种技术利用多光子显微镜观察急性制备的大鼠小脑脑片.带荧光的葡萄糖类似物2NBDG和6NBDG在小脑皮质的分子层中的转运速度比其在蒲肯野细胞胞体和颗粒细胞中快若干倍.洗脱游离示踪剂后,可见大部分磷酸化示踪剂都位于Bergmann胶质细胞,用胶质细胞标记物sulforhodamine 101免疫染色后进一步确认这一结果.有效回收荧光光漂白后显示,2NBDG-P可通过Bergmann胶质细胞之间的缝隙连接沿着分子层水平扩散.本文的结果表明在急性小脑切片中,Bergmann胶质细胞对葡萄糖的转运能力和糖酵解率高于蒲肯野细胞若干倍.由于小脑主要由葡萄糖提供能量,蒲肯野神经元被认为比Bergmann胶质细胞更耗能量,这些结果表明,在胶质细胞和神经元之间存在类似乳酸的能量代谢物介导的环路.%Knowing how different cell types handle glucose should help to decipher how energy supply is adjusted to energy demand in the brain. Previously, the uptake of glucose by cultured brain cells was studied in real-time using fluorescent tracers and confocal microscopy. Here, we have adapted this technique to acute slices prepared from the rat cerebellum by means of multiphoton microscopy. The transport of the fluorescent glucose analogs 2NBDG and 6NBDG was several-fold faster in the molecular layer of the cerebellar cortex than in Purkinje cell somata and granule cells. After washout of free tracer, it became apparent that most phosphorylated tracer was located in Bergmann glia, which was confirmed by counterstaining with the glial marker sulforhodamine 101. The effective recovery of fluorescence after photobleaching showed that 2NBDG-P can diffuse

  2. Steroid Receptor Coactivator-3 Regulates Glucose Metabolism in Bladder Cancer Cells through Coactivation of Hypoxia Inducible Factor 1α*

    Zhao, Wei; Chang, Cunjie; Cui, Yangyan; Zhao, Xiaozhi; Yang, Jun; Shen, Lan; Zhou, Ji; Hou, Zhibo; Zhang, Zhen; Ye, Changxiao; Hasenmayer, Donald; Perkins, Robert; Huang, Xiaojing; Yao, Xin; Yu, Like; Huang, Ruimin; Zhang, Dianzheng; Guo, Hongqian; Yan, Jun

    2014-01-01

    Cancer cell proliferation is a metabolically demanding process, requiring high glycolysis, which is known as “Warburg effect,” to support anabolic growth. Steroid receptor coactivator-3 (SRC-3), a steroid receptor coactivator, is overexpressed and/or amplified in multiple cancer types, including non-steroid targeted cancers, such as urinary bladder cancer (UBC). However, whether SRC-3 regulates the metabolic reprogramming for cancer cell growth is unknown. Here, we reported that overexpression of SRC-3 accelerated UBC cell growth, accompanied by the increased expression of genes involved in glycolysis. Knockdown of SRC-3 reduced the UBC cell glycolytic rate under hypoxia, decreased tumor growth in nude mice, with reduction of proliferating cell nuclear antigen and lactate dehydrogenase expression levels. We further revealed that SRC-3 could interact with hypoxia inducible factor 1α (HIF1α), which is a key transcription factor required for glycolysis, and coactivate its transcriptional activity. SRC-3 was recruited to the promoters of HIF1α-target genes, such as glut1 and pgk1. The positive correlation of expression levels between SRC-3 and Glut1 proteins was demonstrated in human UBC patient samples. Inhibition of glycolysis through targeting HK2 or LDHA decelerated SRC-3 overexpression-induced cell growth. In summary, overexpression of SRC-3 promoted glycolysis in bladder cancer cells through HIF1α to facilitate tumorigenesis, which may be an intriguing drug target for bladder cancer therapy. PMID:24584933

  3. Enhanced muscle glucose metabolism after exercise

    Richter, Erik; Garetto, L P; Goodman, M N;

    1984-01-01

    Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase in the...... presence of insulin is found. To determine whether these alterations and in particular those mediated by insulin are due to local or systemic factors, one hindlimb of an anesthetized rat was electrically stimulated, and both hindlimbs were perfused immediately thereafter. Glucose and glycogen metabolism in...... the stimulated leg closely mimicked that observed previously after voluntary exercise on a treadmill. With no insulin added to the perfusate, glucose incorporation into glycogen was markedly enhanced in muscles that were glycogen depleted as were the uptake of 2-deoxyglucose and 3-O...

  4. Osteocalcin as a hormone regulating glucose metabolism

    2015-01-01

    The number of patients with osteoporosis and diabetesis rapidly increasing all over the world. Bone is recentlyrecognized as an endocrine organ. Accumulatingevidence has shown that osteocalcin, which is specificallyexpressed in osteoblasts and secreted into the circulation,regulates glucose homeostasis by stimulating insulinexpression in pancreas and adiponectin expression inadipocytes, resulting in improving glucose intolerance.On the other hand, insulin and adiponectin stimulateosteocalcin expression in osteoblasts, suggesting thatpositive feedforward loops exist among bone, pancreas,and adipose tissue. In addition, recent studies haveshown that osteocalcin enhances insulin sensitivity andthe differentiation in muscle, while secreted factors frommuscle, myokines, regulate bone metabolism. Thesefindings suggest that bone metabolism and glucosemetabolism are associated with each other through theaction of osteocalcin. In this review, I describe the roleof osteocalcin in the interaction among bone, pancreas,brain, adipose tissue, and muscle.

  5. Cerebral glucose metabolism in Parkinson's disease

    Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra

  6. Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome

    Leder, Lena; Kolehmainen, Marjukka; Narverud, Ingunn;

    2016-01-01

    BACKGROUND: Diet has a great impact on the risk of developing features of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). We evaluated whether a long-term healthy Nordic diet (ND) can modify the expression of inflammation and lipid metabolism......-related genes in peripheral blood mononuclear cells (PBMCs) during a 2-h oral glucose tolerance test (OGTT) in individuals with MetS. METHODS: A Nordic multicenter randomized dietary study included subjects (n = 213) with MetS, randomized to a ND group or a control diet (CD) group applying an isocaloric study...... the mRNA gene expression analysis was measured by quantitative real-time polymerase chain reaction (qPCR). We analyzed the mRNA expression changes of 44 genes before and after a 2hOGTT at the beginning and the end of the intervention. RESULTS: The healthy ND significantly down-regulated the expression...

  7. Changes of myocardial glucose metabolism by starvation

    Ischemic heart disease (IHD) is a fatal disease and high food intake is thought one of the important risk factor for IHD. Biochemical analyse of the relation between food and IHD is necessary. F-18-labeled 2-deoxy-glucose (FDG) is useful pharmaceutical for detection of myocardial glucose metabolism. The effect of starvation on myocardial uptake and retention of FDG was investigated. Control rats which were fed ad libitum were killed 10, 30, 60 and 120 minutes after the injection of FDG (10 uCi). The other rats were starved for 12, 24, 36 and 48 hours each. The rats were killed 30 minutes after the injection of FDG. Myocardial uptakes of FDG were high enough 30 minutes after the injection of FDG. Decrease of myocardial uptake was showed in 12 hours starvation alrealdy and decrease was greater according to the starvation time. From this result myocardial glucose metabolism is considered to be suppressed early stage of starvation another energy metabolic pathway is considered to be used

  8. Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production

    Lam, Tony K.T.

    2007-01-01

    Brain glucose-sensing mechanisms are implicated in the regulation of feeding behavior and hypoglycemic-induced hormonal counter-regulation. This commentary discusses recent findings indicating that the brain senses glucose to regulate both hepatic glucose and lipid production.

  9. Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia

    SONG, KUI; Li, Min; Xu, Xiaojun; Xuan, Li; HUANG, GUINIAN; Liu, Qifa

    2016-01-01

    Altered glucose metabolism has been described as a cause of chemoresistance in multiple tumor types. The present study aimed to identify the expression profile of glucose metabolism in drug-resistant acute myeloid leukemia (AML) cells and provide potential strategies for the treatment of drug-resistant AML. Bone marrow and serum samples were obtained from patients with AML that were newly diagnosed or had relapsed. The messenger RNA expression of hypoxia inducible factor (HIF)-1α, glucose tra...

  10. The Role of Glucose, Serum, and Three-Dimensional Cell Culture on the Metabolism of Bone Marrow-Derived Mesenchymal Stem Cells

    Byron Deorosan

    2011-01-01

    factors in the metabolic response of the cells. However, cells cultured in low density collagen exhibited considerable cell death, likely because of physical contraction of the collagen hydrogel which was not observed in the higher density collagen. These findings will be useful to the development of in vitro cell culture models that properly mimic in vivo physiological processes.

  11. Uric acid as a modulator of glucose and lipid metabolism.

    Lima, William Gustavo; Martins-Santos, Maria Emília Soares; Chaves, Valéria Ernestânia

    2015-09-01

    In humans, uric acid is the final oxidation product of purine catabolism. The serum uric acid level is based on the balance between the absorption, production and excretion of purine. Uric acid is similarly produced in the liver, adipose tissue and muscle and is primarily excreted through the urinary tract. Several factors, including a high-fructose diet and the use of xenobiotics and alcohol, contribute to hyperuricaemia. Hyperuricaemia belongs to a cluster of metabolic and haemodynamic abnormalities, called metabolic syndrome, characterised by abdominal obesity, glucose intolerance, insulin resistance, dyslipidaemia and hypertension. Hyperuricaemia reduction in the Pound mouse or fructose-fed rats, as well as hyperuricaemia induction by uricase inhibition in rodents and studies using cell culture have suggested that uric acid plays an important role in the development of metabolic syndrome. These studies have shown that high uric acid levels regulate the oxidative stress, inflammation and enzymes associated with glucose and lipid metabolism, suggesting a mechanism for the impairment of metabolic homeostasis. Humans lacking uricase, the enzyme responsible for uric acid degradation, are susceptible to these effects. In this review, we summarise the current knowledge of the effects of uric acid on the regulation of metabolism, primarily focusing on liver, adipose tissue and skeletal muscle. PMID:26133655

  12. Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring

    Ma, Ya-Hong; Yu, Caiguo; Kayoumu, Abudurexiti; Guo, Xin; Ji, Zhili; Liu, George

    2015-01-01

    Abstract Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH. However, it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance. In this study, we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice. ApoCIII transgenic mice with severe hypertriglyceridemia...

  13. The Role of Glucose, Serum, and Three-Dimensional Cell Culture on the Metabolism of Bone Marrow-Derived Mesenchymal Stem Cells

    Byron Deorosan; Nauman, Eric A.

    2011-01-01

    Mesenchymal stem cells (MSCs) have become a critical addition to all facets of tissue engineering. While most in vitro research has focused on their behavior in two-dimensional culture, relatively little is known about the cells' behavior in three-dimensional culture, especially with regard to their metabolic state. To evaluate MSC metabolism during twodimensional culture, murine bone marrow-derived MSCs were cultured for one week using twelve different medium compositions, varying in both gl...

  14. Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin

    Jin Shao

    2015-01-01

    Full Text Available Skeleton was considered as a dynamic connective tissue, which was essential for mobility, calcium homeostasis, and hematopoietic niche. However more and more evidences indicate that skeleton works not only as a structural scaffold but also as an endocrine organ, which regulates several metabolic processes. Besides osteoprotegerin (OPG, sclerostin (SOST, and Dickopf (DKK which play essential roles in bone formation, modelling, remodelling, and homeostasis, bone can also secret hormones, such as osteocalcin (OCN, which promotes proliferation of β cells, insulin secretion, and insulin sensitivity. Additionally OCN can also regulate the fat cells and male gonad endocrine activity and be regulated by insulin and the neural system. In summary, skeleton has endocrine function via OCN and plays an important role in energy metabolism, especially in glucose metabolism.

  15. Neuronal Cell Death Induced by Mechanical Percussion Trauma in Cultured Neurons is not Preceded by Alterations in Glucose, Lactate and Glutamine Metabolism.

    Jayakumar, A R; Bak, L K; Rama Rao, K V; Waagepetersen, H S; Schousboe, A; Norenberg, M D

    2016-02-01

    Traumatic brain injury (TBI) is a devastating neurological disorder that usually presents in acute and chronic forms. Brain edema and associated increased intracranial pressure in the early phase following TBI are major consequences of acute trauma. On the other hand, neuronal injury, leading to neurobehavioral and cognitive impairments, that usually develop months to years after single or repetitive episodes of head trauma, are major consequences of chronic TBI. The molecular mechanisms responsible for TBI-induced injury, however, are unclear. Recent studies have suggested that early mitochondrial dysfunction and subsequent energy failure play a role in the pathogenesis of TBI. We therefore examined whether oxidative metabolism of (13)C-labeled glucose, lactate or glutamine is altered early following in vitro mechanical percussion-induced trauma (5 atm) to neurons (4-24 h), and whether such events contribute to the development of neuronal injury. Cell viability was assayed using the release of the cytoplasmic enzyme lactate dehydrogenase (LDH), together with fluorescence-based cell staining (calcein and ethidium homodimer-1 for live and dead cells, respectively). Trauma had no effect on the LDH release in neurons from 1 to 18 h. However, a significant increase in LDH release was detected at 24 h after trauma. Similar findings were identified when traumatized neurons were stained with fluorescent markers. Additionally (13)C-labeling of glutamate showed a small, but statistically significant decrease at 14 h after trauma. However, trauma had no effect on the cycling ratio of the TCA cycle at any time-period examined. These findings indicate that trauma does not cause a disturbance in oxidative metabolism of any of the substrates used for neurons. Accordingly, such metabolic disturbance does not appear to contribute to the neuronal death in the early stages following trauma. PMID:26729365

  16. Gut microbiota may have influence on glucose and lipid metabolism

    Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost; Tvede, Michael;

    2013-01-01

    prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism....

  17. The importance of glucose metabolism in the hypoxic cytotoxicity of Misonidazole

    The authors are investigating the mechanism of inhibition of glucose metabolism and its role in the hypoxic cytotoxicity of Misonidazole (Miso). Preincubation of hypoxic exponential EMT6/Ro cells with Miso and 5.5 mM glucose containing media caused a time-dependent inhibition of both glucose consumption and lactate formation. This inhibition began after 90 min, 45 min, and 15 min preincubation with 1mM, 2.5mM, and 5mM Miso respectively. The inhibition closely correlated with the kinetics and extent of decreased viability of these cells as measured by dye exclusion and colony forming efficiency. Miso does not inhibit glucose transport in these phloretin-sensitive cells. Transport was measured by the uptake of 3-0-methyl-D-glucose, a non-metabolized glucose analog. The initial rate was determined to be the same (1.66 +- 0.18 nmoles cell/second at 250C)

  18. Association among heterogeneity of intratumoral anti-CD20 antibody distribution, glucose metabolism and therapeutic response in radioimmunotherapy for B-cell lymphoma

    Full text of publication follows. Aim: in Zevalin therapy for CD20 positive low-grade lymphoma, heterogeneity of intratumoral anti-CD20 antibody distribution as well as status of lesional glucose metabolism prior to therapy may affect tumor response. The aim of this study was to evaluate association of heterogeneity of intratumoral In-111 Zevalin (In-Zevalin), accumulation of F-18 FDG (FDG), and therapeutic response in patients receiving Zevalin therapy. Methods: 16 patients with CD20 positive B-cell non-Hodgkin's lymphoma who underwent Y-90 Zevalin therapy after imaging with In-Zevalin SPECT/CT and FDG PET/CT were enrolled. Patients received In-Zevalin, followed by SPECT/CT scanning at 48 hours after administration. SUVmax of FDG of lesions was measured on PET/CT while lesion accumulation of In-Zevalin as %ID/g and SUVmax of In-Zevalin (In-Zevalin SUVmax) was measured on SPECT/CT. To evaluate heterogeneity of anti-CD20 antibody distribution, skewness and kurtosis of voxel distribution were calculated by placing there-dimensional volumes of interest (3-D VOIs) on SPECT/CT images. As another intratumoral heterogeneity index, cumulative SUVmax-volume histograms describing percentage of total tumor volume above thresholds of In-Zevalin SUVmax (AUC-CSH) were calculated by placing 3-D VOIs. All lesions (n=42) were classified into responders and non-responders lesion-by-lesion on pre- and post-therapeutic CT images. Results: by lesion-based analysis, a positive correlation was observed between FDG SUVmax and accumulation of In-Zevalin. Accumulation of In-Zevalin was 0.0022 ± 0.0009 and 0.0024 ± 0.0008 %ID/g (n.s.), and 2.74 ± 1.43 and 3.29 ± 1.47 SUVmax (n.s.) for responders and non-responders, respectively. In contrast, voxel distribution of In-Zevalin demonstrated skewness of 0.58 ± 0.16 and 0.73 ± 0.24 (p<0.05), kurtosis of 2.39 ± 0.32 and 2.78 ± 0.53 (p<0.02), and AUC-CSH of 0.37 ± 0.04 and 0.34 ± 0.05 (p<0.05) for responders and non

  19. Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic beta-cells

    Haugaard, Steen B; Andersen, Ove; Dela, Flemming;

    2005-01-01

    ), 18 patients without lipodystrophy on HAART (NONLIPO) and seven patients who were naive to antiretroviral therapy (NAIVE) respectively). beta-cell function was evaluated by an intravenous glucose tolerance test. RESULTS: Compared with NONLIPO and NAIVE separately, LIPO displayed markedly reduced ratio...... of limb to trunk fat (RLF; > 34%, P < 0.001), hepatic insulin sensitivity (> 40%, P < 0.03), incremental glucose disposal (>50%, P < 0.001) and incremental exogenous glucose storage (>50%, P < 0.05). Furthermore, LIPO displayed reduced incremental glucose oxidation (P < 0.01), increased clamp free...... fatty acids (P < 0.05) and attenuated insulin-mediated suppression of lipid oxidation (P < 0.05) compared with NONLIPO. In combined study groups, RLF correlated with hepatic insulin sensitivity (r = 0.69), incremental glucose disposal (r = 0.71) and incremental exogenous glucose storage (r = 0.40), all...

  20. Energetics of Glucose Metabolism: A Phenomenological Approach to Metabolic Network Modeling

    Frank Diederichs

    2010-08-01

    Full Text Available A new formalism to describe metabolic fluxes as well as membrane transport processes was developed. The new flux equations are comparable to other phenomenological laws. Michaelis-Menten like expressions, as well as flux equations of nonequilibrium thermodynamics, can be regarded as special cases of these new equations. For metabolic network modeling, variable conductances and driving forces are required to enable pathway control and to allow a rapid response to perturbations. When applied to oxidative phosphorylation, results of simulations show that whole oxidative phosphorylation cannot be described as a two-flux-system according to nonequilibrium thermodynamics, although all coupled reactions per se fulfill the equations of this theory. Simulations show that activation of ATP-coupled load reactions plus glucose oxidation is brought about by an increase of only two different conductances: a [Ca2+] dependent increase of cytosolic load conductances, and an increase of phosphofructokinase conductance by [AMP], which in turn becomes increased through [ADP] generation by those load reactions. In ventricular myocytes, this feedback mechanism is sufficient to increase cellular power output and O2 consumption several fold, without any appreciable impairment of energetic parameters. Glucose oxidation proceeds near maximal power output, since transformed input and output conductances are nearly equal, yielding an efficiency of about 0.5. This conductance matching is fulfilled also by glucose oxidation of β-cells. But, as a price for the metabolic mechanism of glucose recognition, β-cells have only a limited capability to increase their power output.

  1. Neuronal Cell Death Induced by Mechanical Percussion Trauma in Cultured Neurons is not Preceded by Alterations in Glucose, Lactate and Glutamine Metabolism

    Jayakumar, A R; Bak, L K; Rama Rao, K V;

    2016-01-01

    dysfunction and subsequent energy failure play a role in the pathogenesis of TBI. We therefore examined whether oxidative metabolism of (13)C-labeled glucose, lactate or glutamine is altered early following in vitro mechanical percussion-induced trauma (5 atm) to neurons (4-24 h), and whether such events...

  2. Increased insulin sensitivity and responsiveness of glucose metabolism in adipocytes from female versus male rats.

    Guerre-Millo, M.; Leturque, A.; Girard, J.; Lavau, M

    1985-01-01

    This study was undertaken to examine whether there were sex-associated differences in the action of insulin on glucose metabolism in adipocytes. Insulin binding and the dose-response curves for glucose transport (assessed by measuring the cell-associated radioactivity after 15-s incubation with 50 microM [6-14C]glucose) and [U-14C]glucose (5 mM) metabolism into CO2 and lipids were compared in retroperitoneal adipocytes from age-matched (84 d) male and female rats. In addition, the activity of...

  3. Effects of fluctuating glucose levels on neuronal cells in vitro.

    Russo, Vincenzo C; Higgins, Sandra; Werther, George A; Cameron, Fergus J

    2012-08-01

    There is increasing evidence for glucose fluctuation playing a role in the damaging effects of diabetes on various organs, including the brain. We aimed to study the effects of glycaemic variation (GV) upon mitochondrial activity using an in vitro human neuronal model. The metabolic disturbance of GV in neuronal cells, was mimicked via exposure of neuroblastoma cells SH-SY5Y to constant glucose or fluctuating (i.e. 6 h cycles) for 24 and 48 h. Mitochondrial dehydrogenase activity was determined via MTT assay. Cell mitochondrial activity (MTT) was moderately decreased in constant high glucose, but markedly decreased following 24 and 48 h of cyclical glucose fluctuations. Glucose transport determined via 2-deoxy-D-[1-(14)C] glucose uptake was regulated in an exaggerated manner in response to glucose variance, accompanied by modest changes in GLUT 1 mRNA abundance. Osmotic components of these glucose effects were investigated in the presence of the osmotic-mimics mannitol and L: -glucose. Both treatments showed that fluctuating osmolality did not result in a significant change in mitochondrial activity and had no effects on (14)Cglucose uptake, suggesting that adverse effects on mitochondrial function were specifically related to metabolically active glucose fluctuations. Apoptosis gene expression showed that both intrinsic and extrinsic apoptotic pathways were modulated by glucose variance, with two major response clusters corresponding to (i) glucose stress-modulated genes, (ii) glucose mediated osmotic stress-modulated genes. Gene clustering analysis by STRING showed that most of the glucose stress-modulated genes were components of the intrinsic/mitochondrial apoptotic pathway including Bcl-2, Caspases and apoptosis executors. On the other hand the glucose mediated osmotic stress-modulated genes were mostly within the extrinsic apoptotic pathway, including TNF receptor and their ligands and adaptors/activators/initiators of apoptosis. Fluctuating glucose levels

  4. In Vivo Correlation of Glucose Metabolism, Cell Density and Microcirculatory Parameters in Patients with Head and Neck Cancer: Initial Results Using Simultaneous PET/MRI.

    Matthias Gawlitza

    Full Text Available To demonstrate the feasibility of simultaneous acquisition of 18F-FDG-PET, diffusion-weighted imaging (DWI and T1-weighted dynamic contrast-enhanced MRI (T1w-DCE in an integrated simultaneous PET/MRI in patients with head and neck squamous cell cancer (HNSCC and to investigate possible correlations between these parameters.17 patients that had given informed consent (15 male, 2 female with biopsy-proven HNSCC underwent simultaneous 18F-FDG-PET/MRI including DWI and T1w-DCE. SUVmax, SUVmean, ADCmean, ADCmin and Ktrans, kep and ve were measured for each tumour and correlated using Spearman's ρ.Significant correlations were observed between SUVmean and Ktrans (ρ = 0.43; p ≤ 0.05; SUVmean and kep (ρ = 0.44; p ≤ 0.05; Ktrans and kep (ρ = 0.53; p ≤ 0.05; and between kep and ve (ρ = -0.74; p ≤ 0.01. There was a trend towards statistical significance when correlating SUVmax and ADCmin (ρ = -0.35; p = 0.08; SUVmax and Ktrans (ρ = 0.37; p = 0.07; SUVmax and kep (ρ = 0.39; p = 0.06; and ADCmean and ve (ρ = 0.4; p = 0.06.Simultaneous 18F-FDG-PET/MRI including DWI and T1w-DCE in patients with HNSCC is feasible and allows depiction of complex interactions between glucose metabolism, microcirculatory parameters and cellular density.

  5. Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review

    Shengxi Meng

    2013-01-01

    Full Text Available Intracellular glucose and lipid metabolic homeostasis is vital for maintaining basic life activities of a cell or an organism. Glucose and lipid metabolic disorders are closely related with the occurrence and progression of diabetes, obesity, hepatic steatosis, cardiovascular disease, and cancer. Chlorogenic acid (CGA, one of the most abundant polyphenol compounds in the human diet, is a group of phenolic secondary metabolites produced by certain plant species and is an important component of coffee. Accumulating evidence has demonstrated that CGA exerts many biological properties, including antibacterial, antioxidant, and anticarcinogenic activities. Recently, the roles and applications of CGA, particularly in relation to glucose and lipid metabolism, have been highlighted. This review addresses current studies investigating the roles of CGA in glucose and lipid metabolism.

  6. Regional glucose metabolism using PETT in normal and psychiatric populations

    Brodie, J.D.; Wolf, A.P.; Volkow, N.

    1982-01-01

    The metabolism of /sup 18/F-2-deoxy-2-fluoro-D-glucose (/sup 18/FDG) in 150 subjects including normals, schizophrenics, senile dementias, and primary affective disorders was studied. Some of the data analyzed to date are discussed.

  7. Regional glucose metabolism using PETT in normal and psychiatric populations

    The metabolism of 18F-2-deoxy-2-fluoro-D-glucose (18FDG) in 150 subjects including normals, schizophrenics, senile dementias, and primary affective disorders was studied. Some of the data analyzed to date are discussed

  8. Glucose metabolism in pregnant sheep when placental growth is restricted

    The effect of restricting placental growth on glucose metabolism in pregnant sheep in late gestation was determined by primed constant infusions of D-[U-14C]- and D-[2-3H]glucose and antipyrine into fetuses of six control sheep and six sheep from which endometrial caruncles had been removed before pregnancy (caruncle sheep). In the latter, placental and fetal weights were reduced, as was the concentration of glucose in fetal arterial blood. Fetal glucose turnover in caruncle sheep was only 52-59% of that in controls, largely because of lower umbilical loss of glucose back to the placenta (38-39% of control) and lower fetal glucose utilization (61-74% of control). However, fetal glucose utilization on a weight-specific basis was similar in control and caruncle sheep. Significant endogenous glucose production occurred in control and caruncle fetal sheep. Maternal glucose production and partition of glucose between the gravid uterus and other maternal tissues were similar in control and caruncle sheep. In conclusion, when placental and fetal growth are restricted, fetal glucose utilization is maintained by reduced loss of glucose back to the placenta and mother and by maintaining endogenous glucose production

  9. Adult glucose metabolism in extremely birthweight-discordant monozygotic twins

    Frost, M; Petersen, I; Brixen, K;

    2012-01-01

    Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment.......Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment....

  10. Evidence of non-pancreatic beta cell-dependent roles of Tcf7l2 in the regulation of glucose metabolism in mice

    Bailey, Kathleen A.; Savic, Daniel; Zielinski, Mark; Park, Soo-Young; Wang, Ling-Jia; Witkowski, Piotr; Brady, Matthew; Hara, Manami; Bell, Graeme I.; Nobrega, Marcelo A.

    2014-01-01

    Non-coding variation within TCF7L2 remains the strongest genetic determinant of type 2 diabetes risk in humans. A considerable effort has been placed in understanding the functional roles of TCF7L2 in pancreatic beta cells, despite evidence of TCF7L2 expression in various peripheral tissues important in glucose homeostasis. Here, we use a humanized mouse model overexpressing Tcf7l2, resulting in glucose intolerance, to infer the contribution of Tcf7l2 overexpression in beta cells and in other...

  11. Cancer stem cell metabolism

    Peiris-Pagès, Maria; Martinez-Outschoorn, Ubaldo E.; Pestell, Richard G.; Sotgia, Federica; Lisanti, Michael P

    2016-01-01

    Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes. Deter...

  12. Effects of MDMA on blood glucose levels and brain glucose metabolism

    Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M. [Hospital General Universitario Gregorio Maranon, Laboratorio de Imagen, Medicina Experimental, Madrid (Spain); Arango, C. [Hospital General Gregorio Maranon, Departamento de Psiquiatria, Madrid (Spain); Ricaurte, G. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States)

    2007-06-15

    This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

  13. Effects of MDMA on blood glucose levels and brain glucose metabolism

    This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

  14. Evaluation of glucose metabolism in women with multiple ovarian follicles

    Shulan Lü; Xiaoyan Guo; Zuansun Cao; Wenjun Mao

    2007-01-01

    Objective:To investigate glucose metabolism in women with multiple ovarian follicles (MOF) and explore the relationship between glucose metabolism, insulin resistance and body weight. Methods:We evaluated 46 women with MFO and 30 nor mal women as controls. All the subjects were given 75g of glucose orally in order to perform the oral glucose tolerance test(OGTT) and insulin releasing test(IRT), and they were also evaluated for insulin resistance using the insulin resistance index with homeostatic model assessment (HOMA). Results:The occurrence of impaired glucose tolerance in women with MOF was 10.87%, which was significantly higher than that in the control group (3.33% ,P < 0.05). The rate of insulin resistance was 30.43% in the study group as compared to 10.00% in the control group. The results showed that there was significant difference between the two groups(P < 0.05). The levels of FSH,LH,PRL,E2,T and P between the two groups had no significant difference (P > 0.05). BMI in women with impaired glucose tolerance was correlated positively to insulin resistance (r =0.567, P < 0.05). Conclusion :Abnormal glucose metabolism was observed in women with unitary multiple ovarian follicles,and this could be attributed to obesity and insulin resistance. Women with MOF and associated obesity should be subjected to OGTT so that their glucose levels can be monitored as a preventive measure.

  15. Peripheral glucose metabolism and insulin sensitivity in Alzheimer's disease.

    Kilander, L; Boberg, M; Lithell, H

    1993-04-01

    Twenty-four patients with Alzheimer's disease and matched controls were examined with reference to metabolic parameters such as peripheral insulin and glucose metabolism, serum lipid concentrations and blood pressure levels. Blood glucose levels and insulin response were measured during an intravenous glucose tolerance test and peripheral insulin sensitivity was estimated with the hyperinsulinemic euglycemic clamp technique. There were no differences recorded between the two groups in glucose metabolism, triglyceride, cholesterol or HDL-cholesterol levels. The patients with Alzheimer's disease had significantly lower blood pressure levels, which partly could be explained by ongoing treatment with neuroleptics and antidepressives. Previous findings of higher insulin levels in Alzheimer's disease could not be verified. PMID:8503259

  16. Utilization of dietary glucose in the metabolic syndrome

    Alemany Marià

    2011-10-01

    Full Text Available Abstract This review is focused on the fate of dietary glucose under conditions of chronically high energy (largely fat intake, evolving into the metabolic syndrome. We are adapted to carbohydrate-rich diets similar to those of our ancestors. Glucose is the main energy staple, but fats are our main energy reserves. Starvation drastically reduces glucose availability, forcing the body to shift to fatty acids as main energy substrate, sparing glucose and amino acids. We are not prepared for excess dietary energy, our main defenses being decreased food intake and increased energy expenditure, largely enhanced metabolic activity and thermogenesis. High lipid availability is a powerful factor decreasing glucose and amino acid oxidation. Present-day diets are often hyperenergetic, high on lipids, with abundant protein and limited amounts of starchy carbohydrates. Dietary lipids favor their metabolic processing, saving glucose, which additionally spares amino acids. The glucose excess elicits hyperinsulinemia, which may derive, in the end, into insulin resistance. The available systems of energy disposal could not cope with the excess of substrates, since they are geared for saving not for spendthrift, which results in an unbearable overload of the storage mechanisms. Adipose tissue is the last energy sink, it has to store the energy that cannot be used otherwise. However, adipose tissue growth also has limits, and the excess of energy induces inflammation, helped by the ineffective intervention of the immune system. However, even under this acute situation, the excess of glucose remains, favoring its final conversion to fat. The sum of inflammatory signals and deranged substrate handling induce most of the metabolic syndrome traits: insulin resistance, obesity, diabetes, liver steatosis, hyperlipidemia and their compounded combined effects. Thus, a maintained excess of energy in the diet may result in difficulties in the disposal of glucose, eliciting

  17. Regional cerebral glucose metabolism in patients with alcoholic Korsakoff's syndrome

    Seven alcoholic male subjects diagnosed as having Korsakoff's syndrome and eight age-matched male normal volunteers were studied with /sup 18/F 2-fluoro-2-deoxy-D-glucose (2/sup 18/FDG). All subjects were examined at rest with eyes covered in a quiet, darkened room. Serial plasma samples were obtained following injection of 4 to 5 mCi of 2/sup 18/FDG. Tomographic slices spaced at 10mm axial increments were obtained (in-plane resolution = 1.75 cm, axial resolution = 1.78 cm). Four planes were selected from each subject, and a total of 46 regions of interest were sampled and glucose metabolic rates for each region calculated. The mean glucose metalbolic rate for the 46 regions in the Korsakoff subjects was significantly lower than that in the normal controls (5.17 +- .43 versus 6.6 +- 1.31). A Q-component analysis, which examined each subject's regional rates relative to his mean rate, revealed two distinct patterns in the Korsakoff group. Glucose metabolism was significantly reduced in 37 of the 46 regions sampled. Reduced cerebral glucose metabolism in a nondemented group of subjects has not previously been reported. The reduction in cortical metabolism may be the result of damage to sub-cortical projecting systems. The differing patterns of cerebral metabolism in Korsakoff's syndrome suggests subgroups with differing neuropathology. Regions implicated in memory function, medial temporal, thalamic and medial prefrontal were among the regions reduced in metabolism

  18. Cerebral glucose transport and metabolism with dynamic PET

    A comprehensive model describing the response of the steady-state tissue distribution of glucose to changes in plasma glucose concentration was developed. In the model, the steady-state glucose content can be used to predict the steady-state distribution spaces of both phosphorylatable and non-phosphorylatable glucose analogs, and thus the value of the lumped constant (LC) required to convert measured rates of analog metabolism to the desired rate of glucose metabolism. Models of the sensitivity of the kinetic rate constants for phosphorylatable glucose analogs to tissue glucose content were developed. The use of the measured distribution space of a non-phosphorylatable analog such as methyl glucose as an indicator of the LC, is only useful for hyperglycemia. We determined that a particular aspect of the kinetics of phosphorylatable analogs, the ratio of the phosphorylation rate constant to the membrane transport rate constant, is very sensitive to glucose content over the entire physiological range of values. Considerable effort is being made to optimize the use of venous blood that is ''arterialized'' by limb warming methods. Similarly, final refinements have been made to the non-linear least squares fitting routines, allowing for blood-borne radioactivity and for the loss of phosphorylation product

  19. Lymphocyte Glucose and Glutamine Metabolism as Targets of the Anti-Inflammatory and Immunomodulatory Effects of Exercise

    Frederick Wasinski; Gregnani, Marcos F.; Ornellas, Fábio H.; Aline V N Bacurau; Câmara, Niels O.; Ronaldo C Araujo; Reury F. Bacurau

    2014-01-01

    Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight ...

  20. The effects of hypoglycin on glucose metabolism in the rat

    The kinetics of glucose metabolism were evaluated in rats deprived of food 15 to 21 h after the administration of hypoglycaemic doses of hypoglycin (100 mg/kg body wt.) by following changes in the specific radioactivities of 14C and 3H in blood glucose after an intravenous dose of [U-14C,2-3H]glucose. During this time, recycling of glucose through the Cori cycle was virtually abolished, the rate of irreversible disposal of glucose and its total body mass were both decreased by about 70%, whereas there was little effect on the mean transit time for glucose. It was concluded that hypoglycaemia is due to inhibition of gluconeogenesis. (author)

  1. Convergence role of transcriptional coactivator p300 and apparent modification on HMCs metabolic memory induced by high glucose

    Su, Hong; Bo ZHOU; Ya-qian DUAN; Du, Chao

    2013-01-01

    Objective  To investigate the protein expression of transcriptional coactivator p300, acetylated histone H3 (Ac-H3) and Ac-H4 in human renal mesangial cell (HMCs) as imitative "metabolic memory" in vitro, and explore the potential role of convergence point of p300. Methods  The HMCs were divided into the following groups: ① High glucose metabolic memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d), high glucose group (HG, 25mmol/L D-glucose×2d), memory groups (M1, M2, M3, 25mmol/L...

  2. A link between sleep loss, glucose metabolism and adipokines

    H.G. Padilha

    2011-10-01

    Full Text Available The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modified release of adipokines resulting from sleep deprivation could lead to a chronic sub-inflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.

  3. UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets

    Dalgaard, Louise Torp

    2012-01-01

    Uncoupling Protein 2 (UCP2) is expressed in the pancreatic β-cell, where it partially uncouples the mitochondrial proton gradient, decreasing both ATP-production and glucose-stimulated insulin secretion (GSIS). Increased glucose levels up-regulate UCP2 mRNA and protein levels, but the mechanism for...... UCP2 up-regulation in response to increased glucose is unknown. The aim was to examine the effects of glucokinase (GK) deficiency on UCP2 mRNA levels and to characterize the interaction between UCP2 and GK with regard to glucose-stimulated insulin secretion in pancreatic islets. UCP2 mRNA expression...... was reduced in GK+/- islets and GK heterozygosity prevented glucose-induced up-regulation of islet UCP2 mRNA. In contrast to UCP2 protein function UCP2 mRNA regulation was not dependent on superoxide generation, but rather on products of glucose metabolism, because MnTBAP, a superoxide dismutase...

  4. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

    Mirco Galiè; Paolo Farace; Cristina Nanni; Antonello Spinelli; Elena Nicolato; Federico Boschi; Paolo Magnani; Silvia Trespidi; Valentina Ambrosini; Stefano Fanti; Flavia Merigo; Francesco Osculati; Pasquina Marzola; Andrea Sbarbati

    2007-01-01

    Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular ...

  5. Serum Visfatin Levels, Adiposity and Glucose Metabolism in Obese Adolescents

    Taşkesen, Derya; Kirel, Birgül; Us, Tercan

    2012-01-01

    Objective: Visfatin, an adipokine, has insulin-mimetic effects. The main determinants of both the production and the physiologic role of visfatin are still unclear. The aim of this study is to determine the relation of serum visfatin to adiposity and glucose metabolism. Methods: 40 pubertal adolescents (20 females, 20 males; age range: 9-17 years) with exogenous obesity and 20 age- and sex-matched healthy adolescents (10 females, 10 males) were enrolled in the study. Oral glucose tolerance te...

  6. Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism.

    Murai, Hideki; Suzuki, Yukihisa; Kiyosawa, Motohiro; Wakakura, Masato; Mochizuki, Manabu; Ishiwata, Kiichi; Ishii, Kenji

    2011-01-01

    A 43-year-old woman with drug-related blepharospasm was followed up for 22 months. She had undergone etizolam treatment for 19 years for indefinite complaints. We examined her cerebral glucose metabolism 5 times (between days 149 and 688 since presentation), using positron emission tomography, and identified regions of interest in the thalamus, caudate nucleus, putamen, and primary somatosensory area on both sides. The severity of the blepharospasm was evaluated by PET scanning using the Wakakura classification. Sixteen women (mean age 42.4 ± 11.7 years) were examined as normal controls. The thalamic glucose metabolism in our patient was significantly increased on days 149, 212, and 688. The severity of the blepharospasm was positively correlated with the thalamic glucose metabolism, suggesting that the severity of blepharospasms reflects thalamic activity. PMID:22110436

  7. Parameters of glucose metabolism and the aging brain

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild;

    2015-01-01

    MRI was used to detect macro-structural damage (atrophy, white matter hyper-intensities, infarcts and/or micro-bleeds) and magnetization transfer imaging (MTI) to detect loss of micro-structural homogeneity that remains otherwise invisible on conventional MRI. Macro-structurally, higher fasted glucose......Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean...... age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain...

  8. Glucose metabolism in rats submitted to skeletal muscle denervation

    Wilton Marlindo Santana Nunes; Maria Alice Rostom de Mello

    2005-01-01

    This study analyzed the local and systemic effects of immobilization by denervation of the skeletal muscle on glucose metabolism. The rats were submitted to section of the right paw sciatic nerve. A reduction was observed in glucose uptake by the isolated soleus muscle of the denervated paw after 3 and 7 days, but not after 28 days in relation to the control animals. There was no difference after 3 and 7 days in glucose uptake by the soleus muscle of the opposite intact paw in relation to the...

  9. Muscle glucose metabolism following exercise in the rat

    Richter, Erik; Garetto, L P; Goodman, M N;

    1982-01-01

    perfusion of their isolated hindquarters. Glucose utilization by the hindquarter was the same in exercised and control rats perfused in the absence of added insulin; however, when insulin (30-40,000 muU/ml) was added to the perfusate, glucose utilization was greater after exercise. Prior exercise lowered...... both, the concentration of insulin that half-maximally stimulated glucose utilization (exercise, 150 muU/ml; control, 480 muU/ml) and modestly increased its maximum effect. The increase in insulin sensitivity persisted for 4 h following exercise, but was not present after 24 h. The rate-limiting step...... in glucose utilization enhanced by prior exercise appeared to be glucose transport across the cell membrane, as in neither control nor exercised rats did free glucose accumulate in the muscle cell. Following exercise, the ability of insulin to stimulate the release of lactate into the perfusate was...

  10. Snail modulates cell metabolism in MDCK cells

    Highlights: ► MDCK/snail cells were more sensitive to glucose deprivation than MDCK/neo cells. ► MDCK/snail cells had decreased oxidative phosphorylation, O2 consumption and ATP content. ► TCA cycle enzyme activity, but not expression, was lower in MDCK/snail cells. ► MDCK/snail cells showed reduced PDH activity and increased PDK1 expression. ► MDCK/snail cells showed reduced expression of GLS2 and ACLY. -- Abstract: Snail, a repressor of E-cadherin gene transcription, induces epithelial-to-mesenchymal transition and is involved in tumor progression. Snail also mediates resistance to cell death induced by serum depletion. By contrast, we observed that snail-expressing MDCK (MDCK/snail) cells undergo cell death at a higher rate than control (MDCK/neo) cells in low-glucose medium. Therefore, we investigated whether snail expression influences cell metabolism in MDCK cells. Although gylcolysis was not affected in MDCK/snail cells, they did exhibit reduced pyruvate dehydrogenase (PDH) activity, which controls pyruvate entry into the tricarboxylic acid (TCA) cycle. Indeed, the activity of multiple enzymes involved in the TCA cycle was decreased in MDCK/snail cells, including that of mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2), succinate dehydrogenase (SDH), and electron transport Complex II and Complex IV. Consequently, lower ATP content, lower oxygen consumption and increased survival under hypoxic conditions was also observed in MDCK/snail cells compared to MDCK/neo cells. In addition, the expression and promoter activity of pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inhibits the activity of PDH, was increased in MDCK/snail cells, while expression levels of glutaminase 2 (GLS2) and ATP-citrate lyase (ACLY), which are involved in glutaminolysis and fatty acid synthesis, were decreased in MDCK/snail cells. These results suggest that snail modulates cell metabolism by altering the expression and activity of key enzymes

  11. Snail modulates cell metabolism in MDCK cells

    Haraguchi, Misako, E-mail: haraguci@m3.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Indo, Hiroko P. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Iwasaki, Yasumasa [Health Care Center, Kochi University, Kochi 780-8520 (Japan); Iwashita, Yoichiro [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Fukushige, Tomoko [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Majima, Hideyuki J. [Department of Maxillofacial Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Izumo, Kimiko; Horiuchi, Masahisa [Department of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Kanekura, Takuro [Department of Dermatology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Furukawa, Tatsuhiko [Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan); Ozawa, Masayuki [Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544 (Japan)

    2013-03-22

    Highlights: ► MDCK/snail cells were more sensitive to glucose deprivation than MDCK/neo cells. ► MDCK/snail cells had decreased oxidative phosphorylation, O{sub 2} consumption and ATP content. ► TCA cycle enzyme activity, but not expression, was lower in MDCK/snail cells. ► MDCK/snail cells showed reduced PDH activity and increased PDK1 expression. ► MDCK/snail cells showed reduced expression of GLS2 and ACLY. -- Abstract: Snail, a repressor of E-cadherin gene transcription, induces epithelial-to-mesenchymal transition and is involved in tumor progression. Snail also mediates resistance to cell death induced by serum depletion. By contrast, we observed that snail-expressing MDCK (MDCK/snail) cells undergo cell death at a higher rate than control (MDCK/neo) cells in low-glucose medium. Therefore, we investigated whether snail expression influences cell metabolism in MDCK cells. Although gylcolysis was not affected in MDCK/snail cells, they did exhibit reduced pyruvate dehydrogenase (PDH) activity, which controls pyruvate entry into the tricarboxylic acid (TCA) cycle. Indeed, the activity of multiple enzymes involved in the TCA cycle was decreased in MDCK/snail cells, including that of mitochondrial NADP{sup +}-dependent isocitrate dehydrogenase (IDH2), succinate dehydrogenase (SDH), and electron transport Complex II and Complex IV. Consequently, lower ATP content, lower oxygen consumption and increased survival under hypoxic conditions was also observed in MDCK/snail cells compared to MDCK/neo cells. In addition, the expression and promoter activity of pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inhibits the activity of PDH, was increased in MDCK/snail cells, while expression levels of glutaminase 2 (GLS2) and ATP-citrate lyase (ACLY), which are involved in glutaminolysis and fatty acid synthesis, were decreased in MDCK/snail cells. These results suggest that snail modulates cell metabolism by altering the expression and activity of

  12. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    Bentzen, Joan; Poulsen, Pernille; Vaag, Allan; Fenger, Mogens

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI R...... five polymorphisms was seen in the dizygotic twins. The effect of the polymorphisms on lipid and glucose parameters could be mediated through linkage to genes with known effect on glucose metabolism or through free fatty acids exerting their effect on glucose metabolism.......The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco......RI RFLP) were established using polymerase chain reaction and restriction enzyme digests. The effect of genotypes on lipid levels and on glucose, insulin, and HOMA (i.e., calculated parameters of beta-cell function and insulin resistance) was assessed by multivariate analyses of variance correcting for...

  13. Gastric emptying, glucose metabolism and gut hormones

    Vermeulen, Mechteld A R; Richir, Milan C; Garretsen, Martijn K;

    2011-01-01

    To study the gastric-emptying rate and gut hormonal response of two carbohydrate-rich beverages. A specifically designed carbohydrate-rich beverage is currently used to support the surgical patient metabolically. Fruit-based beverages may also promote recovery, due to natural antioxidant and carb......To study the gastric-emptying rate and gut hormonal response of two carbohydrate-rich beverages. A specifically designed carbohydrate-rich beverage is currently used to support the surgical patient metabolically. Fruit-based beverages may also promote recovery, due to natural antioxidant...... and carbohydrate content. However, gastric emptying of fluids is influenced by its nutrient composition; hence, safety of preoperative carbohydrate loading should be confirmed. Because gut hormones link carbohydrate metabolism and gastric emptying, hormonal responses were studied....

  14. Glucose regulates lipid metabolism in fasting king penguins.

    Bernard, Servane F; Orvoine, Jord; Groscolas, René

    2003-08-01

    This study aims to determine whether glucose intervenes in the regulation of lipid metabolism in long-term fasting birds, using the king penguin as an animal model. Changes in the plasma concentration of various metabolites and hormones, and in lipolytic fluxes as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo before, during, and after a 2-h glucose infusion under field conditions. All the birds were in the phase II fasting status (large fat stores, protein sparing) but differed by their metabolic and hormonal statuses, being either nonstressed (NSB; n = 5) or stressed (SB; n = 5). In both groups, glucose infusion at 5 mg.kg-1.min-1 induced a twofold increase in glycemia. In NSB, glucose had no effect on lipolysis (maintenance of plasma concentrations and rates of appearance of glycerol and nonesterified fatty acids) and no effect on the plasma concentrations of triacylglycerols (TAG), glucagon, insulin, or corticosterone. However, it limited fatty acid (FA) oxidation, as indicated by a 25% decrease in the plasma level of beta-hydroxybutyrate (beta-OHB). In SB, glucose infusion induced an approximately 2.5-fold decrease in lipolytic fluxes and a large decrease in FA oxidation, as reflected by a 64% decrease in the plasma concentration of beta-OHB. There were also a 35% decrease in plasma TAG, a 6.5- and 2.8-fold decrease in plasma glucagon and corticosterone, respectively, and a threefold increase in insulinemia. These data show that in fasting king penguins, glucose regulates lipid metabolism (inhibition of lipolysis and/or of FA oxidation) and affects hormonal status differently in stressed vs. nonstressed individuals. The results also suggest that in birds, as in humans, the availability of glucose, not of FA, is an important determinant of the substrate mix (glucose vs. FA) that is oxidized for energy production. PMID:12738609

  15. Non-invasive in-cell determination of free cytosolic [NAD+]/[NADH] ratios using hyperpolarized glucose show large variations in metabolic phenotypes

    Christensen, Caspar Elo; Karlsson, Magnus; Winther, Jakob R.;

    2014-01-01

    Accumulating evidence suggest that the pyridine nucleotide NAD has far wider biological functions than its classical role in energy metabolism. NAD is used by hundreds of enzymes that catalyse substrate oxidation and as such it plays a key role in various biological processes such as aging, cell...

  16. Glucose metabolism in critically ill patients

    Nielsen, Signe Tellerup; Krogh-Madsen, Rikke; Møller, Kirsten

    2015-01-01

    compared to normoglycemia. Insulin is used for treating hyperglycemia in the critically ill patients but may be complicated by hypoglycemia, which is difficult to detect in these patients and which may lead to serious neurological sequelae and death. The incretin hormone, glucagon-like peptide (GLP) 1...... glucose (BG). This is taken advantage of in the treatment of patients with T2DM, for whom GLP-1 analogs have been introduced during the recent years. Infusion of GLP-1 also lowers the BG level in critically ill patients without causing severe hypoglycemia. The T2DM and critical illness share similar...

