WorldWideScience

Sample records for cell glucose metabolism

  1. Glucose starvation is required for insulin stimulation of glucose uptake and metabolism in cultured microvascular endothelial cells

    In the present study we determined the uptake and disposition of glucose in serum-deprived rabbit coronary microvessel endothelial (RCME) cells. RCME cells exhibited stereospecific hexose uptake inhibited by cytochalasin B. Pretreatment of the RCME cells with potassium cyanide or 2,4-dinitrophenol inhibited 2-deoxyglucose uptake but not 3-O-methylglucose transport. A major proportion (30-60%) of the 2-deoxyglucose present in the RCME cells was not phosphorylated. These two observations suggested that the rate-limiting step in the uptake of 2-deoxyglucose was not transport but rather the phosphorylation of 2-deoxyglucose to 2-deoxyglucose 6-phosphate. When glucose-deprived cells were incubated 2 hr with [U-14C]glucose the disposition of the label was as follows: glycogen 60%, acid-soluble fraction 30%, and lipid less than 5%. In contrast glucose-fed cells exhibited lower overall glucose incorporation, and a slightly different disposition: glycogen 45%, acid-soluble fraction 50%, and lipid 5%. Glucose-deprived RCME cells also exhibited greater basal levels of 2-deoxyglucose uptake compared to glucose-fed cells. RCME cells incubated in the absence of glucose and serum for 16 hr exhibited dose-dependent insulin stimulation of hexose uptake and subsequent metabolism to macromolecules (i.e., glycogen and the acid-soluble fraction). Significant effects of insulin were observed with concentrations as low as 2 x 10(-10) M, well within the physiological range. In contrast, cells preincubated in serum-free culture medium containing 5.5 mM glucose did not exhibit insulin-enhanced hexose uptake or glucose metabolism (even at doses as high as 10(-7) M). These studies indicate that the effects of insulin on rabbit coronary microvascular endothelial cell glucose uptake and metabolism require both serum and glucose deprivation

  2. 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)

  3. Glucose Metabolism Attenuates p53 and Puma-dependent Cell Death upon Growth Factor Deprivation*

    Zhao, Yuxing; Coloff, Jonathan L.; Ferguson, Emily C.; Jacobs, Sarah R.; Cui, Kai; Rathmell, Jeffrey C.

    2008-01-01

    Growth factor stimulation and oncogenic transformation lead to increased glucose metabolism that may provide resistance to cell death. We have previously demonstrated that elevated glucose metabolism characteristic of stimulated or cancerous cells can stabilize the anti-apoptotic Bcl-2 family protein Mcl-1 through inhibition of GSK-3. Here we show that the pro-apoptotic Bcl-2 family protein, Puma, is also metabolically regulated. Growth factor deprivation led to the lo...

  4. Metabolic activation of glucose low-responsive beta-cells by glyceraldehyde correlates with their biosynthetic activation in lower glucose concentration range but not at high glucose.

    Martens, G A; Wang, Q; Kerckhofs, K; Stangé, G; Ling, Z; Pipeleers, D

    2006-11-01

    Insulin synthesis and release activities of beta-cells can be acutely regulated by glucose through its glycolytic and mitochondrial breakdown involving a glucokinase-dependent rate-limiting step. Isolated beta-cell populations are composed of cells with intercellular differences in acute glucose responsiveness that have been attributed to differences in glucokinase (GK) expression and activity. This study first shows that glyceraldehyde can be used as GK-bypassing oxidative substrate and then examines whether the triose can metabolically activate beta-cells with low glucose responsiveness. Glyceraldehyde 1 mm induced a similar cellular (14)CO(2) output and metabolic redox state as glucose 4 mM. Using flow cytometric analysis, glyceraldehyde (0.25-2 mM) was shown to concentration-dependently increase the percent metabolically activated cells at all tested glucose concentrations (2.5-20 mM). Its ability to activate beta-cells that are unresponsive to the prevailing glucose level was further illustrated in glucose low-responsive cells that were isolated by flow sorting. Metabolic activation by glyceraldehyde was associated with an activation of nutrient-driven translational control proteins and an increased protein synthetic response to glucose, however not beyond the maximal rates that are inducible by glucose alone. It is concluded that glucose low-responsive beta-cells can be metabolically activated by the GK-bypassing glyceraldehyde, increasing their acute biosynthetic response to glucose but not their maximal glucose-inducible biosynthetic capacity, which is considered subject to chronic regulation. PMID:16916947

  5. Development of the method of determining the 3H-Glucose metabolism by tumor cells

    Objective: To measure the glucose metabolic rate (GMR) in tumor cells. Methods: HCT116 cells were seeded in a density of 2 x 105 and grown to 90% confluence. Then 5- 3H-glucose was added into the medium. Thirty minutes later, cells were killed while 3H-H2O was separated from the labeled glucose by column chromatography. Radioactivity of 3H-H2O was counted using scintillation counter. At last glucose metabolic rate (GMR) in 30 minutes was calculated. Results: The chromatography column was found to exclude more than 99% of the total H-glucose from the perfusate if there was more than 5.0 ml of suspension loaded into the column. The glucose metabolic rate (GMR) of 3.7 x 105 HCT116 cells was 1.23% in 30 minutes. Conclusion: It is proved that by using this method one can determine the glucose metabolic rate precisely via adding 5-3H-glucose into the medium. Using this method, the tumor cells' glucose metabolism and energy providing will be studied better. (authors)

  6. Glycated albumin suppresses glucose-induced insulin secretion by impairing glucose metabolism in rat pancreatic ?-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 ? 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 ?U/3 islets/h for G3 (P = 0.920, and 154 9.3 and 126.1 7.3 ?U/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 ?-cells through impairment of intracellular glucose metabolism.