  17. Glucose metabolism and effect of acetate in ovine adipocytes.

    Yang, Y T; White, L S; Muir, L A

    1982-08-01

    Isolated ovine adipocytes were incubated in vitro with specifically labeled 14C-glucose in the presence or absence of acetate. The flux patterns of glucose carbon through major metabolic pathways were estimated. When glucose was added as the sole substrate, approximately equal portions of glucose carbon (10%) were oxidized to CO2 in the pentose phosphate pathway, in the pyruvate dehydrogenase reaction and in the citrate cycle. Fifteen percent of the glucose carbon was incorporated into fatty acids and 43% was released as lactate and pyruvate. Addition of acetate to the medium increased glucose carbon uptake by 1.5-fold. Most of this increase was accounted for by a sevenfold increase in the activity of the pentose phosphate pathway. Acetate increased glucose carbon fluxes via pentose phosphate pathway to triose phosphates, from triose phosphate to pyruvate, into glyceride glycerol, into lactate and pyruvate and into pyruvate dehydrogenase and citrate cycle CO2. Glucose carbon incorporated into fatty acids was decreased 50% by acetate while, carbon fluxes through the phosphofructokinase-aldolase reactions were not significantly increased. Results of this study suggest that, when glucose is the sole substrate, the conversion of glucose to fatty acids in ovine adipocytes may not be limited by the maximum capacity of hexokinase, the pentose phosphate pathway or enzymes involved in the conversion of triose phosphates to pyruvate and of pyruvate to fatty acid. Acetate increased glucose utilization apparently by increasing activity of the pentose phosphate pathway as a result of enhanced NADPH utilization for fatty acid synthesis. PMID:7142048

  18. An in vitro assessment of the effect of Athrixia phylicoides DC. aqueous extract on glucose metabolism.

    Chellan, N; Muller, C J F; de Beer, D; Joubert, E; Page, B J; Louw, J

    2012-06-15

    Athrixia phylicoides DC. is an aromatic shrub indigenous to the eastern parts of Southern Africa. Indigenous communities brew "bush tea" from dried twigs and leaves of A. phylicoides, which is consumed as a beverage and used for its medicinal properties. Plant polyphenols have been shown to be beneficial to Type 2 diabetes mellitus (T2D) and obesity. Aqueous extracts of the plant have been shown to be rich in polyphenols, in particular phenolic acids, which may enhance glucose uptake and metabolism. The aim of this study was to determine the phenolic composition of a hot water A. phylicoides extract and assess its in vitro effect on cellular glucose utilisation. The most abundant phenolic compounds in the extract were 6-hydroxyluteolin-7-O-glucoside, chlorogenic acid, protocatechuic acid, a di-caffeoylquinic acid and a methoxy-flavonol derivative. The extract increased glucose uptake in C2C12, Chang and 3T3-L1 cells, respectively. Intracellular glucose was utilised by both oxidation (C2C12 myocytes and Chang cells; p < 0.01 and p < 0.05, respectively) and by increased glycogen storage (Chang cells; p < 0.05). No cytotoxicity was observed in Chang cells at the concentrations tested. The effects of the extract were not dose-dependent. A. phylicoides aqueous extract stimulated in vitro glucose uptake and metabolism, suggesting that consumption of this phenolic-rich extract could potentially ameliorate metabolic disorders related to obesity and T2D. PMID:22516895

  19. Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes.

    Suzan Wopereis

    Full Text Available BACKGROUND: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism. METHODOLOGY: To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation. CONCLUSIONS: Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men.

  20. Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function

    Sukumar, Madhusudhanan; Liu, Jie; Ji, Yun; Subramanian, Murugan; Crompton, Joseph G.; Yu, Zhiya; Roychoudhuri, Rahul; Palmer, Douglas C.; Muranski, Pawel; Karoly, Edward D; Mohney, Robert P.; Klebanoff, Christopher A.; Lal, Ashish; Finkel, Toren; Restifo, Nicholas P.

    2013-01-01

    Naive CD8+ T cells rely upon oxidation of fatty acids as a primary source of energy. After antigen encounter, T cells shift to a glycolytic metabolism to sustain effector function. It is unclear, however, whether changes in glucose metabolism ultimately influence the ability of activated T cells to become long-lived memory cells. We used a fluorescent glucose analog, 2-NBDG, to quantify glucose uptake in activated CD8+ T cells. We found that cells exhibiting limited glucose incorporation had ...

  1. Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose

    We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMRglc (LCMRglc), using sequentially administered [18F]fluorodeoxyglucose (FDG) and [14C]-6-glucose (GLC). FDG-6-phosphate accumulation is proportional to the rate of glucose phosphorylation, which occurs before the divergence of glycolytic (GMg) and oxidative (GMo) glucose metabolism and is therefore related to total cerebral glucose metabolism GMt: GMg + GMo = GMt. With oxidative metabolism, the 14C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the 14C label is lost from the brain via lactate production and efflux from the brain. Thus, cerebral GLC metabolite concentration may be more closely related to GMo than to GMt. If true, the glycolytic metabolic rate will be related to the difference between FDG- and GLC-derived LCMRglc. Thus far, we have studied normal awake rats, rats with limbic activation induced by kainic acid (KA), and rats visually stimulated with 16-Hz flashes. In KA-treated rats, significant discordance between FDG and GLC accumulation, which we attribute to glycolysis, occurred only in activated limbic structures. In visually stimulated rats, significant discordance occurred only in the optic tectum

  2. Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose

    Ackermann, R.F.; Lear, J.L. (UCLA School of Medicine (USA))

    1989-12-01

    We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMRglc (LCMRglc), using sequentially administered ({sup 18}F)fluorodeoxyglucose (FDG) and ({sup 14}C)-6-glucose (GLC). FDG-6-phosphate accumulation is proportional to the rate of glucose phosphorylation, which occurs before the divergence of glycolytic (GMg) and oxidative (GMo) glucose metabolism and is therefore related to total cerebral glucose metabolism GMt: GMg + GMo = GMt. With oxidative metabolism, the {sup 14}C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the {sup 14}C label is lost from the brain via lactate production and efflux from the brain. Thus, cerebral GLC metabolite concentration may be more closely related to GMo than to GMt. If true, the glycolytic metabolic rate will be related to the difference between FDG- and GLC-derived LCMRglc. Thus far, we have studied normal awake rats, rats with limbic activation induced by kainic acid (KA), and rats visually stimulated with 16-Hz flashes. In KA-treated rats, significant discordance between FDG and GLC accumulation, which we attribute to glycolysis, occurred only in activated limbic structures. In visually stimulated rats, significant discordance occurred only in the optic tectum.

  3. Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose.

    Ackermann, R F; Lear, J L

    1989-12-01

    We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMRglc (LCMRglc), using sequentially administered [18F]fluorodeoxyglucose (FDG) and [14C]-6-glucose (GLC). FDG-6-phosphate accumulation is proportional to the rate of glucose phosphorylation, which occurs before the divergence of glycolytic (GMg) and oxidative (GMo) glucose metabolism and is therefore related to total cerebral glucose metabolism GMt: GMg + GMo = GMt. With oxidative metabolism, the 14C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the 14C label is lost from the brain via lactate production and efflux from the brain. Thus, cerebral GLC metabolite concentration may be more closely related to GMo than to GMt. If true, the glycolytic metabolic rate will be related to the difference between FDG- and GLC-derived LCMRglc. Thus far, we have studied normal awake rats, rats with limbic activation induced by kainic acid (KA), and rats visually stimulated with 16-Hz flashes. In KA-treated rats, significant discordance between FDG and GLC accumulation, which we attribute to glycolysis, occurred only in activated limbic structures. In visually stimulated rats, significant discordance occurred only in the optic tectum. PMID:2584274

  4. Role of insulin-like growth factor binding protein-3 in glucose and lipid metabolism

    Kim, Ho-Seong

    2013-01-01

    Insulin-like growth factor binding protein (IGFBP)-3 has roles in modulating the effect of IGFs by binding to IGFs and inhibiting cell proliferation in an IGF-independent manner. Although recent studies have been reported that IGFBP-3 has also roles in metabolic regulation, their exact roles in adipose tissue are poorly understood. In this review, we summarized the studies about the biological roles in glucose and lipid metabolism. IGFBP-3 overexpression in transgenic mice suggested that IGFB...

  5. The impact of Vitamin D Replacement on Glucose Metabolism

    H, Parildar; O, Cigerli; DA, Unal; O, Gulmez; NG, Demirag

    2013-01-01

    Objective: We investigated the impact of vitamin D supplementation on glucose metabolism in Vitamin D-deficient patients with prediabetes. Methods: A total of 66 subjects with the mean ages 52.2±9.9 years were included in this prospective and a 6-month follow-up study between 2008-2010. Vitamin D deficient patients (

  6. Response of C2C12 Myoblasts to Hypoxia: The Relative Roles of Glucose and Oxygen in Adaptive Cellular Metabolism

    Wei Li

    2013-01-01

    Full Text Available Background. Oxygen and glucose are two important nutrients for mammalian cell function. In this study, the effect of glucose and oxygen concentrations on C2C12 cellular metabolism was characterized with an emphasis on detecting whether cells show oxygen conformance (OC in response to hypoxia. Methods. After C2C12 cells being cultured in the levels of glucose at 0.6 mM (LG, 5.6 mM (MG, or 23.3 mM(HG under normoxic or hypoxic (1% oxygen condition, cellular oxygen consumption, glucose consumption, lactate production, and metabolic status were determined. Short-term oxygen consumption was measured with a novel oxygen biosensor technique. Longer-term measurements were performed with standard glucose, lactate, and cell metabolism assays. Results. It was found that oxygen depletion in normoxia is dependent on the glucose concentration in the medium. Cellular glucose uptake and lactate production increased significantly in hypoxia than those in normoxia. In hypoxia the cellular response to the level of glucose was different to that in normoxia. The metabolic activities decreased while glucose concentration increased in normoxia, while in hypoxia, metabolic activity was reduced in LG and MG, but unchanged in HG condition. The OC phenomenon was not observed in the present study. Conclusions. Our findings suggested that a combination of low oxygen and low glucose damages the viability of C2C12 cells more seriously than low oxygen alone. In addition, when there is sufficient glucose, C2C12 cells will respond to hypoxia by upregulating anaerobic respiration, as shown by lactate production.

  7. Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism

    Qian Zhang

    2011-01-01

    Full Text Available Berberine is known to improve glucose and lipid metabolism disorders, but the mechanism is still under investigation. In this paper, we explored the effects of berberine on the weight, glucose levels, lipid metabolism, and serum insulin of KKAy mice and investigated its possible glucose and lipid-regulating mechanism. We randomly divided KKAy mice into two groups: berberine group (treated with 250 mg/kg/d berberine and control group. Fasting blood glucose (FBG, weight, total cholesterol (TC, triglyceride (TG, high-density lipoprotein-cholesterol (HDL-c, low-density lipoprotein-cholesterol (LDL-c, and fasting serum insulin were measured in both groups. The oral glucose tolerance test (OGTT was performed. RT2 PCR array gene expression analysis was performed using skeletal muscle of KKAy mice. Our data demonstrated that berberine significantly decreased FBG, area under the curve (AUC, fasting serum insulin (FINS, homeostasis model assessment insulin resistance (HOMA-IR index, TC, and TG, compared with those of control group. RT2 profiler PCR array analysis showed that berberine upregulated the expression of glucose transporter 4 (GLUT4, mitogen-activated protein kinase 14 (MAPK14, MAPK8(c-jun N-terminal kinase, JNK, peroxisome proliferator-activated receptor α (PPARα, uncoupling protein 2 (UCP2, and hepatic nuclear factor 4α(HNF4α, whereas it downregulated the expression of PPARγ, CCAAT/enhancer-binding protein (CEBP, PPARγ coactivator 1α(PGC 1α, and resistin. These results suggest that berberine moderates glucose and lipid metabolism through a multipathway mechanism that includes AMP-activated protein kinase-(AMPK- p38 MAPK-GLUT4, JNK pathway, and PPARα pathway.

  8. Glucose metabolism in sheep fed grass supplemented with gliricidia sepium

    The limiting factor on improving ruminant production for most of the available feed in developing countries are low in quality. Therefore high fibre diet must be supplemented by high nutritive feed such as leguminous trees that much available in those regions. Gliricidia sepium was one of very potential candidates. Glucose as a major energy source in fed animals required precursor in form of propionate and amino acids from diet. Those precursors might be supplied by these legume leaves. The aim of this research was to investigate the glucose metabolism in the sheep fed grass supplemented by Gliricidia sepium. Fifteens sheep (18 months old) were used in the experiment. These are were divided into three groups that fed by experimental diet of Mitchell grass (MG group), Gliricidia (GS group), and MG supplemented with GS (MGGS group). D-[U-14C]glucose infusate was infused continuously through the left jugular venous catheter of each animal to measure glucose metabolism in those sheeps measurements were done on feed utilisation and glucose metabolism. The results indicated that there was an improvement in efficiency of feed utilisation in the MGGS group as reflected by lower feed conversion ratio by the group. Plasma glucose concentration profile per unit of OM intake were similar for GS and MGGS groups, but higher than that in the MG group (P<0.01). Glucose entry rate (GER) increased in MG group through GS to the MGGS group, while N retention accordingly was increased. It can be concluded that the utilisation of GS by the ruminant animal could be improved by feeding it with a low quality feed at a ratio of 40:60 (GS:Low quality feed) to achieve an NI:DOMI ratio of 0.03 - 0.04. This improvement would be manifested in increasing DOMI, with subsequent increase in GER or net protein deposition as might be expressed in positive N retention. (author)

  9. Enhanced muscle glucose metabolism after exercise in the rat

    Garetto, L P; Richter, Erik; Goodman, M N;

    1984-01-01

    Thirty minutes after a treadmill run, glucose utilization and glycogen synthesis in perfused rat skeletal muscle are enhanced due to an increase in insulin sensitivity (Richter et al., J. Clin. Invest. 69: 785-793, 1982). The exercise used in these studies was of moderate intensity, and muscle...... glycogen was substantially repleted at the time (30 min postexercise) that glucose metabolism was examined. When rats were run at twice the previous rate (36 m/min), muscle glycogen was still substantially diminished 30 min after the run. At this time the previously noted increase in insulin sensitivity...... was evident. The data suggest that the restoration of muscle glycogen after exercise occurs in two phases. In phase I, muscle glycogen is depleted and insulin-stimulated glucose utilization and glucose utilization in the absence of added insulin may both be enhanced. In phase II glycogen levels have...

  10. Bace1 activity impairs neuronal glucose metabolism: rescue by beta-hydroxybutyrate and lipoic acid

    John A Findlay

    2015-10-01

    Full Text Available Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer’s disease (AD pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP cleaving enzyme 1 (BACE1, responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.

  11. Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non-Diabetics: Results from the GLOBAL Fluid Cohort Study

    Mark Lambie; James Chess; Jun-Young Do; Hyunjin Noh; Hi-Bahl Lee; Yong-Lim Kim; Angela Summers; Paul Ford Williams; Sara Davison; Marc Dorval; Nick Topley; Simon John Davies

    2016-01-01

    Background and Objectives Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD) patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism. Methods and Materials We analysed the Global Fluid Study cohort, a ...

  12. Thyroid hormone’s role in regulating brain glucose metabolism and potentially modulating hippocampal cognitive processes

    Jahagirdar, V; McNay, EC

    2012-01-01

    Cognitive performance is dependent on adequate glucose supply to the brain. Insulin, which regulates systemic glucose metabolism, has been recently shown both to regulate hippocampal metabolism and to be a mandatory component of hippocampally-mediated cognitive performance. Thyroid hormones (TH) regulate systemic glucose metabolism and may also be involved in regulation of brain glucose metabolism. Here we review potential mechanisms for such regulation. Importantly, TH imbalance is often enc...

  13. Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring

    Ya-Hong Ma; Caiguo Yu; Abudurexiti Kayoumu; Xin Guo; Zhili Ji; George Liu

    2015-01-01

    Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH.However,it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance.In this study,we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice.ApoCⅢ transgenic mice with severe hypertriglyceridemia were mated with non-transgenic control mice to obtain 4 types of offspring:maternal non-transgenic control and maternal transgenic offspring,and paternal control and paternal transgenic offspring.Plasma triglycerides (TG),total cholesterol (TC),fasting plasma glucose (FPG) and fasting insulin (FINS) were measured.ApoCⅢ overexpression caused severe hypertriglyceridemia,but the transgenic female mice had unaltered fertility with normal pregnancy and birth of pups.The 4 groups of offspring had similar birth weight and growth rate.The plasma TG of maternal and paternal transgenic offspring were nearly 40-fold higher than maternal and paternal control mice,but there was no difference in plasma TG between maternal and paternal transgenic offspring.Although the FPG of the 4 groups of animals had no difference,the maternal transgenic mice showed impaired glucose tolerance,increased FINS levels and higher homeostasis model assessment insulin resistance index (HOMA-IR) than the other 3 groups.In conclusion,maternally inherited hypertriglyceridemia in ApoCⅢ transgenic mice displayed impaired glucose tolerance,hyperinsulinemia and increased HOMA-R,while paternally inherited hypertriglyceridemia did not have such impacts.

  14. Metabolic flux rewiring in mammalian cell cultures

    Young, Jamey D.

    2013-01-01

    Continuous cell lines (CCLs) engage in “wasteful” glucose and glutamine metabolism that leads to accumulation of inhibitory byproducts, primarily lactate and ammonium. Advances in techniques for mapping intracellular carbon fluxes and profiling global changes in enzyme expression have led to a deeper understanding of the molecular drivers underlying these metabolic alterations. However, recent studies have revealed that CCLs are not necessarily entrenched in a glycolytic or glutaminolytic phe...

  15. Metabolic flux rewiring in mammalian cell cultures.

    Young, Jamey D

    2013-12-01

    Continuous cell lines (CCLs) engage in 'wasteful' glucose and glutamine metabolism that leads to accumulation of inhibitory byproducts, primarily lactate and ammonium. Advances in techniques for mapping intracellular carbon fluxes and profiling global changes in enzyme expression have led to a deeper understanding of the molecular drivers underlying these metabolic alterations. However, recent studies have revealed that CCLs are not necessarily entrenched in a glycolytic or glutaminolytic phenotype, but instead can shift their metabolism toward increased oxidative metabolism as nutrients become depleted and/or growth rate slows. Progress to understand dynamic flux regulation in CCLs has enabled the development of novel strategies to force cultures into desirable metabolic phenotypes, by combining fed-batch feeding strategies with direct metabolic engineering of host cells. PMID:23726154

  16. Cerebral metabolism of glucose in benign hereditary chorea

    Benign hereditary chorea (BHC) is an autosomal dominant disorder characterized by chorea of early onset with little or no progression. There is marked clinical variability in this disease with some subjects having onset in infancy and others with onset in early adulthood. In contrast to Huntington's disease (HD), there is no dementia. Computed tomography is normal in all subjects with no evidence of caudate nucleus atrophy. We present the results of positron emission tomography using 18F-2-fluorodeoxyglucose on three patients with this disorder from two families. Cerebral glucose metabolism in one patient was decreased in the caudate nucleus, as previously reported in HD. The other two persons from a second family showed a relative decrease in metabolic rates of glucose in the caudate when compared with the thalamus. It appears that caudate hypometabolism is not specific for HD. These findings suggest that the caudate nucleus may play a significant role in the pathophysiology of some persons with BHC

  17. Modulation of Glucose Transporter 1 (GLUT1) Expression Levels Alters Mouse Mammary Tumor Cell Growth In Vitro and In Vivo

    Young, Christian D.; Lewis, Andrew S; Rudolph, Michael C; Ruehle, Marisa D; Jackman, Matthew R.; Yun, Ui J.; Ilkun, Olesya; Pereira, Renata; Abel, E. Dale; Anderson, Steven M.

    2011-01-01

    Tumor cells exhibit an altered metabolism characterized by elevated aerobic glycolysis and lactate secretion which is supported by an increase in glucose transport and consumption. We hypothesized that reducing or eliminating the expression of the most prominently expressed glucose transporter(s) would decrease the amount of glucose available to breast cancer cells thereby decreasing their metabolic capacity and proliferative potential. Of the 12 GLUT family glucose transporters expressed in ...

  18. Acute effects of ghrelin administration on glucose and lipid metabolism

    Vestergaard, Esben Thyssen; Djurhuus, Christian Born; Gjedsted, Jakob;

    2007-01-01

    CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate metabolism. DESIGN: This was a randomized, single-blind, p......CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate metabolism. DESIGN: This was a randomized, single......-blind, placebo-controlled two-period crossover study. SETTING: The study was performed in a university clinical research laboratory. PARTICIPANTS: Eight healthy men aged 27.2 +/- 0.9 yr with a body mass index of 23.4 +/- 0.5 kg/m(2) were included in the study. INTERVENTION: Subjects received infusion of ghrelin...... the final 2 h of each infusion. RESULTS: Basal and insulin-stimulated glucose disposal decreased with ghrelin [basal: 1.9 +/- 0.1 (ghrelin) vs. 2.3 +/- 0.1 mg x kg(-1) x min(-1), P = 0.03; clamp: 3.9 +/- 0.6 (ghrelin) vs. 6.1 +/- 0.5 mg x kg(-1) x min(-1), P = 0.02], whereas endogenous glucose...

  19. Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism

    Murai, Hideki; Suzuki, Yukihisa; Kiyosawa, Motohiro; Wakakura, Masato; Mochizuki, Manabu; Ishiwata, Kiichi; Ishii, Kenji

    2011-01-01

    A 43-year-old woman with drug-related blepharospasm was followed up for 22 months. She had undergone etizolam treatment for 19 years for indefinite complaints. We examined her cerebral glucose metabolism 5 times (between days 149 and 688 since presentation), using positron emission tomography, and identified regions of interest in the thalamus, caudate nucleus, putamen, and primary somatosensory area on both sides. The severity of the blepharospasm was evaluated by PET scanning using the Waka...

  20. Skeleton and Glucose Metabolism: A Bone-Pancreas Loop

    2015-01-01

    Bone has been considered a structure essential for mobility, calcium homeostasis, and hematopoietic function. Recent advances in bone biology have highlighted the importance of skeleton as an endocrine organ which regulates some metabolic pathways, in particular, insulin signaling and glucose tolerance. This review will point out the role of bone as an endocrine “gland” and, specifically, of bone-specific proteins, as the osteocalcin (Ocn), and proteins involved in bone remodeling, as osteopr...

  1. Dementia with impaired glucose metabolism in late onset metachromatic leukodystrophy

    Johannsen, P.; Ehlers, L.; Hansen, Hans Jacob

    2001-01-01

    An unusual case of very-late-onset metachromatic leukodystrophy (MLD) with dementia was studied. The patient was a 41-year-old male who presented with mild dementia and a single generalized tonic clonic seizure. Neuropsychological assessment demonstrated mild amnesia, visuospatial dysfunction and...... observed using positron emission tomography and fluor-18-labeled fluorodesoxyglucose. The neuropsychological deficits are related to the location of deficits in glucose metabolism....

  2. Glucose challenge test (50-g GCT) in detection of glucose metabolism disorders in peritoneal dialysis patients: preliminary study

    Madziarska, Katarzyna; Zmonarski, Slawomir; Penar, Jozef; Krajewska, Magdalena; Mazanowska, Oktawia; Augustyniak-Bartosik, Hanna; Gołebiowski, Tomasz; Klak, Renata; Weyde, Waclaw; Klinger, Marian

    2014-01-01

    Background The aim was to evaluate the clinical utility of the oral glucose tolerance screening test (50-g GCT—glucose challenge test) for the detection of glucose metabolism disorders (GMD) in peritoneal dialysis (PD) patients with normal fasting glucose levels. Methods The 50-g GCT was performed in 20 prevalent patients without history of diabetes before PD treatment onset, who had been on dialysis for a median time of 15.34 months. In addition, other indicators of glucose metabolism were m...

  3. Cellular pathways of energy metabolism in the brain: is glucose used by neurons or astrocytes?

    Nehlig, Astrid; Coles, Jonathan A

    2007-09-01

    Most techniques presently available to measure cerebral activity in humans and animals, i.e. positron emission tomography (PET), autoradiography, and functional magnetic resonance imaging, do not record the activity of neurons directly. Furthermore, they do not allow the investigator to discriminate which cell type is using glucose, the predominant fuel provided to the brain by the blood. Here, we review the experimental approaches aimed at determining the percentage of glucose that is taken up by neurons and by astrocytes. This review is integrated in an overview of the current concepts on compartmentation and substrate trafficking between astrocytes and neurons. In the brain in vivo, about half of the glucose leaving the capillaries crosses the extracellular space and directly enters neurons. The other half is taken up by astrocytes. Calculations suggest that neurons consume more energy than do astrocytes, implying that astrocytes transfer an intermediate substrate to neurons. Experimental approaches in vitro on the honeybee drone retina and on the isolated vagus nerve also point to a continuous transfer of intermediate metabolites from glial cells to neurons in these tissues. Solid direct evidence of such transfer in the mammalian brain in vivo is still lacking. PET using [(18)F]fluorodeoxyglucose reflects in part glucose uptake by astrocytes but does not indicate to which step the glucose taken up is metabolized within this cell type. Finally, the sequence of metabolic changes occurring during a transient increase of electrical activity in specific regions of the brain remains to be clarified. PMID:17659529

  4. Danthron activates AMP-activated protein kinase and regulates lipid and glucose metabolism in vitro

    Rong ZHOU; Ling WANG; Xing XU; Jing CHEN; Li-hong HU; Li-li CHEN; Xu SHEN

    2013-01-01

    Aim:To discover the active compound on AMP-activated protein kinase (AMPK) activation and investigate the effects of the active compound 1,8-dihydroxyanthraquinone (danthron) from the traditional Chinese medicine rhubarb on AMPK-mediated lipid and glucose metabolism in vitro.Methods:HepG2 and C2C12 cells were used.Cell viability was determined using MTT assay.Real-time PCR was performed to measure the gene expression.Western blotting assay was applied to investigate the protein phosphorylation level.Enzymatic assay kits were used to detect the total cholesterol (TC),triglyceride (TG) and glucose contents.Results:Danthron (0.1,1,and 10 μmol/L) dose-dependently promoted the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC)in both HepG2 and C2C12 cells.Meanwhile,danthron treatment significantly reduced the lipid synthesis related sterol regulatory element-binding protein 1c (SREBP1c) and fatty acid synthetase (FAS) gene expressions,and the TC and TG levels.In addition,danthron treatment efficiently increased glucose consumption.The actions of danthron on lipid and glucose metabolism were abolished or reversed by co-treatment with the AMPK inhibitor compound C.Conclusion:Danthron effectively reduces intracellular lipid contents and enhanced glucose consumption in vitro via activation of AMPK signaling pathway.

  5. Angiotensin Receptor Blockade Increases Pancreatic Insulin Secretion and Decreases Glucose Intolerance during Glucose Supplementation in a Model of Metabolic Syndrome

    Rodriguez, Ruben; Viscarra, Jose A.; Minas, Jacqueline N.; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M.

    2012-01-01

    Renin-angiotensin system blockade improves glucose intolerance and insulin resistance, which contribute to the development of metabolic syndrome. However, the contribution of impaired insulin secretion to the pathogenesis of metabolic syndrome is not well defined. To assess the contributions of angiotensin receptor type 1 (AT1) activation and high glucose intake on pancreatic function and their effects on insulin signaling in skeletal muscle and adipose tissue, an oral glucose tolerance test ...

  6. Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism.

    Langsetmo, Lisa; Barr, Susan I; Dasgupta, Kaberi; Berger, Claudie; Kovacs, Christopher S; Josse, Robert G; Adachi, Jonathan D; Hanley, David A; Prior, Jerilynn C; Brown, Jacques P; Morin, Suzanne N; Davison, Kenneth S; Goltzman, David; Kreiger, Nancy

    2016-04-01

    We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk. PMID:27001278

  7. Islet glucose metabolism and insulin release in two animal models of glucose intolerance

    Ling, Zong-Chao

    1999-01-01

    Type 2 diabetes is a complex and heterogenous disease resulting from the interaction of defects of both genetic and environmental origin. Abnormalities contributing to the pathogenesis of type 2 diabetes include impaired [beta]-cell function, peripheral insulin resistance and increased hepatic glucose production. In the present study we have mainly used two animal models of glucose intolerance, i.e., spontaneously diabetic GK rats and transgenic mice with overexpressed gluco...

  8. Extracellular glucose supports lactate production but not aerobic metabolism in cardiomyocytes from both normoglycemic Atlantic cod and low glycemic short-horned sculpin.

    Clow, Kathy A; Short, Connie E; Driedzic, William R

    2016-05-01

    Fish exhibit a wide range of species-specific blood glucose levels. How this relates to glucose utilization is yet to be fully realized. Here, we assessed glucose transport and metabolism in myocytes isolated from Atlantic cod (Gadus morhua) and short-horned sculpin (Myoxocephalus scorpius), species with blood glucose levels of 3.7 and 0.57 mmol l(-1), respectively. Glucose metabolism was assessed by the production of (3)H2O from [2-(3)H]glucose. Glucose metabolism was 3.5- to 6-fold higher by myocytes from Atlantic cod than by those from short-horned sculpin at the same level of extracellular glucose. In Atlantic cod myocytes, glucose metabolism displayed what appears to be a saturable component with respect to extracellular glucose, and cytochalasin B inhibited glucose metabolism. These features revealed a facilitated glucose diffusion mechanism that accounts for between 30% and 55% of glucose entry at physiological levels of extracellular glucose. Facilitated glucose diffusion appears to be minimal in myocytes for short-horned sculpin. Glucose entry by simple diffusion occurs in both cell types with the same linear relationship between glucose metabolism and extracellular glucose concentration, presumably due to similarities in membrane composition. Oxygen consumption by myocytes incubated in medium containing physiological levels of extracellular glucose (Atlantic cod 5 mmol l(-1), short-horned sculpin 0.5 mmol l(-1)) was similar in the two species and was not decreased by cytochalasin B, suggesting that these cells have the capability of oxidizing alternative on-board metabolic fuels. Cells produced lactate at low rates but glycogen levels did not change during the incubation period. In cells from both species, glucose utilization assessed by both simple chemical analysis of glucose disappearance from the medium and (3)H2O production was half the rate of lactate production and as such extracellular glucose was not available for oxidative metabolism

  9. Mitochondria, cholesterol and cancer cell metabolism.

    Ribas, Vicent; García-Ruiz, Carmen; Fernández-Checa, José C

    2016-12-01

    Given the role of mitochondria in oxygen consumption, metabolism and cell death regulation, alterations in mitochondrial function or dysregulation of cell death pathways contribute to the genesis and progression of cancer. Cancer cells exhibit an array of metabolic transformations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which ensure cancer progression. Cholesterol metabolism is disturbed in cancer cells and supports uncontrolled cell growth. In particular, the accumulation of cholesterol in mitochondria emerges as a molecular component that orchestrates some of these metabolic alterations in cancer cells by impairing mitochondrial function. As a consequence, mitochondrial cholesterol loading in cancer cells may contribute, in part, to the Warburg effect stimulating aerobic glycolysis to meet the energetic demand of proliferating cells, while protecting cancer cells against mitochondrial apoptosis due to changes in mitochondrial membrane dynamics. Further understanding the complexity in the metabolic alterations of cancer cells, mediated largely through alterations in mitochondrial function, may pave the way to identify more efficient strategies for cancer treatment involving the use of small molecules targeting mitochondria, cholesterol homeostasis/trafficking and specific metabolic pathways. PMID:27455839

  10. Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals

    Jacobsen, Siv H; Bojsen-Møller, Kirstine N; Dirksen, Carsten;

    2013-01-01

    after RYGB is rapid entry of glucose into the systemic circulation due to modified gastrointestinal anatomy, causing hypersecretion of insulin and other hormones influencing glucose disappearance and endogenous glucose production. METHODS: We determined glucose absorption and metabolism and the rate of...... RYGB. Endogenous glucose production was similar before and after surgery. Postoperative glucagon secretion increased and showed a biphasic response after RYGB. Adipose tissue basal rate of lipolysis was higher after RYGB. CONCLUSIONS/INTERPRETATION: A rapid rate of absorption of ingested glucose into...... lipolysis before and 3 months after RYGB in obese glucose-tolerant individuals using the double-tracer technique during a mixed meal. RESULTS: After RYGB, the postprandial plasma glucose profile changed, with a higher peak glucose concentration followed by a faster return to lower than basal levels. These...

  11. Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways1

    Jacobs, Sarah R.; Herman, Catherine E.; MacIver, Nancie J.; Wofford, Jessica A.; Wieman, Heather L.; Hammen, Jeremy J.; Rathmell, Jeffrey C.

    2008-01-01

    T cell activation potently stimulates cellular metabolism to support the elevated energetic and biosynthetic demands of growth, proliferation, and effector function. We show that glucose uptake is limiting in T cell activation and that CD28 costimulation is required to allow maximal glucose uptake following TCR stimulation by up-regulating expression and promoting the cell surface trafficking of the glucose transporter Glut1. Regulation of T cell glucose uptake and Glut1 was critical, as low ...

  12. UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets

    Highlights: ► UCP2 mRNA levels are decreased in islets of Langerhans from glucokinase deficient mice. ► UCP2 mRNA up-regulation by glucose is dependent on glucokinase. ► Absence of UCP2 increases GSIS of glucokinase heterozygous pancreatic islets. ► This may protect glucokinase deficient mice from hyperglycemic damages. -- Abstract: Uncoupling Protein 2 (UCP2) is expressed in the pancreatic β-cell, where it partially uncouples the mitochondrial proton gradient, decreasing both ATP-production and glucose-stimulated insulin secretion (GSIS). Increased glucose levels up-regulate UCP2 mRNA and protein levels, but the mechanism for UCP2 up-regulation in response to increased glucose is unknown. The aim was to examine the effects of glucokinase (GK) deficiency on UCP2 mRNA levels and to characterize the interaction between UCP2 and GK with regard to glucose-stimulated insulin secretion in pancreatic islets. UCP2 mRNA expression was reduced in GK+/− islets and GK heterozygosity prevented glucose-induced up-regulation of islet UCP2 mRNA. In contrast to UCP2 protein function UCP2 mRNA regulation was not dependent on superoxide generation, but rather on products of glucose metabolism, because MnTBAP, a superoxide dismutase mimetic, did not prevent the glucose-induced up-regulation of UCP2. Glucose-stimulated insulin secretion was increased in UCP2−/− and GK+/− islets compared with GK+/− islets and UCP2 deficiency improved glucose tolerance of GK+/− mice. Accordingly, UCP2 deficiency increased ATP-levels of GK+/− mice. Thus, the compensatory down-regulation of UCP2 is involved in preserving the insulin secretory capacity of GK mutant mice and might also be implicated in limiting disease progression in MODY2 patients.

  13. Regional cerebral glucose metabolism in patients with Parkinson's disease with or without dementia

    By means of positron emission tomography, the cerebral glucose metabolism in 5 patients with Parkinson's disease with dementia was compared with that in 9 patients without dementia, and that in 5 normal volunteers. The metabolic rates for glucose were measured by placing one hundred regions of interest. In the demented patients, cerebral glucose metabolism was diffusely decreased compared with that of the non-demented patients and the normal controls. The most significant decrease in glucose metabolism was observed in the angular gyrus (49.7% of the normal controls). The glucose metabolism in the cingulate, pre- and postcentral, occipital and subcortical regions was relatively spared (62.1 to 85.5% of the normal controls). In the patients without dementia, the glucose metabolism in each region was not significantly different from that in the normal controls. These results suggest that diffuse glucose hypometabolism in the cerebral cortex may correlate with that of patients with Parkinson's disease with dementia. (author)

  14. Glucose Metabolism in Legionella pneumophila: Dependence on the Entner-Doudoroff Pathway and Connection with Intracellular Bacterial Growth† ▿

    Harada, Eiji; Iida, Ken-ichiro; Shiota, Susumu; Nakayama, Hiroaki; Yoshida, Shin-ichi

    2010-01-01

    Glucose metabolism in Legionella pneumophila was studied by focusing on the Entner-Doudoroff (ED) pathway with a combined genetic and biochemical approach. The bacterium utilized exogenous glucose for synthesis of acid-insoluble cell components but manifested no discernible increase in the growth rate. Assays with permeabilized cell preparations revealed the activities of three enzymes involved in the pathway, i.e., glucokinase, phosphogluconate dehydratase, and 2-dehydro-3-deoxy-phosphogluco...

  15. Metabolic properties of chicken embryonic stem cells

    2010-01-01

    Cellular energy metabolism correlates with cell fate,but the metabolic properties of chicken embryonic stem (chES) cells are poorly understood.Using a previously established chES cell model and electron microscopy (EM),we found that undifferentiated chES cells stored glycogen.Additionally,undifferentiated chES cells expressed lower levels of glucose transporter 1 (GLUT1) and phosphofructokinase (PFK) mRNAs but higher levels of hexokinase 1 (HK1) and glycogen synthase (GYS) mRNAs compared with control primary chicken embryonic fibroblast (CEF) cells,suggesting that chES cells direct glucose flux towards the glycogenic pathway.Moreover,we demonstrated that undifferentiated chES cells block gluconeogenic outflow and impede the accumulation of glucose-6-phosphate (G6P) from this pathway,as evidenced by the barely detectable levels of pyruvate carboxylase (PCX) and mitochondrial phosphoenolpyruvate carboxykinase (PCK2) mRNAs.Additionally,cell death occurred in undifferentiated chES cells as shown by Hoechst 33342 and propidium iodide (PI) double staining,but it could be rescued by exogenous G6P.However,we found that differentiated chES cells decreased the glycogen reserve through the use of PAS staining.Moreover,differentiated chES cells expressed higher levels of GLUT1,HK1 and PFK mRNAs,while the level of GYS mRNA remained similar in control CEF cells.These data indicate that undifferentiated chES cells continue to synthesize glycogen from glucose at the expense of G6P,while differentiated chES cells have a decreased glycogen reserve,which suggests that the amount of glycogen is indicative of the chES cell state.

  16. Hepatic glucose sensing is required to preserve β cell glucose competence.

    Seyer, Pascal; Vallois, David; Poitry-Yamate, Carole; Schutz, Frédéric; Metref, Salima; Tarussio, David; Maechler, Pierre; Staels, Bart; Lanz, Bernard; Grueter, Rolf; Decaris, Julie; Turner, Scott; Da Costa, Anabela; Preitner, Frédéric; Minehira, Kaori

    2013-01-01

    Liver glucose metabolism plays a central role in glucose homeostasis and may also regulate feeding and energy expenditure. Here we assessed the impact of glucose transporter 2 (Glut2) gene inactivation in adult mouse liver (LG2KO mice). Loss of Glut2 suppressed hepatic glucose uptake but not glucose output. In the fasted state, expression of carbohydrate-responsive element-binding protein (ChREBP) and its glycolytic and lipogenic target genes was abnormally elevated. Feeding, energy expenditu...

  17. DLK1 Regulates Whole-Body Glucose Metabolism

    Abdallah, Basem M; Ditzel, Nicholas; Laborda, Jorge;

    2015-01-01

    due to impaired insulin signaling in OB and lowered Glu-OCN serum levels. Furthermore, Dlk1(-/-) mice treated with Glu-OC experienced significantly lower blood glucose levels than Glu-OCN-treated wild-type mice. The data suggest that Glu-OCN-controlled production of DLK1 by pancreatic β-cells acts as...

  18. Effect of abomasal glucose infusion on splanchnic and whole-body glucose metabolism in periparturient dairy cows

    Larsen, Mogens; Kristensen, Niels Bastian

    2009-01-01

    Six periparturient Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic and whole-body glucose metabolism.......Six periparturient Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic and whole-body glucose metabolism....

  19. Regional cerebral glucose metabolism in frontotemporal lobar degeneration

    Purpose: Frontotemporal lobar degeneration (FTLD) is the third most common cause of dementia, following Alzheimer's disease and Lewy body disease. Four prototypic neuro behavioral syndromes can be produced by FTLD: frontotemporal dementia (FTD), frontotemporal dementia with motor neuron disease (MND), semantic dementia (SD), and progressive aphasia (PA). We investigated patterns of metabolic impairment in patients with FTLD presented with four different clinical syndromes. Methods: We analyzed glucose metabolic patterns on FDG PET images obtained from 34 patients with a clinical diagnosis of FTLD (19 FTD, 6 MND, 6 SD, and 3 PA, according to a consensus criteria for clinical syndromes associated with FTLD) and 7 age-matched healthy controls using SPM99. Results: Patients with FTD had metabolic deficit in the left frontal cortex and bilateral anterior temporal cortex. Hypometabolism in the bilateral pre-motor area was shown in patients with MND. Patients with SD had metabolic deficit in the left posterior temporal cortex including Wernicke's area, while hypometabolism in the bilateral inferior frontal gyrus including Broca's area and left angular gyrus was seen in patients with PA. These metabolic patterns were well correlated with clinical and neuropsychological features of FTLD syndromes. Conclusion: These data provide a biochemical basis of clinical classification of FTLD. FDG PET may help evaluate and classify patients with FTLD

  20. Effects of four aromatic organic pollutants on microbial glucose metabolism and thymidine incorporation in marine sediments

    The metabolism of D-(U-14C)glucose and the incorporation of (methyl-3H)thymidine by aerobic and anaerobic marine sediment microbes exposed to 1 to 1000 ppm anthracene, naphthalene, p,p'-dichlorodiphenyltrichloroethane, and pentachlorophenol were examined. Cell-specific rates of (14C)glucose metabolism averaged 1.7 x 10-21 and 0.5 x 10-21 mol/min per cell for aerobic and anaerobic sediment slurries, respectively; (3H)thymidine incorporation rates averaged 43 x 10-24 and 9 x 10-24 mol/min per cell for aerobic and anaerobic slurries, respectively. Aerobic sediments exposed to three of the organic pollutants for 2 to 7 days showed recovery of both activities. Anaerobic sediments showed little recovery after 2 days of pre-exposure to the pollutants. The authors conclude that (i) anaerobic sediments are more sensitive than aerobic sediments to pollutant additions; (ii) (3H)thymidine incorporation is more sensitive to pollutant additions than is (14C)glucose metabolism; and (iii) the toxicity of the pollutants increased in the following order: anthracene, p,p'-dichlorodiphenyltrichloroethane, naphthalene, and pentachlorophenol

  1. Glucose metabolism in rats submitted to skeletal muscle denervation

    Wilton Marlindo Santana Nunes

    2005-07-01

    Full Text Available This study analyzed the local and systemic effects of immobilization by denervation of the skeletal muscle on glucose metabolism. The rats were submitted to section of the right paw sciatic nerve. A reduction was observed in glucose uptake by the isolated soleus muscle of the denervated paw after 3 and 7 days, but not after 28 days in relation to the control animals. There was no difference after 3 and 7 days in glucose uptake by the soleus muscle of the opposite intact paw in relation to the control. There was increased glucose uptake in the same paw 28 days after denervation. The rate of glucose removal in response to exogenous insulin after 28 days of denervation was significantly higher than in control animals and those observed after 3 and 7 days of denervation. These results suggest that immobilization by denervation interfered not only in glucose metabolism in the skeletal muscle involved but also in other tissues.O estudo analisou os efeitos locais e sistêmicos da imobilização por desnervação do músculo esquelético sobre o metabolismo glicidico. Ratos foram submetidos à secção do nervo ciático da pata direita. Observou-se redução da captação de glicose pelo músculo sóleo isolado da pata desnervada após 3 e 7 mas não após 28 dias em relação a animais controle. Não houve diferença após 3 e 7 dias na captação de glicose pelo músculo sóleo da pata contralateral intacta em relação ao controle. Houve aumento da captação de glicose nesta mesma pata 28 dias após a desnervação. A taxa de remoção da glicose em resposta à insulina exógena após 28 dias de desnervação foi significantemente superior à do controle e àquelas observadas após 3 e 7 dias da desnervação. Esses resultados sugerem que a imobilização por desnervação interfere não só no metabolismo da glicose no músculo esquelético envolvido como também em outros tecidos.

  2. The estrogen hypothesis of schizophrenia implicates glucose metabolism

    Olsen, Line; Hansen, Thomas; Jakobsen, Klaus D;

    2008-01-01

    . We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling networks...... implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated with schizophrenia...

  3. Postprandial gut hormone responses and glucose metabolism in cholecystectomized patients

    Sonne, David P; Hare, Kristine J; Martens, Pernille;

    2013-01-01

    Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We...... examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat......-rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum...

  4. Thyroid hormone induced oxygen consumption and glucose-uptake in human mononuclear cells

    Kvetny, J; Matzen, L E

    1989-01-01

    Cellular oxygen consumption and glucose metabolism were examined in human mononuclear blood cells. The cellular oxygen consumption and glucose uptake were dependent on the number of cells, the temperature and the duration of incubation. Stimulation of the cells by T4 and T3 led to a dose dependent...... increase of oxygen consumption and glucose uptake, whereas T2 and rT3 had no effect. Thyroxine as well as T3 stimulated the cellular glucose metabolism, but lactate production was independent of T3 and T4 stimulation. The data suggested a direct effect of T4 and T3 on oxidative phosphorylation. Further...... thyroid hormones and insulin exerted an additive effect on glucose uptake. Our study indicates a direct intracellular effect of T4 independent of its conversion to T3 and a different mechanism for insulin dependent and thyroid hormone glucose uptake....

  5. Type 2 Diabetes and Breast Cancer: The Interplay between Impaired Glucose Metabolism and Oxidant Stress

    Ferroni, Patrizia; Riondino, Silvia; Buonomo, Oreste; Palmirotta, Raffaele; Guadagni, Fiorella; Roselli, Mario

    2015-01-01

    Metabolic disorders, especially type 2 diabetes and its associated complications, represent a growing public health problem. Epidemiological findings indicate a close relationship between diabetes and many types of cancer (including breast cancer risk), which regards not only the dysmetabolic condition, but also its underlying risk factors and therapeutic interventions. This review discusses the advances in understanding of the mechanisms linking metabolic disorders and breast cancer. Among the proposed mechanisms to explain such an association, a major role is played by the dysregulated glucose metabolism, which concurs with a chronic proinflammatory condition and an associated oxidative stress to promote tumour initiation and progression. As regards the altered glucose metabolism, hyperinsulinaemia, both endogenous due to insulin-resistance and drug-induced, appears to promote tumour cell growth through the involvement of innate immune activation, platelet activation, increased reactive oxygen species, exposure to protumorigenic and proangiogenic cytokines, and increased substrate availability to neoplastic cells. In this context, understanding the relationship between metabolic disorders and cancer is becoming imperative, and an accurate analysis of these associations could be used to identify biomarkers able to predict disease risk and/or prognosis and to help in the choice of proper evidence-based diagnostic and therapeutic protocols. PMID:26171112

  6. Glucose and fatty acid metabolism in a 3 tissue in-vitro model challenged with normo- and hyperglycaemia.

    Elisabetta Iori

    Full Text Available Nutrient balance in the human body is maintained through systemic signaling between different cells and tissues. Breaking down this circuitry to its most basic elements and reconstructing the metabolic network in-vitro provides a systematic method to gain a better understanding of how cross-talk between the organs contributes to the whole body metabolic profile and of the specific role of each different cell type. To this end, a 3-way connected culture of hepatocytes, adipose tissue and endothelial cells representing a simplified model of energetic substrate metabolism in the visceral region was developed. The 3-way culture was shown to maintain glucose and fatty acid homeostasis in-vitro. Subsequently it was challenged with insulin and high glucose concentrations to simulate hyperglycaemia. The aim was to study the capacity of the 3-way culture to maintain or restore normal circulating glucose concentrations in response to insulin and to investigate the effects these conditions on other metabolites involved in glucose and lipid metabolism. The results show that the system's metabolic profile changes dramatically in the presence of high concentrations of glucose, and that these changes are modulated by the presence of insulin. Furthermore, we observed an increase in E-selectin levels in hyperglycaemic conditions and increased IL-6 concentrations in insulin-free-hyperglycaemic conditions, indicating, respectively, endothelial injury and proinflammatory stress in the challenged 3-way system.

  7. Glucose transport by radiation-induced insulinoma and clonal pancreatic beta-cells

    Sugar uptake was measured in dispersed cells prepared from radiation-induced insulinomas transplantable in NEDH rats and in three clonal beta-cell lines maintained in continuous culture (RIN m5F, RIN 1046, HIT). Uptake of D-glucose and 3-O-methyl-D-glucose by insulinoma cells was rapid so that the intracellular concentration of D-hexoses approximated the concentration in the incubation medium by 15-30 s. L-Glucose was taken up only slowly. 3-O-methyl-D-glucose uptake by RIN m5F, RIN 1046, and HIT cells was slow; with 1 mM 3-O-methylglucose in the medium, equilibrium was attained at 20 min, but with 10 mM 3-O-methylglucose, equilibrium was not attained even at 20 min. In HIT cells incubated with D-glucose for 30 min, the intracellular concentration of glucose was less than the medium glucose concentration, indicating glucose transport is a nonequilibrium reaction in this cell line. These data indicate that radiation-induced insulinoma cells retain the capacity of normal beta-cells to transport sugar at high rates. RIN m5F, RIN 1046, and HIT cells transport sugar slowly, however, and thus differ from normal beta-cells. In RIN m5F, RIN 1046, and HIT cells, unlike in normal beta-cells, glucose transport may be the site regulating glucose metabolism

  8. Critical Role of Glucose Metabolism in Rheumatoid Arthritis Fibroblast-like Synoviocytes

    Garcia-Carbonell, Ricard; Divakaruni, Ajit S.; Lodi, Alessia; Vicente-Suarez, Ildefonso; Saha, Arindam; Cheroutre, Hilde; Boss, Gerry R.; Tiziani, Stefano; Murphy, Anne N.; Guma, Monica

    2016-01-01

    Objective Up-regulation of glucose metabolism has been implicated not only in tumor cell growth but also in immune cells upon activation. However, little is known about the metabolite profile in rheumatoid arthritis (RA), particularly in fibroblast-like synoviocytes (FLS). This study was undertaken to evaluate whether changes in glucose metabolism in RA FLS could play a role in inflammation and joint damage. Methods Synovium and FLS were obtained from patients with RA and patients with osteoarthritis (OA). The rate of glycolysis after stimulation of FLS with lipopolysaccharide and platelet-derived growth factor BB was measured using glycolysis stress test technology. FLS function was evaluated using a glycolysis inhibitor, 2-deoxy-D-glucose (2-DG). After stimulation of the FLS, a migration scratch assay, MTT assay, and enzyme-linked immunosorbent assay were performed to measure the effect of 2-DG on FLS migration, viability of the FLS, and cytokine secretion, respectively. IRDye 800CW 2-DG was used to assess glucose uptake in the arthritic joints and stromal cells of mice after K/BxN mouse serum transfer. The mice were injected daily, intraperitoneally, with 3-bromopyruvate (BrPa; 5 mg/kg) to assess the effect of inhibition of glycolysis in vivo. Results Compared to human OA FLS, the balance between glycolysis and oxidative phosphorylation was shifted toward glycolysis in RA FLS. Glucose transporter 1 (GLUT1) messenger RNA (mRNA) expression correlated with baseline functions of the RA FLS. Glucose deprivation or incubation of the FLS with glycolytic inhibitors impaired cytokine secretion and decreased the rate of proliferation and migration of the cells. In a mouse model of inflammatory arthritis, GLUT1 mRNA expression in the synovial lining cells was observed, and increased levels of glucose uptake and glycolytic gene expression were detected in the stromal compartment of the arthritic mouse joints. Inhibition of glycolysis by BrPa, administered in vivo

  9. Lymphocyte glucose and glutamine metabolism as targets of the anti-inflammatory and immunomodulatory effects of exercise.

    Wasinski, Frederick; Gregnani, Marcos F; Ornellas, Fábio H; Bacurau, Aline V N; Câmara, Niels O; Araujo, Ronaldo C; Bacurau, Reury F

    2014-01-01

    Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight association between metabolism and function in these cells was suggested to introduce the possibility of several pathologies resulting from the inability of lymphocytes to meet their nutrient demands under a given condition. In fact, disruptions in lymphocyte metabolism and function have been observed in different inflammatory, metabolic, and autoimmune pathologies. Regular physical exercise and physical activity offer protection against several chronic pathologies, and this benefit has been associated with the anti-inflammatory and immunomodulatory effects of exercise/physical activity. Chronic exercise induces changes in lymphocyte functionality and substrate metabolism. In the present review, we discuss whether the beneficial effects of exercise on lymphocyte function in health and disease are associated with modulation of the glucose and glutamine metabolic pathways. PMID:24987195

  10. Lymphocyte Glucose and Glutamine Metabolism as Targets of the Anti-Inflammatory and Immunomodulatory Effects of Exercise

    Frederick Wasinski

    2014-01-01

    Full Text Available Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight association between metabolism and function in these cells was suggested to introduce the possibility of several pathologies resulting from the inability of lymphocytes to meet their nutrient demands under a given condition. In fact, disruptions in lymphocyte metabolism and function have been observed in different inflammatory, metabolic, and autoimmune pathologies. Regular physical exercise and physical activity offer protection against several chronic pathologies, and this benefit has been associated with the anti-inflammatory and immunomodulatory effects of exercise/physical activity. Chronic exercise induces changes in lymphocyte functionality and substrate metabolism. In the present review, we discuss whether the beneficial effects of exercise on lymphocyte function in health and disease are associated with modulation of the glucose and glutamine metabolic pathways.

  11. Alterations in cancer cell metabolism: the Warburg effect and metabolic adaptation.

    Asgari, Yazdan; Zabihinpour, Zahra; Salehzadeh-Yazdi, Ali; Schreiber, Falk; Masoudi-Nejad, Ali

    2015-05-01

    The Warburg effect means higher glucose uptake of cancer cells compared to normal tissues, whereas a smaller fraction of this glucose is employed for oxidative phosphorylation. With the advent of high throughput technologies and computational systems biology, cancer cell metabolism has been reinvestigated over the last decades toward identifying various events underlying "how" and "why" a cancer cell employs aerobic glycolysis. Significant progress has been shaped to revise the Warburg effect. In this study, we have integrated the gene expression of 13 different cancer cells with the genome-scale metabolic network of human (Recon1) based on the E-Flux method, and analyzed them based on constraint-based modeling. Results show that regardless of significant up- and down-regulated metabolic genes, the distribution of metabolic changes is similar in different cancer types. These findings support the theory that the Warburg effect is a consequence of metabolic adaptation in cancer cells. PMID:25773945

  12. Effects of MDMA on blood glucose levels and brain glucose metabolism

    Soto-Montenegro, M L; Vaquero, Juan José; Arango, C.; Ricaurte, G.; García-Barreno, P; Desco, Manuel

    2007-01-01

    Purpose This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Methods Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated...

  13. Predicting glucose intolerance with normal fasting plasma glucose by the components of the metabolic syndrome

    Surprisingly it is estimated that about half of type 2 diabetics remain undetected. The possible causes may be partly attributable to people with normal fasting plasma glucose (FPG) but abnormal postprandial hyperglycemia. We attempted to develop an effective predictive model by using the metabolic syndrome (MeS) components as parameters to identify such persons. All participants received a standard 75 gm oral glucose tolerance test which showed that 106 had normal glucose tolerance, 61 had impaired glucose tolerance and 6 had diabetes on isolated postchallenge hyperglycemia. We tested five models which included various MeS components. Model 0: FPG; Model 1 (Clinical history model): family history (FH), FPG, age and sex; Model 2 (MeS model): Model 1 plus triglycerides, high-density lipoprotein cholesterol, body mass index, systolic blood pressure and diastolic blood pressure; Model 3: Model 2 plus fasting plasma insulin (FPI); Model 4: Model 3 plus homeostasis model assessment of insulin resistance. A receiver-operating characteristic (ROC) curve was used to determine the predictive discrimination of these models. The area under the ROC curve of the Model 0 was significantly larger than the area under the diagonal reference line. All the other 4 models had a larger area under the ROC curve than Model 0. Considering the simplicity and lower cost of Model 2, it would be the best model to use. Nevertheless, Model 3 had the largest area under the ROC curve. We demonstrated that Model 2 and 3 have a significantly better predictive discrimination to identify persons with normal FPG at high risk for glucose intolerance. (author)

  14. Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression

    Li, Yuanyuan; Liang LIU; Tollefsbol, Trygve O.

    2010-01-01

    Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. However, the precise molecular mechanisms leading to different responses to glucose restriction between normal and cancer cells are not fully understood. We analyzed normal WI-38 and immortalized WI-38/S fetal lung fibroblasts and found that glucose restriction resulted in growth inhibition and apoptosis in WI-38/S cells, whereas it induced lifespan extension in WI-38 cells. Moreover, in WI-3...

  15. Biochemical Hypermedia: Glucose as a Central Molecule in Metabolism

    J.K. Sugai

    2008-05-01

    Full Text Available The technologies of information, together with education resources, have been pointed out as a solution to the improvement of teaching approach, but they still claim for programs to fulfill the demands of didactic materials. So, a biochemical software was developed aiming to contribute for the better understanding of the glycolysis. It was prepared with the help of concept maps, ISIS Draw, ADOBE Photoshop and FLASH MX Program. The introduction screen shows a teacher in a theater presenting glucose as a central molecule in the metabolism of animals, plants and many microorganisms. She invites for a better knowledge of glucose through a view of its discovery and its metabolism. A step by step animation process shows the interaction of glucose in aerobic conditions with the enzymes of the glycolytic pathways and its products. An explanation text of each enzyme catalytic process is provided by links. A static pathway is always available through a link. The fates of pyruvate yielding lactic acid and ethanol under anaerobic conditions are shown as well. The overall reactions of gluconeogenesis and the functional significance of this pathway are presented. The experimental treatment involved the presentation of this hypermedia for Nutrition undergraduate students (UFSC as a tool for better comprehension of the theme. The students revealed that it was extremely effective in promoting the understanding of the enzymatic mechanisms involved in glycolysis. This suggests that there is a significant added value in employing the software as an instructional effort to enhance student’s abilities to understand biochemical pathways.

  16. A comprehensive metabolic profile of cultured astrocytes using isotopic transient metabolic flux analysis and 13C-labeled glucose

    Ursula Sonnewald

    2011-09-01

    Full Text Available Metabolic models have been used to elucidate important aspects of brain metabolism in recent years. This work applies for the first time the concept of isotopic transient 13C metabolic flux analysis (MFA to estimate intracellular fluxes of cultured astrocytes. This methodology comprehensively explores the information provided by 13C labeling time-courses of intracellular metabolites after administration of a 13C labeled substrate. Cells were incubated with medium containing [1-13C]glucose for 24 h and samples of cell supernatant and extracts collected at different time-points were then analyzed by mass spectrometry and/or HPLC. Metabolic fluxes were estimated by fitting a carbon labeling network model to isotopomer profiles experimentally determined. Both the fast isotopic equilibrium of glycolytic metabolite pools and the slow labeling dynamics of TCA cycle intermediates are described well by the model. The large pools of glutamate and aspartate which are linked to the TCA cycle via reversible aminotransferase reactions are likely to be responsible for the observed delay in equilibration of TCA cycle intermediates. Furthermore, it was estimated that 11% of the glucose taken up by astrocytes was diverted to the pentose phosphate pathway. In addition, considerable fluxes through pyruvate carboxylase (PC (PC/pyruvate dehydrogenase (PDH ratio = 0.5, malic enzyme (5% of the total pyruvate production and catabolism of branched-chained amino acids (contributing with ~40% to total acetyl-CoA produced confirmed the significance of these pathways to astrocytic metabolism. Consistent with the need of maintaining cytosolic redox potential, the fluxes through the malate-aspartate shuttle and the PDH pathway were comparable. Finally, the estimated glutamate/α-ketoglutarate exchange rate (~0.7 µmol.mg prot-1.h-1 was similar to the TCA cycle flux. In conclusion, this work demonstrates the potential of isotopic transient MFA for a comprehensive analysis of

  17. Decreased cerebral glucose metabolism associated with mental deterioration in multi-infarct dementia

    Cerebral glucose metabolism of 18 patients with multi-infarct dementia (MID) and 10 age-matched normal subjects were examined with positron emission tomography and the 18-F-fluoro-deoxy-glucose technique. MID patients had significantly lower glucose metabolsim in all the grey matter regions measured and were also characterized by more individuality in metabolic pattern. MID patients were also evaluated as to intelligence quotient (IQ). A positive correlation between IQ as shown by the Tanaka-Binet test and glucose metabolism for the entire grey matter was found. The clinical applicability of this test for predicting cerebral metabolism is discussed. (orig.)

  18. Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia

    SONG, KUI; LI, MIN; XU, XIAOJUN; XUAN, LI; HUANG, GUINIAN; LIU, QIFA

    2016-01-01

    Altered glucose metabolism has been described as a cause of chemoresistance in multiple tumor types. The present study aimed to identify the expression profile of glucose metabolism in drug-resistant acute myeloid leukemia (AML) cells and provide potential strategies for the treatment of drug-resistant AML. Bone marrow and serum samples were obtained from patients with AML that were newly diagnosed or had relapsed. The messenger RNA expression of hypoxia inducible factor (HIF)-1α, glucose transporter (GLUT)1, and hexokinase-II was measured by quantitative polymerase chain reaction. The levels of LDH and β subunit of human F1-F0 adenosine triphosphate synthase (β-F1-ATPase) were detected by enzyme-linked immunosorbent and western blot assays. The HL-60 and HL-60/ADR cell lines were used to evaluate glycolytic activity and effect of glycolysis inhibition on cellular proliferation and apoptosis. Drug-resistant HL-60/ADR cells exhibited a significantly increased level of glycolysis compared with the drug-sensitive HL-60 cell line. The expression of HIF-1α, hexokinase-II, GLUT1 and LDH were increased in AML patients with no remission (NR), compared to healthy control individuals and patients with complete remission (CR) and partial remission. The expression of β-F1-ATPase in patients with NR was decreased compared with the expression in the CR group. Treatment of HL-60/ADR cells with 2-deoxy-D-glucose or 3-bromopyruvate increased in vitro sensitivity to Adriamycin (ADR), while treatment of HL-60 cells did not affect drug cytotoxicity. Subsequent to treatment for 24 h, apoptosis in these two cell lines showed no significant difference. However, glycolytic inhibitors in combination with ADR increased cellular necrosis. These findings indicate that increased glycolysis and low efficiency of oxidative phosphorylation may contribute to drug resistance. Targeting glycolysis is a viable strategy for modulating chemoresistance in AML.

  19. Fructose modifies the hormonal response and modulates lipid metabolism in aerobic exercise after glucose supplementation

    Fernández, Juan Marcelo; Da Silva-Grigoletto, Marzo Edir; Ruano-Ruiz, Juan; Caballero-Villarraso, Javier; Moreno-Luna, Rafael; Tunez-Fiñana, Isaac; Tasset-Cuevas, Inmaculada; Pérez-Martinez, Pablo; López-Miranda, José; Pérez-Jiménez, Francisco

    2008-01-01

    Abstract The metabolic response, when aerobic exercise is performed after the ingestion of glucose plus fructose, is unclear. To compare the hormonal and lipid responses provoked by the ingestion of glucose plus fructose in relation to glucose alone, during aerobic exercise and the recovery phase, we administered two beverages containing glucose plus fructose or glucose in a randomised crossover design, to twenty healthy, aerobically trained volunteers. After a 15-minute resting pe...

  20. Metabolic and mitogenic transduction cascades in skeletal muscle : Implications for exercise effects on glucose metabolism and gene regulation

    Yu, Mei

    2003-01-01

    Level of physical activity is linked to improved glucose homeostasis. The molecular signaling mechanisms by which insulin and exercise/muscle contractions lead to increased glucose transport and metabolism and gene expression have not been completely elucidated. The overall aim of this thesis was to identify novel regulatory mechanisms governing exercisesensitive signaling pathways to glucose metabolism and gene transcription in skeletal muscle. Components of the insulin (IR...

  1. [Metabolism of labeled exogenous glucose in fiber flax tissues].

    Chikov, V I; Avvakumova, N Iu; Bakirova, G G; Khamidullina, L A

    2005-01-01

    A labeled glucose solution was introduced into cut fiber flax plants (45-50 cm high) using a special unit under a pressure of 0.1 atm for 30 min, 1, and 2 h. The highest quantities of labeled carbon were revealed in the woody tissue. Sucrose made up a considerable proportion in low molecular weight products of [ [2-14C]-glucose transformation (23.5%). Metabolism of labeled glucose in the leaves exposed to sunlight yielded a set of metabolites similar to products of 14CO2 photoassimilation. In the shade, the pattern of 14C distribution in labeled compounds of the water/alcohol soluble fraction remained similar in mature leaves, while in juvenile leaves, 14C content decreased in sucrose and increased in organic and amino acids. In the shade, the incorporation of 14C into starch and hot water soluble polysaccharides increased at the expense of the acetone fraction (lipids and pigments), water/salt soluble proteins, and cellulose. Low light conditions increased the radioactivity ratio of sparingly soluble (KOH and Triton X-100 soluble) proteins to albumins and globulins. We propose that the synthesis of components of the photosynthetic apparatus in juvenile leaves is directly powered by photosynthesis and the photosynthesis of glucose and the polymers compete for ATP energy. Appearance of sucrose in the woody tissue is due to its release from the phloem to the stem apoplast and the radial transfer to the xylem, where it is transported to the upper shoot with the transpiration flow. PMID:16004260

  2. A glucose biofuel cell implanted in rats.

    Cinquin, Philippe; Gondran, Chantal; Giroud, Fabien; Mazabrard, Simon; Pellissier, Aymeric; Boucher, François; Alcaraz, Jean-Pierre; Gorgy, Karine; Lenouvel, François; Mathé, Stéphane; Porcu, Paolo; Cosnier, Serge

    2010-01-01

    Powering future generations of implanted medical devices will require cumbersome transcutaneous energy transfer or harvesting energy from the human body. No functional solution that harvests power from the body is currently available, despite attempts to use the Seebeck thermoelectric effect, vibrations or body movements. Glucose fuel cells appear more promising, since they produce electrical energy from glucose and dioxygen, two substrates present in physiological fluids. The most powerful o...

  3. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism1

    Galie, Mirco; Farace, Paolo; Nanni, Cristina; Spinelli, Antonello; Nicolato, Elena; Boschi, Federico; Magnani, Paolo; Trespidi, Silvia; Ambrosini, Valentina; Fanti, Stefano; Merigo, Flavia; Osculati, Francesco; Marzola, Pasquina; Sbarbati, Andrea

    2007-01-01

    Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular ...

  4. Alteration of mammalian cell metabolism by dynamic nutrient feeding

    Zhou, Weichang; Rehm, Jutta; Europa, Anna; Hu, Wei-Shou

    1997-01-01

    The metabolism of hybridoma cells was controlled to reduce metabolic formation in fed-batch cultures by dynamically feeding a salt-free nutrient concentrate. For this purpose, on-line oxygen uptake rate (OUR) measurement was used to estimate the metabolic demand of hybridoma cells and to determine the feeding rate of a concentrated solution of salt-free DMEM/F12 medium supplemented with other medium components. The ratios among glucose, glutamine and other medium components in the feeding nut...

  5. Berberine Improves Glucose Metabolism through Induction of Glycolysis

    Yin, Jun; Gao, Zhanguo; Liu, Dong; Liu, Zhijun; Ye, Jianping

    2007-01-01

    Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has been reported to activate AMPK recently. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after five week administration. Fasting insulin and HOMA-IR were decreased by 46% and 48% in the rats, respectively. In cell lines includin...

  6. Antilipolytic drug boosts glucose metabolism in prostate cancer

    Introduction: The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts. Methods: Subcutaneous tumors were produced in nude mice by injection of PC3 and CWR22Rv1 PCa cells. The mice were divided into two groups (Acipimox vs. controls). Acipimox (50 mg/kg) was administered by oral gavage 1 h before injection of tracers. 1 h after i.v. co-injection of 8.2 MBq (222 ± 6.0 μCi) 18 F-FDG and ∼ 0.0037 MBq (0.1 μCi) 14C-acetate, 18 F-FDG imaging was performed using a small-animal PET scanner. Counting rates in reconstructed images were converted to activity concentrations. Quantification was obtained by region-of-interest analysis using dedicated software. The mice were euthanized, and blood samples and organs were harvested. 18 F radioactivity was measured in a calibrated γ-counter using a dynamic counting window and decay correction. 14C radioactivity was determined by liquid scintillation counting using external standard quench corrections. Counts were converted into activity, and percentage of the injected dose per gram (%ID/g) tissue was calculated. Results: FDG biodistribution data in mice with PC3 xenografts demonstrated doubled average %ID/g tumor tissue after administration of Acipimox compared to controls (7.21 ± 1.93 vs. 3.59 ± 1.35, P = 0.02). Tumor-to-organ ratios were generally higher in mice treated with Acipimox. This was supported by PET imaging data, both semi-quantitatively (mean tumor FDG uptake) and visually (tumor-to-background ratios). In mice with CWR22Rv1 xenografts there was no effect of Acipimox on FDG uptake, either in biodistribution or PET imaging. 14C-acetate uptake was unaffected in PC3 and CWR22Rv1 xenografts. Conclusions: In mice with PC3 PCa xenografts, acute administration of Acipimox increases tumor uptake of 18 F-FDG with general

  7. Abnormal glucose metabolism in acute myocardial infarction: influence on left ventricular function and prognosis

    Høfsten, Dan E; Løgstrup, Brian B; Møller, Jacob E;

    2009-01-01

    OBJECTIVES: We studied the influence of abnormal glucose metabolism on left ventricular (LV) function and prognosis in 203 patients with acute myocardial infarction. BACKGROUND: Abnormal glucose metabolism is associated with increased mortality after acute myocardial infarction. This appears to be...... particularly attributable to an increased incidence of post-infarction congestive heart failure. A relationship between glucose metabolism and LV function could potentially explain this excess mortality. METHODS: In patients without known diabetes, glucose metabolism was determined using an oral glucose...... atrial volume index) and by measuring plasma N-terminal pro-B-type natriuretic peptide levels. RESULTS: After adjustment for age and gender, a linear relationship between the degree of abnormal glucose metabolism was observed for each marker of LV dysfunction (p(trend) < 0.05) with the exception of left...

  8. SGLT2 Deletion Improves Glucose Homeostasis and Preserves Pancreatic β-Cell Function

    Jurczak, Michael J.; Lee, Hui-Young; Birkenfeld, Andreas L; Jornayvaz, Francois R.; Frederick, David W.; Pongratz, Rebecca L.; Zhao, Xiaoxian; Moeckel, Gilbert W.; Samuel, Varman T.; Whaley, Jean M.; Shulman, Gerald I.; Kibbey, Richard G

    2011-01-01

    OBJECTIVE Inhibition of the Na+-glucose cotransporter type 2 (SGLT2) is currently being pursued as an insulin-independent treatment for diabetes; however, the behavioral and metabolic consequences of SGLT2 deletion are unknown. Here, we used a SGLT2 knockout mouse to investigate the effect of increased renal glucose excretion on glucose homeostasis, insulin sensitivity, and pancreatic β-cell function. RESEARCH DESIGN AND METHODS SGLT2 knockout mice were fed regular chow or a high-fat diet (HF...

  9. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

    Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

    2016-01-01

    Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism. PMID:26964832

  10. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

    Mirco Galiè

    2007-11-01

    Full Text Available Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG positron emission tomography (PET, we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition.

  11. suPAR associates to glucose metabolic aberration during glucose stimulation in HIV-infected patients on HAART

    Andersen, Ove; Eugen-Olsen, Jesper; Kofoed, Kristian;

    2008-01-01

    extend these findings by investigating the association of suPAR to glucose metabolic insufficiency during an oral glucose challenge (OGTT). METHODS: In 16 HIV-infected patients with lipodystrophy and 15 HIV-infected patients without lipodystrophy, glucose tolerance, insulin sensitivity (ISI......PAR associated to important glucose metabolic aberrations in HIV-infected patients on HAART. Moreover, suPAR was stable after a glucose challenge. Future research is required to confirm these findings and explore the potential of suPAR as marker of dysmetabolism in HIV-infected patients.......OBJECTIVE: We have recently shown that the level of soluble urokinase plasminogen activator receptor (suPAR), which is associated with the immune status of HIV-infected patients undergoing highly active antiretroviral therapy (HAART), correlates with the insulin action of such patients. Here we...

  12. Delivery-corrected imaging of fluorescently-labeled glucose reveals distinct metabolic phenotypes in murine breast cancer.

    Amy E Frees

    Full Text Available When monitoring response to cancer therapy, it is important to differentiate changes in glucose tracer uptake caused by altered delivery versus a true metabolic shift. Here, we propose an optical imaging method to quantify glucose uptake and correct for in vivo delivery effects. Glucose uptake was measured using a fluorescent D-glucose derivative 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-ylAmino-2-deoxy-D-glucose (2-NBDG in mice implanted with dorsal skin flap window chambers. Additionally, vascular oxygenation (SO2 was calculated using only endogenous hemoglobin contrast. Results showed that the delivery factor proposed for correction, "RD", reported on red blood cell velocity and injected 2-NBDG dose. Delivery-corrected 2-NBDG uptake (2-NBDG60/RD inversely correlated with blood glucose in normal tissue, indicating sensitivity to glucose demand. We further applied our method in metastatic 4T1 and nonmetastatic 4T07 murine mammary adenocarcinomas. The ratio 2-NBDG60/RD was increased in 4T1 tumors relative to 4T07 tumors yet average SO2 was comparable, suggesting a shift toward a "Warburgian" (aerobic glycolysis metabolism in the metastatic 4T1 line. In heterogeneous regions of both 4T1 and 4T07, 2-NBDG60/RD increased slightly but significantly as vascular oxygenation decreased, indicative of the Pasteur effect in both tumors. These data demonstrate the utility of delivery-corrected 2-NBDG and vascular oxygenation imaging for differentiating metabolic phenotypes in vivo.

  13. The Coupling of Cerebral Metabolic Rate of Glucose and Cerebral Blood Flow In Vivo

    Hasselbalch, Steen; Paulson, Olaf Bjarne

    2012-01-01

    The energy supplied to the brain by metabolic substrate is largely utilized for maintaining synaptic transmission. In this regulation cerebral blood flow and glucose consumption is tightly coupled as well in the resting condition as during activation. Quantification of cerebral blood flow and...... not used for aerobic metabolism. Although some of the excess glucose uptake can be explained by lactate production, this phenomenon can still not account for the excess glucose uptake. Thus, more complex metabolic patterns in the brain might be reflected in the excess glucose uptake during activation...

  14. Quantitative on-line monitoring of cellular glucose and lactate metabolism in vitro with slow perfusion

    Leegsma-Vogt, G; Venema, K; Brouwer, N; Gramsbergen, JB; Copray, S; Korf, J

    2004-01-01

    An on-line in vitro perfusion technique is described that allows the continuous quantification of cellular glucose metabolism in vitro. Using biosensor technology, we measure glucose and lactate metabolism at a minute-to-minute time resolution for periods up to several days. The application of our p

  15. Impaired glucose metabolism in HIV-infected pregnant women: a retrospective analysis.

    Moore, Rebecca

    2015-05-20

    Metabolic complications including diabetes mellitus have been increasingly recognised in HIV-infected individuals since the introduction of antiretroviral therapy, particularly protease inhibitors (PIs). Pregnancy is also a risk factor for impaired glucose metabolism, and previous studies have given conflicting results regarding the contribution of PIs to impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) in pregnant HIV-infected women.

  16. The measurement of the nigrostriatal dopaminergic function and glucose metabolism in patients with movement disorders

    The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with 18F-Dopa and 18F-FDG respectively. The 18F-Dopa uptake in the striatum (the caudate head and the putamen) decreased in patients with Parkinson's disease but was relatively unaffected in the caudate. The cerebral glucose metabolism was normal in patients with Parkinson's disease. The 18F-Dopa uptake in the striatum also decreased in cases of atypical parkinsonism and in cases of progressive supranuclear palsy, but there was no difference in the uptake between the caudate and the putamen. The glucose metabolism decreased in the cerebral hemisphere including the striatum; this finding was also different from those of Parkinson's disease. A normal 18F-Dopa uptake in the striatum with a markedly decreased striatal glucose metabolism and a mildly decreased cortical glucose metabolism was observed in cases of Huntington's disease and Wilson's disease. The 18F-Dopa uptake in the striatum increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of 18F-Dopa uptake and glucose metabolism were thus observed in the various movement disorders. These results suggest that the measurements of the 18F-Dopa uptake and the cerebral glucose metabolism would be useful for the evaluation of the striatal function in various movement disorders. (author)

  17. Early and progressive impairment of spinal blood flow–glucose metabolism coupling in motor neuron degeneration of ALS model mice

    Miyazaki, Kazunori; Masamoto, Kazuto; Morimoto, Nobutoshi; Kurata, Tomoko; Mimoto, Takahumi; Obata, Takayuki; Kanno, Iwao; Abe, Koji

    2011-01-01

    The exact mechanism of selective motor neuron death in amyotrophic lateral sclerosis (ALS) remains still unclear. In the present study, we performed in vivo capillary imaging, directly measured spinal blood flow (SBF) and glucose metabolism, and analyzed whether if a possible flow–metabolism coupling is disturbed in motor neuron degeneration of ALS model mice. In vivo capillary imaging showed progressive decrease of capillary diameter, capillary density, and red blood cell speed during the di...

  18. 2-Deoxy-2-fluoro-d-glucose metabolism in Arabidopsis thaliana

    Fatangare, Amol; Paetz, Christian; Saluz, Hanspeter; Svatoš, Aleš

    2015-01-01

    2-Deoxy-2-fluoro-d-glucose (FDG) is glucose analog routinely used in clinical and animal radiotracer studies to trace glucose uptake but it has rarely been used in plants. Previous studies analyzed FDG translocation and distribution pattern in plants and proposed that FDG could be used as a tracer for photoassimilates in plants. Elucidating FDG metabolism in plants is a crucial aspect for establishing its application as a radiotracer in plant imaging. Here, we describe the metabolic fate of F...

  19. Adenovirus-mediated transfection with glucose transporter 3 suppresses PC12 cell apoptosis following ischemic injury

    Junliang Li; Xinke Xu; Shanyi Zhang; Meiguang Zheng; Zhonghua Wu; Yinlun Weng; Leping Ouyang; Jian Yu; Fangcheng Li

    2012-01-01

    In this study, we investigated the effects of adenovirus-mediated transfection of PC12 cells with glucose transporter 3 after ischemic injury. The results of flow cytometry and TUNEL showed that exogenous glucose transporter 3 significantly suppressed PC12 cell apoptosis induced by ischemic injury. The results of isotopic scintiscan and western blot assays showed that, the glucose uptake rate was significantly increased and nuclear factor kappaB expression was significantly decreased after adenovirus-mediated transfection of ischemic PC12 cells with glucose transporter 3. These results suggest that adenovirus-mediated transfection of cells with glucose transporter 3 elevates the energy metabolism of PC12 cells with ischemic injury, and inhibits cell apoptosis.

  20. Implications of Hydrogen Sulfide in Glucose Regulation: How H2S Can Alter Glucose Homeostasis through Metabolic Hormones

    Pichette, Jennifer

    2016-01-01

    Diabetes and its comorbidities continue to be a major health problem worldwide. Understanding the precise mechanisms that control glucose homeostasis and their dysregulation during diabetes are a major research focus. Hydrogen sulfide (H2S) has emerged as an important regulator of glucose homeostasis. This is achieved through its production and action in several metabolic and hormone producing organs including the pancreas, liver, and adipose. Of importance, H2S production and signaling in these tissues are altered during both type 1 and type 2 diabetes mellitus. This review first examines how H2S is produced both endogenously and by gastrointestinal microbes, with a particular focus on the altered production that occurs during obesity and diabetes. Next, the action of H2S on the metabolic organs with key roles in glucose homeostasis, with a particular focus on insulin, is described. Recent work has also suggested that the effects of H2S on glucose homeostasis goes beyond its role in insulin secretion. Several studies have demonstrated important roles for H2S in hepatic glucose output and adipose glucose uptake. The mechanism of H2S action on these metabolic organs is described. In the final part of this review, future directions examining the roles of H2S in other metabolic and glucoregulatory hormone secreting tissues are proposed. PMID:27478532

  1. Distinct metabolic responses of an ovarian cancer stem cell line

    Kathleen A Vermeersch; Wang, Lijuan; McDonald, John F; Styczynski, Mark P.

    2014-01-01

    Background Cancer metabolism is emerging as an important focus area in cancer research. However, the in vitro cell culture conditions under which much cellular metabolism research is performed differ drastically from in vivo tumor conditions, which are characterized by variations in the levels of oxygen, nutrients like glucose, and other molecules like chemotherapeutics. Moreover, it is important to know how the diverse cell types in a tumor, including cancer stem cells that are believed to b...

  2. Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study

    Wahl, Simone; Kunze, Sonja; Molnos, Sophie; Volkova, Nadezda; Schramm, Katharina; Carstensen-Kirberg, Maren; Waldenberger, Melanie; Gieger, Christian; Peters, Annette; Illig, Thomas; Prokisch, Holger; Roden, Michael; Grallert, Harald

    2016-01-01

    Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in the Region of Augsburg F4 study using the Illumina HumanMethylation 450 BeadChip. We identified a total of 31 CpG sites where methylation level was associated with measures of glucose metabolism after adjustment for age, sex, smoking, and estimated white blood cell proportions and correction for multiple testing using the Benjamini-Hochberg (B-H) method (four for fasting glucose, seven for fasting insulin, 25 for homeostasis model assessment-insulin resistance [HOMA-IR]; B-H-adjusted p-values between 9.2x10-5 and 0.047). In addition, DNA methylation at cg06500161 (annotated to ABCG1) was associated with all the aforementioned phenotypes and 2-hour glucose (B-H-adjusted p-values between 9.2x10-5 and 3.0x10-3). Methylation status of additional three CpG sites showed an association with fasting insulin only after additional adjustment for body mass index (BMI) (B-H-adjusted p-values = 0.047). Overall, effect strengths were reduced by around 30% after additional adjustment for BMI, suggesting that this variable has an influence on the investigated phenotypes. Furthermore, we found significant associations between methylation status of 21 of the aforementioned CpG sites and 2-hour insulin in a subset of samples with seven significant associations persisting after additional adjustment for BMI. In a subset of 533 participants, methylation of the CpG site cg06500161 (ABCG1) was inversely associated with ABCG1 gene expression (B-H-adjusted p-value = 1.5x10-9). Additionally, we observed an enrichment of the top 1,000 CpG sites for diabetes-related canonical pathways using Ingenuity Pathway Analysis. In conclusion, our study indicates that DNA methylation and diabetes-related traits

  3. Transport and metabolism of fumaric acid in Saccharomyces cerevisiae in aerobic glucose-limited chemostat culture.

    Shah, Mihir V; van Mastrigt, Oscar; Heijnen, Joseph J; van Gulik, Walter M

    2016-04-01

    Currently, research is being focused on the industrial-scale production of fumaric acid and other relevant organic acids from renewable feedstocks via fermentation, preferably at low pH for better product recovery. However, at low pH a large fraction of the extracellular acid is present in the undissociated form, which is lipophilic and can diffuse into the cell. There have been no studies done on the impact of high extracellular concentrations of fumaric acid under aerobic conditions in S. cerevisiae, which is a relevant issue to study for industrial-scale production. In this work we studied the uptake and metabolism of fumaric acid in S. cerevisiae in glucose-limited chemostat cultures at a cultivation pH of 3.0 (pH exporting fumaric acid. We observed that fumaric acid entered the cells most likely via passive diffusion of the undissociated form. Approximately two-thirds of the fumaric acid in the feed was metabolized together with glucose. From metabolic flux analysis, an increased ATP dissipation was observed only at high intracellular concentrations of fumarate, possibly due to the export of fumarate via an ABC transporter. The implications of our results for the industrial-scale production of fumaric acid are discussed. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26683700

  4. Cattle temperament influences metabolism: metabolic response to glucose tolerance and insulin sensitivity tests in beef steers.

    Burdick Sanchez, N C; Carroll, J A; Broadway, P R; Hughes, H D; Roberts, S L; Richeson, J T; Schmidt, T B; Vann, R C

    2016-07-01

    Cattle temperament, defined as the reactivity of cattle to humans or novel environments, can greatly influence several physiological systems in the body, including immunity, stress, and most recently discovered, metabolism. Greater circulating concentrations of nonesterified fatty acids (NEFAs) found in temperamental cattle suggest that temperamental cattle are metabolically different than calm cattle. Further, elevated NEFA concentrations have been reported to influence insulin sensitivity. Therefore, the objective of this study was to determine whether cattle temperament would influence the metabolic response to a glucose tolerance test (GTT) and insulin sensitivity test (IST). Angus-cross steers (16 calm and 15 temperamental; 216 ± 6 kg BW) were selected based on temperament score measured at weaning. On day 1, steers were moved into indoor stanchions to allow measurement of individual ad libitum feed intake. On day 6, steers were fitted with indwelling rectal temperature probes and jugular catheters. At 9 AM on day 7, steers received the GTT (0.5-mL/kg BW of a 50% dextrose solution), and at 2 PM on day 7, steers received the IST (2.5 IU bovine insulin/kg BW). Blood samples were collected and serum isolated at -60, -45, -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, and 150 min relative to each challenge. Serum was stored at -80°C until analyzed for cortisol, glucose, NEFA, and blood urea nitrogen concentrations. All variables changed over time (P < 0.01). For the duration of the study, temperamental steers maintained greater (P < 0.01) serum NEFA and less (P ≤ 0.01) serum blood urea nitrogen and insulin sensitivity (calculated using Revised Quantitative Insulin Sensitivity Check Index) compared with calm steers. During the GTT, temperamental steers had greater (P < 0.01) serum glucose, yet decreased (P = 0.03) serum insulin and (P < 0.01) serum insulin: serum glucose compared to calm cattle. During the IST, temperamental steers had greater (P < 0.01) serum

  5. Zonation of glucose and fatty acid metabolism in the liver : Mechanism and metabolic consequences

    Hijmans, Brenda S.; Greffiorst, Aldo; Oosterveer, Maaike H.; Groen, Albert K.

    2014-01-01

    The liver is generally considered as a relatively homogeneous organ containing four different cell types. It is however well-known that the liver is not homogeneous and consists of clearly demarcated metabolic zones. Hepatocytes from different zones show phenotypical heterogeneity in metabolic featu

  6. A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability

    Salvatore Fusco

    2016-02-01

    Full Text Available Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1 is modulated in neural stem and progenitor cells (NSCs by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein and Sirt-1 (Sirtuin 1, two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis.

  7. DEFECTS IN INSULIN-SECRETION IN NIDDM - B-CELL GLUCOSE INSENSITIVITY OR GLUCOSE TOXICITY

    VANHAEFTEN, TW

    1993-01-01

    In NIDDM, first-phase insulin release to glucose is (almost) absent. However, in contrast to older studies which suggested that in NIDDM the B-cell is ''blind'' for glucose, recent evidence indicates that the B-cell is not insensitive for glucose as far as second phase release is concerned. This sug

  8. Impaired glucose metabolism in HIV-infected pregnant women: a retrospective analysis.

    Moore, Rebecca; Adler, Hugh; Jackson, Valerie; Lawless, Mairead; Byrne, Maria; Eogan, Maeve; Lambert, John S

    2016-06-01

    Metabolic complications, including diabetes mellitus, have been increasingly recognised in HIV-infected individuals since the introduction of antiretroviral therapy, particularly protease inhibitors (PIs). Pregnancy is also a risk factor for impaired glucose metabolism, and previous studies have given conflicting results regarding the contribution of PIs to impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) in pregnant HIV-infected women. We conducted a retrospective review of all HIV-infected women attending a combined infectious disease and antenatal clinic between 2007 and 2013 who underwent a 100 g oral glucose tolerance test (OGTT) at 24-28 weeks. We grouped the patients based on whether their OGTT result was normal or abnormal, and compared the groups using standard parametric tests (t-test and Fisher's exact test). Of 263 women with HIV who attended the clinic, 142 (53.9%) attended for OGTT and were eligible for inclusion. The mean age was 31 years (SD 5.37), all women were of European or African origin and 33.7% had a body mass index ≥30 kg/m(2) About 93.7% were on PI-based regimens. At delivery, the mean CD4 count was 526 cells/µL, and 13% of patients had a detectable viraemia. The prevalence of IGT was 2.8%, while the prevalence of GDM was 2.1%. Also, 71.4% (n = 5) of women with abnormal glucose metabolism were taking PIs versus 94.8% (n = 128) of normoglycaemic women (p = 0.06). We did not confirm an increased rate of GDM in HIV-infected women in our patient population and found no association between PI use and GDM. PMID:25999164

  9. Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non-Diabetics: Results from the GLOBAL Fluid Cohort Study

    Chess, James; Do, Jun-Young; Noh, Hyunjin; Lee, Hi-Bahl; Kim, Yong-Lim; Summers, Angela; Williams, Paul Ford; Davison, Sara; Dorval, Marc

    2016-01-01

    Background and Objectives Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD) patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism. Methods and Materials We analysed the Global Fluid Study cohort, a prospective, observational cohort study initiated in 2002. A subset of 10 centres from 3 countries with high data quality were selected (368 incident and 272 prevalent non-diabetic patients), with multilevel, multivariable analysis of the reciprocal of random glucose levels, and a stratified-by-centre Cox survival analysis. Results The median follow up was 5.6 and 6.4 years respectively in incident and prevalent patients. On multivariate analysis, serum glucose increased with age (β = -0.007, 95%CI -0.010, -0.004) and decreased with higher serum sodium (β = 0.002, 95%CI 0.0005, 0.003) in incident patients and increased with dialysate glucose (β = -0.0002, 95%CI -0.0004, -0.00006) in prevalent patients. Levels suggested undiagnosed diabetes in 5.4% of prevalent patients. Glucose levels predicted death in unadjusted analyses of both incident and prevalent groups but in an adjusted survival analysis they did not (for random glucose 6–10 compared with diabetic patients, random glucose levels at a diabetic level are under-recognised and increase with dialysate glucose load. Random glucose levels predict mortality in unadjusted analyses, but this association has not been proven in adjusted analyses. PMID:27249020

  10. Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non-Diabetics: Results from the GLOBAL Fluid Cohort Study.

    Mark Lambie

    Full Text Available Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism.We analysed the Global Fluid Study cohort, a prospective, observational cohort study initiated in 2002. A subset of 10 centres from 3 countries with high data quality were selected (368 incident and 272 prevalent non-diabetic patients, with multilevel, multivariable analysis of the reciprocal of random glucose levels, and a stratified-by-centre Cox survival analysis.The median follow up was 5.6 and 6.4 years respectively in incident and prevalent patients. On multivariate analysis, serum glucose increased with age (β = -0.007, 95%CI -0.010, -0.004 and decreased with higher serum sodium (β = 0.002, 95%CI 0.0005, 0.003 in incident patients and increased with dialysate glucose (β = -0.0002, 95%CI -0.0004, -0.00006 in prevalent patients. Levels suggested undiagnosed diabetes in 5.4% of prevalent patients. Glucose levels predicted death in unadjusted analyses of both incident and prevalent groups but in an adjusted survival analysis they did not (for random glucose 6-10 compared with <6, Incident group HR 0.92, 95%CI 0.58, 1.46, Prevalent group HR 1.42, 95%CI 0.86, 2.34.In prevalent non-diabetic patients, random glucose levels at a diabetic level are under-recognised and increase with dialysate glucose load. Random glucose levels predict mortality in unadjusted analyses, but this association has not been proven in adjusted analyses.

  11. Resveratrol supplementation does not improve metabolic function in non-obese women with normal glucose tolerance

    Yoshino, Jun; Conte, Caterina; Fontana, Luigi; Mittendorfer, Bettina; Imai, Shin-ichiro; Kenneth B Schechtman; Gu, Charles; Kunz, Iris; Fanelli, Filippo Rossi; Patterson, Bruce W.; Klein, Samuel

    2012-01-01

    Resveratrol has been reported to improve metabolic function in metabolically-abnormal rodents and humans, but has not been studied in non-obese people with normal glucose tolerance. We conducted a randomized, double-blind, placebo-controlled trial to evaluate the metabolic effects of 12 weeks of resveratrol supplementation (75 mg/day) in non-obese, postmenopausal women with normal glucose tolerance. Although resveratrol supplementation increased plasma resveratrol concentration, it did not ch...

  12. Effects of coumestrol on lipid and glucose metabolism as a farnesoid X receptor ligand

    In the course of an effort to identify novel agonists of the farnesoid X receptor (FXR), coumestrol was determined to be one such ligand. Reporter and in vitro coactivator interaction assays revealed that coumestrol bound and activated FXR. Treatment of Hep G2 cells with coumestrol stimulated the expression of FXR target genes, thereby regulating the expression of target genes of the liver X receptor and hepatocyte nuclear factor-4α. Through these actions, coumestrol is expected to exert beneficial effects on lipid and glucose metabolism

  13. Polychlorinated biphenyl exposure and glucose metabolism in Danish children aged 9 years

    Jensen, Tina K; Timmermann, Clara Amalie Gade; Rossing, Laura I;

    2014-01-01

    Context: Human exposure to polychlorinated biphenyls (PCBs) has been associated to type 2 diabetes in adults. Objectives: To determine whether concurrent serum PCB concentration was associated with markers of glucose metabolism in healthy children. Design: Cross-sectional study. Settings and...... amounts available for PCB and analyses. Main outcome measures: Fasting plasma glucose and serum insulin were measured and a homeostasis assessment model of insulin resistance (HOMA-IR) and β-cell function (HOMA-B) calculated. Serum PCB congeners and other persistent compounds were measured and ΣPCB...... calculated. Results: PCBs were present in serum at low concentrations, median 0.19μ g/g lipid (interquartile range, IQR: 0.12-0.31). After adjustment for putative confounding factors, the second, third, fourth and fifth quintiles of total PCB were significantly inversely associated with serum insulin (-14...

  14. Weight Loss After Bariatric Surgery Reverses Insulin-Induced Increases in Brain Glucose Metabolism of the Morbidly Obese

    Tuulari, Jetro J.; Henry K Karlsson; Hirvonen, Jussi; Hannukainen, Jarna C.; Bucci, Marco; Helmiö, Mika; Ovaska, Jari; Soinio, Minna; Salminen, Paulina; Savisto, Nina; Nummenmaa, Lauri; Nuutila, Pirjo

    2013-01-01

    Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not dif...

  15. A randomized trial comparing the effect of weight loss and exercise training on insulin sensitivity and glucose metabolism in coronary artery disease

    Pedersen, Lene Rørholm; Olsen, Rasmus Huan; Jürs, Anders;

    2015-01-01

    AIM: The majority of patients with coronary artery disease (CAD) exhibit abnormal glucose metabolism, which is associated with mortality even at non-diabetic glucose levels. This trial aims to compare the effects of a considerable weight loss and exercise with limited weight loss on glucose...... followed by 2-4 weeks' weight maintenance diet. Glucose tolerance, insulin action, β-cell function and suppression of lipolysis were assessed using a 3-h oral glucose tolerance test. ISI-composite and ISI-HOMA (=1/HOMA-IR) were calculated as surrogate measures of whole-body and hepatic insulin sensitivity...

  16. Renal proximal tubular cell fibronectin accumulation in response to glucose is polyol pathway dependent

    Morrisey; Steadman; Williams; Phillips

    1999-06-01

    Thickening and reduplication of the tubular basement membrane has been reported as an early event in diabetic nephropathy. In the current study we have examined the polar requirements of proximal tubular cells for the D-glucose stimulated accumulation of fibronectin. We also examined the mechanism by which glucose led to accumulation of fibronectin, with particular emphasis on the polyol pathway. Incubation of confluent monolayers of LLC-PK1 cells grown on tissue culture inserts with 25 mM D-glucose on either their apical or basolateral aspect, led to fibronectin accumulation in the basolateral compartment. This reached statistical significance 24 h following apical addition of glucose (2.7 fold increase compared to 5 mM D-glucose, p = 0.007, n = 6), and 12 h after the basolateral addition of glucose (2.54 fold increase compared to 5 mM D-glucose, p = 0.02, n = 6). The increase in fibronectin concentration in response to glucose was inhibited by the aldose reductase inhibitor sorbinil. At a dose of 100&mgr;M sorbinil there was 59% inhibition of fibronectin accumulation in response to glucose, 48 h after the addition of the inhibitor (4.76 +/- 1.4 vs 11.53 +/- 1.41, mean +/- SD, p = 0.01, n = 3). Exposure of cells to glucose at either their apical or basolateral aspect lead to accumulation of intracellular glucose and polyol pathway activation, as assessed by sorbitol accumulation. Accumulation of intracellular glucose and hence subsequent polyol pathway activation occurred independently of transport of glucose by either apical sodium linked glucose transporter (SLGT) or basolateral GLUT 1. The data demonstrate that fibronectin generation in response to glucose was non-polar in terms application of glucose, but polar in terms of fibronectin accumulation. Furthermore modulation of fibronectin was mediated by polyol pathway activation, and more specifically related to the metabolism of sorbitol to fructose. PMID:10354307

  17. [Relationships of glucose transporter 4 with cognitive changes induced by high fat diet and glucose metabolism in hippocampus].

    Zhang, Yun-Li; Wang, Lin

    2016-06-25

    The hippocampus not only plays a role in appetite and energy balance, but also is particularly important in learning and memory. Figuring out the relationships of hippocampal glucose transporter 4 (GLUT4) with hippocampal glucose metabolism and hippocampus-dependent cognitive function is very important to clearly understand the pathophysiological basis of nutritional obesity and diabetes-related diseases, and treat obesity and cognitive dysfunction. Therefore, this study reviewed recent researches conducted on hippocampal GLUT4, hippocampal glucose metabolism, and hippocampus-dependent cognitive function. In this review, we mainly discussed: (1) The structure of GLUT4 and the distribution and function of GLUT4 in the hippocampus; (2) The translocation of GLUT4 in the hippocampus; (3) The relationships of the PI3K-Akt-GLUT4 signaling pathway with the high fat diet-induced changes of cognitive function and the glucose metabolism in the hippocampus; (4) The associations of the PI3K-Akt-GLUT4 signaling pathway with the diabetes-related cognitive dysfunction in the hippocampus; (5) The potential mechanisms of cognitive dysfunction induced by glucose metabolic disorder. PMID:27350206

  18. Relationship between regional brain glucose metabolism and temperament factor of personality

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24±4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor

  19. Relationship between regional brain glucose metabolism and temperament factor of personality

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24{+-}4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor.

  20. Dynamic modulation of intracellular glucose imaged in single cells using a FRET-based glucose nanosensor

    John, Scott A.; Ottolia, Michela; James N Weiss; Ribalet, Bernard

    2007-01-01

    To study intracellular glucose homeostasis, the glucose nanosensor FLIPglu-600µM, which undergoes changes in fluorescence resonance energy transfer (FRET) upon interaction with glucose, was expressed in four mammalian cell lines: COS-7, CHO, HEK293, and C2C12. Upon addition of extracellular glucose, the intracellular FRET ratio decreased rapidly as intracellular glucose increased. The kinetics were fast (τ =5 to 15 s) in COS and C2C12 cells and slow (τ =20 to 40 s) in HEK and CHO cells. Upon ...

  1. PIP3 but not PIP2 increases GLUT4 surface expression and glucose metabolism mediated by AKT/PKCζ/λ phosphorylation in 3T3L1 adipocytes

    Manna, Prasenjit; Jain, Sushil K.

    2013-01-01

    PIP3 (phosphatidylinositol-3,4,5-triphosphate) and PIP2 (phosphatidylinositol-4,5-biphosphate) are two well-known membrane bound polyphosphoinositides. Diabetes is associated with impaired glucose metabolism. Using a 3T3L1 adipocyte cell model, this study investigated the roles of PIP3 and PIP2 on insulin stimulated glucose metabolism in high glucose (HG) treated cells. Exogenous PIP3 supplementation (1, 5, or 10 nM) increased the phosphorylation of AKT and PKCζ/λ, which in turn upregulated G...

  2. Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells.

    Lucia Natarelli

    Full Text Available Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG. In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9 and effector caspases (caspase 7 and 3 and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins.

  3. Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells

    Smith, Tim A. D.; Phyu, Su M.

    2016-01-01

    Introduction The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho) metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined. Methods MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14...

  4. INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells

    Min, Joong Won [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kwang Il [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Hyun-Ah; Kim, Eun-Kyu; Noh, Woo Chul [Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Jeon, Hong Bae [Biomedical Research Institute, MEDIPOST Co., Ltd., Seoul (Korea, Republic of); Cho, Dong-Hyung [Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do (Korea, Republic of); Oh, Jeong Su [Department of Genetic Engineering, Sungkyunkwan University, Suwon (Korea, Republic of); Park, In-Chul; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jae-Sung, E-mail: jaesung@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2013-10-11

    Highlights: •HIF-1α-regulated INPP4B enhances glycolysis. •INPP4B regulates aerobic glycolysis by inducing HK2 via Akt-mTOR pathway. •Blockage of INPP4B and HK2 sensitizes radioresistant laryngeal cancer cells to radiation and anticancer drug. •INPP4B is associated with HK2 in human laryngeal cancer tissues. -- Abstract: Inositol polyphosphate 4-phosphatase type II (INPP4B) was recently identified as a tumor resistance factor in laryngeal cancer cells. Herein, we show that INPP4B-mediated resistance is associated with increased glycolytic phenotype. INPP4B expression was induced by hypoxia and irradiation. Intriguingly, overexpression of INPP4B enhanced aerobic glycolysis. Of the glycolysis-regulatory genes, hexokinase 2 (HK2) was mainly regulated by INPP4B and this regulation was mediated through the Akt-mTOR pathway. Notably, codepletion of INPP4B and HK2 markedly sensitized radioresistant laryngeal cancer cells to irradiation or anticancer drug. Moreover, INPP4B was significantly associated with HK2 in human laryngeal cancer tissues. Therefore, these results suggest that INPP4B modulates aerobic glycolysis via HK2 regulation in radioresistant laryngeal cancer cells.

  5. Glucose-Sensing Receptor T1R3: A New Signaling Receptor Activated by Glucose in Pancreatic β-Cells.

    Kojima, Itaru; Nakagawa, Yuko; Hamano, Kunihisa; Medina, Johan; Li, Longfei; Nagasawa, Masahiro

    2015-01-01

    Subunits of the sweet taste receptors T1R2 and T1R3 are expressed in pancreatic β-cells. Compared with T1R3, mRNA expression of T1R2 is considerably lower. At the protein level, expression of T1R2 is undetectable in β-cells. Accordingly, a major component of the sweet taste-sensing receptor in β-cells may be a homodimer of T1R3 rather than a heterodimer of T1R2/T1R3. Inhibition of this receptor by gurmarin or deletion of the T1R3 gene attenuates glucose-induced insulin secretion from β-cells. Hence the T1R3 homodimer functions as a glucose-sensing receptor (GSR) in pancreatic β-cells. When GSR is activated by the T1R3 agonist sucralose, elevation of intracellular ATP concentration ([ATP]i) is observed. Sucralose increases [ATP]i even in the absence of ambient glucose, indicating that sucralose increases [ATP]i not simply by activating glucokinase, a rate-limiting enzyme in the glycolytic pathway. In addition, sucralose augments elevation of [ATP]i induced by methylsuccinate, suggesting that sucralose activates mitochondrial metabolism. Nonmetabolizable 3-O-methylglucose also increases [ATP]i and knockdown of T1R3 attenuates elevation of [ATP]i induced by high concentration of glucose. Collectively, these results indicate that the T1R3 homodimer functions as a GSR; this receptor is involved in glucose-induced insulin secretion by activating glucose metabolism probably in mitochondria. PMID:25947913

  6. Hydrocortisone stimulates the development of oligodendrocytes in primary glial cultures and affects glucose metabolism and lipid synthesis in these cultures

    Warringa, R.A.J.; Hoeben, R C; Koper, W.J.; Sykes, J.E.C.; Golde, L.M.G. van; Lopes-Cardozo, M.

    1987-01-01

    Cultures of glial cells were prepared from the brains of one-week-old rat pups. After one day in culture, serum was omitted from the medium and replaced by a combination of growth-stimulating hormones and other factors that enhanced the percentage of oligodendrocytes in the cultures. We investigated the effects of hydrocortisone on the development of oligodendrocytes, on the activities of oligodendrocyte-specific enzymes and on glucose- and lipid-metabolism of the glial cells. (1) Hydrocortis...

  7. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  8. Effect of erythropoietin on the glucose transport of rat erythrocytes and bone marrow cells

    The effect of Ep on radioactive glucose and methyl-alpha-D-glucoside transport by rat erythrocytes and bone marrow cells were studied. There is initial linearity followed by saturation kinetics of [14C]glucose transport by the erythrocytes of starved and starved plus Ep-treated rats at different concentrations of glucose. Starvation caused slight inhibition of glucose transport which increased markedly on Ep administration to starved rats. Normal animals failed to show any significant change in glucose transport after Ep treatment. Methyl-alpha-D-glucoside inhibited the Ep-stimulated glucose transport significantly. Ep also stimulated the transport of radioactive methyl-alpha-D-glucoside which was competitively inhibited in presence of D-glucose. Glucose transport in erythrocytes was found to be sensitive to metabolic inhibitors like azide and DNP. A sulfhydryl reagent and ouabain also inhibited the transport process. Ep stimulated glucose and methyl-alpha-D-glucoside transport in the bone marrow cells of starved rats. The sugar analog competitively inhibited the glucose transport in bone marrow cells and vice versa

  9. Drug-Induced Diabetes Mellitus: Evidence for Statins and Other Drugs Affecting Glucose Metabolism.

    Anyanwagu, U; Idris, I; Donnelly, R

    2016-04-01

    Abnormalities of glucose metabolism and glucose tolerance, either because of a reduction in tissue sensitivity to insulin (e.g., in liver, skeletal muscle, and adipose tissues) and/or a reduction in pancreatic insulin secretion, are associated with a number of unwanted health outcomes. Even small increases in circulating glucose levels (often described as dysglycemia or prediabetes) may confer an increased risk of cardiovascular (CV) disease and progression to overt type 2 diabetes. A number of drug therapies, many of them used long term in chronic disease management, have adverse effects on glucose metabolism, diabetes risk, and glycemic control among patients with preexisting diabetes. In this study, we review the evidence, underlying mechanisms, and the clinical significance of drug-related adverse effects on glucose metabolism. PMID:26440603

  10. Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer.

    Pal, Krishnendu; Cao, Ying; Gaisina, Irina N; Bhattacharya, Santanu; Dutta, Shamit K; Wang, Enfeng; Gunosewoyo, Hendra; Kozikowski, Alan P; Billadeau, Daniel D; Mukhopadhyay, Debabrata

    2014-02-01

    Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, is a key regulator of numerous cellular processes ranging from glycogen metabolism to cell-cycle regulation and proliferation. Consistent with its involvement in many pathways, it has also been implicated in the pathogenesis of various human diseases, including type II diabetes, Alzheimer disease, bipolar disorder, inflammation, and cancer. Consequently, it is recognized as an attractive target for the development of new drugs. In the present study, we investigated the effect of both pharmacologic and genetic inhibition of GSK-3 in two different renal cancer cell lines. We have shown potent antiproliferative activity of 9-ING-41, a maleimide-based GSK-3 inhibitor. The antiproliferative activity is most likely caused by G(0)-G(1) and G(2)-M phase arrest as evident from cell-cycle analysis. We have established that inhibition of GSK-3 imparted a differentiated phenotype in renal cancer cells. We have also shown that GSK-3 inhibition induced autophagy, likely as a result of imbalanced energy homeostasis caused by impaired glucose metabolism. In addition, we have demonstrated the antitumor activity of 9-ING-41 in two different subcutaneous xenograft renal cell carcinoma tumor models. To our knowledge, this is the first report describing autophagy induction due to GSK-3 inhibition in renal cancer cells. PMID:24327518

  11. Assessment of regional glucose metabolism in aging brain and dementia with positron-emission tomography

    Reivich, M.; Alavi, A.; Ferris, S.; Christman, D.; Fowler, J.; MacGregor, R.; Farkas, T.; Greenberg, J.; Dann, R.; Wolf, A.

    1981-01-01

    This paper explores the alterations in regional glucose metabolism that occur in elderly subjects and those with senile dementia compared to normal young volunteers. Results showed a tendency for the frontal regions to have a lower metabolic rate in patients with dementia although this did not reach the level of significance when compared to the elderly control subjects. The changes in glucose metabolism were symmetrical in both the left and right hemispheres. There was a lack of correlation between the mean cortical metabolic rates for glucose and the global mental function in the patients with senile dementia. This is at variance with most of the regional cerebral blood flow data that has been collected. This may be partly related to the use of substrates other than glucose by the brain in elderly and demented subjects. (PSB)

  12. Clinical observation of glucose metabolism disorders in elderly patients with obstructive sleep apnea disorder

    张蔷

    2013-01-01

    Objective To explore the correlation between obstructive sleep apnea hypoventilation syndrome (OSAHS) and glucose metabolism disorders in patients without diabetes mellitus.Methods A total of 88 patients with OSAHS but without diabetes mellitus from 2009 to 2011 in

  13. Associations between red meat intake and biomarkers of inflammation and glucose metabolism in women123

    Ley, Sylvia H.; Sun, Qi; Willett, Walter C.; Eliassen, A. Heather; Wu, Kana; Pan, An; Grodstein, Fran; Hu, Frank B

    2013-01-01

    Background: Greater red meat intake is associated with an increased type 2 diabetes and cardiovascular disease risk. However, the relation of red meat intake to biomarkers of inflammation and glucose metabolism has not been investigated thoroughly.

  14. Influence of tacrolimus on glucose metabolism before and after renal transplantation : a prospective study

    Duijnhoven, E M; Boots, J M; Christiaans, M H; Wolffenbuttel, B H; Van Hooff, J P

    2001-01-01

    Most studies concerning the influence of tacrolimus on glucose metabolism have been performed either in animals or after organ transplantation. These clinical studies have largely been transversal with patients who were using steroids. Therefore, this prospective, longitudinal study investigated the

  15. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain

    Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi Reddy; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M.

    2014-01-01

    Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain-metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustai...

  16. MicroRNA-194 Modulates Glucose Metabolism and Its Skeletal Muscle Expression Is Reduced in Diabetes

    Latouche, Celine; Natoli, Alaina; Reddy-Luthmoodoo, Medini; Heywood, Sarah E.; Armitage, James A.; Kingwell, Bronwyn A.

    2016-01-01

    Background The regulation of microRNAs (miRNAs) at different stages of the progression of type 2 diabetes mellitus (T2DM) and their role in glucose homeostasis was investigated. Methods Microarrays were used to assess miRNA expression in skeletal muscle biopsies taken from healthy individuals and patients with pre-diabetes or T2DM, and insulin resistant offspring of rat dams fed a high fat diet during pregnancy. Results Twenty-three miRNAs were differentially expressed in patients with T2DM, and 7 in the insulin resistant rat offspring compared to their controls. Among these, only one miRNA was similarly regulated: miR-194 expression was significantly reduced by 25 to 50% in both the rat model and in human with pre-diabetes and established diabetes. Knockdown of miR-194 in L6 skeletal muscle cells induced an increase in basal and insulin-stimulated glucose uptake and glycogen synthesis. This occurred in conjunction with an increased glycolysis, indicated by elevated lactate production. Moreover, oxidative capacity was also increased as we found an enhanced glucose oxidation in presence of the mitochondrial uncoupler FCCP. When miR-194 was down-regulated in vitro, western blot analysis showed an increased phosphorylation of AKT and GSK3β in response to insulin, and an increase in expression of proteins controlling mitochondrial oxidative phosphorylation. Conclusions Type 2 diabetes mellitus is associated with regulation of several miRNAs in skeletal muscle. Interestingly, miR-194 was a unique miRNA that appeared regulated across different stages of the disease progression, from the early stages of insulin resistance to the development of T2DM. We have shown miR-194 is involved in multiple aspects of skeletal muscle glucose metabolism from uptake, through to glycolysis, glycogenesis and glucose oxidation, potentially via mechanisms involving AKT, GSK3 and oxidative phosphorylation. MiR-194 could be down-regulated in patients with early features of diabetes as an

  17. Metabolic and Endocrine Profiles in Response to Systemic Infusion of Fructose and Glucose in Rhesus Macaques

    Adams, Sean H.; Stanhope, Kimber L.; Grant, Ryan W.; Cummings, Bethany P.; Havel, Peter J.

    2008-01-01

    Diurnal patterns of circulating leptin concentrations are attenuated after consumption of fructose-sweetened beverages compared with glucose-sweetened beverages, likely a result of limited postprandial glucose and insulin excursions after fructose. Differences in postprandial exposure of adipose tissue to peripheral circulating fructose and glucose or in adipocyte metabolism of the two sugars may also be involved. Thus, we compared plasma leptin concentrations after 6-h iv infusions of saline...

  18. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy

    Domenico Tricò; Simona Baldi; Silvia Frascerra; Elena Venturi; Paolo Marraccini; Danilo Neglia; Andrea Natali

    2015-01-01

    Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Re...

  19. Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism

    Hao, Qin; Yadav, Rachita; Basse, Astrid L.;

    2015-01-01

    exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating...

  20. Effects of dehydroepiandrosterone (DHEA) on glucose metabolism in isolated hepatocytes from Zucker rats

    Finan, A.; Cleary, M.P.

    1986-03-05

    DHEA has been shown to competitively inhibit the pentose phosphate shunt (PPS) enzyme glucose-6-phosphate dehydrogenase (G6PD) when added in vitro to supernatants or homogenates prepared from mammalian tissues. However, no consistent effect on G6PD activity has been determined in tissue removed from DHEA-treated rats. To explore the effects of DHEA on PPS, glucose utilization was measured in hepatocytes from lean and obese male Zucker rats (8 wks of age) following 1 wk of DHEA treatment (0.6% in diet). Incubation of isolated hepatocytes from treated lean Zucker rats with either (1-/sup 14/C) glucose or (6-/sup 14/C) glucose resulted in significant decreases in CO/sub 2/ production and total glucose utilization. DHEA-lean rats also had lowered fat pad weights. In obese rats, there was no effect of 1 wk of treatment on either glucose metabolism or fat pad weight. The calculated percent contribution of the PPS to glucose metabolism in hepatocytes was not changed for either DHEA-lean or obese rats when compared to control rats. In conclusion, 1 wk of DHEA treatment lowered overall glucose metabolism in hepatocytes of lean Zucker rats, but did not selectively affect the PPS. The lack of an effect of short-term treatment in obese rats may be due to differences in their metabolism or storage/release of DHEA in tissues in comparison to lean rats.

  1. Effects of dehydroepiandrosterone (DHEA) on glucose metabolism in isolated hepatocytes from Zucker rats

    DHEA has been shown to competitively inhibit the pentose phosphate shunt (PPS) enzyme glucose-6-phosphate dehydrogenase (G6PD) when added in vitro to supernatants or homogenates prepared from mammalian tissues. However, no consistent effect on G6PD activity has been determined in tissue removed from DHEA-treated rats. To explore the effects of DHEA on PPS, glucose utilization was measured in hepatocytes from lean and obese male Zucker rats (8 wks of age) following 1 wk of DHEA treatment (0.6% in diet). Incubation of isolated hepatocytes from treated lean Zucker rats with either [1-14C] glucose or [6-14C] glucose resulted in significant decreases in CO2 production and total glucose utilization. DHEA-lean rats also had lowered fat pad weights. In obese rats, there was no effect of 1 wk of treatment on either glucose metabolism or fat pad weight. The calculated percent contribution of the PPS to glucose metabolism in hepatocytes was not changed for either DHEA-lean or obese rats when compared to control rats. In conclusion, 1 wk of DHEA treatment lowered overall glucose metabolism in hepatocytes of lean Zucker rats, but did not selectively affect the PPS. The lack of an effect of short-term treatment in obese rats may be due to differences in their metabolism or storage/release of DHEA in tissues in comparison to lean rats

  2. A Novel 3D Liver Organoid System for Elucidation of Hepatic Glucose Metabolism

    Lu, Yanhua; Zhang, Guoliang; Shen, Chong; Uygun, Korkut; Yarmush, Martin L.; Meng, Qin

    2011-01-01

    Hepatic glucose metabolism is a key player in diseases such as obesity and diabetes as well as in antihyperglycemic drugs screening. Hepatocytes culture in two-dimensional configurations is limited in vitro model for hepatocytes to function properly, while truly practical platforms to perform three-dimensional (3D) culture are unavailable. In this work, we present a practical organoid culture method of hepatocytes for elucidation of glucose metabolism under nominal and stress conditions. Empl...

  3. Comparative Metabolic Flux Analysis of Lysine-Producing Corynebacterium glutamicum Cultured on Glucose or Fructose

    Kiefer, Patrick; Heinzle, Elmar; Zelder, Oskar; Wittmann, Christoph

    2004-01-01

    A comprehensive approach to 13C tracer studies, labeling measurements by gas chromatography-mass spectrometry, metabolite balancing, and isotopomer modeling, was applied for comparative metabolic network analysis of lysine-producing Corynebacterium glutamicum on glucose or fructose. Significantly reduced yields of lysine and biomass and enhanced formation of dihydroxyacetone, glycerol, and lactate in comparison to those for glucose resulted on fructose. Metabolic flux analysis revealed drasti...

  4. Nur77 coordinately regulates expression of genes linked to glucose metabolism in skeletal muscle

    Chao, Lily C.; Zhang, Zidong; Pei, Liming; Saito, Tsugumichi; Tontonoz, Peter; Pilch, Paul F.

    2007-01-01

    Innervation is important for normal metabolism in skeletal muscle, including insulin-sensitive glucose uptake. However, the transcription factors that transduce signals from the neuromuscular junction to the nucleus and affect changes in metabolic gene expression are not well defined. We demonstrate here that the orphan nuclear receptor Nur77 is a regulator of gene expression linked to glucose utilization in muscle. In vivo, Nur77 is preferentially expressed in glycolytic compared to oxidativ...

  5. Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L.; Kanekiyo, Takahisa; Bu, Guojun

    2015-01-01

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes durin...

  6. Effect of Modified Atmosphere Composition on the Metabolism of Glucose by Brochothrix thermosphacta

    Pin, Carmen; García de Fernando, Gonzalo D.; Ordóñez, Juan A.

    2002-01-01

    The influence of atmosphere composition on the metabolism of Brochothrix thermosphacta was studied by analyzing the consumption of glucose and the production of ethanol, acetic and lactic acids, acetaldehyde, and diacetyl-acetoin under atmospheres containing different combinations of carbon dioxide and oxygen. When glucose was metabolized under oxygen-free atmospheres, lactic acid was one of the main end products, while under atmospheres rich in oxygen mainly acetoin-diacetyl was produced. Th...

  7. A glucose biofuel cell implanted in rats.

    Cinquin, Philippe; Gondran, Chantal; Giroud, Fabien; Mazabrard, Simon; Pellissier, Aymeric; Boucher, François; Alcaraz, Jean-Pierre; Gorgy, Karine; Lenouvel, François; Mathé, Stéphane; Porcu, Paolo; Cosnier, Serge

    2010-01-01

    Powering future generations of implanted medical devices will require cumbersome transcutaneous energy transfer or harvesting energy from the human body. No functional solution that harvests power from the body is currently available, despite attempts to use the Seebeck thermoelectric effect, vibrations or body movements. Glucose fuel cells appear more promising, since they produce electrical energy from glucose and dioxygen, two substrates present in physiological fluids. The most powerful ones, Glucose BioFuel Cells (GBFCs), are based on enzymes electrically wired by redox mediators. However, GBFCs cannot be implanted in animals, mainly because the enzymes they rely on either require low pH or are inhibited by chloride or urate anions, present in the Extra Cellular Fluid (ECF). Here we present the first functional implantable GBFC, working in the retroperitoneal space of freely moving rats. The breakthrough relies on the design of a new family of GBFCs, characterized by an innovative and simple mechanical confinement of various enzymes and redox mediators: enzymes are no longer covalently bound to the surface of the electron collectors, which enables use of a wide variety of enzymes and redox mediators, augments the quantity of active enzymes, and simplifies GBFC construction. Our most efficient GBFC was based on composite graphite discs containing glucose oxidase and ubiquinone at the anode, polyphenol oxidase (PPO) and quinone at the cathode. PPO reduces dioxygen into water, at pH 7 and in the presence of chloride ions and urates at physiological concentrations. This GBFC, with electrodes of 0.133 mL, produced a peak specific power of 24.4 microW mL(-1), which is better than pacemakers' requirements and paves the way for the development of a new generation of implantable artificial organs, covering a wide range of medical applications. PMID:20454563

  8. A glucose biofuel cell implanted in rats.

    Philippe Cinquin

    Full Text Available Powering future generations of implanted medical devices will require cumbersome transcutaneous energy transfer or harvesting energy from the human body. No functional solution that harvests power from the body is currently available, despite attempts to use the Seebeck thermoelectric effect, vibrations or body movements. Glucose fuel cells appear more promising, since they produce electrical energy from glucose and dioxygen, two substrates present in physiological fluids. The most powerful ones, Glucose BioFuel Cells (GBFCs, are based on enzymes electrically wired by redox mediators. However, GBFCs cannot be implanted in animals, mainly because the enzymes they rely on either require low pH or are inhibited by chloride or urate anions, present in the Extra Cellular Fluid (ECF. Here we present the first functional implantable GBFC, working in the retroperitoneal space of freely moving rats. The breakthrough relies on the design of a new family of GBFCs, characterized by an innovative and simple mechanical confinement of various enzymes and redox mediators: enzymes are no longer covalently bound to the surface of the electron collectors, which enables use of a wide variety of enzymes and redox mediators, augments the quantity of active enzymes, and simplifies GBFC construction. Our most efficient GBFC was based on composite graphite discs containing glucose oxidase and ubiquinone at the anode, polyphenol oxidase (PPO and quinone at the cathode. PPO reduces dioxygen into water, at pH 7 and in the presence of chloride ions and urates at physiological concentrations. This GBFC, with electrodes of 0.133 mL, produced a peak specific power of 24.4 microW mL(-1, which is better than pacemakers' requirements and paves the way for the development of a new generation of implantable artificial organs, covering a wide range of medical applications.

  9. Convergence role of transcriptional coactivator p300 and apparent modification on HMCs metabolic memory induced by high glucose

    Hong SU

    2013-03-01

    Full Text Available Objective  To investigate the protein expression of transcriptional coactivator p300, acetylated histone H3 (Ac-H3 and Ac-H4 in human renal mesangial cell (HMCs as imitative "metabolic memory" in vitro, and explore the potential role of convergence point of p300. Methods  The HMCs were divided into the following groups: ① High glucose metabolic memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d, high glucose group (HG, 25mmol/L D-glucose×2d, memory groups (M1, M2, M3, 25mmol/L D-glucose×2days + 5.5mmol/L D-glucose×3d, 6d or 9d, persisting normal glucose group (NG, 5.5mmol/L D-glucose×9d. ② Advanced glycation end products memory model: normal glucose group (NG, 5.5mmol/ L D-glucose×2d, NG+AGEs group (AGEs, 5.5mmol/L D-glucose+250µg/ml AGEs×2d; AGEs memory group (AGEs-M, 5.5mmol/L D-glucose + 250µg/ml AGEs×2d + 5.5mmol/L D-glucose×3d; BSA control group (NG+BSA, 5.5mmol/L D-glucose + 250µg/ml BSA×2d. ③ H2O2 was used to simulate oxidative stress memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d, NG+H2O2 group (H2O2, 5.5mmol/L D-glucose +100µmol/L H2O2×30min; H2O2 memory group [(5.5mmol/ L D-glucose + 100µmol/L H2O2×30min + 5.5mmol/L D-glucose×3d]; normal glucose control group (NG3, 5.5mmol/L D-glucose×3d. ④ Transfection with PKCβ2 memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d; high glucose group (HG, 25mmol/L D-glucose×2d; memory group (M, 25mmol/L D-glucose×2d + 5.5mmol/L D-glucose×3d; Ad5-null memory group (HN, 25mmol/L D-glucose + Ad5-null×2d + 5.5mmol/L D-glucose×3d; PKCβ2 memory group (PO, 25mmol/L D-glucose + Ad5-PKCβ2×2d + 5.5mmol/L D-glucose×3d; inhibitor of PKCβ2 memory group (PI, 25mmol/L D-glucose×2d + 10µmol/L CGP53353 + 5.5mmol/L D-glucose×3d. The expression of intracellular reactive oxygen species (ROS was detected by fluorescence microscope and fluorescence microplate reader. The expression levels of p300, Ac-H3, Ac-H4 and PKCβ2 proteins were

  10. Glucose metabolism: focus on gut microbiota, the endocannabinoid system and beyond.

    Cani, P D; Geurts, L; Matamoros, S; Plovier, H; Duparc, T

    2014-09-01

    The gut microbiota is now considered as a key factor in the regulation of numerous metabolic pathways. Growing evidence suggests that cross-talk between gut bacteria and host is achieved through specific metabolites (such as short-chain fatty acids) and molecular patterns of microbial membranes (lipopolysaccharides) that activate host cell receptors (such as toll-like receptors and G-protein-coupled receptors). The endocannabinoid (eCB) system is an important target in the context of obesity, type 2 diabetes (T2D) and inflammation. It has been demonstrated that eCB system activity is involved in the control of glucose and energy metabolism, and can be tuned up or down by specific gut microbes (for example, Akkermansia muciniphila). Numerous studies have also shown that the composition of the gut microbiota differs between obese and/or T2D individuals and those who are lean and non-diabetic. Although some shared taxa are often cited, there is still no clear consensus on the precise microbial composition that triggers metabolic disorders, and causality between specific microbes and the development of such diseases is yet to be proven in humans. Nevertheless, gastric bypass is most likely the most efficient procedure for reducing body weight and treating T2D. Interestingly, several reports have shown that the gut microbiota is profoundly affected by the procedure. It has been suggested that the consistent postoperative increase in certain bacterial groups such as Proteobacteria, Bacteroidetes and Verrucomicrobia (A. muciniphila) may explain its beneficial impact in gnotobiotic mice. Taken together, these data suggest that specific gut microbes modulate important host biological systems that contribute to the control of energy homoeostasis, glucose metabolism and inflammation in obesity and T2D. PMID:24631413

  11. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder

    Swedo, S.E.; Schapiro, M.B.; Grady, C.L.; Cheslow, D.L.; Leonard, H.L.; Kumar, A.; Friedland, R.; Rapoport, S.I.; Rapoport, J.L.

    1989-06-01

    The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system.

  12. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder

    The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system

  13. The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

    Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression

  14. The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

    Conde, Vanessa R. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Oliveira, Pedro F. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto – UMIB/ICBAS/UP (Portugal); Nunes, Ana R.; Rocha, Cátia S. [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Ramalhosa, Elsa; Pereira, José A. [Mountain Research Centre (CIMO), School of Agriculture, Polytechnic Institute of Bragança (Portugal); Alves, Marco G., E-mail: alvesmarc@gmail.com [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Silva, Branca M., E-mail: bmcms@ubi.pt [CICS-UBI–Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal)

    2015-07-01

    Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression.

  15. PET measurement of glucose membrane transport using labeled analogs: Distinction of transport from metabolic processes

    Carrier mediated glucose transport rates across brain capillary and myocardial cell membranes are many times higher than those expected for simple diffusion, and transport regulation can be an important determinant of tissue metabolic status. The authors have investigated the use of glucose analogs and dynamic positron tomography for the non-invasive measurement of unidirectional membrane transport rates. If analog extraction is sufficiently low, transport rates can be inferred directly from fitted kinetic rate constants. Fitting calculations were seen to be sensitive to the difficult to measure rapid components of the arterial input curves, to contributions from blood-borne label in the early data points, and to interference from other chemical forms in cases of significant phosphorylation. This last uncertainty was studied using serial scans of normal brain after venous injection of the well-transported but poorly phosphorylated analog 3-deoxy-3-fluoroglucose. Transport rate constants derived from 4-parameter fits of three hours of data were compared to those derived from 2-parameter fits of the first 12-20 minutes of data. Errors due to trapped label were absorbed primarily into the apparent distribution volume, allowing accurate estimation of transport rate constants from a brief data acquisition period. The study of the distinction of transport from phosphorylation also bears on the important question of the significance of the individual rate constants in the four-parameter fitting of brief dynamic scan sequences in studies of metabolic rate using 2-deoxy-2-fluoroglucose

  16. Regulation of glucose and glycogen metabolism during and after exercise

    Jensen, Thomas Elbenhardt; Richter, Erik

    2012-01-01

    Utilization of carbohydrate in the form of intramuscular glycogen stores and glucose delivered from plasma becomes an increasingly important energy substrate to the working muscle with increasing exercise intensity. This review gives an update on the molecular signals by which glucose transport i...... the post-exercise period which can result in an overshoot of intramuscular glycogen resynthesis post exercise (glycogen supercompensation)....

  17. Local cerebral blood flow and glucose metabolism during seizure in spontaneously epileptic El mice

    Local cerebral blood flow and glucose metabolism were examined in spontaneously epileptic El mice using autoradiography with 125I-IMP and 14C-DG in the interictal phase and during seizure. El (+) mice that developed generalized tonic-clonic convulsions and El (-) mice that received no stimulation and had no history of epileptic seizures were examined. The seizure non-susceptible, maternal strain ddY mice were used as control. Uptake ratios for IMP and DG in mouse brain were calculated using the autoradiographic density. In the interictal phase, the pattern of local cerebral blood flow of El (+) mice was similar to that of ddY and El (-) mice, and glucose metabolism in the hippocampus was higher in El (+) mice than in El (-) and ddY mice, but flow and metabolism were nearly matched. During seizure, no significant changed blood flow and increased glucose metabolism in the hippocampus, the epileptic focus, and no markedly changed blood flow and depressed glucose metabolism in other brain regions were observed and considered to be flow-metabolism uncoupling. These observations have never been reported in clinical or experimental studies of epilepsy. Seizures did not cause large regional differences in cerebral blood flow. Therefore, only glucose metabolism is useful for detection of the focus of secondary generalized seizures in El mice, and appeared possibly to be related to the pathophysiology of secondary generalized epilepsy in El mice. (author)

  18. Comparison of clinical types of Wilson's disease and glucose metabolism in extrapyramidal motor brain regions.

    Hermann, W; Barthel, H; Hesse, S; Grahmann, F; Kühn, H-J; Wagner, A; Villmann, T

    2002-07-01

    In Wilson's disease a disturbed glucose metabolism especially in striatal and cerebellar areas has been reported. This is correlated with the severity of extrapyramidal motor symptoms (EPS). These findings are only based on a small number of patients. Up to now it is unknown whether EPS are caused by various patterns of disturbed basal ganglia glucose metabolism. We investigated 37 patients and 9 normal volunteers to characterize the disturbed glucose metabolism in Wilson's disease more precisely. The glucose metabolism was determined in 5 cerebellar and cerebral areas (putamen, caput nuclei caudati, cerebellum, midbrain and thalamic area) by using (18)F-Fluorodesoxyglucose-Positron-Emission-Tomography ( [(18)F]FDG-PET). The database was evaluated by a cluster analysis. Additionally, the severity extrapyramidal motor symptoms were judged by a clinical score system. Three characteristic patterns of glucose metabolism in basal ganglia were obtained. Two of them may be assigned to patients with neurological symptoms whereas the third cluster corresponds to most patients without EPS or normal volunteers. The clusters can be identified by characteristic consumption rates in this 5 brain areas. The severity of EPS can not clearly be assigned to one of the clusters with disturbed glucose metabolism. However, the most severe cases are characterized by the lowest consumption in the striatal area. When there is marked improvement of EPS impaired glucose consumption reveals a persistent brain lesion. Finally, the neurological symptoms in Wilson's disease are caused by (at least) two different patterns of disturbed glucose metabolism in basal ganglia and cerebellum. The severity of EPS seems to be determined by a disturbed consumption in the striatal area. PMID:12140675

  19. Direct neuronal glucose uptake Heralds activity-dependent increases in cerebral metabolism

    Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John D R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two......, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus...

  20. Glycogen and glucose metabolism are essential for early embryonic development of the red flour beetle Tribolium castaneum.

    Amanda Fraga

    Full Text Available Control of energy metabolism is an essential process for life. In insects, egg formation (oogenesis and embryogenesis is dependent on stored molecules deposited by the mother or transcribed later by the zygote. In oviparous insects the egg becomes an isolated system after egg laying with all energy conversion taking place during embryogenesis. Previous studies in a few vector species showed a strong correlation of key morphogenetic events and changes in glucose metabolism. Here, we investigate glycogen and glucose metabolism in the red flour beetle Tribolium castaneum, an insect amenable to functional genomic studies. To examine the role of the key enzymes on glycogen and glucose regulation we cloned and analyzed the function of glycogen synthase kinase 3 (GSK-3 and hexokinase (HexA genes during T. castaneum embryogenesis. Expression analysis via in situ hybridization shows that both genes are expressed only in the embryonic tissue, suggesting that embryonic and extra-embryonic cells display different metabolic activities. dsRNA adult female injection (parental RNAi of both genes lead a reduction in egg laying and to embryonic lethality. Morphological analysis via DAPI stainings indicates that early development is impaired in Tc-GSK-3 and Tc-HexA1 RNAi embryos. Importantly, glycogen levels are upregulated after Tc-GSK-3 RNAi and glucose levels are upregulated after Tc-HexA1 RNAi, indicating that both genes control metabolism during embryogenesis and oogenesis, respectively. Altogether our results show that T. castaneum embryogenesis depends on the proper control of glucose and glycogen.

  1. Significance of insulin for glucose metabolism in skeletal muscle during contractions

    Hespel, P; Vergauwen, Lieven; Vandenberghe, K;

    1996-01-01

    additive stimuli of muscle glucose uptake at any plasma insulin level. In conclusion, the extent to which muscle glucose uptake is stimulated during exercise depends on various factors, including 1) the intensity of the contractile activity, 2) the magnitude of the exercise-associated increase in muscle......Glucose uptake rate in active skeletal muscles is markedly increased during exercise. This increase reflects a multifactorial process involving both local and systemic mechanisms that cooperate to stimulate glucose extraction and glucose delivery to the muscle cells. Increased glucose extraction is...... effected primarily via mechanisms exerted within the muscle cell related to the contractile activity per se. Yet contractions become a more potent stimulus of muscle glucose uptake as the plasma insulin level is increased. In addition, enhanced glucose delivery to muscle, which during exercise is...

  2. Modification of RelA by O-linked N-acetylglucosamine links glucose metabolism to NF-κB acetylation and transcription

    Allison, David F.; Wamsley, J. Jacob; Kumar, Manish; Li, Duo; Gray, Lisa G.; Hart, Gerald W.; David R Jones; Mayo, Marty W.

    2012-01-01

    The molecular mechanisms linking glucose metabolism with active transcription remain undercharacterized in mammalian cells. Using nuclear factor-κB (NF-κB) as a glucose-responsive transcription factor, we show that cells use the hexosamine biosynthesis pathway and O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) to potentiate gene expression in response to tumor necrosis factor (TNF) or etoposide. Chromatin immunoprecipitation assays demonstrate that, upon induction, OGT localizes ...

  3. Steviol Glycosides Modulate Glucose Transport in Different Cell Types

    Benedetta Rizzo

    2013-01-01

    Full Text Available Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway.

  4. JNK1 Deficiency Does Not Enhance Muscle Glucose Metabolism in Lean Mice*

    Witczak, CA; Hirshman, MF; Jessen, N.; Fujii, N; Seifert, M.; Brandauer, J; Hotamisligil, GS; Goodyear, LJ

    2006-01-01

    Mice deficient in c‐jun‐NH2‐terminal kinase 1 (JNK1) exhibit decreased fasting blood glucose and insulin levels, and protection against obesity‐induced insulin resistance, suggesting increased glucose disposal into skeletal muscle. Thus, we assessed whether JNK1 deficiency enhances muscle glucose metabolism. Ex vivo insulin or contraction‐induced muscle [³H]‐2‐deoxyglucose uptake was not altered in JNK1 knockout mice, demonstrating that JNK1 does not regulate blood glucose levels via direct a...

  5. Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

    Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

    2014-09-01

    It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases. PMID:25200293

  6. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

    Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.;

    2014-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin......-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase......, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock...

  7. Relationship of impaired brain glucose metabolism to learning deficit in the senescence-accelerated mouse.

    Ohta, H; Nishikawa, H; Hirai, K; Kato, K; Miyamoto, M

    1996-10-11

    The relationship between brain glucose metabolism and learning deficit was examined in the senescence-accelerated-prone mouse (SAMP) 8, which has been proven to be a useful murine model of age-related behavioral disorders. SAMP8, 7 months old, exhibited marked learning impairment in the passive avoidance task, as compared with the control strain, senescence-accelerated-resistant mice (SAMR) 1. SAMP8 also exhibited a reduction in brain glucose metabolism, as indicated by a reduction in [14C]2-deoxyglucose accumulation in the brain following the intravenous injection impaired glucose metabolism correlated significantly with the learning impairment in all brain regions in SAMR1 and SAMP8. In the SAMP8, a significant correlation was observed in the posterior half of the cerebral cortex. These results suggest that the SAMP8 strain is a useful model of not only age-related behavioral disorders, but also glucose hypometabolism observed in aging and dementias. PMID:8905734

  8. Regulation of glucose and glycogen metabolism during and after exercise.

    Jensen, Thomas E; Richter, Erik A

    2012-03-01

    Utilization of carbohydrate in the form of intramuscular glycogen stores and glucose delivered from plasma becomes an increasingly important energy substrate to the working muscle with increasing exercise intensity. This review gives an update on the molecular signals by which glucose transport is increased in the contracting muscle followed by a discussion of glycogen mobilization and synthesis by the action of glycogen phosphorylase and glycogen synthase, respectively. Finally, this review deals with the signalling relaying the well-described increased sensitivity of glucose transport to insulin in the post-exercise period which can result in an overshoot of intramuscular glycogen resynthesis post exercise (glycogen supercompensation). PMID:22199166

  9. Towards dynamic metabolic flux analysis in CHO cell cultures.

    Ahn, Woo Suk; Antoniewicz, Maciek R

    2012-01-01

    Chinese hamster ovary (CHO) cells are the most widely used mammalian cell line for biopharmaceutical production, with a total global market approaching $100 billion per year. In the pharmaceutical industry CHO cells are grown in fed-batch culture, where cellular metabolism is characterized by high glucose and glutamine uptake rates combined with high rates of ammonium and lactate secretion. The metabolism of CHO cells changes dramatically during a fed-batch culture as the cells adapt to a changing environment and transition from exponential growth phase to stationary phase. Thus far, it has been challenging to study metabolic flux dynamics in CHO cell cultures using conventional metabolic flux analysis techniques that were developed for systems at metabolic steady state. In this paper we review progress on flux analysis in CHO cells and techniques for dynamic metabolic flux analysis. Application of these new tools may allow identification of intracellular metabolic bottlenecks at specific stages in CHO cell cultures and eventually lead to novel strategies for improving CHO cell metabolism and optimizing biopharmaceutical process performance. PMID:22102428

  10. Glucose metabolism in the antibiotic producing actinomycete Nonomuraea sp ATCC 39727

    Gunnarsson, Nina; Bruheim, Per; Nielsen, Jens

    2004-01-01

    The actinomycete Nonomuraea sp. ATCC 39727, producer of the glycopeptide A40926 that is used as precursor for the novel antibiotic dalbavancin, has an unusual carbon metabolism. Glucose is primarily metabolized via the Entner-Doudoroff (ED) pathway, although the energetically more favorable Embde...

  11. Analysis of kinetic, stoichiometry and regulation of glucose and glutamine metabolism in hybridoma batch cultures using logistic equations

    Acosta, María Lourdes; Sánchez, Asterio; García, Francisco; Contreras, Antonio; Molina, Emilio

    2007-01-01

    Batch cultures were carried out to study the kinetic, stoichiometry, and regulation of glucose and glutamine metabolism of a murine hybridoma line. Asymmetric logistic equations (ALEs) were used to fit total and viable cell density, and nutrient and metabolite/product concentrations. Since these equations were analytically differentiable, specific rates and yield coefficients were readily calculated. Asymmetric logistic equations described satisfactorily uncontrolled batch cultures, including...

  12. Glutamate Acts as a Key Signal Linking Glucose Metabolism to Incretin/cAMP Action to Amplify Insulin Secretion

    Ghupurjan Gheni

    2014-10-01

    Full Text Available Incretins, hormones released by the gut after meal ingestion, are essential for maintaining systemic glucose homeostasis by stimulating insulin secretion. The effect of incretins on insulin secretion occurs only at elevated glucose concentrations and is mediated by cAMP signaling, but the mechanism linking glucose metabolism and cAMP action in insulin secretion is unknown. We show here, using a metabolomics-based approach, that cytosolic glutamate derived from the malate-aspartate shuttle upon glucose stimulation underlies the stimulatory effect of incretins and that glutamate uptake into insulin granules mediated by cAMP/PKA signaling amplifies insulin release. Glutamate production is diminished in an incretin-unresponsive, insulin-secreting β cell line and pancreatic islets of animal models of human diabetes and obesity. Conversely, a membrane-permeable glutamate precursor restores amplification of insulin secretion in these models. Thus, cytosolic glutamate represents the elusive link between glucose metabolism and cAMP action in incretin-induced insulin secretion.

  13. Cerebral glucose metabolism in corticobasal degeneration comparison with progressive supranuclear palsy using statistical mapping analysis.

    Juh, Rahyeong; Pae, Chi-Un; Kim, Tae-Suk; Lee, Chang-Uk; Choe, Boyoung; Suh, Taesuk

    This study measured the cerebral glucose metabolism in patients suffering from corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). The aim was to determine if there is a different metabolic pattern using (18)F-labeled 2-deoxyglucose ((18)F-FDG) positron emission tomography (PET). The regional cerebral glucose metabolism was examined in 8 patients diagnosed clinically with CBD (mean age 69.6 +/- 7.8 years; male/female: 5/3), 8 patients with probable PSP (mean age 67.8 +/- 4.5 years; male/female: 4/4) and 22 healthy controls. The regional cerebral glucose metabolism between the three groups was compared using statistical parametric mapping (SPM) with a voxel-by-voxel approach (p < 0.001, 200-voxel level). Compared with the normal controls, asymmetry in the regional glucose metabolism was observed in the parietal, frontal and cingulate in the CBD patients. In the PSP patients, the glucose metabolism was lower in the orbitofrontal, middle frontal, cingulate, thalamus and mid-brain than their age matched normal controls. A comparison of the two patient groups demonstrated relative hypometabolism in the thalamus, the mid-brain in the PSP patients and the parietal lobe in CBD patients. These results suggest that when making a differential diagnosis of CBD and PSP, voxel-based analysis of the (18)F-FDG PET images using a SPM might be a useful tool in clinical examinations. PMID:15936506

  14. Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt

    Marini, Cecilia; Ravera, Silvia; Buschiazzo, Ambra; Bianchi, Giovanna; Orengo, Anna Maria; Bruno, Silvia; Bottoni, Gianluca; Emionite, Laura; Pastorino, Fabio; Monteverde, Elena; Garaboldi, Lucia; Martella, Roberto; Salani, Barbara; Maggi, Davide; Ponzoni, Mirco; Fais, Franco; Raffaghello, Lizzia; Sambuceti, Gianmario

    2016-01-01

    Cancer metabolism is characterized by an accelerated glycolytic rate facing reduced activity of oxidative phosphorylation. This “Warburg effect” represents a standard to diagnose and monitor tumor aggressiveness with 18F-fluorodeoxyglucose whose uptake is currently regarded as an accurate index of total glucose consumption. Studying cancer metabolic response to respiratory chain inhibition by metformin, we repeatedly observed a reduction of tracer uptake facing a marked increase in glucose consumption. This puzzling discordance brought us to discover that 18F-fluorodeoxyglucose preferentially accumulates within endoplasmic reticulum by exploiting the catalytic function of hexose-6-phosphate-dehydrogenase. Silencing enzyme expression and activity decreased both tracer uptake and glucose consumption, caused severe energy depletion and decreased NADPH content without altering mitochondrial function. These data document the existence of an unknown glucose metabolism triggered by hexose-6-phosphate-dehydrogenase within endoplasmic reticulum of cancer cells. Besides its basic relevance, this finding can improve clinical cancer diagnosis and might represent potential target for therapy. PMID:27121192

  15. Metabolic network analysis of Bacillus clausii on minimal and semirich medium using C-13-Labeled glucose

    Christiansen, Torben; Christensen, Bjarke; Nielsen, Jens

    2002-01-01

    to increase with increasing specific growth rate but at a much lower level than previously reported for Bacillus subtilis. Two futile cycles in the pyruvate metabolism were included in the metabolic network. A substantial flux in the futile cycle involving malic enzyme was estimated, whereas only a...... very small or zero flux through PEP carboxykinase was estimated, indicating that the latter enzyme was not active during growth on glucose. The uptake of the amino acids in a semirich medium containing 15 of the 20 amino acids normally present in proteins was estimated using fully labeled glucose in...... partly taken up from the medium and partly synthesized from glucose. The metabolic network analysis was extended to include analysis of growth on the semirich medium containing amino acids, and the metabolic flux distribution on this medium was estimated and compared with growth on minimal medium....

  16. Program for PET image alignment: Effects on calculated differences in cerebral metabolic rates for glucose

    A program was developed to align positron emission tomography images from multiple studies on the same subject. The program allowed alignment of two images with a fineness of one-tenth the width of a pixel. The indications and effects of misalignment were assessed in eight subjects from a placebo-controlled double-blind crossover study on the effects of cocaine on regional cerebral metabolic rates for glucose. Visual examination of a difference image provided a sensitive and accurate tool for assessing image alignment. Image alignment within 2.8 mm was essential to reduce variability of measured cerebral metabolic rates for glucose. Misalignment by this amount introduced errors on the order of 20% in the computed metabolic rate for glucose. These errors propagate to the difference between metabolic rates for a subject measured in basal versus perturbed states

  17. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions

  18. Plasma Glucose and Serum Ceruloplasmin in Metabolic Syndrome and Diabetes Mellitus Type 2

    Ashok Kumar Jeppu; Asha Augusthy; Kavitha Ashok Kumar

    2016-01-01

    Diabetes mellitus type 2 and metabolic syndrome are conditions associated with insulin resistance and hyperglycemia. Metabolic syndrome is a risk factor for diabetes mellitus type 2. Plasma glucose (fasting/postprandial) and serum ceruloplasmin levels and their relationship were studied. Study population consisted of 150 individuals—50 individuals with diabetes mellitus type 2, 50 individuals with metabolic syndrome, and 50 age- and sex-matched healthy controls. Plasma levels of fasting and p...

  19. Determination of optimal glucose concentration for microcalorimetric metabolic evaluation of equine spermatozoa

    André Belico de Vasconcelos

    2009-10-01

    Full Text Available The heat conduction microcalorimeter can be used to evaluate the metabolic rates of the sperm cell. Two ejaculates of four stallions were cooled to +5ºC and checked for sperm motility (bright field microscopy, viability (eosin 3%, functional membrane integrity (hyposmotic swelling test, and heat production (microcalorimetry. Glucose and sperm cell concentrations were determined in order to measure the heat outputs resulting from sperm metabolism. Sperm viability, membrane integrity and sperm motility did not differ among the different glucose concentrations tested. Nevertheless, the highest heat output detected by the microcalorimeter was obtained with 6 mM glucose and 10(8 spermatozoa/mL. Since conduction microcalorimetry offered additional information on equine sperm metabolism, it could be used as a method to study equine semen preservation.O microcalorímetro de condução pode ser usado para avaliar as taxas metabólicas do espermatozóide eqüino. Dois ejaculados de quatro garanhões foram avaliados quanto à motilidade progressiva pela microscopia, viabilidade espermática (eosina 3%, integridade funcional da membrana (teste hiposmótico e produção de calor (microcalorimetria. Concentrações ótimas de glicose e de células espermáticas foram determinadas, para mensurar o calor liberado resultante do metabolismo espermático em relação à capacidade de detecção do calor pelo microcalorímetro. Não foi observada diferença da motilidade, viabilidade e integridade funcional de membrana espermática quando adicionada glicose nas três concentrações estudadas. No entanto a avaliação por microcalorimetria ressaltou um maior fluxo de calor a uma concentração de 6 mM de glicose e uma concentração espermática de 10(8 espermatozóides/mL. Portanto, a técnica de microcalorimetria oferece informações adicionais sobre o metabolismo tornando-se uma ferramenta importante no estudo do processo de preservação do sêmen eqüino.

  20. Temporal metabolomic responses of cultured HepG2 liver cells to high fructose and high glucose exposures

    Meissen, John K.; Hirahatake, Kristin M.; Adams, Sean H.; Fiehn, Oliver

    2014-01-01

    High fructose consumption has been implicated with deleterious effects on human health, including hyperlipidemia elicited through de novo lipogenesis. However, more global effects of fructose on cellular metabolism have not been elucidated. In order to explore the metabolic impact of fructose-containing nutrients, we applied both GC-TOF and HILIC-QTOF mass spectrometry metabolomic strategies using extracts from cultured HepG2 cells exposed to fructose, glucose, or fructose + glucose. Cellular...

  1. Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

    Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

    2015-01-01

    Purpose Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused ...

  2. Evidence that glucose metabolism is decreased in the cerebrum of aged female senescence-accelerated mouse; possible involvement of a low hexokinase activity.

    Kurokawa, T; Sato, E; Inoue, A; Ishibashi, S

    1996-08-16

    d-Glucose metabolism in cerebral cells prepared from aged senescence-accelerated mouse (SAM), was investigated in consideration of a sex difference. The production of 14CO2 from 6-[14C]D-glucose was reduced in female senescence-accelerated-prone mouse (SAMP) 8, a prone substrain, in comparison with that in female senescence-accelerated-resistant mouse (SAMR) 2, a control substrain, whereas there was no difference in males. The 2-deoxy-D-glucose uptake into cerebral cells from female SAMP8 was also lower than that of control mice. But, the 3-O-methyl-D-glucose uptake in SAMP8 was higher than that of SAMR2, suggesting that the low hexokinase activity was involved in the decreased glucose metabolism in cerebrum of SAMP8 females irrespective of glucose transporter. This possibility was supported by the finding that the contents of glucose 6-phosphate produced from glucose added to cerebral cells from SAMP8 was lower than that in ICR mice. PMID:8873128

  3. Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.

    Bordicchia, M; Ceresiani, M; Pavani, M; Minardi, D; Polito, M; Wabitsch, M; Cannone, V; Burnett, J C; Dessì-Fulgheri, P; Sarzani, R

    2016-07-01

    Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes. PMID:27101299

  4. Effect of glucocorticoid therapy upon glucose metabolism in COPD patients with acute exacerbation

    Objective: To study the effect of glucocorticoids therapy upon glucose metabolism in COPD patients with acute exacerbation. Methods: Plasma glucose and insulin levels in COPD patients after intravenous administration of 10 mg dexamethasone daily for 5 days were determined oral with glucose tolerance test (OGTT) and insulin release test (IRT). Results: 1) The levels of basal plasma glucose and insulin were significantly higher in severe hypoxemic group than those in moderate hypoxemic group (p 2 (r = -0.5242, p < 0.05). 2) The levels of plasma glucose in intermediate and severe hypoxemic groups were remarkable higher (p < 0.05) than those in mild group. The two peak times of glucose curve were observed at one and two hour after oral glucose load. 3) After the administration of glucocorticoids, at half an hour and one hour plasma glucose levels were significantly higher than those before, the peak time of glucose levels appeared earlier and the insulin release levels were higher than they were before therapy (p < 0.05). Conclusion: COPD patients with acute exacerbation complicated with hypoxemia had problems of impaired glucose tolerance. The administration of glucocorticoids made the impairment worse

  5. Plant oils were associated with low prevalence of impaired glucose metabolism in Japanese workers.

    Kayo Kurotani

    Full Text Available Fatty acid has been suggested to be involved in development of diabetes. However, its association is unclear among Japanese populations, which consume large amounts of fish rich in n-3 polyunsaturated fatty acids. The present cross-sectional study examined the association of individual dietary fatty acids and dietary fatty acid patterns with abnormal glucose metabolism among 1065 Japanese employees, aged 18-69 years. Impaired glucose metabolism is defined if a person has a history of diabetes, current use of anti-diabetic drug, fasting plasma glucose of 110 mg/dl (≥6.1 mmol/L or greater, or hemoglobin A1C of 6.0% (≥42 mmol/mol or greater. Dietary intake was assessed with a self-administered diet history questionnaire. Dietary fatty acid patterns were extracted by principal component analysis. Odds ratios of impaired glucose metabolism according to tertile categories of each fatty acids and dietary fatty acid patterns were estimated using logistic regression with adjustment for potential confounding variables. A higher intake of polyunsaturated fatty acid, n-6 fatty acid, linoleic acid, and oleic acid were significantly associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.03, 0.01, 0.02, and 0.04, respectively. Alpha-linolenic acid was marginally significantly associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.12. Of three fatty acid patterns identified, a higher plant oil pattern score, which characterized by high intake of alpha-linolenic acid, linoleic acid, and oleic acid, was associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.03. No association was observed for other patterns. In conclusion, plant source fatty acids might be protectively associated with development of diabetes in Japanese adults.

  6. Cerebral glucose metabolism change in patients with complex regional pain syndrome. A PET study

    The aim of this study was to examine abnormalities of the central nervous system in patients with chronic pain who were diagnosed with complex regional pain syndrome (CRPS). Brain activity was assessed using 18F-fluorodeoxyglucose positron emission tomography. The data collected from 18 patients were compared with data obtained from 13 normal age-matched controls. Our results showed that glucose metabolism was bilaterally increased in the secondary somatosensory cortex, mid-anterior cingulated cortex (ACC) or posterior cingulated cortex (PCC) (or both), parietal cortex, posterior parietal cortex (PPC), and cerebellum as well as in the right posterior insula and right thalamus in our patients. In contrast, glucose metabolism was reduced contralaterally in the dorsal prefrontal cortex and primary motor cortex. Glucose metabolism was bilaterally elevated in the mid-ACC/PCC and the PPC, which correlated with pain duration. These data suggested that glucose metabolism in the brains of patients with CRPS changes dramatically at each location. In particular, glucose metabolism was increased in the areas concerned with somatosensory perception, possibly due to continuous painful stimulation. (author)

  7. Glucose metabolism in gamma-irradiated rice seeds

    Gamma-irradiation of 30 kR in rice seeds caused marked inhibition in seedling growth, and prevented the release of reduced sugar during the period of 25 to 76hr after soaking. The C6/C1 ratio following irradiation continued to decrease up to the 76th hour of soaking; the control's ratio tended to increase with comparable soaking time. The percentage recovery of 14C in carbon dioxide from glucose -1-14C was lower in irradiated than in control seeds. These results indicate that gamma-irradiation reduces the participation of the pentose phosphate pathway in glucose catabolism during an early period of germination. (author)

  8. Inhibition of glucose turnover by 3-bromopyruvate counteracts pancreatic cancer stem cell features and sensitizes cells to gemcitabine

    Isayev, Orkhan; Rausch, Vanessa; BAUER, NATHALIE; Liu, Li; Fan, Pei; Zhang, Yiyao; Gladkich, Jury; Nwaeburu, Clifford C.; Mattern, Jürgen; Mollenhauer, Martin; Rückert, Felix; Zach, Sebastian; Haberkorn, Uwe; Gross, Wolfgang; Schönsiegel, Frank

    2014-01-01

    According to the cancer stem cell (CSC) hypothesis, the aggressive growth and early metastasis of pancreatic ductal adenocarcinoma (PDA) is due to the activity of CSCs, which are not targeted by current therapies. Otto Warburg suggested that the growth of cancer cells is driven by a high glucose metabolism. Here, we investigated whether glycolysis inhibition targets CSCs and thus may enhance therapeutic efficacy. Four established and 3 primary PDA cell lines, non-malignant cells, and 3 patien...

  9. Effects of glucose and insulin on the H9c2 (2-1) cell proliferation may be mediated through regulating glucose transporter 4 expression

    LIU Qian; HUANG Qing-xian; LOU Fu-chen; ZHANG Li; WANG Kun; YU Shan; XU Hua

    2013-01-01

    Background The change of glucose transporter 4 (GLUT4) expression could influence glucose uptake in the myocardial cells and then effect myocardial metabolism,which maybe one of the factor for the diabetes cardiovascular disease.This study aimed to explore the influence of glucose and insulin at different concentrations on H9c2 (2-1) cell proliferation and its GLUT4 expression in vitro,and evaluate the correlation between myocardial cells proliferation and GLUT4 expression.This might be helpful for understanding the relationship between glucose metabolism and cardiovascular disease.Methods According to glucose concentrations in culture medium,cultured H9c2 rat myocardial cells were divided into five groups:control group (NC,glucose concentration 5.0 mmol/L),low glucose group (LG,glucose concentration 0.1 mmol/L),high glucose group 1 (HG1,glucose concentration 10 mmol/L),high glucose group 2 (HG2,glucose concentration 15 mmol/L),high glucose group 3 (HG3,glucose concentration 20 mmol/L).Then according to different insulin concentrations in culture medium,each group was further divided into two subgroups:normal insulin subgroup (INSc,insulin concentration 3.8 mU/L),high insulin subgroup (INSh,insulin concentration 7.6 mU/L).H9c2 (2-1) cells were cultured for 1,2,3 days,the proliferation of cells were assayed by cell counting Kit-8 assay,the expressions of GLUT4 mRNA and protein were detected with RT-PCR and Western Blotting technique,and the relation between myocardial cells proliferation and GLUT4 expression was evaluated.Results Compared with NC group,cell proliferation (OD value) was lower in LG,HG2,HG3 group but higher in HG1 group on the second and the third day (P <0.05).There was a negative correlation between OD value and the glucose level in HG1,HG2,HG3 groups (P <0.05).OD value in INSc subgroups was lower than that in INSh subgroups (P <0.05).GLUT4 mRNA was lower in LG,HG2,HG3 groups than that in NC group (P <0.05).Compared with NC group,GLUT4 m

  10. Designing a highly active soluble PQQ-glucose dehydrogenase for efficient glucose biosensors and biofuel cells

    Research highlights: → A new mutant of PQQ-GDH designed for glucose biosensors application. → First mutant of PQQ-GDH with higher activity for D-glucose than the Wild type. → Position N428 is a key point to increase the enzyme activity. → Molecular modeling shows that the N428 C mutant displays a better interaction for PQQ than the WT. -- Abstract: We report for the first time a soluble PQQ-glucose dehydrogenase that is twice more active than the wild type for glucose oxidation and was obtained by combining site directed mutagenesis, modelling and steady-state kinetics. The observed enhancement is attributed to a better interaction between the cofactor and the enzyme leading to a better electron transfer. Electrochemical experiments also demonstrate the superiority of the new mutant for glucose oxidation and make it a promising enzyme for the development of high-performance glucose biosensors and biofuel cells.

  11. Analysis of Patients With Coronary Heart Disease Combined With Impaired Glucose Metabolism

    Zhi-ping GAO; Li-wen LIE; Ying-ling ZHOU; Hao-jian DONG

    2009-01-01

    Objectives To study the morbidity of patients with coronary artery disease (CAD) combined with impaired glucose metabolism. Methods Retrospective analysis of clinical data about patients with CAD in 1997, 2002 and 2007, sepa-rately. A total of 2951 patients were enrolled, among whom had coexistence of 457 abnormal glycometabolism, inclu-ding impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus. Results The prevalence of ab-normal glycometabolism in patients with CAD was increasing year by year. The morbidity raised from 3.8% and 16. 5% to 10. 8% in these three years. Contusion It is more and more common to detect CAD with impaired glucose metabolism, and it should be emphasized in the secondary prevention of CAD.

  12. Bradykinin enhances membrane electrical activity of pancreatic beta cells in the presence of low glucose concentrations

    A.S. Moura

    2000-09-01

    Full Text Available In most of cells bradykinin (BK induces intracellular calcium mobilization. In pancreatic beta cells intracellular calcium is a major signal for insulin secretion. In these cells, glucose metabolism yields intracellular ATP which blocks membrane potassium channels. The membrane depolarizes, voltage-dependent Ca2+ channels are activated and the intracellular calcium load allows insulin secretion. Repolarization occurs due to activation of the Ca2+-dependent K+ channel. The insulin secretion depends on the integrity of this oscillatory process (bursts. Therefore, we decided to determine whether BK (100 nM induces bursts in the presence of a non-stimulatory glucose concentration (5.6 mM. During continuous membrane voltage recording, our results showed that bursts were obtained with 11 mM glucose, blocked with 5.6 mM glucose and recovered with 5.6 mM glucose plus 100 nM BK. Thus, the stimulatory process obtained in the presence of BK and of a non-stimulatory concentration of glucose in the present study suggests that BK may facilitate the action of glucose on beta cell secretion.

  13. Profiling the control of hepatic glucose and lipid metabolism for evaluating novel strategies of insulin delivery

    Soares, Ana Francisca Leal Silva

    2011-01-01

    Diabetes mellitus (DM) is a metabolic disorder that results from a dysfunction of insulin secretion (type 1) and/or sensitivity (type 2). Type 1 and in many cases type 2 diabetic patients require daily insulin injections to control blood glucose levels and retard the appearance of diabetes-related complications. The liver plays a central role in the context of whole-body glucose homoeostasis and fuel management in general. Under physiological conditions, insulin is released by the pancr...

  14. Diabetes, Glucose Metabolism, and Glaucoma: The 2005–2008 National Health and Nutrition Examination Survey

    Di Zhao; Juhee Cho; Myung Hun Kim; David Friedman; Eliseo Guallar

    2014-01-01

    BACKGROUND: Diabetes may affect vascular autoregulation of the retina and optic nerve and may be associated with an increased risk of glaucoma,but the association of prediabetes, insulin resistance, markers of glucose metabolismwith glaucoma has not beenevaluated in general population samples. OBJECTIVE: To examine the relation between diabetes, pre-diabetes, metabolic syndrome and its components and the levels of fasting glucose, HbA1c and HOMA-IR with the prevalence of glaucoma in the gener...

  15. Insulin-resistant glucose metabolism in patients with microvascular angina--syndrome X

    Vestergaard, H; Skøtt, P; Steffensen, R;

    1995-01-01

    < .02) and the rate of insulin-stimulated glucose disposal to peripheral tissues was lower in patients with MA (13.4 +/- 1.0 v 18.2 +/- 1.4 mg.kg fat-free mass [FFM]-1.min-1, P < .02) due to a decrease in nonoxidative glucose metabolism (8.4 +/- 0.9 v 12.5 +/- 1.3 mg.kg FFM-1.min-1, P < .02). No...

  16. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

    Kenneth A. Dyar; Ciciliot, Stefano; Wright, Lauren E.; Biensø, Rasmus Sjørup; Tagliazucchi, Guidantonio M.; Patel, Vishal R.; Forcato, Mattia; Paz, Marcia I.P.; Gudiksen, Anders; Solagna, Francesca; Albiero, Mattia; Moretti, Irene; Eckel-Mahan, Kristin L.; Baldi, Pierre; Sassone-Corsi, Paolo

    2014-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activit...

  17. Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

    Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain;

    2015-01-01

    The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Meal tests...... 12 lean and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition. Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in...... antibiotics course with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males. clinicaltrials.gov NCT01633762....

  18. Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One–Carbon Cycle Energy Producing Pathway

    Vijayalakshmi Varma; Boros, László G.; Nolen, Greg T.; Ching-Wei Chang; Martin Wabitsch; Beger, Richard D.; Jim Kaput

    2015-01-01

    Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS) preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructose added to a medium containing 5 mM of glucose representing the normal blood glucose concentration. Targeted tracer [1,2-13C2]-d-glucose fate asso...

  19. 14C-glucose binding assay of the glucose transporter binding sites in muscular cell membrane

    A method of determining the binding sites of glucose transporter in rat muscular cell membrane was introduced. The crude products of cell membrane form the skeletal muscle of control and insulin treated rats were prepared, and then fractionated in sucrose gradient. Both plasma membrane and microsome membrane were incubated with D-[U-14C] glucose respectively for the measurement of radioactivity and Scatchard plot analysis. It was found that the binding sites of glucose transporter in plasma membrane and intracellular membrane were 5.6 nmol 14C-glucose/mg protein and 8.7 nmol 14C-glucose-mg protein respectively at basic state. Insulin treatment in experimental groups caused approximately 146% increase in plasma membrane fraction and 88% decrease in intracellular membrane fraction. Moreover, the kinetic data of Scatchard plot curve were similar to those of the [3H]-cytochalasin B binding assay. D-[U-14C] glucose binding assay of glucose transporter binding sites in muscular cell membrane is simple, easy and practicable. The D-[U-14C] glucose is commercially available

  20. Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.

    Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio

    2016-04-01

    Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver. PMID:26908609

  1. Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging

    Nugent Scott

    2016-01-01

    Full Text Available Brain energy metabolism in Alzheimer’s disease (AD is characterized mainly by temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a consequence of the disease, i.e. deteriorating neuronal function leading to lower demand for glucose. This review will address deteriorating glucose metabolism as a problem specific to glucose and one that precedes AD. Hence, ketones and medium chain fatty acids (MCFA could be an alternative source of energy for the aging brain that could compensate for low brain glucose uptake. MCFA in the form of dietary medium chain triglycerides (MCT have a long history in clinical nutrition and are widely regarded as safe by government regulatory agencies. The importance of ketones in meeting the high energy and anabolic requirements of the infant brain suggest they may be able to contribute in the same way in the aging brain. Clinical studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive effects on cognition.

  2. Current-Voltage Modeling of the Enzymatic Glucose Fuel Cells

    Vladimir Zeev Rubin

    2015-01-01

    Enzymatic fuel cells produce electrical power by oxidation of renewable energy sources. An enzymatic glucose biofuel cell uses glucose as fuel and enzymes as biocatalyst, to convert biochemical energy into electrical energy. The applications which need low electrical voltages and low currents have much of the interest in developing enzymatic fuel cells. An analytical modelling of an enzymatic fuel cell should be used, while developing fuel cell, to estimate its various parameters, to attain t...

  3. Glucose metabolism in small subcortical structures in Parkinson's disease

    Borghammer, Per; Hansen, Søren B; Eggers, Carsten;

    2012-01-01

    Evidence from experimental animal models of Parkinson's disease (PD) suggests a characteristic pattern of metabolic perturbation in discrete, very small basal ganglia structures. These structures are generally too small to allow valid investigation by conventional positron emission tomography (PE...

  4. Glucose and maltose metabolism in MIG1-disrupted and MAL-constitutive strains of Saccharomyces cerevisiae

    Klein, Christopher; Olsson, Lisbeth; Rønnow, B; Mikkelsen, Jørn Dalgaard; Nielsen, Jens Bredal

    1997-01-01

    The alleviation of glucose control of maltose metabolism brought about by MIG1 disruption was compared to that by MAL overexpression in a haploid Saccharomyces cerevisiae strain. The sugar consumption profiles during cultivation of the wild type, single transformants and a double transformant in a...... mixed glucose-maltose medium revealed that the MAL-constitutive strains were more alleviated than the single MIG1-disrupted transformant. While all transformants exhibited higher maximum specific growth rates (0.24-0.25 h(-1)) in glucose-maltose mixtures than the wild type strain (0.20 h(-1)), the MAL...

  5. Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men

    Jensen, Christine B; Storgaard, Heidi; Holst, Jens Juul; Dela, Flemming; Madsbad, Sten; Vaag, Allan A

    2003-01-01

    not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes.......We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp...

  6. Disturbed postprandial glucose metabolism and gut hormone responses in non-diabetic patients with psoriasis

    Gyldenløve, M; Vilsbøll, T; Holst, Jens Juul;

    2016-01-01

    patients with psoriasis has only been sparsely investigated. Previous studies are based on fasting blood samples analysed for glucose and insulin or various forms of glucose and/or insulin challenges.(5-11) The results are generally difficult to compare due to methodological differences and limitations in......Patients with psoriasis have increased risk of developing type 2 diabetes.(1-4) Though the aetiology is not fully understood, overrepresentation of traditional diabetes risk factors, shared genetics, and chronic inflammation likely explain some of the increased susceptibility. Glucose metabolism in...

  7. Leptin regulates energy metabolism in MCF-7 breast cancer cells.

    Blanquer-Rosselló, Maria del Mar; Oliver, Jordi; Sastre-Serra, Jorge; Valle, Adamo; Roca, Pilar

    2016-03-01

    Obesity is known to be a poorer prognosis factor for breast cancer in postmenopausal women. Among the diverse endocrine factors associated to obesity, leptin has received special attention since it promotes breast cancer cell growth and invasiveness, processes which force cells to adapt their metabolism to satisfy the increased demands of energy and biosynthetic intermediates. Taking this into account, our aim was to explore the effects of leptin in the metabolism of MCF-7 breast cancer cells. Polarographic analysis revealed that leptin increased oxygen consumption rate and cellular ATP levels were more dependent on mitochondrial oxidative metabolism in leptin-treated cells compared to the more glycolytic control cells. Experiments with selective inhibitors of glycolysis (2-DG), fatty acid oxidation (etomoxir) or aminoacid deprivation showed that ATP levels were more reliant on fatty acid oxidation. In agreement, levels of key proteins involved in lipid catabolism (FAT/CD36, CPT1, PPARα) and phosphorylation of the energy sensor AMPK were increased by leptin. Regarding glucose, cellular uptake was not affected by leptin, but lactate release was deeply repressed. Analysis of pyruvate dehydrogenase (PDH), lactate dehydrogenase (LDH) and pyruvate carboxylase (PC) together with the pentose-phosphate pathway enzyme glucose-6 phosphate dehydrogenase (G6PDH) revealed that leptin favors the use of glucose for biosynthesis. These results point towards a role of leptin in metabolic reprogramming, consisting of an enhanced use of glucose for biosynthesis and lipids for energy production. This metabolic adaptations induced by leptin may provide benefits for MCF-7 growth and give support to the reverse Warburg effect described in breast cancer. PMID:26772821

  8. An analogue of atrial natriuretic peptide (C-ANP4-23) modulates glucose metabolism in human differentiated adipocytes.

    Ruiz-Ojeda, Francisco Javier; Aguilera, Concepción María; Rupérez, Azahara Iris; Gil, Ángel; Gomez-Llorente, Carolina

    2016-08-15

    The present study was undertaken to investigate the effects of C-atrial natriuretic peptide (C-ANP4-23) in human adipose-derived stem cells differentiated into adipocytes over 10 days (1 μM for 4 h). The intracellular cAMP, cGMP and protein kinase A levels were determined by ELISA and gene and protein expression were determined by qRT-PCR and Western blot, respectively, in the presence or absence of C-ANP4-23. The levels of lipolysis and glucose uptake were also determined. C-ANP4-23 treatment significantly increased the intracellular cAMP levels and the gene expression of glucose transporter type 4 (GLUT4) and protein kinase, AMP-activated, alpha 1 catalytic subunit (AMPK). Western blot showed a significant increase in GLUT4 and phosphor-AMPKα levels. Importantly, the adenylate cyclase inhibitor SQ22536 abolished these effects. Additionally, C-ANP4-23 increased glucose uptake by 2-fold. Our results show that C-ANP4-23 enhances glucose metabolism and might contribute to the development of new peptide-based therapies for metabolic diseases. PMID:27181211

  9. Effects of oral administration of benzylamine on glucose tolerance and lipid metabolism in rats.

    Bour, S; Visentin, V; Prévot, D; Daviaud, D; Saulnier-Blache, J S; Guigne, C; Valet, P; Carpéné, C

    2005-06-01

    Repeated administration of benzylamine plus vanadate have been reported to exhibit anti-hyperglycemic effects in different models of diabetic rats. Likewise oral treatment with Moringa oleifera extracts which contain the alkaloïd moringine, identical to benzylamine, has also been shown to prevent hyperglycemia in alloxan-induced diabetic rats. With these observations we tested whether prolonged oral administration of benzylamine could interact with glucose and/or lipid metabolism. Seven week old male Wistar rats were treated for seven weeks with benzylamine 2.9 g/l in drinking water and were submitted to glucose tolerance tests. A slight decrease in water consumption was observed in benzylamine-treated animals while there was no change in body and adipose tissue weights at the end of treatment. Blood glucose and plasma insulin, triacylglycerol or cholesterol levels were not modified. However, benzylamine treatment resulted in a decrease in plasma free fatty acids in both fed and fasted conditions. Benzylamine treatment improved glucose tolerance as shown by the reduction of hyperglycemic response to intra-peritoneal glucose load. Oral benzylamine treatment did not alter the response of adipocytes to insulin nor to insulin-like actions of benzylamine plus vanadate, via in vitro activation of glucose transport or inhibition of lipolysis. This work demonstrates for the first time that oral administration of benzylamine alone influences glucose and lipid metabolism. However, these results obtained in normoglycemic rats require to be confirmed in diabetic models. PMID:16180335

  10. Impact of glucagon-like peptide-1 on myocardial glucose metabolism revisited

    Hansen, Jan; Brock, Birgitte; Bøtker, Hans Erik;

    2014-01-01

    . The potentially beneficial effect of GLP-1 stimulation may rely on, among others, improved myocardial glucose metabolism. This review focuses on the dogma that GLP-1 receptor stimulation may provide beneficial cardiovascular effects, possibly due to enhanced myocardial energetic efficiency, by increasing...... myocardial glucose uptake. The published literature was systematically reviewed and the applied models evaluated since the outcomes of varying studies differ substantially. Reports on the effect of GLP-1R stimulation on myocardial metabolism are conflicting and should be evaluated carefully. There is limited...

  11. Metabolism of glucose in brain of patients with Parkinson's disease

    We examined 11C accumulation by positron emission computed tomography in the region of interest (ROI) in the brain of 8 patients with Parkinson's disease and 5 normal controls when administered with 11C-glucose (per os). 11C-glucose was prepared from 11CO2 by photosynthesis. 1) No significant difference was observed in the 11C accumulation in the striatum and cerebral cortex (frontal cortex, temporal cortex and occipital cortex) in 4 patients with Parkinson's disease between continuous medication and 7--10 day interruption of medication. 2) No difference was observed in the 11C accumulation in the striatum and cerebral cortex between 8 patients with Parkinson's disease and 5 normal controls. (author)

  12. Metabolism of D-glucose in a wall-less mutant of Neurospora crassa examined by 13C and 31P nuclear magnetic resonances: effects of insulin

    13C NMR and 31P NMR have been used to investigate the metabolism of glucose by a wall-less strain of Neurospora crassa (slime), grown in a supplemented nutritionally defined medium and harvested in the early stationary stage of growth. With D-[1-13C]- or D-[6-13C]glucose as substrates, the major metabolic products identified from 13C NMR spectra were [2-13C]ethanol, [3-13C]alanine, and C1- and C6-labeled trehalose. Several observations suggested the existence of a substantial hexose monophosphate (HMP) shunt: (i) a 70% greater yield of ethanol from C6- than from C1-labeled glucose; (ii) C1-labeled glucose yielded 19% C6-labeled trehalose, while C6-labeled glucose yielded only 4% C1-labeled trehalose; (iii) a substantial transfer of 13C from C2-labeled glucose to the C2-position of ethanol. 31P NMR spectra showed millimolar levels of intracellular inorganic phosphate (Pi), phosphodiesters, and diphosphates including sugar diphosphates and polyphosphate. Addition of glucose resulted in a decrease in cytoplasmic Pi and an increase in sugar monophosphates, which continued for at least 30 min. Phosphate resonances corresponding to metabolic intermediates of both the glycolytic and HMP pathways were identified in cell extracts. Addition of insulin (100 nM) with the glucose had the following effects relative to glucose alone: (i) a 24% increase (P less than 0.01) in the rate of ethanol production; (ii) a 38% increase (P less than 0.05) in the rate of alanine production; (iii) a 27% increase (P less than 0.05) in the rate of glucose disappearance. Insulin thus increases the rates of production of ethanol and alanine in these cells, in addition to increasing production of CO2 and glycogen, as previously shown. (author)

  13. Germ band retraction as a landmark in glucose metabolism during Aedes aegypti embryogenesis

    Logullo Carlos

    2010-02-01

    Full Text Available Abstract Background The mosquito A. aegypti is vector of dengue and other viruses. New methods of vector control are needed and can be achieved by a better understanding of the life cycle of this insect. Embryogenesis is a part of A. aegypty life cycle that is poorly understood. In insects in general and in mosquitoes in particular energetic metabolism is well studied during oogenesis, when the oocyte exhibits fast growth, accumulating carbohydrates, lipids and proteins that will meet the regulatory and metabolic needs of the developing embryo. On the other hand, events related with energetic metabolism during A. aegypti embryogenesis are unknown. Results Glucose metabolism was investigated throughout Aedes aegypti (Diptera embryonic development. Both cellular blastoderm formation (CBf, 5 h after egg laying - HAE and germ band retraction (GBr, 24 HAE may be considered landmarks regarding glucose 6-phosphate (G6P destination. We observed high levels of glucose 6-phosphate dehydrogenase (G6PDH activity at the very beginning of embryogenesis, which nevertheless decreased up to 5 HAE. This activity is correlated with the need for nucleotide precursors generated by the pentose phosphate pathway (PPP, of which G6PDH is the key enzyme. We suggest the synchronism of egg metabolism with carbohydrate distribution based on the decreasing levels of phosphoenolpyruvate carboxykinase (PEPCK activity and on the elevation observed in protein content up to 24 HAE. Concomitantly, increasing levels of hexokinase (HK and pyruvate kinase (PK activity were observed, and PEPCK reached a peak around 48 HAE. Glycogen synthase kinase (GSK3 activity was also monitored and shown to be inversely correlated with glycogen distribution during embryogenesis. Conclusions The results herein support the hypothesis that glucose metabolic fate changes according to developmental embryonic stages. Germ band retraction is a moment that was characterized as a landmark in glucose

  14. Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity.

    Jais, Alexander; Solas, Maite; Backes, Heiko; Chaurasia, Bhagirath; Kleinridders, André; Theurich, Sebastian; Mauer, Jan; Steculorum, Sophie M; Hampel, Brigitte; Goldau, Julia; Alber, Jens; Förster, Carola Y; Eming, Sabine A; Schwaninger, Markus; Ferrara, Napoleone; Karsenty, Gerard; Brüning, Jens C

    2016-05-01

    High-fat diet (HFD) feeding induces rapid reprogramming of systemic metabolism. Here, we demonstrate that HFD feeding of mice downregulates glucose transporter (GLUT)-1 expression in blood-brain barrier (BBB) vascular endothelial cells (BECs) and reduces brain glucose uptake. Upon prolonged HFD feeding, GLUT1 expression is restored, which is paralleled by increased expression of vascular endothelial growth factor (VEGF) in macrophages at the BBB. In turn, inducible reduction of GLUT1 expression specifically in BECs reduces brain glucose uptake and increases VEGF serum concentrations in lean mice. Conversely, myeloid-cell-specific deletion of VEGF in VEGF(Δmyel) mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not in lean mice. Moreover, obese VEGF(Δmyel) mice exhibit exaggerated progression of cognitive decline and neuroinflammation on an Alzheimer's disease background. These experiments reveal that transient, HFD-elicited reduction of brain glucose uptake initiates a compensatory increase of VEGF production and assign obesity-associated macrophage activation a homeostatic role to restore cerebral glucose metabolism, preserve cognitive function, and limit neurodegeneration in obesity. PMID:27133169

  15. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism1

    Galie, Mirco; Farace, Paolo; Nanni, Cristina; Spinelli, Antonello; Nicolato, Elena; Boschi, Federico; Magnani, Paolo; Trespidi, Silvia; Ambrosini, Valentina; Fanti, Stefano; Merigo, Flavia; Osculati, Francesco; Marzola, Pasquina; Sbarbati, Andrea

    2007-01-01

    Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition. PMID:18030358

  16. Aldolase B knockdown prevents high glucose-induced methylglyoxal overproduction and cellular dysfunction in endothelial cells.

    Jianghai Liu

    Full Text Available We used cultured endothelial cells as a model to examine whether up-regulation of aldolase B and enhanced methylglyoxal (MG formation play an important role in high glucose-induced overproduction of advanced glycosylation endproducts (AGEs, oxidative stress and cellular dysfunction. High glucose (25 mM incubation up-regulated mRNA levels of aldose reductase (an enzyme converting glucose to fructose and aldolase B (a key enzyme that catalyzes MG formation from fructose and enhanced MG formation in human umbilical vein endothelial cells (HUVECs and HUVEC-derived EA. hy926 cells. High glucose-increased MG production in EA. hy926 cells was completely prevented by siRNA knockdown of aldolase B, but unaffected by siRNA knockdown of aldolase A, an enzyme responsible for MG formation during glycolysis. In addition, inhibition of cytochrome P450 2E1 or semicarbazide-sensitive amine oxidase which produces MG during the metabolism of lipid and proteins, respectively, did not alter MG production. Both high glucose (25 mM and MG (30, 100 µM increased the formation of N(ε-carboxyethyl-lysine (CEL, a MG-induced AGE, oxidative stress (determined by the generation of oxidized DCF, H(2O(2, protein carbonyls and 8-oxo-dG, O-GlcNAc modification (product of the hexosamine pathway, membrane protein kinase C activity and nuclear translocation of NF-κB in EA. hy926 cells. However, the above metabolic and signaling alterations induced by high glucose were completely prevented by knockdown of aldolase B and partially by application of aminoguanidine (a MG scavenger or alagebrium (an AGEs breaker. In conclusion, efficient inhibition of aldolase B can prevent high glucose-induced overproduction of MG and related cellular dysfunction in endothelial cells.

  17. Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

    The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than walking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep

  18. Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

    Buchsbaum, M.S.; Wu, J.; Hazlett, E.; Sicotte, N.; Bunney, W.E. Jr. (Univ. of California, Irvine (USA)); Gillin, J.C. (Univ. of California, San Diego (USA))

    1989-01-01

    The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than walking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep.

  19. c-MYC responds to glucose deprivation in a cell-type-dependent manner.

    Wu, S; Yin, X; Fang, X; Zheng, J; Li, L; Liu, X; Chu, L

    2015-01-01

    Metabolic reprogramming supports cancer cells' demands for rapid proliferation and growth. Previous work shows that oncogenes, such as MYC, hypoxia-inducible factor 1 (HIF1), have a central role in driving metabolic reprogramming. A lot of metabolic enzymes, which are deregulated in most cancer cells, are the targets of these oncogenes. However, whether metabolic change affects these oncogenes is still unclear. Here we show that glucose deprivation (GD) affects c-MYC protein levels in a cell-type-dependent manner regardless of P53 mutation status. GD dephosphorylates and then decreases c-MYC protein stability through PI3K signaling pathway in HeLa cells, but not in MDA-MB-231 cells. Role of c-MYC in sensitivity of GD also varies with cell types. c-MYC-mediated glutamine metabolism partially improves the sensitivity of GD in MDA-MB-231 cells. Our results reveal that the heterogeneity of cancer cells in response to metabolic stress should be considered in metabolic therapy for cancer. PMID:27551483

  20. Physical Modeling of the Enzymatic Glucose-Fuelled Fuel Cells

    Vladimir (Zeev) Rubin; Lea Mor

    2013-01-01

    An enzymatic glucose biofuel cell uses glucose as fuel and enzymes as biocatalyst, to transform biochemical energy into electrical energy. An analytical modelling of an enzymatic biofuel cell should be used, while developing fuel cell, to estimate its various enzymatic parameters, to obtain the highest voltage feasibly. The analytical model was developed, and the open circuit voltage (OCV) calculated by the model for various parameters of the fuel cell is in agreement with the experimental re...

  1. Noninvasive measurement of regional myocardial glucose metabolism by positron emission computed tomography. [Dogs

    Schelbert, H.R.; Phelps, M.E.

    1980-06-01

    While the results of regional myocardial glucose metabolism measurements using positron emission computed tomography (/sup 13/N-ammonia) are promising, their utility and value remains to be determined in man. If this technique can be applied to patients with acute myocardial ischemia or infarction it may permit delineation of regional myocardial segments with altered, yet still active metabolism. Further, it may become possible to evaluate the effects of interventions designed to salvage reversibly injured myocardium by this technique.

  2. Noninvasive measurement of regional myocardial glucose metabolism by positron emission computed tomography

    While the results of regional myocardial glucose metabolism measurements using positron emission computed tomography (13N-ammonia) are promising, their utility and value remains to be determined in man. If this technique can be applied to patients with acute myocardial ischemia or infarction it may permit delineation of regional myocardial segments with altered, yet still active metabolism. Further, it may become possible to evaluate the effects of interventions designed to salvage reversibly injured myocardium by this technique

  3. Cortical Glucose Metabolism Positively Correlates with Gamma-Oscillations in Nonlesional Focal Epilepsy

    Nishida, Masaaki; Juhász, Csaba; Sood, Sandeep; Chugani, Harry T.; Asano, Eishi

    2008-01-01

    Why do the epileptogenic foci appear hypometabolic on interictal glucose metabolism positron emission tomography (PET) in a substantial proportion of patients with focal epilepsy but appear normo- or even hyper-metabolic in others? Such observations on interictal PET have not been fully explained by the frequency of interictal spike discharges alone. In the present study using digital electrocorticography monitoring system with high-frequency sampling, we determined how well regression models...

  4. Elevated glucose metabolism in the amygdala during an inhibitory avoidance task

    Sandusky, Leslie A.; Flint, Robert W.; McNay, Ewan C.

    2013-01-01

    There is a long-standing debate as to whether the memory process of consolidation is neurochemically similar to or the same as the set of processes involved in retrieval and reconsolidation of that memory. In addition, although we have previously shown that initial memory processing in the hippocampus causes a drainage of hippocampal glucose because of increased local metabolic demand, it is unknown what metabolic changes occur elsewhere in the brain or during subsequent processing of a previ...

  5. Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells.

    Tim A D Smith

    Full Text Available The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined.MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK, CTP:phosphocholine cytidylyl transferase (CCT and PtdCho-phospholipase C (PLC were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography.Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U]glucose.This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.

  6. [18F]-2-fluoro-2-deoxyglucose transport kinetics as a function of extracellular glucose concentration in malignant glioma, fibroblast and macrophage cells in vitro

    FDG-PET is used to measure the metabolic rate of glucose. Transport and phosphorylation determine the amount of hexose analog that is phosphorylated and trapped. Competition occurs for both events, such that extracellular glucose concentration affects the FDG image. This study investigated the effect of glucose concentration on the rate of FDG accumulation in three cell lines. The results show that extracellular glucose concentration has a greater impact on the rate of FDG accumulation than the relative abundance of GLUT transporter subtypes

  7. Regional cerebral glucose metabolism in patients with alcoholic Korsakoff's syndrome

    Kessler, R.M.; Parker, E.S.; Clark, C.M.; Martin, P.R.; George, D.T.; Weingartner, H.; Sokoloff, L.; Ebert, M.H.; Mishkin, M.

    1985-05-01

    Seven alcoholic male subjects diagnosed as having Korsakoff's syndrome and eight age-matched male normal volunteers were studied with /sup 18/F 2-fluoro-2-deoxy-D-glucose (2/sup 18/FDG). All subjects were examined at rest with eyes covered in a quiet, darkened room. Serial plasma samples were obtained following injection of 4 to 5 mCi of 2/sup 18/FDG. Tomographic slices spaced at 10mm axial increments were obtained (in-plane resolution = 1.75 cm, axial resolution = 1.78 cm). Four planes were selected from each subject, and a total of 46 regions of interest were sampled and glucose metabolic rates for each region calculated. The mean glucose metalbolic rate for the 46 regions in the Korsakoff subjects was significantly lower than that in the normal controls (5.17 +- .43 versus 6.6 +- 1.31). A Q-component analysis, which examined each subject's regional rates relative to his mean rate, revealed two distinct patterns in the Korsakoff group. Glucose metabolism was significantly reduced in 37 of the 46 regions sampled. Reduced cerebral glucose metabolism in a nondemented group of subjects has not previously been reported. The reduction in cortical metabolism may be the result of damage to sub-cortical projecting systems. The differing patterns of cerebral metabolism in Korsakoff's syndrome suggests subgroups with differing neuropathology. Regions implicated in memory function, medial temporal, thalamic and medial prefrontal were among the regions reduced in metabolism.

  8. Oral cancer cells may rewire alternative metabolic pathways to survive from siRNA silencing of metabolic enzymes

    Cancer cells may undergo metabolic adaptations that support their growth as well as drug resistance properties. The purpose of this study is to test if oral cancer cells can overcome the metabolic defects introduced by using small interfering RNA (siRNA) to knock down their expression of important metabolic enzymes. UM1 and UM2 oral cancer cells were transfected with siRNA to transketolase (TKT) or siRNA to adenylate kinase (AK2), and Western blotting was used to confirm the knockdown. Cellular uptake of glucose and glutamine and production of lactate were compared between the cancer cells with either TKT or AK2 knockdown and those transfected with control siRNA. Statistical analysis was performed with student T-test. Despite the defect in the pentose phosphate pathway caused by siRNA knockdown of TKT, the survived UM1 or UM2 cells utilized more glucose and glutamine and secreted a significantly higher amount of lactate than the cells transferred with control siRNA. We also demonstrated that siRNA knockdown of AK2 constrained the proliferation of UM1 and UM2 cells but similarly led to an increased uptake of glucose/glutamine and production of lactate by the UM1 or UM2 cells survived from siRNA silencing of AK2. Our results indicate that the metabolic defects introduced by siRNA silencing of metabolic enzymes TKT or AK2 may be compensated by alternative feedback metabolic mechanisms, suggesting that cancer cells may overcome single defective pathways through secondary metabolic network adaptations. The highly robust nature of oral cancer cell metabolism implies that a systematic medical approach targeting multiple metabolic pathways may be needed to accomplish the continued improvement of cancer treatment

  9. Analysis of oral glucose tolerance test in pregnant women with abnormal glucose metabolism

    YANG Hui-xia; GAO Xue-lian; DONG Yue; SHI Chun-yan

    2005-01-01

    Background Due to the controversy of the oral glucose tolerance test (OGTT), diagnostic criteria for gestational diabetes mellitus (GDM) in the world and researches on GDM remain undeveloped in China. American Diabetes Association recently recommended the clinicians to diagnose GDM by OGTT results without the third-hour glucose value. This new criteria has not been used in China. Research on the value and sensitivity of the criteria in detecting GDM is rare. The aim of our study is to analyze the characteristics of OGTT in Chinese women with GDM or gestational impaired glucose tolerance (GIGT) and to evaluate the effect of omission of the third-hour plasma glucose (PG) level in OGTT on the sensitivity of diagnosing GDM and GIGT, and the relationship between PG values of 50 g GCT or OGTT and insulin therapy. Methods A retrospective analysis was performed on medical records of 647 cases with GDM from January 1, 1989 to December 31, 2002, and 233 with GIGT. Among 647 cases of GDM, 535 cases were diagnosed by 75 g OGTT. All OGTT results including 535 cases of GDM and 233 patients with GIGT were evaluated. Results There were 112 cases of GDM diagnosed by elevated fasting PG (FPG) without OGTT performed. Of 535 cases of GDM diagnosed by OGTT, 49.2% (263/535) women had FPG value ≥5.8 mmol/L; 90.1% (482/535) women with 1-hour PG values ≥10.6 mmol/L; 64.7% (359/535) with 2-hour PG levels ≥9.2 mmol/L. There were only 114 cases (21.3%) with abnormal 3-hour PG levels among 535 women with OGTT. Among those with abnormal 3-hour PG level, 49.1% (56/114) had abnormal glucose values in the other three points of OGTT, and 34.2% (39/114) with two other abnormal values of OGTT. Our study showed that omission of the 3-hour PG of OGTT only missed 19 cases of GDM and they would be diagnosed as GIGT. Among the 233 women with GIGT, only 4 cases had abnormal 3-hour PG. So, omission of the third-hour glucose value of OGTT only resulted in failure to diagnose 3.6% (19/535) women with

  10. Obesity, metabolic syndrome, impaired fasting glucose, and microvascular dysfunction: a principal component analysis approach

    Panazzolo Diogo G

    2012-11-01

    Full Text Available Abstract Background We aimed to evaluate the multivariate association between functional microvascular variables and clinical-laboratorial-anthropometrical measurements. Methods Data from 189 female subjects (34.0±15.5 years, 30.5±7.1 kg/m2, who were non-smokers, non-regular drug users, without a history of diabetes and/or hypertension, were analyzed by principal component analysis (PCA. PCA is a classical multivariate exploratory tool because it highlights common variation between variables allowing inferences about possible biological meaning of associations between them, without pre-establishing cause-effect relationships. In total, 15 variables were used for PCA: body mass index (BMI, waist circumference, systolic and diastolic blood pressure (BP, fasting plasma glucose, levels of total cholesterol, high-density lipoprotein cholesterol (HDL-c, low-density lipoprotein cholesterol (LDL-c, triglycerides (TG, insulin, C-reactive protein (CRP, and functional microvascular variables measured by nailfold videocapillaroscopy. Nailfold videocapillaroscopy was used for direct visualization of nutritive capillaries, assessing functional capillary density, red blood cell velocity (RBCV at rest and peak after 1 min of arterial occlusion (RBCVmax, and the time taken to reach RBCVmax (TRBCVmax. Results A total of 35% of subjects had metabolic syndrome, 77% were overweight/obese, and 9.5% had impaired fasting glucose. PCA was able to recognize that functional microvascular variables and clinical-laboratorial-anthropometrical measurements had a similar variation. The first five principal components explained most of the intrinsic variation of the data. For example, principal component 1 was associated with BMI, waist circumference, systolic BP, diastolic BP, insulin, TG, CRP, and TRBCVmax varying in the same way. Principal component 1 also showed a strong association among HDL-c, RBCV, and RBCVmax, but in the opposite way. Principal component 3 was

  11. Low non-oxidative glucose metabolism and violent offending: an 8-year prospective follow-up study.

    Virkkunen, Matti; Rissanen, Aila; Franssila-Kallunki, Anja; Tiihonen, Jari

    2009-06-30

    Violent offenders have abnormalities in their glucose metabolism as indicated by decreased glucose uptake in their prefrontal cortex and a low blood glucose nadir in the glucose tolerance test. We tested the hypothesis that low non-oxidative glucose metabolism (NOG) predicts forthcoming violent offending among antisocial males. Glucose metabolism was measured using the insulin clamp method among 49 impulsive, violent, antisocial offenders during a forensic psychiatric examination. Those offenders who committed at least one new violent crime during the 8-year follow-up had a mean NOG of 1.4 standard deviations lower than non-recidivistic offenders. In logistic regression analysis, NOG alone explained 27% of the variation in the recidivistic offending. Low non-oxidative metabolism may be a crucial component in the pathophysiology of habitually violent behavior among subjects with antisocial personality disorder. This might suggest that substances increasing glycogen formation and decreasing the risk of hypoglycemia might be potential treatments for impulsive violent behavior. PMID:19446886

  12. Effect of heparin on high glucose induced proliferation and expression of matrix metalloproteinases in normal human mesangial cells

    ZHOU Qiao-ling; Arima Terukatsu; Yasumoto Yuichiro; Tsukamoto Masatoshi; Nozaki Tsuyoshi; Sogabe Atsushi; Harada Kouji; ZHANG Yi-xiang; LIN Xiao-yan; ZHANG Yang-de

    2005-01-01

    Background The pathogenesis of diabetic nephropathy (DN) is a complex pathophysiological process.Its precise mechanism is not fully known. In recent years it has been recognized that synthesis of various extracelluar matrix (ECM) components may increase, and that degradation of ECM may decrease in DN. It was reported heparin could inhibit mesangial cells proliferation in vitro. The main aim of this study is to explore whether heparin inhibits proliferation of mesangial cells grown in high glucose concentration and to measure the effect of heparin on matrix metalloproteinases (MMPs) expression in mesangial cells. Methods The medium contained either low glucose (5 mmol/L) or high glucose (25 mmol/L). The concentrations of heparin in the culture medium were 0, 25, 50,100, 200 or 400 μg/mL. A metabolic (WST-1) assay was used to measure mesangial cell proliferation and Western blot analysis was used to measure MMPs expression of mesangial cells. Results Normal human mesangial cell (NHMC) proliferation was higher in high glucose (HG) medium than in low glucose (LG) medium. They showed a 1.93 fold expansion after 72 h in high glucose in contrast to a 1.63 fold expansion in low glucose. In the presence of heparin, mesangial cells proliferation was inhibited, which was more obvious at high glucose concentrations than at low glucose concentrations. In high glucose, with heparin concentration of 50, 100, 200 and 400 μg/mL, the mesangial cells showed a 0. 61 fold, 0.52 fold, 0.52 fold and 0.41 fold reductions in cell number compared to cells grown without heparin. In low glucose, only concentrations of 200 μg/mL and 400 μg/mL showed reduction in cell number, namely 0.54 fold and 0.45 fold, when compared to cells grown without heparin. In Western blot analysis,MMP1, MMP2, MMP3 and MMP9 was expressed by mesangial cells expressed in both high and low glucose concentrations, which was more prominent in high glucose medium. Incubation of heparin further increased expression of

  13. Ovarian tumor-initiating cells display a flexible metabolism

    Anderson, Angela S. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Roberts, Paul C. [Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA (United States); Frisard, Madlyn I. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Hulver, Matthew W., E-mail: hulvermw@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Schmelz, Eva M., E-mail: eschmelz@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States)

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  14. Ovarian tumor-initiating cells display a flexible metabolism

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-LFFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth

  15. Metabolic responses to prolonged consumption of glucose- and fructose-sweetened beverages are not associated with postprandial or 24-hour glucose and insulin excursions

    It has been proposed that the adverse metabolic effects of chronic consumption of sugar-sweetened beverages which contain both glucose and fructose are a consequence of increased circulating glucose and insulin excursions, i.e dietary glycemic index (GI). Objective: We determined if the greater adv...

  16. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis.

    Xuan Xia

    Full Text Available Berberine (BBR is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French. It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK and Glucose-6-phosphatase (G6Pase, were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1, sterol regulatory element-binding protein 1c (SREBP1 and carbohydrate responsive element-binding protein (ChREBP were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.

  17. Association between serum uric acid and different states of glucose metabolism and glomerular filtration rate

    CAI Xiao-ling; HAN Xue-yao; JI Li-nong

    2010-01-01

    Background Recently, it has been suggested that the serum uric acid (SUA) level decreased in diabetic patients. The aim of this study was to explore the association between SUA level and different state of glucose metabolism and glomerular filtration rate (GFR) reflected by the simplified Modification of Diet in Renal Disease (MDRD) equation and to test the hypothesis that high MDRD is one of the determinants of SUA level.Methods This cross-sectional study included 2373 subjects in Beijing who underwent a 75 g oral glucose tolerance test (OGTT) for screening of diabetes. According to the states of glucose metabolism, they were divided into normal glucose tolerance, impaired glucose regulation and diabetes.Results Multiple stepwise linear regression analysis showed that adjusted by gender, SUA was positively correlated with body mass index (BMI), waist/hippo ratio, systolic blood pressure (SBP) and triglyceride, meanwhile negatively correlated with age, hemoglobin A1c, fasting insulin and MDRD. There was an increasing trend in SUA concentration and a decreasing trend in MDRD when the levels of fasting plasma glucose (FPG) increased from low to high up to the FPG level of 8.0 mmol/L; thereafter, the SUA concentration started to decrease with further increases in FPG levels, and the MDRD started to increase with further increases in FPG levels.Conclusion This study confirmed the previous finding that SUA decreased in diabetes and provided the supporting evidence that the increased MDRD might contribute to the fall of SUA.

  18. Increased response to insulin of glucose metabolism in the 6-day unloaded rat soleus muscle

    Henriksen, Erik J.; Tischler, Marc E.; Johnson, David G.

    1986-01-01

    Hind leg muscles of female rats were unloaded by tail cast suspension for 6 days. In the fresh-frozen unloaded soleus, the significantly greater concentration of glycogen correlated with a lower activity ratio of glycogen phosphorylase (p less than 0.02). The activity ratio of glycogen synthase also was lower (p less than 0.001), possibly due to the higher concentration of glycogen. In isolated unloaded soleus, insulin (0.1 milliunit/ml) increased the oxidation of D(U-C-14) glucose, release of lactate and pyruvate, incorporation of D-(U-C-14) glucose into glycogen, and the concentration of glucose 6-phosphate more (p less than 0.05) than in the weight-bearing soleus. At physiological doses of insulin, the percent of maximal uptake of 2-deoxy-D-(1,2-H-3) glucose/muscle also was greater in the unloaded soleus. Unloading of the soleus increased, by 50 percent the concentration of insuling receptors, due to no decrease in total receptor number during muscle atrophy. This increase may account for the greater response of glucose metabolism to insulin in this muscle. The extensor digitorum longus, which generally shows little response to unloading, displayed no differential response of glucose metabolism to insulin.

  19. Chemosensitizing and cytotoxic effects of 2-deoxy-D-glucose on breast cancer cells

    Zhang Fanjie

    2009-09-01

    Full Text Available Background: Accelerated glucose uptake for anerobic glycolysis is one of the major metabolic changes found in malignant cells. This property has been exploited for imaging malignancies and as a possible anticancer therapy. The nonmetabolizable glucose analog 2-deoxyglucose (2 DG interferes with glucose metabolism leading to breast cancer cell death. Aims: To determine whether 2DG can synergize with chemotherapeutic agents commonly used in breast cancer treatment and identify cellular characteristics associated with sensitivity to 2DG. Materials and Methods: SkBr3 breast cancer cells were incubated with varying concentrations of 5-fluorouracil (5FU, doxorubicin, cisplatin, cyclophosphamide, or herceptin with or without 2DG. Cell viability was measured using the MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Results: Combining 2DG with doxorubicin, 5 FU, cyclophosphamide, and herceptin resulted in enhanced cell death compared with each agent alone, while in combination with cisplatin, the amount of cell death was additive. Mouse embryo fibroblasts (MEF mutated for p53 (-/- were 30% more sensitive to the cytotoxic effects of 2DG than the parental cell lines. Cells mutated for Bax/Bac, genes involved in protection from apoptosis, are slightly more sensitive than the parental cell lines. Conclusions: These results indicate that 2DG acts synergistically with specific chemotherapeutic agents in causing cell death and the class of chemicals most sensitive appear to be those which cause DNA damage.

  20. Sleep deprivation and its impact on circadian rhythms and glucose metabolism

    P.K. Jha

    2016-01-01

    The mammalian master pacemaker is located in the hypothalamic suprachiasmatic nucleus (SCN). The SCN generates rhythms of behavioural and metabolic processes throughout the body via both endocrine and neuronal outputs. For example, daily rhythms of sleep-wake, fasting-feeding, plasma glucose, glucos

  1. Chromium supplementation alters both glucose and lipid metabolism in feedlot cattle during the receiving period

    Crossbred steers (n = 20; 235 +/- 4 kg) were fed 53 days during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brandChromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0...

  2. Chromium supplementation alters the glucose and lipid metabolism of feedlot cattle during the receiving period

    Crossbreed steers (n = 20; 235 ± 4 kg) were fed 53 d during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brand Chromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0 (C...

  3. Effect of opium on glucose metabolism and lipid profiles in rats with streptozotocin-induced diabetes

    Sadeghian, Saeed; Boroumand, Mohammad Ali; Sotoudeh-Anvari, Maryam; Rahbani, Shahram; Sheikhfathollahi, Mahmood; Abbasi, Ali

    2009-01-01

    Background: This experimental study was performed to determine the impact of opium use on serum lipid profile and glucose metabolism in rats with streptozotocin-induced diabetes. Material and methods: To determine the effect of opium, 20 male rats were divided into control (n = 10) and opium-treated

  4. Insulin resistance for glucose metabolism in disused soleus muscle of mice

    Seider, M. J.; Nicholson, W. F.; Booth, F. W.

    1981-01-01

    Results of this study on mice provide the first direct evidence of insulin resistance for glucose metabolism in skeletal muscle that has undergone a previous period of reduced muscle usage. This lack of responsiveness to insulin developed in one day and in the presence of hypoinsulinemia. Future studies will utilize the model of hindlimb immobilization to determine the causes of these changes.

  5. Effects of 5-thio-d-glucose on hexose transport and metabolism

    Using the everted sac technique, the mouse small intestine was found to transport 5-thio-D-glucose (5TG) against a concentration gradient, by a sodium- and energy-dependent, phloridzin- and ouabain-sensitive mechanism. At incubation periods of one hour, 5TG inhibited 3-O-methyl-D-glucose (3MG) and D-galactose transport while enhancing net transport of D-glucose. Addition of 5TG and D-glucose produced a dose-related increase in mucosal tissue water D-glucose concentration with a concomitant decrease in L-lactate production. These results suggest that 5TG decreased intestinal utilization of D-glucose via anaerobic glycolysis to partially account for the increased net transport of D-glucose. However, when incubation periods were less than 45 minutes duration, 5TG inhibited net D-glucose transport without affecting L-lactate production. A time- and dose-dependent inhibition of 14CO2 production from [1-14C] or [6-14C] D-glucose by 5TG was observed in everted rings of mouse intestine. The 14CO2 produced from [6-14C]-D-glucose was not markedly inhibited until incubations were 45 minutes or longer. This study demonstrated that 5TG inhibits D-glucose utilization in the mouse small intestine, which may contribute to the diabetogenic effect observed in vivo. Addition of 5TG stimulated 14CO2 production from [1-14C] and [6-14C] D-glucose in Ehrlich-Lettre (EL) ascites cells, while failing to affect 14CO2 production from the tumor bearing mouse (TBM) intestine at any dose employed. When tumor bearing mice were treated with 5TG, stimulation of the HMS occurred in the tumor cells, while variable effects were demonstrated on the HMS of the TBM intestine

  6. Effects of Reductions of Body Fat and Regional Adipose Tissue on Glucose and Lipid Metabolism Among Eldery Japanese

    Shigeto, Kazuhiro; Koyama, Hiroshi; Takemoto, Tai-ichiro

    1989-01-01

    To evaluate effects of improvement of obesity on glucose and lipid metabolism, changes of body weight, skinfolds and biochemical parameters in glucose and lipid metabolism were examined through a six month health education on excercise and diet. Subjects were 20 men and 36 women aged from 48 to 87, who had overweight and/or glucose intolerance. Weight, relative weight and fat mass were significantly reduced after the program in both sexes. Circumference ratios were reduced only in women. The ...

  7. NF-κB在高糖诱导“代谢记忆”致心肌细胞损伤的作用机制%NF-κB in High Glucose-induced "metabolic memory" Induced Myocardial Cell Injury Mechanisms

    祝文静; 刘畅; 孟林燕; 张秀云

    2011-01-01

    Objective Discussion on metabolic memory of the molecular mechanisms of myocar-dial cell injury. Methods 20 SD rats were cultured neonatal rat cardiomyocytes,n = 5,divided into four groups continuous low-sugar group; sustained high glucose group; metabolic memory group; PDTC group. Calculated apoptotic index, immunohistochemical nuclear expression of NF-κB, Western Blot test NF-κB protein, TUNEL detection of apoptosis. Results Metabolic memory (15. 12±2. 32)and sustained high group (17. 10±3. 12)levels of protein expression of the glucose group compared with continuous low-sugar group(5. 23 ± 2. 13) of NF-κB nuclear protein levels were significantly increased (P<0. 01) ,PDTC(7. 12±2. 41) pretreatment,NF-κB nuclear protein levels compared with significantly lower metabolic memory(17. 10±3. 12);the same time,metabolic memory group (19. 42 it 3. 22) and the apoptotic index of sustained high glucose group (22. 36 ± 3. 45) compared with continuous low-sugar group (8. 56 ± 0. 23) significantly increased (P<0. 05), while PDTC group(10. 33 ± 1. 34) than in metabolic memory myocardial (19. 42 ± 3. 22) apoptosis index decreased significantly (P<0. 05). Conclusion PDTC can inhibit the metabolism of the memory of the damage caused by myocardial cells,NF-κB activation might be mediated by high glucose-induced metabolic memory induced myocardial cell injury.%目的 探讨代谢记忆损伤心肌细胞的分子机制.方法 体外培养20只SD大鼠乳鼠心肌细胞,每组5只,分为4组:持续低糖组、持续高糖组、代谢记忆组和PDTC组.计算细胞凋亡指数,免疫组化检测核内NF-κB的表达,Western Blot检测NF-κB蛋白,TUNEL检测细胞凋亡.结果 代谢记忆组蛋白表达水平(15.12±2.32)和持续高糖组的(17.10±3.12)均较持续低糖组(5.23±2.13)的NF-κB核内蛋白水平显著升高(P<0.01),PDTC预处理后,NF-κB核内蛋白水平(7.12±2.41)较代谢记忆组(17.10±3.12)显著降低(P<0.05);同时,代谢记忆组(19

  8. Role of gut microbiota in maternal glucose metabolism

    Mao, Yushi; 毛雨詩

    2015-01-01

    Gut microbiota plays an important role in daily biological reactions. It is proved that many metabolic diseases are accompanied with pattern change of gut microbiota and pregnancy is also a process with gut microbiota remodeling. Besides, serum IGF-1 level is increased during pregnancy, but the source of increased IGF-1 remains unclear. So far, there is a paper that explored the gut microbiota in pregnant women. However, the diet of pregnant women was not unified in the study, which might hav...

  9. Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin

    2015-01-01

    Skeleton was considered as a dynamic connective tissue, which was essential for mobility, calcium homeostasis, and hematopoietic niche. However more and more evidences indicate that skeleton works not only as a structural scaffold but also as an endocrine organ, which regulates several metabolic processes. Besides osteoprotegerin (OPG), sclerostin (SOST), and Dickopf (DKK) which play essential roles in bone formation, modelling, remodelling, and homeostasis, bone can also secret hormones, suc...

  10. The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism in skeletal muscle

    Stöckli, Jacqueline; Meoli, Christopher C; Hoffman, Nolan J;

    2015-01-01

    Insulin and exercise stimulate glucose uptake into skeletal muscle via different pathways. Both stimuli converge on the translocation of the glucose transporter GLUT4 from intracellular vesicles to the cell surface. Two Rab guanosine triphosphatases-activating proteins (GAPs) have been implicated...... in this process: AS160 for insulin stimulation and its homolog, TBC1D1, are suggested to regulate exercise-mediated glucose uptake into muscle. TBC1D1 has also been implicated in obesity in humans and mice. We investigated the role of TBC1D1 in glucose metabolism by generating TBC1D1(-/-) mice and...... analyzing body weight, insulin action, and exercise. TBC1D1(-/-) mice showed normal glucose and insulin tolerance, with no difference in body weight compared with wild-type littermates. GLUT4 protein levels were reduced by ∼40% in white TBC1D1(-/-) muscle, and TBC1D1(-/-) mice showed impaired exercise...

  11. Osthole enhances glucose uptake through activation of AMP-activated protein kinase in skeletal muscle cells.

    Lee, Wei-Hwa; Lin, Ren-Jye; Lin, Shyr-Yi; Chen, Yu-Chien; Lin, Hsiu-Ming; Liang, Yu-Chih

    2011-12-28

    AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism. Activation of AMPK in skeletal muscles, the liver, and adipose tissues results in a favorable metabolic milieu for preventing and treating type 2 diabetes, i.e., decreased levels of circulating glucose, plasma lipids, and ectopic fat accumulation and enhanced insulin sensitivity. Osthole was extracted from a Chinese herbal medicine, and we found that it had glucose lowering activity in our previous study. However, the detailed glucose lowering mechanisms of osthole are still unclear. In this study, we used skeletal muscle cells to examine the underlying molecular mechanisms of osthole's glucose lowering activity. A Western blot analysis revealed that osthole significantly induced phosphorylation of AMPK and acetyl-CoA carboxylase (ACC). Next, we found that osthole significantly increased the level of translocation of glucose transporter 4 (GLUT4) to plasma membranes and glucose uptake in a dose-dependent manner. Osthole-induced glucose uptake was reversed by treatment with Compound C, an AMPK inhibitor, suggesting that osthole-induced glucose uptake was mediated in an AMPK-dependent manner. The increase in the AMP:ATP ratio was involved in osthole's activation of AMPK. Finally, we found that osthole counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that the increase in the AMP:ATP ratio by osthole triggered activation of the AMPK signaling pathway and led to increases in plasma membrane GLUT4 content and glucose uptake level. Therefore, osthole might have potential as an antidiabetic agent for treating diabetes. PMID:22098542

  12. Clinical significance of determination of serum leptin, insulin levels and blood sugar in pregnant women with glucose metabolism disturbances

    Objective: To investigate the changes of serum leptin, insulin levels and blood sugar contents in pregnant women with gestational glucose metabolism disturbances. Methods: Fasting and 3h after oral 50g glucose serum levels of leptin were measured with RIA in 36 pregnant women with glucose metabolism disturbances (gestational diabetes mellitus or gestational impaired glucose tolerance) and 34 controls. Also, fasting serum insulin levels (with CLIA) and blood sugar contents 1h after oral 50 glucose (with glucose oxidase method) were determined in all these subjects. Results: 1. Serum levels of leptin in pregnant women with glucose metabolism disturbances were 14.9 ± 4.3 μg/L (vs controls 9.8 ± 1.7 μg/L, P<0.01). 2. The serum levels of insulin and 1 h post - 50g glucose blood sugar contents in pregnant women with glucose metabolism disturbances were 12.9±4.3mU/L and 11.0±1.4mmol/L respectively, which were both significantly positively correlated with the serum leptin levels (r=0.835, r=0.758 respectively) (vs levels in controls: 8.45±3.0mU/L and 7.84±1.3mmol/L). Conclusion: Elevation of fasting serum levels of leptin was demonstrated in pregnant women with glucose metabolism disturbances and the level of leptin was positively correlated with that of insulin and blood sugar. (authors)

  13. Aerobic glucose metabolism of Saccharomyces kluyveri: Growth, metabolite production, and quantification of metabolic fluxes

    Møller, Kasper; Christensen, B.; Förster, Jochen;

    2002-01-01

    The growth and product formation of Saccharomyces kluyveri was characterized in aerobic batch cultivation on glucose. At these conditions it was found that ethyl acetate was a major overflow metabolite in S. kluyveri. During the exponential-growth phase on glucose ethyl acetate was produced at a ...

  14. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Amandine Girousse

    Full Text Available When energy is needed, white adipose tissue (WAT provides fatty acids (FAs for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.

  15. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity. PMID:23431266

  16. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

    Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C

    2016-08-25

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment. PMID:27509858

  17. Increased adiposity, dysregulated glucose metabolism and systemic inflammation in Galectin-3 KO mice.

    Jingbo Pang

    Full Text Available Obesity and type 2 diabetes are associated with increased production of Galectin-3 (Gal-3, a protein that modulates inflammation and clearance of glucose adducts. We used Lean and Diet-induced Obese (DIO WT and Gal-3 KO mice to investigate the role of Gal-3 in modulation of adiposity, glucose metabolism and inflammation. Deficiency of Gal-3 lead to age-dependent development of excess adiposity and systemic inflammation, as indicated by elevated production of acute-phase proteins, number of circulating pro-inflammatory Ly6C(high monocytes and development of neutrophilia, microcytic anemia and thrombocytosis in 20-week-old Lean and DIO male Gal-3 KO mice. This was associated with impaired fasting glucose, heightened response to a glucose tolerance test and reduced adipose tissue expression of adiponectin, Gal-12, ATGL and PPARγ, in the presence of maintained insulin sensitivity and hepatic expression of gluconeogenic enzymes in 20-week-old Gal-3 KO mice compared to their diet-matched WT controls. Expression of PGC-1α and FGF-21 in the liver of Lean Gal-3 KO mice was comparable to that observed in DIO animals. Impaired fasting glucose and altered responsiveness to a glucose load preceded development of excess adiposity and systemic inflammation, as demonstrated in 12-week-old Gal-3 KO mice. Finally, a role for the microflora in mediating the fasting hyperglycemia, but not the excessive response to a glucose load, of 12-week-old Gal-3 KO mice was demonstrated by administration of antibiotics. In conclusion, Gal-3 is an important modulator of glucose metabolism, adiposity and inflammation.

  18. Regional Cerebral Glucose Metabolism in Novelty Seeking and Antisocial Personality: A Positron Emission Tomography Study

    Park, So Hyeon; Park, Hyun Soo

    2016-01-01

    Novelty seeking (NS) and antisocial personality (ASP) are commonly exhibited by those who suffer from addictions, such as substance abuse. NS has been suggested to be a fundamental aspect of ASP. To investigate the neurobiological substrate of NS and ASP, we tested the relationship between regional cerebral glucose metabolism and the level of NS, determining the differences between individuals with and without ASP. Seventy-two healthy adults (43 males, mean age±SD=38.8±16.6 years, range=20~70 years; 29 females, 44.2±20.1 years, range=19~72 years) underwent resting-state brain positron emission tomography (PET) 40 minutes after 18F-fluorodeoxyglucose (FDG) injection. Within 10 days of the FDG PET study, participants completed Cloninger's 240-item Temperament and Character Inventory (TCI) to determine NS scores. Participants with and without ASP were grouped according to their TCI profiles. Statistical parametric mapping analysis was performed using the FDG PET and TCI profile data. NS scores positively correlated with metabolism in the left anterior cingulate gyrus and the insula on both sides of the brain and negatively correlated with metabolism in the right pallidum and putamen. Participants with ASP showed differences in cerebral glucose metabolism across various cortical and subcortical regions, mainly in the frontal and prefrontal areas. These data demonstrate altered regional cerebral glucose metabolism in individuals with NS and ASP and inform our understanding of the neurobiological substrates of problematic behaviors and personality disorders. PMID:27574485

  19. Deoxyglucose method for the estimation of local myocardial glucose metabolism with positron computed tomography

    The deoxyglucose method originally developed for measurements of the local cerebral metabolic rate for glucose has been investigated in terms of its application to studies of the heart with positron computed tomography (PCT) and FDG. Studies were performed in dogs to measure the tissue kinetics of FDG with PCT and by direct arterial-venous sampling. The operational equation developed in our laboratory as an extension of the Sokoloff model was used to analyze the data. The FDG method accurately predicted the true MMRGlc even when the glucose metabolic rate was normal but myocardial blood flow (MBF) was elevated 5 times the control value or when metabolism was reduced to 10% of normal and MBF increased 5 times normal. Improvements in PCT resolution are required to improve the accuracy of the estimates of the rate constants and the MMRGlc

  20. Cerebral blood flow, oxygen and glucose metabolism with PET in progressive supranuclear palsy

    Otsuka, Makoto; Ichiya, Yuici; Kuwabara, Yasuo (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine) (and others)

    1989-11-01

    Cerebral blood flow, cerebral oxygen metabolic rate and cerebral glucose metabolic rate were measured with positron emission tomography (PET) in four patients with progressive supranuclear palsy (PSP). Decreased blood flow and hypometabolism of oxygen and glucose were found in both subcortical and cortical regions, particularly in the striatum including the head of the caudate nucleus and the frontal cortex. The coupling between blood flow and metabolism was preserved even in the regions which showed decreased blood flow and hypometabolism. These findings indicated the hypofunction, as revealed by decreased blood flow and hypometablolism on PET, both in the striatum and the frontal cortex, and which may underlie the pathophysiological mechanism of motor and mental disturbance in PSP. (author).

  1. Cerebral oxygen and glucose metabolism and blood flow in mitochondrial encephalomyopathy: a PET study

    Cerebral blood flow (CBF), oxygen metabolism (CMRO2), and glucose metabolism (CMRGlc) were measured using positron emission tomography in five patients diagnosed as having mitochondrial encephalomyopathy. The molar ratio between the oxygen and glucose consumptions was reduced diffusely, as CMRO2 was markedly decreased and CMRGlc was slightly reduced. The CBF showed less changes. The CBF increase on hypercapnia was smaller than normal, though this was not significant. CBF with hypocapnia demonstrated a significant reduction compared with the normal. These results suggest that oxidative metabolism is impaired and anaerobic glycolysis relatively stimulated, due to a primary defect of mitochondrial function, and that mild lactic acidosis occurs in brain tissue because of impaired utilisation of pyruvate in the TCA cycle. As these findings appear to indicate directly a characteristic of this disease, such measurements may be a useful tool for assessment of the pathophysiology and for diagnosis of mitochondrial encephalomyopathy. (orig.). With 1 fig., 4 tabs

  2. Cerebral blood flow, oxygen and glucose metabolism with PET in progressive supranuclear palsy

    Cerebral blood flow, cerebral oxygen metabolic rate and cerebral glucose metabolic rate were measured with positron emission tomography (PET) in four patients with progressive supranuclear palsy (PSP). Decreased blood flow and hypometabolism of oxygen and glucose were found in both subcortical and cortical regions, particularly in the striatum including the head of the caudate nucleus and the frontal cortex. The coupling between blood flow and metabolism was preserved even in the regions which showed decreased blood flow and hypometabolism. These findings indicated the hypofunction, as revealed by decreased blood flow and hypometablolism on PET, both in the striatum and the frontal cortex, and which may underlie the pathophysiological mechanism of motor and mental disturbance in PSP. (author)

  3. Similarities of cerebral glucose metabolism in Alzheimer's and Parkinsonian dementia

    In the dementia of probable Alzheimer's Disease (AD), there is a decrease in the metabolic ratio of parietal cortex/caudate-thalamus which relates measures in the most and in the least severely affected locations. Since some demented patients with Parkinson's Disease (PDD) are known to share pathological and neurochemical features with AD patients, the authors evaluated if the distribution of cerebral hypometabolism in PDD and AD were the same. Local cerebral metabolic rates were determined using the FDG method and positron tomography in subjects with AD (N=23), and PDD (N=7), multiple infarct dementia (MID)(N=6), and controls (N=10). In MID, the mean par/caudthal ratio was normal (0.79 +- 0.9, N=6). In AD and PDD patients, this ratio correlated negatively with both the severity (r=-0.624, rho=0.001) and duration (r=-0.657, rho=0.001) of dementia. The ratio was markedly decreased in subjects with mild to severe dementia (0.46 +- 0.09, N=21) and with dementia duration greater than two years (0.44 +- 0.08, N=18), but the ratio was also significantly decreased in patients with less advanced disease, i.e., when dementia was only questionable (0.64 +- 0.14, N=9) (t=2.27, rho<0.037) and when duration was two years or less (0.62 +- 0.13, N=12)(t=2.88, rho<0.009). This similarity of hypometabolism in AD and PDD is additional evidence that a common mechanism may operate in both disorders. The par/caud-thal metabolic ratio may be an index useful in the differential diagnosis of early dementia

  4. Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α2-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2 > 1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation. - Highlights: • Air pollutants have been associated with increased diabetes in humans. • Acute ozone exposure produces profound metabolic alterations in rats. • Age influences metabolic risk factors in aging BN rats. • Acute metabolic effects are reversible and repeated exposure reduces these effects. • Ozone metabolic

  5. Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats

    Bass, V. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Gordon, C.J.; Jarema, K.A.; MacPhail, R.C. [Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Cascio, W.E. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Phillips, P.M. [Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Ledbetter, A.D.; Schladweiler, M.C. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Andrews, D. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Miller, D. [Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC (United States); Doerfler, D.L. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Kodavanti, U.P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2013-12-15

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α{sub 2}-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2 > 1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation. - Highlights: • Air pollutants have been associated with increased diabetes in humans. • Acute ozone exposure produces profound metabolic alterations in rats. • Age influences metabolic risk factors in aging BN rats. • Acute metabolic effects are reversible and repeated exposure reduces these effects. • Ozone

  6. Effect of polyphenols on glucose and lactate transport by breast cancer cells.

    Martel, F; Guedes, M; Keating, E

    2016-05-01

    One of the cancer molecular hallmarks is a deviant energetic metabolism, known as the Warburg effect, whereby the rate of glucose uptake is significantly increased and a high rate of glycolysis and lactic acid production occurs even when oxygen is present-"aerobic lactatogenesis". Accordingly, GLUT1 and MCT1, which are the main glucose and lactate transporters in cancer cells, respectively, have been proposed as oncogenes and are currently seen as potential therapeutic targets in cancer treatment. Polyphenols, commonly contained in fruits and vegetables, have long been associated with a protective role against cancer. Generally considered as nontoxic, dietary polyphenols are considered ideal chemopreventive and possibly chemotherapeutic agents. Several mechanisms of action of polyphenols in breast cancer cells have been proposed including modulation of intracellular signaling, induction of apoptosis through redox regulation or modulation of epigenetic alterations. Additionally, in vitro studies have shown that several polyphenols act as specific inhibitors of glucose transport in breast cancer cell lines and an association between their anticarcinogenic effect and inhibition of glucose cellular uptake has been described. Also, some polyphenols were found to inhibit lactate transport. Importantly, some polyphenols behave as inhibitors of both glucose and lactate cellular uptake by breast cancer cells and these compounds are thus very interesting in the context of a chemopreventive effect, because they deplete breast cancer cells of their two most important energy suppliers. So, the antimetabolic effect of polyphenols should be regarded as a mechanism of action contributing to their chemopreventive/chemotherapeutic potential in relation to breast cancer. PMID:27097608

  7. Factor analysis of regional cerebral glucose metabolic rates in healthy men

    Cerebral glucose utilization measured with fluorine-18-fluoro-2-deoxy-D-glucose is characterized by considerable variability both among different persons and for the same person examined on different occasions. The goal of this study was to explore whether some regions of the brain were more variable than others with respect to glucose utilization and whether there was a pattern in their covariance. The global and regional cerebral utilization of glucose was measured in 12 healthy young volunteers on 3 or 4 occasions. In all, 24 regions were examined. The interrelation of the glucose utilization rates of the brain regions was investigated by factor analysis of the metabolic rates. Some 70% of the total variance was attributable to only 1 factor, while 80% of the total variance could be attributed to 2 factors. Regions making up the first factor were the frontal and temporal cortex, cingulate gyrus, caudate nucleus, thalamus and putamen. These regions are functionally related to the limbic system. Regions of the second factor were the parietal cortex, occipital cortex and cerebellum, regions more clearly related to sensory and motor functions. The 2-factor pattern was highly reproducible, being found with different algorithms for factor extraction and rotation. Under resting conditions, the variance of cerebral metabolism seems to be primarily related to regions which are closely involved with the limbic system. Cortical regions involved primarily in motor and sensory functions have less influence on the variance. (orig.)

  8. Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress.

    Zaugg, Kathrin; Yao, Yi; Reilly, Patrick T; Kannan, Karuppiah; Kiarash, Reza; Mason, Jacqueline; Huang, Ping; Sawyer, Suzanne K; Fuerth, Benjamin; Faubert, Brandon; Kalliomäki, Tuula; Elia, Andrew; Luo, Xunyi; Nadeem, Vincent; Bungard, David; Yalavarthi, Sireesha; Growney, Joseph D; Wakeham, Andrew; Moolani, Yasmin; Silvester, Jennifer; Ten, Annick You; Bakker, Walbert; Tsuchihara, Katsuya; Berger, Shelley L; Hill, Richard P; Jones, Russell G; Tsao, Ming; Robinson, Murray O; Thompson, Craig B; Pan, Guohua; Mak, Tak W

    2011-05-15

    Tumor cells gain a survival/growth advantage by adapting their metabolism to respond to environmental stress, a process known as metabolic transformation. The best-known aspect of metabolic transformation is the Warburg effect, whereby cancer cells up-regulate glycolysis under aerobic conditions. However, other mechanisms mediating metabolic transformation remain undefined. Here we report that carnitine palmitoyltransferase 1C (CPT1C), a brain-specific metabolic enzyme, may participate in metabolic transformation. CPT1C expression correlates inversely with mammalian target of rapamycin (mTOR) pathway activation, contributes to rapamycin resistance in murine primary tumors, and is frequently up-regulated in human lung tumors. Tumor cells constitutively expressing CPT1C show increased fatty acid (FA) oxidation, ATP production, and resistance to glucose deprivation or hypoxia. Conversely, cancer cells lacking CPT1C produce less ATP and are more sensitive to metabolic stress. CPT1C depletion via siRNA suppresses xenograft tumor growth and metformin responsiveness in vivo. CPT1C can be induced by hypoxia or glucose deprivation and is regulated by AMPKα. Cpt1c-deficient murine embryonic stem (ES) cells show sensitivity to hypoxia and glucose deprivation and altered FA homeostasis. Our results indicate that cells can use a novel mechanism involving CPT1C and FA metabolism to protect against metabolic stress. CPT1C may thus be a new therapeutic target for the treatment of hypoxic tumors. PMID:21576264

  9. Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions

    Lin, Shu-Hai; Liu, Tengfei; Ming, Xiaoyan; Tang, Zhi; Fu, Li; Schmitt-Kopplin, Philippe; Kanawati, Basem; Guan, Xin-Yuan; Cai, Zongwei

    2016-02-01

    Cancer was hypothesized to be driven by cancer stem cells (CSCs), but the metabolic determinants of CSC-like phenotype still remain elusive. Here, we present that hexosamine biosynthetic pathway (HBP) at least in part rescues cancer cell fate with inactivation of glycolysis. Firstly, metabolomic analysis profiled cellular metabolome in CSCs of hepatocellular carcinoma using CD133 cell-surface marker. The metabolic signatures of CD133-positive subpopulation compared to CD133-negative cells highlighted HBP as one of the distinct metabolic pathways, prompting us to uncover the role of HBP in maintenance of CSC-like phenotype. To address this, CSC-like phenotypes and cell survival were investigated in cancer cells under low glucose conditions. As a result, HBP inhibitor azaserine reduced CD133-positive subpopulation and CD133 expression under high glucose condition. Furthermore, treatment of N-Acetylglucosamine in part restores CD133-positive subpopulation when either 2.5 mM glucose in culture media or glycolytic inhibitor 2-deoxy-D-glucose in HCC cell lines was applied, enhancing CD133 expression as well as promoting cancer cell survival. Together, HBP might be a key metabolic determinant in the functions of hepatic CSC marker CD133.

  10. High glucose-mediated oxidative stress impairs cell migration.

    Marcelo L Lamers

    Full Text Available Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit cell migration. Using CHO.K1 cells, NIH-3T3 fibroblasts, mouse embryonic fibroblasts and primary skin fibroblasts from control and diabetic rats cultured in 5 mM D-glucose (low glucose, LG, 25 mM D-glucose (high glucose, HG or 25 mM L-glucose medium (osmotic control--OC, we analyzed the migration speed, protrusion stability, cell polarity, adhesion maturation and the activity of the small Rho GTPase Rac1. We also analyzed the effects of reactive oxygen species by incubating cells with the antioxidant N-Acetyl-Cysteine (NAC. We observed that HG conditions inhibited cell migration when compared to LG or OC. This inhibition resulted from impaired cell polarity, protrusion destabilization and inhibition of adhesion maturation. Conversely, Rac1 activity, which promotes protrusion and blocks adhesion maturation, was increased in HG conditions, thus providing a mechanistic basis for the HG phenotype. Most of the HG effects were partially or completely rescued by treatment with NAC. These findings demonstrate that HG impairs cell migration due to an increase in oxidative stress that causes polarity loss, deficient adhesion and protrusion. These alterations arise, in large part, from increased Rac1 activity and may contribute to the poor wound healing observed in diabetic patients.

  11. Hyperglycemia and anthocyanin inhibit quercetin metabolism in HepG2 cells

    A high glucose (Glu) milieu promotes generation of reactive oxygen species, which may not only cause cellular damage, but also modulate phase II enzymes that are responsible for the metabolism of flavonoids. Thus, we examined the effect of a high Glu milieu on quercetin (Q) metabolism in HepG2 cells...

  12. Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

    Picco, Agnese; Ferrara, Michela; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio [University of Genoa and IRCCS San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Largo P. Daneo, 3, 16132, Genoa (Italy); Polidori, M.C. [University of Cologne, Institute of Geriatrics, Cologne (Germany); Cecchetti, Roberta; Baglioni, Mauro; Bastiani, Patrizia; Mecocci, Patrizia [University of Perugia, Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, Perugia (Italy); Morbelli, Silvia; Bossert, Irene [University of Genoa and IRCCS San Martino-IST, Nuclear Medicine, Department of Health Science (DISSAL), Genoa (Italy); Fiorucci, Giuliana; Dottorini, Massimo Eugenio [Nuclear Medicine, S. M. della Misericordia Hospital, Perugia (Italy)

    2014-04-15

    The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain{sup 18}F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

  13. Diabetes, glucose metabolism, and glaucoma: the 2005-2008 National Health and Nutrition Examination Survey.

    Di Zhao

    Full Text Available BACKGROUND: Diabetes may affect vascular autoregulation of the retina and optic nerve and may be associated with an increased risk of glaucoma,but the association of prediabetes, insulin resistance, markers of glucose metabolismwith glaucoma has not beenevaluated in general population samples. OBJECTIVE: To examine the relation between diabetes, pre-diabetes, metabolic syndrome and its components and the levels of fasting glucose, HbA1c and HOMA-IR with the prevalence of glaucoma in the general U.S. population. METHODS: Cross-sectional study of 3,299 adult men and women from the 2005-2008 National Health and NutritionExamination Survey (NHANES. The presence of diabetes, prediabetes, the metabolic syndrome and its individual components and biomarkers of glucose metabolisms were based on standardized questionnaire and physical exam data and laboratory tests. The history of glaucoma was assessed through questionnaire during the home interview. RESULTS: Diabetes was strongly associated with prevalent glaucoma.In fully adjusted models, the odds ratiofor glaucoma comparing participants with diabetes with participants in the reference group with neither pre-diabetes nor diabetes was 2.12 (95% CI: 1.23, 3.67. The corresponding odd ratio comparing participants with pre-diabetes to those in the reference group was 1.01 (95% CI: 0.57, 1.82. Patients with 5 or more years of diabetes duration hadan OR for glaucoma of 3.90 (95% CI: 1.63, 9.32 compared with patients with <5 years of diabetes duration. We also found a hockey-stick shaped associations between biomarkers of glucose metabolisms and the prevalence of glaucoma. CONCLUSIONS: Diabetes was associated with higher risk of glaucoma. Participants without diabetes but at the higher levels of fasting glucose, fasting insulin, HbA1c and HOMA-IR spectrum may also be at greater risk of glaucoma.

  14. Effect of peripheral 5-HT on glucose and lipid metabolism in wether sheep.

    Hitoshi Watanabe

    Full Text Available In mice, peripheral 5-HT induces an increase in the plasma concentrations of glucose, insulin and bile acids, and a decrease in plasma triglyceride, NEFA and cholesterol concentrations. However, given the unique characteristics of the metabolism of ruminants relative to monogastric animals, the physiological role of peripheral 5-HT on glucose and lipid metabolism in sheep remains to be established. Therefore, in this study, we investigated the effect of 5-HT on the circulating concentrations of metabolites and insulin using five 5-HT receptor (5HTR antagonists in sheep. After fasting for 24 h, sheep were intravenously injected with 5-HT, following which-, plasma glucose, insulin, triglyceride and NEFA concentrations were significantly elevated. In contrast, 5-HT did not affect the plasma cholesterol concentration, and it induced a decrease in bile acid concentrations. Increases in plasma glucose and insulin concentrations induced by 5-HT were attenuated by pre-treatment with Methysergide, a 5HTR 1, 2 and 7 antagonist. Additionally, decreased plasma bile acid concentrations induced by 5-HT were blocked by pre-treatment with Ketanserin, a 5HTR 2A antagonist. However, none of the 5HTR antagonists inhibited the increase in plasma triglyceride and NEFA levels induced by 5-HT. On the other hand, mRNA expressions of 5HTR1D and 1E were observed in the liver, pancreas and skeletal muscle. These results suggest that there are a number of differences in the physiological functions of peripheral 5-HT with respect to lipid metabolism between mice and sheep, though its effect on glucose metabolism appears to be similar between these species.

  15. Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

    The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain18F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

  16. Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One–Carbon Cycle Energy Producing Pathway

    Vijayalakshmi Varma

    2015-06-01

    Full Text Available Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructose added to a medium containing 5 mM of glucose representing the normal blood glucose concentration. Targeted tracer [1,2-13C2]-d-glucose fate association approach was employed to examine the influence of fructose on the intermediary metabolism of glucose. Increasing concentrations of fructose robustly increased the oxidation of [1,2-13C2]-d-glucose to 13CO2 (p < 0.000001. However, glucose-derived 13CO2 negatively correlated with 13C labeled glutamate, 13C palmitate, and M+1 labeled lactate. These are strong markers of limited tricarboxylic acid (TCA cycle, fatty acid synthesis, pentose cycle fluxes, substrate turnover and NAD+/NADP+ or ATP production from glucose via complete oxidation, indicating diminished mitochondrial energy metabolism. Contrarily, a positive correlation was observed between glucose-derived 13CO2 formed and 13C oleate and doses of fructose which indicate the elongation and desaturation of palmitate to oleate for storage. Collectively, these results suggest that fructose preferentially drives glucose through serine oxidation glycine cleavage (SOGC pathway one-carbon cycle for NAD+/NADP+ production that is utilized in fructose-induced lipogenesis and storage in adipocytes.

  17. Melphalan metabolism in cultured cells

    Procedures are presented for the adaptation of reversed-phase-HPLC methods to accomplish separation and isolation of the cancer therapeutic drug melphalan (L-phenylalanine mustard) and its metabolic products from whole cells. Five major degradation products of melphalan were observed following its hydrolysis in phosphate buffer in vitro. The two most polar of these products (or modifications of them) were also found in the cytosol of Chinese hamster CHO cells. The amounts of these two polar products (shown not to be mono- or dihydroxymelphalan) were significantly changed by the pretreatment of cells with ZnC12, one being increased in amount while the other was reduced to an insignificant level. In ZnC12-treated cells, there was also an increased binding of melphalan (or its derivatives) to one protein fraction resolved by gel filtration-HPLC. These observations suggest that changes in polar melphalan products, and perhaps their interaction with a protein, may by involved in the reduction of melphalan cytotoxicity observed in ZnC12-treated cells. While ZnC12 is also known to increase the level of glutathione in cells, no significant amounts of glutathione-melphalan derivatives of the type formed non-enzymatically in vitro could be detected in ZnC12-treated or untreated cells. Formation of derivatives of melphalan with glutathione catabolic products in ZnC12-treated cells has not yet been eliminated, however. 17 refs., 5 figs., 1 tab

  18. Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function

    Sukumar, Madhusudhanan; Liu, Jie; Ji, Yun; Subramanian, Murugan; Crompton, Joseph G.; Yu, Zhiya; Roychoudhuri, Rahul; Palmer, Douglas C.; Muranski, Pawel; Karoly, Edward D.; Mohney, Robert P.; Klebanoff, Christopher A.; Lal, Ashish; Finkel, Toren; Restifo, Nicholas P.; Gattinoni, Luca

    2013-01-01

    Naive CD8+ T cells rely upon oxidation of fatty acids as a primary source of energy. After antigen encounter, T cells shift to a glycolytic metabolism to sustain effector function. It is unclear, however, whether changes in glucose metabolism ultimately influence the ability of activated T cells to become long-lived memory cells. We used a fluorescent glucose analog, 2-NBDG, to quantify glucose uptake in activated CD8+ T cells. We found that cells exhibiting limited glucose incorporation had a molecular profile characteristic of memory precursor cells and an increased capacity to enter the memory pool compared with cells taking up high amounts of glucose. Accordingly, enforcing glycolytic metabolism by overexpressing the glycolytic enzyme phosphoglycerate mutase-1 severely impaired the ability of CD8+ T cells to form long-term memory. Conversely, activation of CD8+ T cells in the presence of an inhibitor of glycolysis, 2-deoxyglucose, enhanced the generation of memory cells and antitumor functionality. Our data indicate that augmenting glycolytic flux drives CD8+ T cells toward a terminally differentiated state, while its inhibition preserves the formation of long-lived memory CD8+ T cells. These results have important implications for improving the efficacy of T cell–based therapies against chronic infectious diseases and cancer. PMID:24091329

  19. Insulin sensitizes FGF21 in glucose and lipid metabolisms via activating common AKT pathway.

    Yu, Dan; Ye, Xianlong; Wu, Qiang; Li, Shujie; Yang, Yongbi; He, Jinjiao; Liu, Yunye; Zhang, Xiaoyu; Yuan, Qingyan; Liu, Mingyao; Li, Deshan; Ren, Guiping

    2016-06-01

    Previous studies reveal that fibroblast growth factor 21 (FGF21) sensitizes insulin to achieve a synergy in regulating glucose metabolism. Here, we report that insulin sensitizes FGF21 in regulating both glucose and lipid metabolisms. db/db diabetic mice were subcutaneously administrated once a day for 6 weeks. Effective dose of insulin (1 U) could control blood glucose level of the db/db mice for maximum of 2 h, increased the body weight of the db/db mice and did not improve serum lipid parameters. In contrast, effective dose of FGF21 (0.5 mg/kg) could maintain blood glucose of the db/db mice at normal level for at least 24 h, repressed the weight gain of the mice and significantly improved lipid parameters. Ineffective doses of FGF21 (0.125 mg/kg) and insulin had no effect on blood glucose level of the db/db mice after 24 h administration, body weight or lipid parameters. However, combination of the two ineffective doses could maintain blood glucose level of the db/db mice for at least 24 h, suppressed weight gain and significantly improved lipid parameters. These results suggest that insulin sensitizes FGF21 in regulating both glucose and lipid metabolism. The results aimed to study the molecular basis of FGF21 sensitization indicates that combination of the two ineffective doses increased the mRNA expression of glut1, glut4, β-Klotho, sirt1, pgc-1α, ucp-1 and AKT phosphorylation, decreased fasn. The results demonstrate that insulin sensitizes FGF21 through elevating the phosphorylation of common gene Akt and amplifying FGF21 downstream signaling, including increasing expression of glut1 sirt1, pgc-1α, ucp-1, and decreasing fasn expression. In summary, we reports herein for the first time that insulin sensitizes FGF21 to achieve a synergy in regulating glucose and lipid metabolism. Along with previous studies, we conclude that the synergistic effect between FGF21 and insulin is realized through mutual sensitization. PMID:26607153

  20. Cereal Processing Influences Postprandial Glucose Metabolism as Well as the GI Effect

    Vinoy, Sophie; Normand, Sylvie; Meynier, Alexandra; Sothier, Monique; Louche-Pelissier, Corinne; Peyrat, Jocelyne; Maitrepierre, Christine; Nazare, Julie-Anne; Brand-Miller, Jeannie; Laville, Martine

    2015-01-01

    Objective: Technological processes may influence the release of glucose in starch. The aim of this study was to compare the metabolic response and the kinetics of appearance of exogenous glucose from 2 cereal products consumed at breakfast. Methods: Twenty-five healthy men were submitted to a randomized, open, crossover study that was divided into 2 parts: 12 of the 25 subjects were included in the “isotope part,” and the 13 other subjects were included in the “glycemic part.” On test days, s...

  1. Effect of abomasal glucose infusion on splanchnic amino acid metabolism in periparturient dairy cows

    Larsen, Mogens; Kristensen, Niels Bastian

    2009-01-01

    Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic AA metabolism. The experimental design was a split plot, with cow as the whole...... plot, treatment as the whole-plot factor and days in milk (DIM) as the subplot factor. Cows were assigned to 1 of 2 treatments: control or infusion of 1,500 g/d of glucose into the abomasum from the day of calving to 29 DIM....

  2. Hormone and glucose metabolic effects of compound cyproterone acetate in women with polycystic ovarian syndrome

    To investigate the clinical efficacy of compound cyproterone acetate(CPY) in the treatment of polycystic ovarian syndrome(PCOS) and study hormone and glucose metabolic effects, thirty-five PCOS patients were treated by compound cyproterone acetate for 3 cycles. The serum LH, FSH and T levels, fasting glucose and fasting insulin were determined before and after 3 cycle's treatment. The results showed that 34 patients had regular menses during CPY therapy. The hirsute and acne score decreased significantly(P0.05). The results indicate that the compound cyproterone acetate had anti-androgenic effects on PCOS patients and improved their endocrine function and clinical syndrome. (authors)

  3. Regulation of. beta. -cell glucose transporter gene expression

    Chen, Ling; Alam, Tausif; Johnson, J.H.; Unger, R.H. (Univ. of Texas Southwestern Medical Center, Dallas (USA) Department of Veterans Affairs Medical Center, Dallas, TX (USA)); Hughes, S.; Newgard, C.B. (Univ. of Texas Southwestern Medical Center, Dallas (USA))

    1990-06-01

    It has been postulated that a glucose transporter of {beta} cells (GLUT-2) may be important in glucose-stimulated insulin secretion. To determine whether this transporter is constitutively expressed or regulated, the authors subjected conscious unrestrained Wistar rats to perturbations in glucose homeostasis and quantitated {beta}-cell GLUT-2 mRNA by in situ hybridization. After 3 hr of hypoglycemia, GLUT-2 and proinsulin mRNA signal densities were reduced by 25% of the level in control rats. After 4 days, GLUT-2 and proinsulin mRNA densities were reduced by 85% and 65%, respectively. After 12 days of hypoglycemia, the K{sub m} for 3-O-methyl-D-glucose transport in isolated rat islets, normally 18-20 mM, was 2.5 mM. This provides functional evidence of a profound reduction of high K{sub m} glucose transporter in {beta} cells. In contrast, GLUT-2 was only slightly reduced by hypoglycemia in liver. To determine the effect of prolonged hyperglycemia, they also infused animals with 50% (wt/vol) glucose for 5 days. Hyperglycemic clamping increased GLUT-2 mRNA by 46% whereas proinsulin mRNA doubled. They conclude that GLUT-2 expression in {beta} cells, but not liver, is subject to regulation by certain perturbations in blood glucose homeostasis.

  4. Regulation of β-cell glucose transporter gene expression

    It has been postulated that a glucose transporter of β cells (GLUT-2) may be important in glucose-stimulated insulin secretion. To determine whether this transporter is constitutively expressed or regulated, the authors subjected conscious unrestrained Wistar rats to perturbations in glucose homeostasis and quantitated β-cell GLUT-2 mRNA by in situ hybridization. After 3 hr of hypoglycemia, GLUT-2 and proinsulin mRNA signal densities were reduced by 25% of the level in control rats. After 4 days, GLUT-2 and proinsulin mRNA densities were reduced by 85% and 65%, respectively. After 12 days of hypoglycemia, the Km for 3-O-methyl-D-glucose transport in isolated rat islets, normally 18-20 mM, was 2.5 mM. This provides functional evidence of a profound reduction of high Km glucose transporter in β cells. In contrast, GLUT-2 was only slightly reduced by hypoglycemia in liver. To determine the effect of prolonged hyperglycemia, they also infused animals with 50% (wt/vol) glucose for 5 days. Hyperglycemic clamping increased GLUT-2 mRNA by 46% whereas proinsulin mRNA doubled. They conclude that GLUT-2 expression in β cells, but not liver, is subject to regulation by certain perturbations in blood glucose homeostasis

  5. Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism.

    Molehin, Deborah; Dekker Nitert, Marloes; Richard, Kerry

    2016-01-01

    Background. Thyroid hormones (THs) are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs) are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers. PMID:26989557

  6. Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients.

    Stender, Johan; Kupers, Ron; Rodell, Anders; Thibaut, Aurore; Chatelle, Camille; Bruno, Marie-Aurélie; Gejl, Michael; Bernard, Claire; Hustinx, Roland; Laureys, Steven; Gjedde, Albert

    2015-01-01

    The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients. PMID:25294128

  7. Visceral adiposity influences glucose and glycogen metabolism in control and hyperlipidic-fed animals

    Danielle Kaiser de Souza

    2013-04-01

    Full Text Available Introduction: Evidences suggest that fat intake, visceral obesity and intracellular lipids are related to insulin impairment. Objective: The objective of the present paper was correlate visceral obesity and metabolic alterations in control (CTR and hyperlipidic cafeteria diet (CFT fed animals. Methods: After 6 months of diet treatment, liver and muscle of the male rats were utilized to determined glucose uptake and glycogen metabolism after administration of 0.4I U/kg insulin in vivo, and correlate the visceral adiposity to these two parameters. Results: Ample range of physiologic answers to body composition in metabolic profile of the both diets was found. No differences were found in glycemia and triacylglycerol after insulin action in both groups, however CFT group accumulated higher adiposity, mostly visceral fat, and showed lower glycogen content in the liver. We also found an inverse correlation between visceral adiposity and glucose uptake and a decrease of the glycogen synthase active form in the liver. CTR animals demonstrated an inverse correlation between glucose uptake and visceral adiposity in the muscle. Discussion and conclusion: It was observed a variability of metabolic alterations in animals which can be related to degree of accumulation of abdominal adiposity and ingestion of diet fats. Further studies will be required to clarify the reasons for the observed liver alterations in CFT and muscle alterations in CTR animals.

  8. Effects of 5 Thio-D-Glucose on cellular adenosine triphosphate levels and deoxyribonucleic acid rejoining in hypoxic and aerobic Chinese hamster cells

    Intracellular adenosine triphosphate (ATP) levels were measured in both hypoxic and aerobic cultures of V79 Chinese hamster cells treated with 5-thio-D-glucose (5-SH-D-Glc). This glucose analog, a known inhibitor of D-glucose transport and metabolism, reduced ATP in cell cultures allowed to become hypoxic by cell metabolism, but not in aerobic cultures treated similarly. Cells depleted of ATP were unable to rejoin x-ray induced deoxyribonucleic acid (DNA) strand breaks as measured by the alkaline sucrose gradient sedimentation technique. The inference for radiation therapy is that inhibition of glucose metabolism selectively depletes energy reserves in hypoxic cells, rendering these cells more radiosensitive and leading to a more effective tumor treatment

  9. Involvement of senescence marker protein-30 in glucose metabolism disorder and non-alcoholic fatty liver disease.

    Kondo, Yoshitaka; Ishigami, Akihito

    2016-03-01

    Senescence marker protein-30 (SMP30) was found to decrease in the liver, kidneys and lungs of mice during aging. SMP30 is a pleiotropic protein that acts to protect cells from apoptosis by enhancing plasma membrane Ca(2+) -pump activity and is bona fide gluconolactonase (EC 3.1.1.17) that participates in the penultimate step of the vitamin C biosynthetic pathway. For the past several years, we have obtained strong evidence showing the close relationship between SMP30, glucose metabolism disorder and non-alchoholic fatty liver disease in experiments with SMP30 knockout mice. Emerging proof links the following abnormalities: (i) the reduction of SMP30 by aging and/or excessive dietary fat or genetic deficiency causes a loss of Ca(2+) pumping activity, which impairs acute insulin release in pancreatic β-cells, initiates inflammatory responses with oxidative stress and endoplasmic reticulum stress in non-alchoholic steatohepatitis, exacerbates renal tubule damage, and introduces tubulointerstitial inflammation and fibrosis in diabetic nephropathy; (ii) vitamin C insufficiency also impairs acute insulin secretion in pancreatic β-cells by a mechanism distinct from that of the SMP30 deficiency; and (iii) the increased oxidative stress by concomitant deficiencies of SMP30, superoxide dismutase 1 and vitamin C similarly causes hepatic steatosis. Here, we review recent advances in our understanding of SMP30 in glucose metabolism disorder and non-alchoholic fatty liver disease. PMID:27018279

  10. Assessment of incretins in oral glucose and lipid tolerance tests may be indicative in the diagnosis of metabolic syndrome aggravation.

    Kiec-Klimczak, M; Malczewska-Malec, M; Razny, U; Zdzienicka, A; Gruca, A; Goralska, J; Pach, D; Gilis-Januszewska, A; Dembinska-Kiec, A; Hubalewska-Dydejczyk, A

    2016-04-01

    Incretins stimulated by oral meals are claimed to be protective for the pancreatic beta cells, to increase insulin secretion, to inhibit glucagon release, slow gastric emptying (glucagon-like peptide-1) and suppress appetite. Recently it has however been suggested that glucagon-like peptide-1 (GLP-1) is putative early biomarker of metabolic consequences of the obesity associated proinflammatory state. The study was aimed to compare the release of incretins and some of early markers of inflammation at the fasting and postprandial period induced by functional oral glucose as well as lipid load in healthy controls and patients with metabolic syndrome (MS) to see if functional tests may be helpful in searching for the inflammatory status of patients. Fifty patients with MS and 20 healthy volunteers (C) participated in this study. The 3-hour oral glucose (OGTT) and the 8-hour oral lipid (OLTT) tolerance tests were performed. At fasting leptin and adiponectin, as well as every 30 minutes of OGTT and every 2 hours of OLTT blood concentration of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, insulin, triglycerides, free fatty acids, glutathione peroxidase, interleukin-6, sE-selectin, monocyte chemoattractant protein-1 (MCP1) and visfatin were measured. At fasting and during both OGTT and OLTT the level of incretins did not differ between the MS and the C group. Both glucose and lipids reach food activated incretins secretion. Glucose was the main GLP-1 release activator, while the lipid load activated evidently GIP secretion. A significantly larger AUC-GIP after the lipid-rich meal over the carbohydrate meal was observed, while statistically bigger value of AUC-GLP-1 was noticed in OGTT than in OLTT (P fasting plasma GIP concentration (3(rd) tertile), IL-6, MCP-1, sE-selectin and visfatin blood levels were increased and correlated with glutathione peroxydase, leptin/adiponectin ratio, higher visfatin and interleukin-6 levels. The fat containing meals

  11. Enhanced muscle glucose metabolism after exercise in the rat: the two phases.

    Garetto, L P; Richter, E A; Goodman, M N; Ruderman, N B

    1984-06-01

    Thirty minutes after a treadmill run, glucose utilization and glycogen synthesis in perfused rat skeletal muscle are enhanced due to an increase in insulin sensitivity (Richter et al., J. Clin. Invest. 69: 785-793, 1982). The exercise used in these studies was of moderate intensity, and muscle glycogen was substantially repleted at the time (30 min postexercise) that glucose metabolism was examined. When rats were run at twice the previous rate (36 m/min), muscle glycogen was still substantially diminished 30 min after the run. At this time the previously noted increase in insulin sensitivity was still observed in perfused muscle; however, glucose utilization was also increased in the absence of added insulin (1.5 vs. 4.2 mumol X g-1 X h-1). In contrast 2.5 h after the run, muscle glycogen had returned to near preexercise values, and only the insulin-induced increase in glucose utilization was evident. The data suggest that the restoration of muscle glycogen after exercise occurs in two phases. In phase I, muscle glycogen is depleted and insulin-stimulated glucose utilization and glucose utilization in the absence of added insulin may both be enhanced. In phase II glycogen levels have returned to near base-line values and only the increase in insulin sensitivity persists. It is proposed that phase I corresponds to the period of rapid glycogen repletion that immediately follows exercise and phase II to the period of supercompensation. PMID:6377909

  12. Protective Pleiotropic Effect of Flavonoids on NAD + Levels in Endothelial Cells Exposed to High Glucose

    Boesten, Daniëlle M. P. H. J.; von Ungern-Sternberg, Saskia N. I.; den Hartog, Gertjan J. M.; Aalt Bast

    2015-01-01

    NAD+ is important for oxidative metabolism by serving as an electron transporter. Hyperglycemia decreases NAD+ levels by activation of the polyol pathway and by overactivation of poly(ADP-ribose)-polymerase (PARP). We examined the protective role of three structurally related flavonoids (rutin, quercetin, and flavone) during high glucose conditions in an in vitro model using human umbilical vein endothelial cells (HUVECs). Additionally we assessed the ability of these flavonoids to inhibit al...

  13. Inhibition of glucose turnover by 3-bromopyruvate counteracts pancreatic cancer stem cell features and sensitizes cells to gemcitabine.

    Isayev, Orkhan; Rausch, Vanessa; Bauer, Nathalie; Liu, Li; Fan, Pei; Zhang, Yiyao; Gladkich, Jury; Nwaeburu, Clifford C; Mattern, Jürgen; Mollenhauer, Martin; Rückert, Felix; Zach, Sebastian; Haberkorn, Uwe; Gross, Wolfgang; Schönsiegel, Frank; Bazhin, Alexandr V; Herr, Ingrid

    2014-07-15

    According to the cancer stem cell (CSC) hypothesis, the aggressive growth and early metastasis of pancreatic ductal adenocarcinoma (PDA) is due to the activity of CSCs, which are not targeted by current therapies. Otto Warburg suggested that the growth of cancer cells is driven by a high glucose metabolism. Here, we investigated whether glycolysis inhibition targets CSCs and thus may enhance therapeutic efficacy. Four established and 3 primary PDA cell lines, non-malignant cells, and 3 patient-tumor-derived CSC-enriched spheroidal cultures were analyzed by glucose turnover measurements, MTT and ATP assays, flow cytometry of ALDH1 activity and annexin positivity, colony and spheroid formation, western blotting, electrophoretic mobility shift assay, xenotransplantation, and immunohistochemistry. The effect of siRNA-mediated inhibition of LDH-A and LDH-B was also investigated. The PDA cells exhibited a high glucose metabolism, and glucose withdrawal or LDH inhibition by siRNA prevented growth and colony formation. Treatment with the anti-glycolytic agent 3-bromopyruvate almost completely blocked cell viability, self-renewal potential, NF-κB binding activity, and stem cell-related signaling and reverted gemcitabine resistance. 3-bromopyruvate was less effective in weakly malignant PDA cells and did not affect non-malignant cells, predicting minimal side effects. 3-bromopyruvate inhibited in vivo tumor engraftment and growth on chicken eggs and mice and enhanced the efficacy of gemcitabine by influencing the expression of markers of proliferation, apoptosis, self-renewal, and metastasis. Most importantly, primary CSC-enriched spheroidal cultures were eliminated by 3-bromopyruvate. These findings propose that CSCs may be specifically dependent on a high glucose turnover and suggest 3-bromopyruvate for therapeutic intervention. PMID:25015789

  14. Amperometric biosensor with nanostructured electrodes by using multi-alled carbon nanotubes for glucose detection in cell culture medium

    Boero, Cristina; Carrara, Sandro; De Micheli, Giovanni

    2009-01-01

    The monitoring of metabolic compounds such as glucose is largely reported in literature. The applications of this type of analysis are mainly related to clinical purposes, e.g. in diabetes pathology, where a lot of studies are presented in literature. Recently, some authors presented studies about glucose and lactate detection in cell culture monitoring [1], [2]. A clear identification of medium compounds could be interesting for biologists and biotechnologists, since they may be identified a...

  15. Changes in metabolism during a fasting period and a subsequent vegetarian diet with particular reference to glucose metabolism.

    Lithell, H; Vessby, B; Hellsing, K; Ljunghall, K; Höglund, N J; Werner, I; Bruce, A

    1983-01-01

    During an investigation on the effect of fasting and a vegetarian diet on the symptoms and signs in chronic cutaneous and arthritic diseases studies were made of glucose metabolism, liver function and the plasma concentration and urine excretion of some minerals. The study was performed on 27 patients who stayed as in-patients on a metabolic ward for five weeks. After the fasting period the blood glucose and serum insulin concentrations were lower (p less than 0.01) than before the fast. At the end of the period on the vegetarian (vegan) diet (three weeks) the insulin/glucose ratio was lower than at the start of the fast. Serum enzyme concentrations reflecting liver function increased during the fast, but normalized during the vegan diet. The intake of vitamin B12 and of selenium due to the vegan diets was very low, which may give reason for some concern during long-term use of this type of vegetarian diet. PMID:6359625

  16. Re-thinking cell cycle regulators : the cross-talk with metabolism.

    Lluis eFajas

    2013-01-01

    Full Text Available Analyses of genetically engineered mice deficient for cell cycle regulators, including E2F1, cdk4, or, pRB showed that the major phenotypes are metabolic perturbations. These key cell cycle regulators contribute to lipid synthesis, glucose production, insulin secretion, and glycolytic metabolism and it has been shown how deregulation of those pathways can lead to metabolic perturbations and related metabolic diseases, such as obesity and type II diabetes. The cyclin-cdk-Rb-E2F1 pathway regulates adipogenesis in addition to its well-described roles in cell cycle regulation and cancer. It was also proved that E2F1 directly participates in the regulation of pancreatic growth and function. Similarly, cyclin D3, cdk4, and cdk9 are also adipogenic factors with strong effects on whole organism metabolism. These examples illustrate the growing notion that cell cycle regulatory proteins can also modulate metabolic processes. Cell cycle regulators are activated by insulin and glucose, even in non-proliferating cells. Most importantly cell cycle regulators trigger the adaptive metabolic switch that normal and cancer cells require in order to proliferate. These changes include increased lipid synthesis, decreased oxidative, and increased glycolytic metabolism. In summary, cell cycle regulators are essential in the control of anabolic, biosynthetic processes, and block at the same time oxidative and catabolic pathways, which are the metabolic hallmarks of cancer.

  17. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    Bentzen, Joan; Poulsen, Pernille; Vaag, Allan;

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco...... on the insulin-to-glucose ratio (p = 0.04), and E4154K (EcoRI RFLP) influenced HOMAbeta (p = 0.04). Significant interactions were observed between genotype in T71I (ApaLI RFLP), A591V (AluI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI RFLP) and glucose tolerance on lipid-related parameters (0.03 < p...

  18. Tumor glucose metabolism imaged in vivo in small animals with whole-body photoacoustic computed tomography

    Chatni, Muhammad Rameez; Xia, Jun; Sohn, Rebecca; Maslov, Konstantin; Guo, Zijian; Zhang, Yu; Wang, Kun; Xia, Younan; Anastasio, Mark; Arbeit, Jeffrey; Wang, Lihong V.

    2012-07-01

    With the increasing use of small animals for human disease studies, small-animal whole-body molecular imaging plays an important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose molecular information, leading to higher costs of building dual-modality systems. Even with image co-registration, the spatial resolution of the molecular imaging modality is not improved. Utilizing a ring-shaped confocal photoacoustic computed tomography system, we demonstrate, for the first time, that both anatomy and glucose uptake can be imaged in a single modality. Anatomy was imaged with the endogenous hemoglobin contrast, and glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose.

  19. Anorexia and Impaired Glucose Metabolism in Mice With Hypothalamic Ablation of Glut4 Neurons

    Ren, Hongxia; Lu, Taylor Y.; McGraw, Timothy E.; Accili, Domenico

    2014-01-01

    The central nervous system (CNS) uses glucose independent of insulin. Nonetheless, insulin receptors and insulin-responsive glucose transporters (Glut4) often colocalize in neurons (Glut4 neurons) in anatomically and functionally distinct areas of the CNS. The apparent heterogeneity of Glut4 neurons has thus far thwarted attempts to understand their function. To answer this question, we used Cre-dependent, diphtheria toxin–mediated cell ablation to selectively remove basal hypothalamic Glut4 ...

  20. The Relationship between Serum Ferritin and Insulin Resistance in Different Glucose Metabolism in Nonobese Han Adults

    Bo-wei Liu; Xu-min Xuan; Jun-ru Liu; Fang-ning Li; Fu-Zai Yin

    2015-01-01

    The exact mechanism through which elevated serum ferritin promotes the development of type 2 diabetes is unknown. This study showed that ferritin concentration in impaired glucose regulation and newly diagnosed diabetes mellitus subjects of nonobesity already significantly increased when compared with normal glucose tolerant subjects of nonobesity. Elevated serum ferritin levels are associated with insulin resistance and may be not associated with the decline of insulin beta cells in differen...

  1. Co-ordination of hepatic and adipose tissue lipid metabolism after oral glucose

    Bülow, J; Simonsen, L; Wiggins, D; Humphreys, S M; Frayn, K N; Powell, D; Gibbons, G F

    1999-01-01

    The integration of lipid metabolism in the splanchnic bed and in subcutaneous adipose tissue before and after ingestion of a 75 g glucose load was studied by Fick's principle in seven healthy subjects. Six additional subjects were studied during a hyperinsulinemic euglycemic clamp. Release of non...... NEFA was significantly lower than that for output of VLDL, implying depletion of hepatic TAG stores during the experiment. In the hyperinsulinemic clamp experiments, there was on average suppression of splanchnic VLDL-TAG output although between-person variability was marked. This suppression could be...... explained by a very low supply of NEFA during the clamp. We conclude that there is an integrated pattern of metabolism in splanchnic and adipose tissues in the postabsorptive and post-glucose states. Flux of NEFA from adipose tissue drives splanchnic NEFA uptake. Splanchnic VLDL-TAG secretion appears to be...

  2. Enhancement of energy production by black ginger extract containing polymethoxy flavonoids in myocytes through improving glucose, lactic acid and lipid metabolism.

    Toda, Kazuya; Takeda, Shogo; Hitoe, Shoketsu; Nakamura, Seikou; Matsuda, Hisashi; Shimoda, Hiroshi

    2016-04-01

    Enhancement of muscular energy production is thought to improve locomotive functions and prevent metabolic syndromes including diabetes and lipidemia. Black ginger (Kaempferia parviflora) has been cultivated for traditional medicine in Thailand. Recent studies have shown that black ginger extract (KPE) activated brown adipocytes and lipolysis in white adipose tissue, which may cure obesity-related dysfunction of lipid metabolism. However, the effect of KPE on glucose and lipid utilization in muscle cells has not been examined yet. Hence, we evaluated the effect of KPE and its constituents on energy metabolism in pre-differentiated (p) and differentiated (d) C2C12 myoblasts. KPE (0.1-10 μg/ml) was added to pC2C12 cells in the differentiation process for a week or used to treat dC2C12 cells for 24 h. After culturing, parameters of glucose and lipid metabolism and mitochondrial biogenesis were assessed. In terms of the results, KPE enhanced the uptake of 2-deoxyglucose and lactic acid as well as the mRNA expression of glucose transporter (GLUT) 4 and monocarboxylate transporter (MCT) 1 in both types of cells. The expression of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α was enhanced in pC2C12 cells. In addition, KPE enhanced the production of ATP and mitochondrial biogenesis. Polymethoxy flavonoids in KPE including 5-hydroxy-7-methoxyflavone, 5-hydroxy-3,7,4'-trimethoxyflavone and 5,7-dimethoxyflavone enhanced the expression of GLUT4 and PGC-1α. Moreover, KPE and 5,7-dimethoxyflavone enhanced the phosphorylation of 5'AMP-activated protein kinase (AMPK). In conclusion, KPE and its polymethoxy flavonoids were found to enhance energy metabolism in myocytes. KPE may improve the dysfunction of muscle metabolism that leads to metabolic syndrome and locomotive dysfunction. PMID:26581843

  3. (14C)-glucose metabolism during shoot bud development in cultured cotyledon explants of Pinus radiata

    Excised cotyledons of Pinus radiata D. Don cultured under shoot-forming (plus benzyladenine) and non shoot-forming (minus benzyladenine) conditions for 10 and 21 days were fed U-[14C]-glucose for 3 h in the light followed by a 3 h chase period. The labelling of individual metabolites as well as 14C incorporation into protein was assessed. It was found that the general metabolic patterns were qualitatively the same in shoot-forming and non shoot-forming conditions, however, metabolism leading to respiration as well as to the synthesis of some amino acids and protein synthesis was enhanced in the shoot-forming cultures. (author)

  4. Effect of antibiotics on gut microbiota, glucose metabolism and bodyweight regulation - a review of the literature

    Mikkelsen, Kristian Hallundbaek; Allin, Kristine Højgaard; Knop, Filip Krag

    2016-01-01

    Gut bacteria are involved in a number of host metabolic processes and have been implicated in the development of obesity and type 2 diabetes in humans. Use of antibiotics changes the composition of the gut microbiota and there is accumulating evidence from observational studies for an association...... between exposure to antibiotics and development of obesity and type 2 diabetes. Here we review human studies examining effects of antibiotics on bodyweight regulation and glucose metabolism and discuss whether the observed findings may relate to alterations in the composition and function of the gut...... microbiota....

  5. Quantitative Rates of Brain Glucose Metabolism Distinguish Minimally Conscious from Vegetative State Patients

    Stender, Johan; Kupers, Ron; Rodell, Anders;

    2015-01-01

    The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these...... indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these...

  6. Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer

    Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an increased risk of metastasis and decreased survival. The uptake of glucose into cells is carried out via glucose transporters or GLUTs. Of these, GLUT-4 is essential for insulin-stimulated glucose uptake. Following treatment with the epigenetic targeting agents histone deacetylase inhibitors (HDACi), GLUT-3 and GLUT-4 expression were found to be induced in NSCLC cell lines, with minimal responses in transformed normal human bronchial epithelial cells (HBECs). Similar results for GLUT-4 were observed in cells derived from liver, muscle, kidney and pre-adipocytes. Bioinformatic analysis of the promoter for GLUT-4 indicates that it may also be regulated by several chromatin binding factors or complexes including CTCF, SP1 and SMYD3. Chromatin immunoprecipitation studies demonstrate that the promoter for GLUT-4 is dynamically remodeled in response to HDACi. Overall, these results may have value within the clinical setting as (a) it may be possible to use this to enhance fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) imaging sensitivity; (b) it may be possible to target NSCLC through the use of HDACi and insulin mediated uptake of the metabolic targeting drugs such as 2-deoxyglucose (2-DG); or (c) enhance or sensitize NSCLC to chemotherapy

  7. Associations of fatty acids in cerebrospinal fluid with peripheral glucose concentrations and energy metabolism.

    Reiner Jumpertz

    Full Text Available Rodent experiments have emphasized a role of central fatty acid (FA species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT followed by measurements of 24 hour (24EE and sleep energy expenditure (SLEEP as well as respiratory quotient (RQ in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16:1, C18:1 and very-long-chain saturated (C24:0, C26:0 FAs.Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.

  8. A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats

    Motoyama Caio SM

    2011-09-01

    Full Text Available Abstract Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H or the alternation of chow (C and an H diet (CH regimen induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

  9. Effect of tangeretin, a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats.

    Sundaram, Ramalingam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2014-05-15

    The present study was designed to evaluate the antihyperglycemic potential of tangeretin on the activities of key enzymes of carbohydrate and glycogen metabolism in control and streptozotocin induced diabetic rats. The daily oral administration of tangeretin (100mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of tangeretin. Further, tangeretin administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of tangeretin in diabetic rats. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide - a standard oral hypoglycemic drug. Thus, these results show that tangeretin modulates the activities of hepatic enzymes via enhanced secretion of insulin and decreases the blood glucose in streptozotocin induced diabetic rats by its antioxidant potential. PMID:24629597

  10. Effects of nicotine on regional cerebral glucose metabolism in awake resting tobacco smokers.

    Domino, E F; Minoshima, S; Guthrie, S K; Ohl, L; Ni, L; Koeppe, R A; Cross, D J; Zubieta, J

    2000-01-01

    Eleven healthy tobacco smoking adult male volunteers of mixed race were tobacco abstinent overnight for this study. In each subject, positron emission tomographic images of regional cerebral metabolism of glucose with [18F]fluorodeoxyglucose were obtained in two conditions in the morning on different days: about 3min after approximately 1-2mg of nasal nicotine spray and after an equivalent volume of an active placebo spray of oleoresin of pepper in a random counterbalanced design. A Siemens/CTI 931/08-12 scanner with the capability of 15 horizontal brain slices was used. The images were further converted into a standard uniform brain format in which the mean data of all 11 subjects were obtained. Images were analysed in stereotactic coordinates using pixel-wise t statistics and a smoothed Gaussian model. Peak plasma nicotine levels varied three-fold and the areas under the curve(0-30min) varied seven-fold among the individual subjects. Nicotine caused a small overall reduction in global cerebral metabolism of glucose but, when the data were normalized, several brain regions showed relative increases in activity. Cerebral structures specifically activated by nicotine (nicotine minus pepper, Z score >4.0) included: left inferior frontal gyrus, left posterior cingulate gyrus and right thalamus. The visual cortex, including the right and left cuneus and left lateral occipito-temporal gyrus fusiformis, also showed an increase in regional cerebral metabolism of glucose with Z scores >3. 6. Structures with a decrease in regional cerebral metabolism of glucose (pepper minus nicotine) were the left insula and right inferior occipital gyrus, with Z scores >3.5. Especially important is the fact that the thalamus is activated by nicotine. This is consistent with the high density of nicotinic cholinoceptors in that brain region. However, not all brain regions affected by nicotine are known to have many nicotinic cholinoceptors. The results are discussed in relation to the

  11. Improved Estimation of Local Cerebral Glucose Metabolic Rate Using Bayes Regression Analysis of PET Scan Data

    Wilson, P D; Huang, S. C.; Links, J M

    1984-01-01

    The current method for measurement of local cerebral metabolic rate of glucose (LCMRG) has relatively small errors when applied to normal healthy tissue. But when applied to ischemic regions in brains of stroke patients, the method gives estimates which average about 50% too low. Here we introduce a modified Bayes Regression (BR) to compute LCMRG, and use computer simulation studies to demonstrate that BR has relatively small errors for either ischemic or normal tissue.

  12. Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle

    Yasuhiko Minokoshi; Chitoku Toda; Shiki Okamoto

    2012-01-01

    Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulation of food intake, energy expenditure, and neuroendocrine function. Several lines of evidences indicate that independent of the anorexic effect, leptin regulates glucose and lipid metabolism in peripheral tissues in rodents and humans. It has been shown that leptin improves the diabetes phenotype in lipodystrophic patients and rodents. Moreover, leptin suppresses the development of severe, progressive impairment o...

  13. Blood Flow and Glucose Metabolism in Stage IV Breast Cancer: Heterogeneity of Response During Chemotherapy

    Krak, Nanda; Hoeven, John; Hoekstra, Otto; Twisk, Jos; Wall, Ernst; Lammertsma, A. A.

    2008-01-01

    textabstractObjective: The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy. Methods: Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone were scanned before treatment and after the first course of chemotherapy. BF, distribution volume of water (Vd), MRglu/BF ratio, MRgluand its corresponding rate constants K1and k3were compared per tum...

  14. Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

    Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8±0.75 y, 5 IGAs: male, 22.6±2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA

  15. Influence of creatine supplementation on indicators of glucose metabolism in skeletal muscle of exercised rats

    Michel Barbosa de Araújo; Roberto Carlos Vieira Junior; Leandro Pereira de Moura; Marcelo Costa Junior; Rodrigo Augusto Dalia; Amanda Christine da Silva Sponton; Carla Ribeiro; Maria Alice Rostom de Mello

    2013-01-01

    The purpose of this study was to evaluate the effect of creatine supplementation in the diet on indicators of glucose metabolism in skeletal muscle of exercised rats. Forty Wistar adult rats were distributed into four groups for eight weeks: 1) Control: sedentary rats that received balanced diet; 2) Creatine control: sedentary rats that received supplementation of 2% creatine in the balanced diet; 3) Trained: rats that ran on a treadmill at the Maximal Lactate Steady State and received balanc...

  16. Insights into the molecular mechanism of glucose metabolism regulation under stress in chicken skeletal muscle tissues

    Liu, Wuyi; Zhao, Jingpeng

    2014-01-01

    As substantial progress has been achieved in modern poultry production with large-scale and intensive feeding and farming in recent years, stress becomes a vital factor affecting chicken growth, development, and production yield, especially the quality and quantity of skeletal muscle mass. The review was aimed to outline and understand the stress-related genetic regulatory mechanism, which significantly affects glucose metabolism regulation in chicken skeletal muscle tissues. Progress in curr...

  17. Nosocomial pneumonia caused by a glucose-metabolizing strain of Neisseria cinerea.

    Boyce, J M; Taylor, M R; Mitchell, E B; Knapp, J S

    1985-01-01

    We describe what appears to be the first reported case of nosocomial pneumonia caused by Neisseria cinerea. The isolate metabolized glucose when tested in BACTEC Neisseria Differentiation Kits (Johnston Laboratories), but did not produce detectable acid in cystine-Trypticase (BBL Microbiology Systems) agar medium or in modified oxidation-fermentation medium. Clinical laboratories that rely on the BACTEC method for differentiation of pathogenic neisseriae should be aware of the fact that N. ci...

  18. The Relationship between Selenoprotein P and Glucose Metabolism in Experimental Studies

    Jinyuan Mao; Weiping Teng

    2013-01-01

    Selenium is an essential trace element in the diet of mammals which is important for many physiological functions. However, a number of epidemiological studies have suggested that high selenium status is a possible risk factor for the development of type 2 diabetes, although they cannot distinguish between cause and effect. Selenoprotein P (Sepp1) is central to selenium homeostasis and widely expressed in the organism. Here we review the interaction between Sepp1 and glucose metabolism with a...

  19. Changes in glucose metabolism and gene expression after transfer of anti-angiogenic genes in rat hepatoma

    Human troponin I (TROP), the soluble receptor for vascular endothelial growth factor (sFLT) and angiostatin (ASTAT) are potent inhibitors of endothelial cell proliferation, angiogenesis and tumour growth in vivo. Transfer of these genes into tumours may induce changes not only in perfusion, but also more general ones such as changes in metabolism. The aim of this study was to assess these reactions using FDG-PET and high-throughput methods such as gene profiling. We established Morris hepatoma (MH3924A) cell lines expressing TROP, sFLT or ASTAT and quantified 18F-fluorodeoxyglucose (18FDG) uptake by dynamic positron emission tomography (PET) after tumour inoculation in ACI rats. Furthermore, expression of glucose transporter-1 and -3 (GLUT-1 and GLUT-3) as well as hexokinase-1 and -2 were investigated by RT-PCR and immunohistomorphometry. In addition, gene array analyses were performed. 18FDG uptake, vascular fraction and distribution volume were significantly higher in all genetically modified tumours. Immunohistomorphometry showed an increased percentage of hexokinase-1 and -2 as well as GLUT-1 and -3 immunoreactive (ir) cells. Using gene arrays and comparing all three groups of genetically modified tumours, we found upregulated expression of 36 genes related to apoptosis, signal transduction, stress or metabolism. TROP-, sFLT- or ASTAT-expressing MH3924A tumours show enhanced influx of 18FDG, which seems to be caused by several factors: enhanced exchange of nutrients between blood and tumour, increased amounts of glucose transporters and hexokinases, and increased expression of genes related to apoptosis, matrix and stress, which induce an increased demand for glucose. (orig.)

  20. Hexachlorobenzene impairs glucose metabolism in a rat model of porphyria cutanea tarda: a mechanistic approach

    Mazzetti, Marta Blanca; Taira, Maria Cristina; Lelli, Sandra Marcela; Viale, Leonor Carmen San Martin de [Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428BGA, Ciudad Autonoma Buenos Aires (Argentina); Dascal, Eduardo; Basabe, Juan Carlos [Centro de Investigaciones Endocrinologicas (CEDIE). Hospital de Ninos, Dr. Ricardo Gutierrez, C1425EDF, Ciudad Autonoma Buenos Aires (Argentina)

    2004-01-01

    Hexachlobenzene (HCB), one of the most persistent environmental pollutants, induces porphyria cutanea tarda (PCT). The aim of this work was to analyze the effect of HCB on some aspects of glucose metabolism, particularly those related to its neosynthesis in vivo. For this purpose, a time-course study on gluconeogenic enzymes, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase) and on pyruvate kinase (PK), a glycolytic enzyme, was carried out. Plasma glucose and insulin levels, hepatic glycogen, tryptophan contents, and the pancreatic insulin secretion pattern stimulated by glucose were investigated. Oxidative stress and heme pathway parameters were also evaluated. HCB treatment decreased PC, PEPCK, and G-6-Pase activities. The effect was observed at an early time point and grew as the treatment progressed. Loss of 60, 56, and 37%, respectively, was noted at the end of the treatment when a considerable amount of porphyrins had accumulated in the liver as a result of drastic blockage of uroporphyrinogen decarboxylase (URO-D) (95% inhibition). The plasma glucose level was reduced (one-third loss), while storage of hepatic glucose was stimulated in a time-dependent way by HCB treatment. A decay in the normal plasma insulin level was observed as fungicide intoxication progressed (twice to four times lower). However, normal insulin secretion of perifused pancreatic Langerhans islets stimulated by glucose during the 3rd and 6th weeks of treatment did not prove to be significantly affected. HCB promoted a time-dependent increase in urinary chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content (fivefold), while the liver tryptophan level was only raised at the longest intoxication times. These results would suggest that HCB treatment does not cause a primary alteration in the mechanism of pancreatic insulin secretion and that the changes induced by the fungicide on insulin levels would be an adaptative

  1. Glucose allostasis

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert;

    2003-01-01

    In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy...... individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose...... chronic stress (insulin resistance), we propose to use the term "glucose allostasis." Allostasis (stability through change) ensures the continued homeostatic response (stability through staying the same) to acute stress at some cumulative costs to the system. With increasing severity and over time, the...

  2. Peroxisome proliferator-activated receptor-alpha control of lipid and glucose metabolism in human white adipocytes.

    Ribet, Carole; Montastier, Emilie; Valle, Carine; Bezaire, Véronic; Mazzucotelli, Anne; Mairal, Aline; Viguerie, Nathalie; Langin, Dominique

    2010-01-01

    This work aimed at characterizing the role of peroxisome proliferator-activated receptors (PPAR)alpha in human white adipocyte metabolism and at comparing PPAR alpha and PPAR gamma actions in these cells. Primary cultures of human fat cells were treated with the PPAR alpha agonist GW7647 or the PPAR gamma agonist rosiglitazone. Changes in gene expression were determined using DNA microarrays and quantitative RT-PCR. Western blot and metabolic studies were performed to identify the biological effects elicited by PPAR agonist treatments. GW7647 induced an up-regulation of beta-oxidation gene expression and increased palmitate oxidation. Unexpectedly, glycolysis was strongly reduced at transcriptional and functional levels by GW7647 leading to a decrease in pyruvate and lactate production. Glucose oxidation was decreased. Triglyceride esterification and de novo lipogenesis were inhibited by the PPAR alpha agonist. GW7647-induced alterations were abolished by a treatment with a PPAR alpha antagonist. Small interfering RNA-mediated extinction of PPAR alpha gene expression in hMADS adipocytes attenuated GW7647 induction of palmitate oxidation. Rosiglitazone had no major impact on glycolysis and beta-oxidation. Altogether these results show that PPAR alpha can selectively up-regulate beta-oxidation and decrease glucose utilization in human white adipocytes. PMID:19887568

  3. Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply

    Spoden, Gilles A. [Department of Cell Metabolism and Differentiation, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck (Austria); Tumorvirology Research Group, Tyrolean Cancer Research Institute, Medical University Innsbruck, Innrain 66, 6020 Innsbruck (Austria); Rostek, Ursula; Lechner, Stefan; Mitterberger, Maria [Department of Cell Metabolism and Differentiation, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck (Austria); Mazurek, Sybille [Department for Biochemistry and Endocrinology, Veterinary Faculty, University of Giessen, 35392 Giessen (Germany); ScheBo Biotech AG, Netanyastrasse 3, 35394 Giessen (Germany); Zwerschke, Werner, E-mail: werner.zwerschke@oeaw.ac.at [Department of Cell Metabolism and Differentiation, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck (Austria); Tumorvirology Research Group, Tyrolean Cancer Research Institute, Medical University Innsbruck, Innrain 66, 6020 Innsbruck (Austria)

    2009-10-01

    The glycolytic key regulator pyruvate kinase M2 (M2-PK or PKM2) can switch between a highly active tetrameric and an inactive dimeric form. The transition between the two conformations regulates the glycolytic flux in tumor cells. We developed specific M2-PK-binding peptide aptamers which inhibit M2-PK, but not the 96% homologous M1-PK isoenzyme. In this study we demonstrate that, at normal blood glucose concentrations, peptide aptamer-mediated inhibition of M2-PK induces a significant decrease of the population doubling (PDL rate) and cell proliferation rate as well as an increase in cell size, whereas under glucose restriction an increase in PDL and cell proliferation rates but a decrease in cell size was observed. Moreover, M2-PK inhibition rescues cells from glucose starvation-induced apoptotic cell death by increasing the metabolic activity. These findings suggest that M2-PK is a metabolic sensor which regulates cell proliferation, cell growth and apoptotic cell death in a glucose supply-dependent manner.

  4. High glucose augments stress-induced apoptosis in endothelial cells

    Wenwen Zhong; Yang Liu; Hui Tian

    2009-01-01

    Hyperglycemia has been identified as one of the important factors involved in the microvascular complications of diabetes, and has been related to increased cardiovascular mortality. Endothelial damage and dysfunction result from diabetes; therefore, the aim of this study was to determine the response of endothelial cells to stressful stimuli, modelled in normal and high glucose concentrations in vitro. Eahy 926 endothelial cells were cultured in 5 mmol/L or 30 mmol/L glucose conditions for a 24 hour period and oxidative stress was induced by exposure to hydrogen peroxide (H2O2) or tumour necrosis factor- α (TNF- α ), following which the protective effect of the glucocorticoid dexamethasone was assessed. Apoptosis, necrosis and cell viability were determined using an ELISA for DNA fragmentation, an enzymatic lactate dehydrogenase assay and an MTT assay, respectively. High glucose significantly increased the susceptibility of Eahy 926 cells to apoptosis in the presence of 500 μmol/L H2O2, above that induced in normal glucose (P<0.02). A reduction of H2O2- and TNF- α -induced apoptosis occurred in both high and low glucose after treatment with dexametha-sone (P<0.05). Conclusion high glucose is effective in significantly augmenting stress caused by H2O2, but not in causing stress alone. These findings suggest a mechanism by which short term hyperglycemia may facilitate and augment endothelial damage.

  5. Metabolic regulation and maximal reaction optimization in the central metabolism of a yeast cell

    Kasbawati, Gunawan, A. Y.; Hertadi, R.; Sidarto, K. A.

    2015-03-01

    Regulation of fluxes in a metabolic system aims to enhance the production rates of biotechnologically important compounds. Regulation is held via modification the cellular activities of a metabolic system. In this study, we present a metabolic analysis of ethanol fermentation process of a yeast cell in terms of continuous culture scheme. The metabolic regulation is based on the kinetic formulation in combination with metabolic control analysis to indicate the key enzymes which can be modified to enhance ethanol production. The model is used to calculate the intracellular fluxes in the central metabolism of the yeast cell. Optimal control is then applied to the kinetic model to find the optimal regulation for the fermentation system. The sensitivity results show that there are external and internal control parameters which are adjusted in enhancing ethanol production. As an external control parameter, glucose supply should be chosen in appropriate way such that the optimal ethanol production can be achieved. For the internal control parameter, we find three enzymes as regulation targets namely acetaldehyde dehydrogenase, pyruvate decarboxylase, and alcohol dehydrogenase which reside in the acetaldehyde branch. Among the three enzymes, however, only acetaldehyde dehydrogenase has a significant effect to obtain optimal ethanol production efficiently.

  6. FXR: a metabolic regulator and cell protector

    Yan-Dong Wang; Wei-Dong Chen; David D Moore; Wendong Huang

    2008-01-01

    Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription fac-tors. As a metabolic regulator, FXR plays key roles in bile acid, cholesterol, lipid, and glucose metabolism. Therefore, FXR is a potential drug target for a number of metabolic disorders, especially those related to the metabolic syn-drome. More recently, our group and others have extended the functions of FXR to more than metabolic regulation, which include anti-bacterial growth in intestine, liver regeneration, and hepatocarcinogenesis. These new findings suggest that FXR has much broader roles than previously thought, and also higl light FXR as a drug target for mul-tiple diseases. This review summarizes the basic information of FXR but focuses on its new functions.

  7. Glucose transporter expression in developing fetal lungs and lung neoplasms

    Ito, T.; Noguchi, Y.; Udaka, N.; Kitamura, H; Satoh, S.

    1999-01-01

    Glucose uptake and metabolism are essential for proliferation and survival of cells, and are supposed to be enhanced in actively proliferating cell systems such as embryonic and cancer tissues. Glucose uptake is usually carried out through glucose transporters. In the developing fetal lung, metabolism of glucose is thought to be an important process in cell proliferation, differentiation and maturation. Active glucose uptake could result in accumulation of glyc...

  8. Metabolic connections during apoptotic cell engulfment

    Han, Claudia Z.; Ravichandran, Kodi S.

    2011-01-01

    Billions of cells die via apoptosis every day and are swiftly and efficiently removed. When a phagocyte engulfs an apoptotic cell, it essentially doubles its cellular contents, raising the question of how a phagocyte may manage the excess metabolic load. This review discusses phagocyte cellular metabolism, the digestion of the ingested apoptotic cell and the impact of these processes on engulfment.

  9. Time-dependent Mechanisms in Beta-cell Glucose Sensing

    Vagn Korsgaard, Thomas; Colding-Jørgensen, Morten

    2006-01-01

    The relation between plasma glucose and insulin release from pancreatic beta-cells is not stationary in the sense that a given glucose concentration leads to a specific rate of insulin secretion. A number of time-dependent mechanisms appear to exist that modify insulin release both on a short and a longer time scale. Typically, two phases are described. The first phase, lasting up to 10 min, is a pulse of insulin release in response to fast changes in glucose concentration. The second phase i...

  10. Single Glucose Biofuel Cells Implanted in Rats Power Electronic Devices

    Zebda, A.; Cosnier, S.; J.-P. Alcaraz; Holzinger, M.; A. Le Goff; Gondran, C.; Boucher, F.; Giroud, F.; Gorgy, K.; Lamraoui, H.; Cinquin, P.

    2013-01-01

    We describe the first implanted glucose biofuel cell (GBFC) that is capable of generating sufficient power from a mammal's body fluids to act as the sole power source for electronic devices. This GBFC is based on carbon nanotube/enzyme electrodes, which utilize glucose oxidase for glucose oxidation and laccase for dioxygen reduction. The GBFC, implanted in the abdominal cavity of a rat, produces an average open-circuit voltage of 0.57 V. This implanted GBFC delivered a power output of 38.7 μW...

  11. Influence of free fatty acids on glucose uptake in prostate cancer cells

    Introduction: The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-D-glucose (FDG) and acetate. Methods: Human prostate cancer cell lines (PC3, CWR22Rv1, LNCaP, and DU145) were incubated for 2 h and 24 h in glucose-containing (5.5 mM) Dulbecco’s Modified Eagle’s Medium (DMEM) with varying concentrations of the free fatty acid palmitate (0–1.0 mM). Then the cells were incubated with [18 F]-FDG (1 μCi/mL; 0.037 MBq/mL) in DMEM either in presence or absence of glucose and in presence of varying concentrations of palmitate for 1 h. Standardized procedures regarding cell counting and measuring for 18 F radioactivity were applied. Cell uptake studies with 14C-1-acetate under the same conditions were performed on PC3 cells. Results: In glucose containing media there was significantly increased FDG uptake after 24 h incubation in all cell lines, except DU145, when upper physiological levels of palmitate were added. A 4-fold increase of FDG uptake in PC3 cells (15.11% vs. 3.94%/106 cells) was observed in media with 1.0 mM palmitate compared to media with no palmitate. The same tendency was observed in PC3 and CWR22Rv1 cells after 2 h incubation. In glucose-free media no significant differences in FDG uptake after 24 h incubation were observed. The significant differences after 2 h incubation all pointed in the direction of increased FDG uptake when palmitate was added. Acetate uptake in PC3 cells was significantly lower when palmitate was added in glucose-free DMEM. No clear tendency when comparing FDG or acetate uptake in the same media at different time points of incubation was observed. Conclusions: Our results indicate a FFA dependent metabolic boost/switch of glucose uptake in PCa, with patterns reflecting the true heterogeneity of the disease

  12. Compartmentalised cerebral metabolism of [1,6-13C]glucose determined by in vivo 13C NMR spectroscopy at 14.1 T

    João M.N. Duarte

    2011-06-01

    Full Text Available Cerebral metabolism is compartmentalised between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by 13C NMR spectroscopy upon infusion of 13C-enriched compounds, especially glucose. Rats under light α-chloralose anaesthesia were infused with [1,6-13C]glucose and 13C enrichment in the brain metabolites was measured by 13C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining 13C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%. We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (VTCA and neurotransmission rate (VNT were 0.45±0.01 and 0.11±0.01 µmol/g/min, respectively. Glial VTCA was found to be for 38±3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (VPC was 0.069±0.004 µmol/g/min, i.e. 25±1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism.

  13. Identifying Metabolic Syndrome in African American Children Using Fasting HOMA-IR in Place of Glucose

    Sushma Sharma, PhD

    2011-05-01

    Full Text Available IntroductionMetabolic syndrome (MetS is increasing among young people. We compared the use of homeostasis model assessment of insulin resistance (HOMA-IR with the use of fasting blood glucose to identify MetS in African American children.MethodsWe performed a cross-sectional analysis of data from a sample of 105 children (45 boys, 60 girls aged 9 to 13 years with body mass indexes at or above the 85th percentile for age and sex. Waist circumference, blood pressure, and fasting levels of blood glucose, insulin, triglycerides, and high-density lipoprotein cholesterol were measured.ResultsWe found that HOMA-IR is a stronger indicator of MetS in children than blood glucose. Using HOMA-IR as 1 of the 5 components, we found a 38% prevalence of MetS in this sample of African American children and the proportion of false negatives decreased from 94% with blood glucose alone to 13% with HOMA-IR. The prevalence of MetS was higher in obese than overweight children and higher among girls than boys.ConclusionUsing HOMA-IR was preferred to fasting blood glucose because insulin resistance was more significantly interrelated with the other 4 MetS components.

  14. Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

    The metabolism of glucose in brains during sustained hypoglycemia was studied. [U-14C]Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia

  15. Vibrational imaging of glucose uptake activity in live cells and tissues by stimulated Raman scattering microscopy (Conference Presentation)

    Hu, Fanghao; Chen, Zhixing; Zhang, Luyuan; Shen, Yihui; Wei, Lu; Min, Wei

    2016-03-01

    Glucose is consumed as an energy source by virtually all living organisms, from bacteria to humans. Its uptake activity closely reflects the cellular metabolic status in various pathophysiological transformations, such as diabetes and cancer. Extensive efforts such as positron emission tomography, magnetic resonance imaging and fluorescence microscopy have been made to specifically image glucose uptake activity but all with technical limitations. Here, we report a new platform to visualize glucose uptake activity in live cells and tissues with subcellular resolution and minimal perturbation. A novel glucose analogue with a small alkyne tag (carbon-carbon triple bond) is developed to mimic natural glucose for cellular uptake, which can be imaged with high sensitivity and specificity by targeting the strong and characteristic alkyne vibration on stimulated Raman scattering (SRS) microscope to generate a quantitative three dimensional concentration map. Cancer cells with differing metabolic characteristics can be distinguished. Heterogeneous uptake patterns are observed in tumor xenograft tissues, neuronal culture and mouse brain tissues with clear cell-cell variations. Therefore, by offering the distinct advantage of optical resolution but without the undesirable influence of bulky fluorophores, our method of coupling SRS with alkyne labeled glucose will be an attractive tool to study energy demands of living systems at the single cell level.

  16. Sodium-glucose cotransport inhibitors: mechanisms, metabolic effects and implications for the treatment of diabetic patients with chronic kidney disease.

    Vlotides, George; Mertens, Peter R

    2015-08-01

    Remarkable progress has been achieved in the field of diabetes with the development of incretin analogues, dipeptidyl peptidase IV inhibitors and novel insulin analogues; nevertheless, there is an unmet need for additional therapeutic options. Individualization of HbA1c target levels is a recent progress within the field. Approximately 50% of diabetics do not reach a previously aspired treatment goal of glycosylated HbA1 levels below 7% and often face a vicious circle with accelerated weight gain. Current antidiabetic therapeutics mainly target the decline in insulin secretion and ameliorate insulin resistance. In this regard a new generation of drugs, denoted gliflozines, that specifically interfere with sodium-glucose cotransporters (SGLT)-2 and exhibit a favourable impact on glucose metabolism in patients with type 2 diabetes are emerging as hopeful avenues. The resultant negative energy balance caused by glucosuria results in long-term weight losses, significantly reduced HbA1c levels approximating 0.5-1.0% and may in addition exert beneficial effects on blood pressure, reactive oxygen products and inflammatory mediators. Recent studies indicate improvement in β-cell glucose sensitivity and insulin sensitivity in patients treated with gliflozines, a decrease in tissue glucose disposal and interestingly an increase in endogenous glucose production. The list of side effects observed under SGLT2 inhibition includes increased rates of genitourinary infections, balanitis, vulvovaginitis, hypotensive episodes and acute deterioration of kidney function. Main questions towards the safety profile are still unanswered given that long-term clinical outcome data with SGLT2 inhibition are lacking and the cardiovascular safety profile is under scrutiny in large trials. Thus, the successful development of selective SGLT2 inhibitors for therapeutic use in diabetics has a huge potential to meet patients' needs. However, it awaits quick results from clinical trials with

  17. Changes of regional cerebral glucose metabolism in normal aging process : A study with FDG PET

    Normal aging results in detectable changes in the brain structure and function. We evaluated the changes of regional cerebral glucose metabolism in the normal aging process with FDG PET. Brain PET images were obtained in 44 healthy volunteers (age range 20-69'y'; M:F = 29:15) who had no history of neuropsychiatric disorders. On 6 representative transaxial images, ROls were drawn in the cortical and subcortical areas. Regional FDG uptake was normalized using whole brain uptake to adjust for the injection dose and correct for nonspecific declines of glucose metabolism affecting all brain areas equally. In the prefrontal, temporoparietal and primary sensorimotor cortex, the normalized FDG uptake (NFU) reached a peak In subjects in their 30s. The NFU in the prefrontal and primary sensorimotor cortex declined with age after 30s at a rate of 3.15%/decade and 1.93%/decade, respectively. However, the NFU in the lernporoparietal cortex did not change significantly with age after 30s. The anterior (prefrontal) posterior (temporoparietal) gradient peaked in subjects in their 30s and declined with age the reafter at a rate of 35%/decade. The NFU in the caudate nucleus was decreased with age after 20s at a rate of 2.39%/decade. In the primary visual cortex, putamen, and thalamus, the NFU values did not change significantly throughout the ages covered. These patterns were not significantly different between right and left cerebral hemispheres. Of interest was that the NFU in the left cerebellar cortex was increased with age after 20s at a rate of 2.86%/decade. These data demonstrate regional variation of the age-related changes in the cerebral glucose metabolism, with the most prominent age-related decline of metabolism in the prefrontal cortex. The increase in the cerebellar metabolism with age might reflect a process of neuronal plasticity associated with aging

  18. Effect of Chromium Supplementation on Glucose Metabolism and Lipids: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

    Objective. A systematic review of the effect of chromium supplementation on glucose metabolism and lipid levels. Research Design and Methods. Literature search conducted in MEDLINE and Commonwealth Agricultural Bureau. Eligible studies were English language randomized controlled trials of chromium ...

  19. Effects of acupuncture on the citrate and glucose metabolism in the liver under various types of stress

    A study was made of the effect of acupuncture on citrate and glucose metabolism in the liver in terms of incorporation of 14C-1, 5-citric acid and 14C-u-glucose in some metabolites. The effect of acupuncture on citrate metabolism in the liver under control conditions was such as to increase production of G and reduce that of KB, FC and FFA. No effect of acupuncture on glucose metabolism in the liver under such conditions was observed. Both citrate and glucose metabolism were affected to a marked extent by immobilization stress or exposure to heat or cold. The deleterious effect of these types of stress was less prominent in animals receiving acupuncture at the Tsu-San-Li locus than in those treated otherwise or receiving no treatment

  20. Effects of acupuncture on the citrate and glucose metabolism in the liver under various types of stress

    Liao, Y.Y.; Seto, K.; Saito, H.; Kawakami, M.

    A study was made of the effect of acupuncture on citrate and glucose metabolism in the liver in terms of incorporation of /sup 14/C-1, 5-citric acid and /sup 14/C-u-glucose in some metabolites. The effect of acupuncture on citrate metabolism in the liver under control conditions was such as to increase production of G and reduce that of KB, FC and FFA. No effect of acupuncture on glucose metabolism in the liver under such conditions was observed. Both citrate and glucose metabolism were affected to a marked extent by immobilization stress or exposure to heat or cold. The deleterious effect of these types of stress was less prominent in animals receiving acupuncture at the Tsu-San-Li locus than in those treated otherwise or receiving no treatment.

  1. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET-18FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

  2. 31P NMR studies of intracellular pH and phosphate metabolism during cell division cycle of Saccharomyces cerevisiae.

    Gillies, R.J.; Ugurbil, K; den Hollander, J A; Shulman, R G

    1981-01-01

    We have analyzed changes in intracellular pH and phosphate metabolism during the cell cycle of Saccharomyces cerevisiae (NCYC 239) by using high-resolution 31P NMR spectroscopy. High-density yeast cultures (2 x 10(8) cells per ml) were arrested prior to "start" by sequential glucose deprivation, after which they synchronously replicated DNA and divided after a final glucose feeding. Oxygenation of arrested cultures in the absence of glucose led to increased levels of sugar phosphates and ATP ...

  3. Glucose restriction decreases telomerase activity and enhances its inhibitor response on breast cancer cells: possible extra-telomerase role of BIBR 1532

    Wardi, Layal; Alaaeddine, Nada; Raad, Issam; Sarkis, Riad; Serhal, Rim; Khalil, Charbel; Hilal, George

    2014-01-01

    Background Considerable progress has been made to understand the association between lifestyle and diet in cancer initiation and promotion. Because excessive glucose consumption is a key metabolic hallmark of cancer cells, glucose restriction (GR) decreases the proliferation, and promotes the differentiation and transformation of cancer cells to quiescent cells. The immortality of cancerous cells is largely assured by telomerase, which is an interesting target for inhibition by BIBR 1532. In ...

  4. High levels of glucose induce "metabolic memory" in cardiomyocyte via epigenetic histone H3 lysine 9 methylation.

    Yu, Xi-Yong; Geng, Yong-Jian; Liang, Jia-Liang; Zhang, Saidan; Lei, He-Ping; Zhong, Shi-Long; Lin, Qiu-Xiong; Shan, Zhi-Xin; Lin, Shu-Guang; Li, Yangxin

    2012-09-01

    Diabetic patients continue to develop inflammation and cardiovascular complication even after achieving glycemic control, suggesting a "metabolic memory". Metabolic memory is a major challenge in the treatment of diabetic complication, and the mechanisms underlying metabolic memory are not clear. Recent studies suggest a link between chromatin histone methylation and metabolic memory. In this study, we tested whether histone 3 lysine-9 tri-methylation (H3K9me3), a key epigenetic chromatin marker, was involved in high glucose (HG)-induced inflammation and metabolic memory. Incubating cardiomyocyte cells in HG resulted in increased levels of inflammatory cytokine IL-6 mRNA when compared with myocytes incubated in normal culture media, whereas mannitol (osmotic control) has no effect. Chromatin immunoprecipitation (ChIP) assays showed that H3K9me3 levels were significantly decreased at the promoters of IL-6. Immunoblotting demonstrated that protein levels of the H3K9me3 methyltransferase, Suv39h1, were also reduced after HG treatment. HG-induced apoptosis, mitochondrial dysfunction and cytochrome-c release were reversible. However, the effects of HG on the expression of IL-6 and the levels of H3K9me3 were irreversible after the removal of HG from the culture. These results suggest that HG-induced sustained inflammatory phenotype and epigenetic histone modification, rather than HG-induced mitochondrial dysfunction and apoptosis, are main mechanisms responsible for metabolic memory. In conclusion, our data demonstrate that HG increases expression of inflammatory cytokine and decreases the levels of histone-3 methylation at the cytokine promoter, and suggest that modulating histone 3 methylation and inflammatory cytokine expression may be a useful strategy to prevent metabolic memory and cardiomyopathy in diabetic patients. PMID:22707199

  5. SH2B1 regulation of energy balance, body weight, and glucose metabolism

    Liangyou; Rui

    2014-01-01

    The Src homology 2B(SH2B)family members(SH2B1,SH2B2 and SH2B3)are adaptor signaling proteins containing characteristic SH2 and PH domains.SH2B1(also called SH2-B and PSM)and SH2B2(also called APS)are able to form homo-or hetero-dimers via their N-terminal dimerization domains.Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins,including Janus kinase 2(JAK2),TrkA,insulin receptors,insulin-like growth factor-1 receptors,insulin receptor substrate-1(IRS1),and IRS2.SH2B1 enhances leptin signaling by both stimulating JAK2 activity and assembling a JAK2/IRS1/2 signaling complex.SH2B1 promotes insulin signaling by both enhancing insulin receptor catalytic activity and protecting against dephosphorylation of IRS proteins.Accordingly,genetic deletion of SH2B1 results in severe leptin resistance,insulin resistance,hyperphagia,obesity,and type 2 diabetes in mice.Neuronspecific overexpression of SH2B1βtransgenes protects against diet-induced obesity and insulin resistance.SH2B1 in pancreaticβcells promotesβcell expansion and insulin secretion to counteract insulin resistance in obesity.Moreover,numerous SH2B1 mutations are genetically linked to leptin resistance,insulin resistance,obesity,and type 2 diabetes in humans.Unlike SH2B1,SH2B2 and SH2B3 are not required for the maintenance of normal energy and glucose homeostasis.The metabolic function of the SH2B family is conserved from insects to humans.

  6. Glutamate Acts as a Key Signal Linking Glucose Metabolism to Incretin/cAMP Action to Amplify Insulin Secretion

    Ghupurjan Gheni; Masahito Ogura; Masahiro Iwasaki; Norihide Yokoi; Kohtaro Minami; Yasumune Nakayama; Kazuo Harada; Benoit Hastoy; Xichen Wu; Harumi Takahashi; Kazushi Kimura; Toshiya Matsubara; Ritsuko Hoshikawa; Naoya Hatano; Kenji Sugawara

    2014-01-01

    Summary Incretins, hormones released by the gut after meal ingestion, are essential for maintaining systemic glucose homeostasis by stimulating insulin secretion. The effect of incretins on insulin secretion occurs only at elevated glucose concentrations and is mediated by cAMP signaling, but the mechanism linking glucose metabolism and cAMP action in insulin secretion is unknown. We show here, using a metabolomics-based approach, that cytosolic glutamate derived from the malate-aspartate shu...

  7. Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane.

    Chichger, Havovi; Cleasby, Mark E; Srai, Surjit K; Unwin, Robert J; Debnam, Edward S; Marks, Joanne

    2016-06-01

    What is the central question of this study? Although SGLT2 inhibitors represent a promising treatment for patients suffering from diabetic nephropathy, the influence of metabolic disruption on the expression and function of glucose transporters is largely unknown. What is the main finding and its importance? In vivo models of metabolic disruption (Goto-Kakizaki type II diabetic rat and junk-food diet) demonstrate increased expression of SGLT1, SGLT2 and GLUT2 in the proximal tubule brush border. In the type II diabetic model, this is accompanied by increased SGLT- and GLUT-mediated glucose uptake. A fasted model of metabolic disruption (high-fat diet) demonstrated increased GLUT2 expression only. The differential alterations of glucose transporters in response to varying metabolic stress offer insight into the therapeutic value of inhibitors. SGLT2 inhibitors are now in clinical use to reduce hyperglycaemia in type II diabetes. However, renal glucose reabsorption across the brush border membrane (BBM) is not completely understood in diabetes. Increased consumption of a Western diet is strongly linked to type II diabetes. This study aimed to investigate the adaptations that occur in renal glucose transporters in response to experimental models of diet-induced insulin resistance. The study used Goto-Kakizaki type II diabetic rats and normal rats rendered insulin resistant using junk-food or high-fat diets. Levels of protein kinase C-βI (PKC-βI), GLUT2, SGLT1 and SGLT2 were determined by Western blotting of purified renal BBM. GLUT- and SGLT-mediated d-[(3) H]glucose uptake by BBM vesicles was measured in the presence and absence of the SGLT inhibitor phlorizin. GLUT- and SGLT-mediated glucose transport was elevated in type II diabetic rats, accompanied by increased expression of GLUT2, its upstream regulator PKC-βI and SGLT1 protein. Junk-food and high-fat diet feeding also caused higher membrane expression of GLUT2 and its upstream regulator PKC

  8. Effects of Cooling and Supplemental Bovine Somatotropin on Milk Production relating to Body Glucose Metabolism and Utilization of Glucose by the Mammary Gland in Crossbred Holstein Cattle

    Siravit Sitprija

    2010-01-01

    Full Text Available Problem statement: The low milk yield and shorter persistency of lactation of dairy cattle is the major problem for the dairy practices in the tropics. High environmental temperatures and rapid decline of plasma growth hormone level can influence milk production. Regulation of the milk yield of animals is mainly based on the mechanisms governing the quantity of glucose extracted by the mammary gland for lactose biosynthetic pathways. The mechanism(s underlying the effects of cooling and supplemental bovine somatotropin on milk production relating to body glucose metabolism and intracellular metabolism of glucose in the mammary gland of crossbred Holstein cattle in the tropics have not been investigated to date. Approach: Ten crossbred 87.5% Holstein cows were divided into two groups of five animals each. Animals were housed in Normal Shade barn (NS as non-cooled cows and cows in the second group were housed in barn which was equipped with a two Misty-Fan cooling system (MF as cooled cows. Supplementation of recombinant bovine Somatotropin (rbST (POSILAC, 500 mg per cow were performed in both groups to study body glucose metabolism and the utilization of glucose in the mammary gland using a continuous infusion of [3-3H] glucose and [U- 14C] glucose as markers in early, mid and late stages of lactation. Results: Milk yield significantly increased in both groups during supplemental rbST with a high level of mammary blood flow. Body glucose turnover rates were not significant different between cooled and non-cooled cows whether supplemental rbST or not. The glucose taken up by the mammary gland of both non-cooled and cooled cows increased flux through the lactose synthesis and the pentose cycle pathway with significant increases in NADPH formation for fatty acid synthesis during rbST supplementation. The utilization of glucose carbon incorporation into milk appeared to increase in milk lactose and milk triacylglycerol but not for

  9. Liver X receptor antagonist reduces lipid formation and increases glucose metabolism in myotubes from lean, obese and type 2 diabetic individuals

    Kase, E T; Thoresen, G H; Westerlund, S; Højlund, Kurt; Rustan, A C; Gaster, M

    2007-01-01

    the synthetic agonist T0901317 on lipid and glucose metabolism in human skeletal muscle cells (myotubes). METHODS: Myotubes established from lean and obese control volunteers and from obese type 2 diabetic volunteers were treated with LXR ligands for 4 days. Lipid and glucose metabolisms were studied...... with labelled precursors, and gene expression was analysed using real-time PCR. RESULTS: Treatment with T0901317 increased lipogenesis (de novo lipid synthesis) and lipid accumulation in myotubes, this increase being more pronounced in myotubes from type 2 diabetic volunteers than from lean volunteers......AIMS/HYPOTHESIS: Liver X receptors (LXRs) play important roles in lipid and carbohydrate metabolism. The purpose of the present study was to evaluate effects of the endogenous LXR agonist 22-R-hydroxycholesterol (22-R-HC) and its stereoisomer 22-S-hydroxycholesterol (22-S-HC), in comparison with...

  10. Effect of Intermittent Hypoxia and Rimonabant on Glucose Metabolism in Rats: Involvement of Expression of GLUT4 in Skeletal Muscle

    Wang, Xiaoya; Yu, Qin; Yue, Hongmei; Zeng, Shuang; Cui, Fenfen

    2015-01-01

    Background Obstructive sleep apnea (OSA) and its main feature, chronic intermittent hypoxia (IH) during sleep, is closely associated with insulin resistance (IR) and diabetes. Rimonabant can regulate glucose metabolism and improve IR. The present study aimed to assess the effect of IH and rimonabant on glucose metabolism and insulin sensitivity, and to explore the possible mechanisms. Material/Methods Thirty-two rats were randomly assigned into 4 groups: Control group, subjected to intermitte...

  11. Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs.

    Sun, H; Huang, Y; Yin, C; Guo, J; Zhao, R; Yang, X

    2016-07-01

    Most previous studies on the effects of lipopolysaccharide (LPS) in pigs focused on the body's immune response, and few reports paid attention to body metabolism changes. To better understand the glucose metabolism changes in skeletal muscle following LPS challenge and to clarify the possible mechanism, 12 growing pigs were employed. Animals were treated with either 2 ml of saline or 15 µg/kg BW LPS, and samples were collected 6 h later. The glycolysis status and mitochondrial function in the longissimus dorsi (LD) muscle of pigs were analyzed. The results showed that serum lactate content and NADH content in LD muscle significantly increased compared with the control group. Most glycolysis-related genes expression, as well as hexokinase, pyruvate kinase and lactic dehydrogenase activity, in LD muscle was significantly higher compared with the control group. Mitochondrial complexes I and IV significantly increased, while mitochondrial ATP concentration markedly decreased. Significantly increased calcium content in the mitochondria was observed, and endoplasm reticulum (ER) stress has been demonstrated in the present study. The results showed that LPS treatment markedly changes glucose metabolism and mitochondrial function in the LD muscle of pigs, and increased calcium content induced by ER stress was possibly involved. The results provide new clues for clarifying metabolic diseases in muscle induced by LPS. PMID:26863995

  12. A glucose fuel cell for implantable brain-machine interfaces.

    Benjamin I Rapoport

    Full Text Available We have developed an implantable fuel cell that generates power through glucose oxidation, producing 3.4 μW cm(-2 steady-state power and up to 180 μW cm(-2 peak power. The fuel cell is manufactured using a novel approach, employing semiconductor fabrication techniques, and is therefore well suited for manufacture together with integrated circuits on a single silicon wafer. Thus, it can help enable implantable microelectronic systems with long-lifetime power sources that harvest energy from their surrounds. The fuel reactions are mediated by robust, solid state catalysts. Glucose is oxidized at the nanostructured surface of an activated platinum anode. Oxygen is reduced to water at the surface of a self-assembled network of single-walled carbon nanotubes, embedded in a Nafion film that forms the cathode and is exposed to the biological environment. The catalytic electrodes are separated by a Nafion membrane. The availability of fuel cell reactants, oxygen and glucose, only as a mixture in the physiologic environment, has traditionally posed a design challenge: Net current production requires oxidation and reduction to occur separately and selectively at the anode and cathode, respectively, to prevent electrochemical short circuits. Our fuel cell is configured in a half-open geometry that shields the anode while exposing the cathode, resulting in an oxygen gradient that strongly favors oxygen reduction at the cathode. Glucose reaches the shielded anode by diffusing through the nanotube mesh, which does not catalyze glucose oxidation, and the Nafion layers, which are permeable to small neutral and cationic species. We demonstrate computationally that the natural recirculation of cerebrospinal fluid around the human brain theoretically permits glucose energy harvesting at a rate on the order of at least 1 mW with no adverse physiologic effects. Low-power brain-machine interfaces can thus potentially benefit from having their implanted units

  13. Chronic fatigue syndrome in middle-aged women: the role of disorders of glucose metabolism

    Anastasiya V Pleshcheva

    2014-12-01

    Full Text Available Objectives: To determine the prevalence of chronic fatigue syndrome (CFS among middle-aged women and to assess the role of glucose metabolism disturbances in the development of this pathology. Materials and Methods: The study included 231 women from 40 to 60 years old (mean age 52.3 ± 5 years, observed at urban polyclinic in Moscow, who was referred to or was observed by an endocrinologist (n = 142, group 1, therapist (n = 56, group 2 or had a prophylactic medical examinations (n = 33, group 3. We recorded demographic and anthropometric data, accessed levels of glucose, glycated hemoglobin, insulin and calculated BMI and HOMA indexes. Results: The prevalence of CFS in the whole group of patients studied was 27%. The highest frequency of CFS is registered in the group of patients observed by the endocrinologist – 35%, and at dispensary examination – 21%, which was significantly different from the prevalence of CFS in patients seeking an appointment with a therapist – 13% (p = 0.002 and p = 0.03 for Fisher's exact test, respectively. Higher BMI, blood glucose, glycosylated hemoglobin, and HOMA insulin resistance index as naturally expected were observed in group 1, but after further division for the presence or absence of CFS, significant differences for patients with CFS were only higher fasting glucose levels in group 2. Conclusions: We determined the prevalence of CFS in the examined groups of patients and showed only a weak correlation of CFS and disturbances of glucose metabolism.

  14. Cocoa and Whey Protein Differentially Affect Markers of Lipid and Glucose Metabolism and Satiety.

    Campbell, Caroline L; Foegeding, E Allen; Harris, G Keith

    2016-03-01

    Food formulation with bioactive ingredients is a potential strategy to promote satiety and weight management. Whey proteins are high in leucine and are shown to decrease hunger ratings and increase satiety hormone levels; cocoa polyphenolics moderate glucose levels and slow digestion. This study examined the effects of cocoa and whey proteins on lipid and glucose metabolism and satiety in vitro and in a clinical trial. In vitro, 3T3-L1 preadipocytes were treated with 0.5-100 μg/mL cocoa polyphenolic extract (CPE) and/or 1-15 mM leucine (Leu) and assayed for lipid accumulation and leptin production. In vivo, a 6-week clinical trial consisted of nine panelists (age: 22.6 ± 1.7; BMI: 22.3 ± 2.1) consuming chocolate-protein beverages once per week, including placebo, whey protein isolate (WPI), low polyphenolic cocoa (LP), high polyphenolic cocoa (HP), LP-WPI, and HP-WPI. Measurements included blood glucose and adiponectin levels, and hunger ratings at baseline and 0.5-4.0 h following beverage consumption. At levels of 50 and 100 μg/mL, CPE significantly inhibited preadipocyte lipid accumulation by 35% and 50%, respectively, and by 22% and 36% when combined with 15 mM Leu. Leu treatment increased adipocyte leptin production by 26-37%. In the clinical trial, all beverages significantly moderated blood glucose levels 30 min postconsumption. WPI beverages elicited lowest peak glucose levels and HP levels were significantly lower than LP. The WPI and HP beverage treatments significantly increased adiponectin levels, but elicited no significant changes in hunger ratings. These trends suggest that combinations of WPI and cocoa polyphenols may improve markers of metabolic syndrome and satiety. PMID:26987021

  15. The influence of social status on hepatic glucose metabolism in rainbow trout Oncorhynchus mykiss.

    Gilmour, Kathleen M; Kirkpatrick, Sheryn; Massarsky, Andrey; Pearce, Brenda; Saliba, Sarah; Stephany, Céleste-Élise; Moon, Thomas W

    2012-01-01

    The effects of chronic social stress on hepatic glycogen metabolism were examined in rainbow trout Oncorhynchus mykiss by comparing hepatocyte glucose production, liver glycogen phosphorylase (GP) activity, and liver β-adrenergic receptors in dominant, subordinate, control, fasted, and cortisol-treated fish. Hepatocyte glucose production in subordinate fish was approximately half that of dominant fish, reflecting hepatocyte glycogen stores in subordinate trout that were just 16% of those in dominant fish. Fasting and/or chronic elevation of cortisol likely contributed to these differences based on similarities among subordinate, fasted, and cortisol-treated fish. However, calculation of the "glycogen gap"--the difference between glycogen stores used and glucose produced--suggested an enhanced gluconeogenic potential in subordinate fish that was not present in fasted or cortisol-treated trout. Subordinate, fasted, and cortisol-treated trout also exhibited similar GP activities (both total activity and that of the active or a form), and these activities were in all cases significantly lower than those in control trout, perhaps reflecting an attempt to protect liver glycogen stores or a modified capacity to activate GP. Dominant trout exhibited the lowest GP activities (20%-24% of the values in control trout). Low GP activities, presumably in conjunction with incoming energy from feeding, allowed dominant fish to achieve the highest liver glycogen concentrations (double the value in control trout). Liver membrane β-adrenoceptor numbers (assessed as the number of (3)H-CGP binding sites) were significantly lower in subordinate than in dominant trout, although this difference did not translate into attenuated adrenergic responsiveness in hepatocyte glucose production in vitro. Transcriptional regulation, likely as a result of fasting, was indicated by significantly lower β(2)-adrenoceptor relative mRNA levels in subordinate and fasted trout. Collectively, the data

  16. Investigation of [18F]2-fluoro-2-deoxyglucose for the measure of myocardial glucose metabolism

    Fluorine-18-labeled 2-deoxyglucose (FDG) was studied as a glucose analog for the measure of myocardial glucose metabolism. Myocardial uptake and retention, blood clearance, species dependence (dog, monkey, man), and effect of diet on uptake were investigated. Normal myocardial uptake of FDG was 3 to 4% of injected dose in dog and monkey, and 1 to 4% in man, compared with brain uptakes of 1.5 to 3% in dog, 5 to 6% in monkey, and 4 to 8% in man. The myocardial metabolic rate (MR) for glucose in the nonfasting (glycolytic) state was 2.8 times that in the fasting (ketogenic) state. Human subjects showed higher myocardial uptake after a normal meal than after a meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t/sub 1/2/ of 0.2 to 0.3 min, followed by a t/sub 1/2/ of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had half-times of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. With the ECAT positron tomograph, high image-contrast ratios were found between heart and blood (dog 3.5/1, man 14/1), heart and lung (dog 9/1, man 20/1), and heart and liver (dog 15/1, man 10/1). The FDG was taken up rapidly by the myocardium without any significant tissue clearance over a 4-hr period. The FDG exhibited excellent imaging properties. Average counting rates of 12K, 20K, and 40K c/min-mCi injected are obtained in human subjects with high, medium, and low resolutions of the ECAT tomograph. Determination of glucose and FFA MR in vivo with EACT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man

  17. Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction.

    Barry, James S; Rozance, Paul J; Brown, Laura D; Anthony, Russell V; Thornburg, Kent L; Hay, William W

    2016-04-01

    Unlike other visceral organs, myocardial weight is maintained in relation to fetal body weight in intrauterine growth restriction (IUGR) fetal sheep despite hypoinsulinemia and global nutrient restriction. We designed experiments in fetal sheep with placental insufficiency and restricted growth to determine basal and insulin-stimulated myocardial glucose and oxygen metabolism and test the hypothesis that myocardial insulin sensitivity would be increased in the IUGR heart. IUGR was induced by maternal hyperthermia during gestation. Control (C) and IUGR fetal myocardial metabolism were measured at baseline and under acute hyperinsulinemic/euglycemic clamp conditions at 128-132 days gestation using fluorescent microspheres to determine myocardial blood flow. Fetal body and heart weights were reduced by 33% (P = 0.008) and 30% (P = 0.027), respectively. Heart weight to body weight ratios were not different. Basal left ventricular (LV) myocardial blood flow per gram of LV tissue was maintained in IUGR fetuses compared to controls. Insulin increased LV myocardial blood flow by ∼38% (P flow in IUGR fetuses was 73% greater than controls. Similar to previous reports testing acute hypoxia, LV blood flow was inversely related to arterial oxygen concentration (r(2 )= 0.71) in both control and IUGR animals. Basal LV myocardial glucose delivery and uptake rates were not different between IUGR and control fetuses. Insulin increased LV myocardial glucose delivery (by 40%) and uptake (by 78%) (P < 0.01), but to a greater extent in the IUGR fetuses compared to controls. During basal and hyperinsulinemic-euglycemic clamp conditions LV myocardial oxygen delivery, oxygen uptake, and oxygen extraction efficiency were not different between groups. These novel results demonstrate that the fetal heart exposed to nutrient and oxygen deprivation from placental insufficiency appears to maintain myocardial energy supply in the IUGR condition via increased glucose uptake and

  18. Glucose Metabolism Gene Expression Patterns and Tumor Uptake of {sup 18}F-Fluorodeoxyglucose After Radiation Treatment

    Wilson, George D., E-mail: george.wilson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Thibodeau, Bryan J.; Fortier, Laura E.; Pruetz, Barbara L. [Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Galoforo, Sandra; Baschnagel, Andrew M.; Chunta, John [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Oliver Wong, Ching Yee [Department of Diagnostic Radiology and Molecular Imaging Medicine, William Beaumont Hospital, Royal Oak, Michigan (United States); Yan, Di; Marples, Brian [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Huang, Jiayi [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2014-11-01

    Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT). Methods and Materials: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm{sup 3} they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data. Results: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport–related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index. Conclusion: {sup 18}F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism.

  19. Voxel-based statistical analysis of cerebral glucose metabolism in patients with permanent vegetative state after acquired brain injury

    Yong Wook Kim; Hyoung Seop Kim; Young-Sil An; Sang Hee Im

    2010-01-01

    Background Permanent vegetative state is defined as the impaired level of consciousness longer than 12 months after traumatic causes and 3 months after non-traumatic causes of brain injury. Although many studies assessed the cerebral metabolism in patients with acute and persistent vegetative state after brain injury, few studies investigated the cerebral metabolism in patients with permanent vegetative state. In this study, we performed the voxel-based analysis of cerebral glucose metabolism and investigated the relationship between regional cerebral glucose metabolism and the severity of impaired consciousness in patients with permanent vegetative state after acquired brain injury.Methods We compared the regional cerebral glucose metabolism as demonstrated by F-18 fluorodeoxyglucose positron emission tomography from 12 patients with permanent vegetative state after acquired brain injury with those from 12 control subjects. Additionally, covariance analysis was performed to identify regions where decreased changes in regional cerebral glucose metabolism significantly correlated with a decrease of level of consciousness measured by JFK-coma recovery scare. Statistical analysis was performed using statistical parametric mapping.Results Compared with controls, patients with permanent vegetative state demonstrated decreased cerebral glucose metabolism in the left precuneus, both posterior cingulate cortices, the left superior parietal lobule (Pcorrected <0.001), and increased cerebral glucose metabolism in the both cerebellum and the right supramarginal cortices (Pcorrected <0.001). In the covariance analysis, a decrease in the level of consciousness was significantly correlated with decreased cerebral glucose metabolism in the both posterior cingulate cortices (Puncorrected <0.005).Conclusion Our findings suggest that the posteromedial parietal cortex, which are part of neural network for consciousness, may be relevant structure for pathophysiological mechanism

  20. 高糖“代谢记忆”介导对血管内皮细胞功能的损伤%Effects of metabolic memory mediated by high glucose on functional injury of human umbilical vein endothelial cells

    黎慧清; 宋惠杰; 廖云飞; 刘振华; 邓秀玲; 张皎月; 陈璐璐

    2012-01-01

    Cultured primary human umbilical vein endothelial cells (HUVECs) were divided into 4 groups:normal control( NG ),persistent high glucose ( HG ),hyperglycemia group ( TG ),and mannitol control ( MA )groups.After 1,4,and 7 days of culture,cells were collected.Cell proliferation,cell apoptosis,ROS,SOD,MDA,and NO level,eNOS mRNA and protein level were measured.Endothelial cell proliferation was inhibited in HG,TG,and MA groups compared with NG group.Hyperglycemia memory induced apoptosis of endothelial cells,increased ROS and MDA generation,and down-regulated intracellular SOD level,findings similar to those in HG group.After 24 h of culturing,eNOS expression and NO generation in both HG and TG groups were higher than those in NG group.However,after 7 days of culturing,eNOS expression and NO generation in both HG and TG groups were lower than those in NG group.These results suggest that in hyperglycemia memory cell model,transient hyperglysemia may lead to persistent imbalance in oxidative stress and reduce endothelium-derived relaxing factor NO level,indicating that hyperglycemia memory may play an important role in persistent vascular endothelial cell injury.%原代人脐静脉内皮细胞分为:正常对照组、持续高糖组、高糖记忆组、渗透压对照组.各组细胞培养第1、4、7天评估内皮细胞增殖、凋亡水平,测定细胞内ROS、SOD、丙二醛活性,eNOS mRNA和蛋白水平,测定内皮细胞上清液中NO水平.高糖组及高糖记忆组人原代脐静脉内皮细胞增殖受到抑制,甘露醇对照组亦受到抑制,高糖使脐静脉内皮细胞凋亡增加,ROS,丙二醛水平升高,SOD水平下降.脐静脉内皮细胞恢复正糖培养后,上述指标未能恢复至正常对照组水平.与正常对照组相比,高糖组及高糖记忆组eNOS及NO水平呈先升高后下降趋势,而高渗对照组与正常对照组相比无差异.结果提示血管内皮细胞存在高血糖代谢记忆现象;短暂高血糖可导致血管

  1. Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats.

    Ren, Bei; Qin, Weiwei; Wu, Feihua; Wang, Shanshan; Pan, Cheng; Wang, Liying; Zeng, Biao; Ma, Shiping; Liang, Jingyu

    2016-02-15

    Vascular endothelial dysfunction is regarded as the initial step of vascular complications in diabetes mellitus. This study investigated the amelioration of apigenin and naringenin in type 2 diabetic (T2D) rats induced by high-fat diet and streptozotocin and explored the underlying mechanism. Apigenin or naringenin was intragastrically administered at 50 or 100mg/kg once a day for 6 weeks. Biochemical parameters including blood glucose, glycated serum protein, serum lipid, insulin, superoxide dismutase (SOD), malonaldehyde and intercellular adhesion molecule-1 (ICAM-1) were measured. Vascular reactivity in isolated thoracic aortic rings was examined. Pathological features of the thoracic aorta were further observed through optical microscopy and transmission electron microscopy. Lastly, we evaluated their effects on insulin resistance of palmitic acid (PA)-induced endothelial cells. Compared with diabetic control group, apigenin and naringenin significantly decreased the levels of blood glucose, serum lipid, malonaldehyde, ICAM-1 and insulin resistance index, increased SOD activity and improved impaired glucose tolerance. Apigenin and naringenin restored phenylephrine-mediated contractions and acetylcholine or insulin-induced relaxations in aortic tissues. Furthermore, pathological damage in the thoracic aorta of apigenin and naringenin groups was more remissive than diabetic control group. In vitro, apigenin and naringenin inhibited NF-κB activation and ICAM-1 mRNA expression in PA-treated endothelial cells and improved nitric oxide production in the presence of insulin. In conclusion, both apigenin and naringenin can ameliorate glucose and lipid metabolism, as well as endothelial dysfunction in T2D rats at least in part by down-regulating oxidative stress and inflammation. In general, apigenin showed greater potency than naringenin equivalent. PMID:26801071

  2. Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism.

    Thomas Galbo

    Full Text Available In type 2 Diabetes (T2D free fatty acids (FFAs in plasma are increased and hepatic insulin resistance is "selective", in the sense that the insulin-mediated decrease of glucose production is blunted while insulin's effect on stimulating lipogenesis is maintained. We investigated the molecular mechanisms underlying this pathogenic paradox. Primary rat hepatocytes were exposed to palmitate for twenty hours. To establish the physiological relevance of the in vitro findings, we also studied insulin-resistant Zucker Diabetic Fatty (ZDF rats. While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1 was inhibited in palmitate-exposed cells. Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. In contrast, similar to findings in human T2D, the ability of insulin to induce triglyceride (TG accumulation and transcription of the enzymes that catalyze de novo lipogenesis and TG assembly was unaffected. Insulin-induction of these genes could, however, be blocked by inhibition of the atypical PKCs (aPKCs. The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A was increased in the insulin-resistant cells. Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity.

  3. Associations between ultrasound measures of abdominal fat distribution and indices of glucose metabolism in a population at high risk of type 2 diabetes: the ADDITION-PRO study.

    Annelotte Philipsen

    Full Text Available Visceral adipose tissue measured by CT or MRI is strongly associated with an adverse metabolic risk profile. We assessed whether similar associations can be found with ultrasonography, by quantifying the strength of the relationship between different measures of obesity and indices of glucose metabolism in a population at high risk of type 2 diabetes.A cross-sectional analysis of 1342 participants of the ADDITION-PRO study. We measured visceral adipose tissue and subcutaneous adipose tissue with ultrasonography, anthropometrics and body fat percentage by bioelectrical impedance. Indices of glucose metabolism were derived from a three point oral glucose tolerance test. Linear regression of obesity measures on indices of glucose metabolism was performed.Mean age was 66.2 years, BMI 26.9kg/m2, subcutaneous adipose tissue 2.5cm and visceral adipose tissue 8.0cm. All measures of obesity were positively associated with indicators of glycaemia and inversely associated with indicators of insulin sensitivity. Associations were of equivalent magnitude except for subcutaneous adipose tissue and the visceral/subcutaneous adipose tissue ratio, which showed weaker associations. One standard deviation difference in BMI, visceral adipose tissue, waist circumference, waist/height ratio and body fat percentage corresponded approximately to 0.2mmol/l higher fasting glucose, 0.7mmol/l higher 2-hr glucose, 0.06-0.1% higher HbA1c, 30 % lower HOMA index of insulin sensitivity, 20% lower Gutt's index of insulin sensitivity, and 100 unit higher Stumvoll's index of beta-cell function. After adjustment for waist circumference visceral adipose tissue was still significantly associated with glucose intolerance and insulin resistance, whereas there was a trend towards inverse or no associations with subcutaneous adipose tissue. After adjustment, a 1cm increase in visceral adipose tissue was associated with ~5% lower insulin sensitivity (p≤0.0004 and ~0.18mmol/l higher 2-hr

  4. Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles

    Hu C

    2015-03-01

    Full Text Available Chenxia Hu,1 Martin Niestroj,2,3 Daniel Yuan,4 Steven Chang,5 Jie Chen5,6 1Faculty of Chinese Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Canadian Light Source, Saskatoon, SK, Canada; 3Physics Department, Bonn University, Bonn, Germany; 4Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA; 5Faculty of Engineering, University of Alberta, Edmonton, AB, Canada; 6Canadian National Research Council/National Institute for Nanotechnology, Edmonton, AB, Canada Abstract: Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain. Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs with thio-PEG (polyethylene glycol and thio-glucose, the resulting functionalized GNPs (Glu-GNPs were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells’ elevated glucose consumption

  5. Regional cerebral glucose metabolism in frontotemporal dementia: a study with FDG PET

    Frontotemporal dementia (FTD) is a common cause of presenile dementia. We investigated the regional cerebral glucose metabolic impairments in patients with FTD using FDG PET. We analysed the regional metabolic patterns on FDG PET images obtained from 30 patients with FTD and age- and sex-matched 15 patients with Alzheimers disease (AD) and 11 healthy subjects using SPM99. We also compared the inter-hemispheric metabolic asymmetry among the three groups by counting the total metabolic activity of each hemisphere and computing asymmetry index (AL) between hemispheres. The hypometabolic brain regions in FTD patients compared with healthy controls were as follows: superior middle and medial frontal lobules, superior and middle temporal lobules, anterior and posterior cingulate gyri, uncus, insula, lateral globus pallidus and thalamus. The regions with decreased metabolism in FTD patients compared with AD patients were as follows: superior, inferior and medial frontal lobules, anterior cingulate gyrus, and caudate nucleus. Twenty-five (83%) out of the 30 FTD patients had AI values that was beyond the 95% confidence interval of the AI values obtained from healthy controls; 10 patients had hypometabolism more severe on the right and 15 patients had the opposite pattern. In comparison, 10 (67%) out of the 15 AD patients had asymmetric metabolism. Our SPM analysis of FDG PET revealed additional areas of decreased metabolism in FTD patients compared with prior studies using the ROI method, involving frontal, temporal, cingulate gyrus, corpus callosum, uncus, insula, and some subcortical areas. The inter-hemispheric metabolic asymmetry was common in FTD patients, which can be another metabolic feature that helps differentiate FTD from AD

  6. Regional cerebral glucose metabolism in frontotemporal dementia: a study with FDG PET

    Cho, S. S.; Jeong, J.; Kang, S. J.; Na, D. L.; Choe, Y. S.; Lee, K. H.; Choi, Y.; Kim, B. T.; Kim, S. E. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    Frontotemporal dementia (FTD) is a common cause of presenile dementia. We investigated the regional cerebral glucose metabolic impairments in patients with FTD using FDG PET. We analysed the regional metabolic patterns on FDG PET images obtained from 30 patients with FTD and age- and sex-matched 15 patients with Alzheimers disease (AD) and 11 healthy subjects using SPM99. We also compared the inter-hemispheric metabolic asymmetry among the three groups by counting the total metabolic activity of each hemisphere and computing asymmetry index (AL) between hemispheres. The hypometabolic brain regions in FTD patients compared with healthy controls were as follows: superior middle and medial frontal lobules, superior and middle temporal lobules, anterior and posterior cingulate gyri, uncus, insula, lateral globus pallidus and thalamus. The regions with decreased metabolism in FTD patients compared with AD patients were as follows: superior, inferior and medial frontal lobules, anterior cingulate gyrus, and caudate nucleus. Twenty-five (83%) out of the 30 FTD patients had AI values that was beyond the 95% confidence interval of the AI values obtained from healthy controls; 10 patients had hypometabolism more severe on the right and 15 patients had the opposite pattern. In comparison, 10 (67%) out of the 15 AD patients had asymmetric metabolism. Our SPM analysis of FDG PET revealed additional areas of decreased metabolism in FTD patients compared with prior studies using the ROI method, involving frontal, temporal, cingulate gyrus, corpus callosum, uncus, insula, and some subcortical areas. The inter-hemispheric metabolic asymmetry was common in FTD patients, which can be another metabolic feature that helps differentiate FTD from AD.

  7. Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the Sysdimet study.

    Maria Lankinen

    Full Text Available BACKGROUND: Due to the growing prevalence of type 2 diabetes, new dietary solutions are needed to help improve glucose and lipid metabolism in persons at high risk of developing the disease. Herein we investigated the effects of low-insulin-response grain products, fatty fish, and berries on glucose metabolism and plasma lipidomic profiles in persons with impaired glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Altogether 106 men and women with impaired glucose metabolism and with at least two other features of the metabolic syndrome were included in a 12-week parallel dietary intervention. The participants were randomized into three diet intervention groups: (1 whole grain and low postprandial insulin response grain products, fatty fish three times a week, and bilberries three portions per day (HealthyDiet group, (2 Whole grain enriched diet (WGED group, which includes principally the same grain products as group (1, but with no change in fish or berry consumption, and (3 refined wheat breads (Control. Oral glucose tolerance, plasma fatty acids and lipidomic profiles were measured before and after the intervention. Self-reported compliance with the diets was good and the body weight remained constant. Within the HealthyDiet group two hour glucose concentration and area-under-the-curve for glucose decreased and plasma proportion of (n-3 long-chain PUFAs increased (False Discovery Rate p-values <0.05. Increases in eicosapentaenoic acid and docosahexaenoic acid associated curvilinearly with the improved insulin secretion and glucose disposal. Among the 364 characterized lipids, 25 changed significantly in the HealthyDiet group, including multiple triglycerides incorporating the long chain (n-3 PUFA. CONCLUSIONS/SIGNIFICANCE: The results suggest that the diet rich in whole grain and low insulin response grain products, bilberries, and fatty fish improve glucose metabolism and alter the lipidomic profile. Therefore, such a diet may have a

  8. Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells.

    Hamano, Kunihisa; Nakagawa, Yuko; Ohtsu, Yoshiaki; Li, Longfei; Medina, Johan; Tanaka, Yuji; Masuda, Katsuyoshi; Komatsu, Mitsuhisa; Kojima, Itaru

    2015-07-01

    Glucose activates the glucose-sensing receptor T1R3 and facilitates its own metabolism in pancreatic β-cells. An inhibitor of this receptor would be helpful in elucidating the physiological function of the glucose-sensing receptor. The present study was conducted to examine whether or not lactisole can be used as an inhibitor of the glucose-sensing receptor. In MIN6 cells, in a dose-dependent manner, lactisole inhibited insulin secretion induced by sweeteners, acesulfame-K, sucralose and glycyrrhizin. The IC50 was ∼4 mmol/l. Lactisole attenuated the elevation of cytoplasmic Ca2+ concentration ([Ca2+]c) evoked by sucralose and acesulfame-K but did not affect the elevation of intracellular cAMP concentration ([cAMP]c) induced by these sweeteners. Lactisole also inhibited the action of glucose in MIN6 cells. Thus, lactisole significantly reduced elevations of intracellular [NADH] and intracellular [ATP] induced by glucose, and also inhibited glucose-induced insulin secretion. To further examine the effect of lactisole on T1R3, we prepared HEK293 cells stably expressing mouse T1R3. In these cells, sucralose elevated both [Ca2+]c and [cAMP]c. Lactisole attenuated the sucralose-induced increase in [Ca2+]c but did not affect the elevation of [cAMP]c. Finally, lactisole inhibited insulin secretion induced by a high concentration of glucose in mouse islets. These results indicate that the mouse glucose-sensing receptor was inhibited by lactisole. Lactisole may be useful in assessing the role of the glucose-sensing receptor in mouse pancreatic β-cells. PMID:25994004

  9. Three-body system metaphor for the two-slit experiment and Escherichia coli lactose-glucose metabolism.

    Asano, Masanari; Khrennikov, Andrei; Ohya, Masanori; Tanaka, Yoshiharu; Yamato, Ichiro

    2016-05-28

    We compare the contextual probabilistic structures of the seminal two-slit experiment (quantum interference experiment), the system of three interacting bodies andEscherichia colilactose-glucose metabolism. We show that they have the same non-Kolmogorov probabilistic structure resulting from multi-contextuality. There are plenty of statistical data with non-Kolmogorov features; in particular, the probabilistic behaviour of neither quantum nor biological systems can be described classically. Biological systems (even cells and proteins) are macroscopic systems and one may try to present a more detailed model of interactions in such systems that lead to quantum-like probabilistic behaviour. The system of interactions between three bodies is one of the simplest metaphoric examples for such interactions. By proceeding further in this way (by playing withn-body systems) we shall be able to find metaphoric mechanical models for complex bio-interactions, e.g. signalling between cells, leading to non-Kolmogorov probabilistic data. PMID:27091163

  10. Magnetic Resonance Imaging of Glucose Uptake and Metabolism in Patients with Head and Neck Cancer

    Wang, Jihong; Weygand, Joseph; Hwang, Ken-Pin; Mohamed, Abdallah S. R.; Ding, Yao; Fuller, Clifton D.; Lai, Stephen Y.; Frank, Steven J.; Zhou, Jinyuan

    2016-01-01

    Imaging metabolic dysfunction, a hallmark of solid tumors, usually requires radioactive tracers. Chemical exchange saturation transfer (CEST) imaging can potentially detect and visualize glucose uptake and metabolism, without the need for radioisotopes. Here, we tested the feasibility of using glucose CEST (glucoCEST) to image unlabeled glucose uptake in head and neck cancer by using a clinical 3T magnetic resonance imaging (MRI) scanner. The average CEST contrast between tumors and normal tissue in 17 patients was 7.58% (P = 0.006) in the 3–4 ppm offset frequency range and 5.06% (P = 0.02) in 1–5 ppm range. In a subgroup of eight patients, glucoCEST signal enhancement was higher in tumors than in normal muscle (4.98% vs. 1.28%, P < 0.021). We conclude that glucoCEST images of head and neck cancer can be obtained with a clinical 3T MRI scanner. PMID:27461165

  11. Roles of peroxisome proliferator-activated receptors in glucose metabolism in HepG2 cells%过氧化物酶体增殖激活受体γ或α在改善HepG2细胞糖代谢中的作用

    宋璐璐; 萧建中; 邢小燕; 张敏; 杨文英

    2011-01-01

    目的:探讨过氧化物酶体增殖激活受体γ(PPAR-γ)或α(PPAR-α)激动剂改善HepG2细胞胰岛素抵抗的机制.方法:体外培养人肝癌细胞系HepG2细胞并用棕榈酸处理造成胰岛素抵抗模型,分别给予或PPAR-γ激动剂吡格列酮或高选择性PPAR-α激动剂WY14643处理,酶法测定葡萄糖的消耗量和糖酵解产物;同时定量PCR测定PPAR-γ、PPAR-α及糖酵解基因的表达变化.结果:吡格列酮增加胰岛素抵抗的HepG2细胞葡萄糖消耗,诱导糖酵解糖相关基因表达上调,促进糖酵解产物生成.WY14643部分改善胰岛素抵抗,对糖酵解相关基因表达及糖酵解产物水平没有显著影响.结论:PPAR-y激动剂可能通过促进糖酵解改善HepG2细胞的胰岛素抵抗.%Objective:To characterize the mechanisms of peroxisome proliferator-activated receptors(PPAR)γ or α agonists in improving insulin resistance of human hepatoma cells.Methods:The model of insulin resistance was established with HepG2 cells cultured at high concentrations of palmitate.Insulin resistant HepG2 cells were treated with the PPAR-γ agonist pioglitazone or the PPAR-α agonist WY14643.Quantification of glucose consumption and glycolysis products pyruvate and lactate were performed. Quantitative RT-PCR was employed to analyze mRNA expression of PPAR-γ/α and glycolysis related genes. Results:Palmitate treatment decreased glucose consumption of HepG2 cells and induces insulin resistance. Pioglitazone increased glucose consumption of both normal and insulin resistant HepG2 cells.It induced an up-regulation of glycolysis related gene expression and strongly increased glycolysis reflected by elevated pyruvate and lactate production. WY14643 slightly increased glucose consumption of insulin resistant HepG2 cells,but had no effect on glycolysis gene expression. Conelusion:PPAR-γ or PPAR-α can enhance glucose metabolism in HepG2 cells through different mechanisms.PPAR-γ probablely improver insulin

  12. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

  13. Metabolism of stromal and immune cells in health and disease

    Ghesquière, Bart; Wong, Brian W.; Kuchnio, Anna; Carmeliet, Peter

    2014-01-01

    Cancer cells have been at the centre of cell metabolism research, but the metabolism of stromal and immune cells has received less attention. Nonetheless, these cells influence the progression of malignant, inflammatory and metabolic disorders. Here we discuss the metabolic adaptations of stromal and immune cells in health and disease, and highlight how metabolism determines their differentiation and function.

  14. Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

    Vladimir O Murovets

    Full Text Available The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+ inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-. Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain.

  15. The click-compatible sugar 6-deoxy-alkynyl glucose metabolically incorporates into Arabidopsis root hair tips and arrests their growth.

    McClosky, Daniel D; Wang, Bo; Chen, Gong; Anderson, Charles T

    2016-03-01

    Plant cell walls are dynamic structures whose polysaccharide components are rearranged and recycled during growth and morphogenesis. Covalent fluorescent tagging of these polysaccharides following a metabolic labeling approach can help elucidate these changes. Herein reported are the synthesis and seedling-incorporation of a plant polysaccharide chemical reporter, 6-deoxy-alkynyl glucose (6dAG), that is modeled on D-glucose. Whereas fucose-alkyne, a previously reported chemical reporter for pectin, incorporates diffusely throughout growing cell walls, 6dAG incorporated specifically into root hair tips. This incorporation occurs in a time- and concentration-dependent manner. 6dAG exposure both induces and colocalizes with callose deposition in this tissue, and arrests both root hair and root growth. These results show that plants can incorporate an additional alkynyl-modified sugar analog into their metabolism, and into a discrete subcellular location. PMID:26833385

  16. Effect of dietary protein on lipid and glucose metabolism: implications for metabolic health

    Rietman, A.

    2015-01-01

    Abstract Background: Diet is an important factor in the development of the Metabolic Syndrome (Mets) and type 2 Diabetes Mellitus. Accumulation of intra hepatic lipid (IHL) can result in non-alcoholic fatty liver disease (NAFLD), which is sometimes considered the he

  17. Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

    Darren J Creek

    2015-03-01

    Full Text Available Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been widely held to be the sole route of glucose metabolism. Whilst pyruvate is the major end-product of glucose catabolism, its transamination product, alanine, is also produced in significant quantities. The oxidative branch of the pentose phosphate pathway is operative, although the non-oxidative branch is not. Ribose 5-phosphate generated through this pathway distributes widely into nucleotide synthesis and other branches of metabolism. Acetate, derived from glucose, is found associated with a range of acetylated amino acids and, to a lesser extent, fatty acids; while labelled glycerol is found in many glycerophospholipids. Glucose also enters inositol and several sugar nucleotides that serve as precursors to macromolecule biosynthesis. Although a Krebs cycle is not operative, malate, fumarate and succinate, primarily labelled in three carbons, were present, indicating an origin from phosphoenolpyruvate via oxaloacetate. Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression. In addition, glucose derivatives enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and orotate.

  18. The effect of 3-bromopyruvate on human colorectal cancer cells is dependent on glucose concentration but not hexokinase II expression

    Ho, Nelson; Morrison, Jodi; Silva, Andreza; Coomber, Brenda L.

    2016-01-01

    Cancer cells heavily rely on the glycolytic pathway regardless of oxygen tension. Hexokinase II (HKII) catalyses the first irreversible step of glycolysis and is often overexpressed in cancer cells. 3-Bromopyruvate (3BP) has been shown to primarily target HKII, and is a promising anti-cancer compound capable of altering critical metabolic pathways in cancer cells. Abnormal vasculature within tumours leads to heterogeneous microenvironments, including glucose availability, which may affect dru...

  19. Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells.

    Yilin Cao

    Full Text Available T lymphocytes (T cells undergo metabolic reprogramming after activation to provide energy and biosynthetic materials for growth, proliferation and differentiation. Distinct T cell subsets, however, adopt metabolic programs specific to support their needs. As CD4 T cells coordinate adaptive immune responses while CD8 T cells become cytotoxic effectors, we compared activation-induced proliferation and metabolic reprogramming of these subsets. Resting CD4 and CD8 T cells were metabolically similar and used a predominantly oxidative metabolism. Following activation CD8 T cells proliferated more rapidly. Stimulation led both CD4 and CD8 T cells to sharply increase glucose metabolism and adopt aerobic glycolysis as a primary metabolic program. Activated CD4 T cells, however, remained more oxidative and had greater maximal respiratory capacity than activated CD8 T cells. CD4 T cells were also associated with greater levels of ROS and increased mitochondrial content, irrespective of the activation context. CD8 cells were better able, however, to oxidize glutamine as an alternative fuel source. The more glycolytic metabolism of activated CD8 T cells correlated with increased capacity for growth and proliferation, along with reduced sensitivity of cell growth to metabolic inhibition. These specific metabolic programs may promote greater growth and proliferation of CD8 T cells and enhance survival in diverse nutrient conditions.

  20. The Relationship Between Coronary Artery Disease and Undiagnosed Glucose Metabolism Disorders in Patients who Have Undergone Angiography

    Halil Akbulut

    2013-12-01

    Full Text Available Purpose: Diabetes mellitus (DM and coronary artery disease (CAD, seen frequently in the general population, are major causes of morbidity and mortality. DM, controllable through treatment, is one of the most important risk factors for the development of cardiovascular diseases. Material and Method: Our study included patients who had undiagnosed glucose metabolism disorders and had undergone an angiography under elective conditions. To diagnose the glucose metabolism disorders, these patients were given the oral glucose tolerance test (OGTT (75 g within 5-10 days after angiography. Results: In our study, 24.5% (n=79 of patients had isolated impaired fasting glucose, 9.3% (n=30 had isolated impaired glucose tolerance, 21.1% (n=68 had both impaired fasting glucose and impaired glucose tolerance, and 5% (n=16 had DM. None of these patients knew about their condition beforehand. Only 40.1% (n=129 of patients had normal OGTT results. Discussion: If patients with suspected CAD found to have blocked arteries after an angiography are screened for DM, glucose metabolism disorders can be diagnosed early. When caught early, the long-term complications can be avoided, resulting in significant savings for health care costs. Turk Jem 2013; 17: 111-5