  7. Glucose consumption of inflammatory cells masks metabolic deficits in the brain.

    Backes, Heiko; Walberer, Maureen; Ladwig, Anne; Rueger, Maria A; Neumaier, Bernd; Endepols, Heike; Hoehn, Mathias; Fink, Gereon R; Schroeter, Michael; Graf, Rudolf

    2016-03-01

    Inflammatory cells such as microglia need energy to exert their functions and to maintain their cellular integrity and membrane potential. Subsequent to cerebral ischemia, inflammatory cells infiltrate tissue with limited blood flow where neurons and astrocytes died due to insufficient supply with oxygen and glucose. Using dual tracer positron emission tomography (PET), we found that concomitant with the presence of inflammatory cells, transport and consumption of glucose increased up to normal levels but returned to pathological levels as soon as inflammatory cells disappeared. Thus, inflammatory cells established sufficient glucose supply to satisfy their energy demands even in regions with insufficient supply for neurons and astrocytes to survive. Our data suggest that neurons and astrocytes died from oxygen deficiency and inflammatory cells metabolized glucose non-oxidatively in regions with residual availability. As a consequence, glucose metabolism of inflammatory cells can mask metabolic deficits in neurodegenerative diseases. We further found that the PET tracer did not bind to inflammatory cells in severely hypoperfused regions and thus only a part of the inflammation was detected. We conclude that glucose consumption of inflammatory cells should be taken into account when analyzing disease-related alterations of local cerebral metabolism. PMID:26747749

  8. Glucose consumption of inflammatory cells masks metabolic deficits in the brain

    Backes, Heiko; Walberer, Maureen; Ladwig, Anne; Rueger, Maria A.; Neumaier, Bernd; Endepols, Heike; Hoehn, Mathias; Fink, Gereon R.; Schroeter, Michael; Graf, Rudolf

    2016-01-01

    Inflammatory cells such as microglia need energy to exert their functions and to maintain their cellular integrity and membrane potential. Subsequent to cerebral ischemia, inflammatory cells infiltrate tissue with limited blood flow where neurons and astrocytes died due to insufficient supply with oxygen and glucose. Using dual tracer positron emission tomography (PET), we found that concomitant with the presence of inflammatory cells, transport and consumption of glucose increased up to normal levels but returned to pathological levels as soon as inflammatory cells disappeared. Thus, inflammatory cells established sufficient glucose supply to satisfy their energy demands even in regions with insufficient supply for neurons and astrocytes to survive. Our data suggest that neurons and astrocytes died from oxygen deficiency and inflammatory cells metabolized glucose non-oxidatively in regions with residual availability. As a consequence, glucose metabolism of inflammatory cells can mask metabolic deficits in neurodegenerative diseases. We further found that the PET tracer did not bind to inflammatory cells in severely hypoperfused regions and thus only a part of the inflammation was detected. We conclude that glucose consumption of inflammatory cells should be taken into account when analyzing disease-related alterations of local cerebral metabolism. PMID:26747749

  9. GRP78 enhances the glutamine metabolism to support cell survival from glucose deficiency by modulating the ?-catenin signaling

    Li, Zongwei; Wang, Yingying; Wu, Haili; Zhang, Lichao; Yang, Peng; Li, Zhuoyu

    2014-01-01

    To support the high rates of proliferation, cancer cells undergo the metabolic reprogramming: aerobic glycolysis and glutamine addiction. Though glucose regulated protein 78 (GRP78) is a glucose-sensing protein and frequently highly expressed in tumor cells, its roles in glucose and glutamine metabolic regulation remain poorly unknown. We report here that glucose deficiency-induced GRP78 enhances ?-catenin signaling and consequently promotes its downstream c-Myc-mediated glutamine metabolism ...

  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. Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides

    Birsoy, Kıvanç; Possemato, Richard; Lorbeer, Franziska K.; Bayraktar, Erol C.; Thiru, Prathapan; Yucel, Burcu; Wang, Tim; Chen, Walter W.; Clish, Clary B.; Sabatini, David M.

    2014-04-01

    As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues, cancer cells must adapt their metabolism to the tumour microenvironment. A better understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function. Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.

  12. Quantitative aspects of glucose and glutamine metabolism by intestinal cells.

    Newsholme, E. A.; Carrié, A L

    1994-01-01

    Gut fuel utilisation has several unique features. Arterial and luminal fuels provide nutrition for the enterocyte, the former being of more importance. This factor, and the heterogeneity of cell types within the gut makes it difficult to define its fuel utilisation. Metabolic control logic suggests that modulation of the maximal activity of any pathway resides in those enzymes that operate in vivo at rates far below their maximal capacity and that catalyse non-equilibrium reactions. On this b...

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

    Renato Martins da Silva; Bárbara Della Noce; Camila Fernanda Waltero; Evenilton Pessoa Costa; Leonardo Araujo de Abreu; Naftaly Wang'ombe Githaka; Jorge Moraes; Helga Fernandes Gomes; Satoru Konnai; Itabajara da Silva Vaz; Kazuhiko Ohashi; Carlos Logullo

    2015-01-01

    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 ...

  14. SCAP links glucose to lipid metabolism in cancer cells

    Guo, Deliang

    2016-01-01

    We recently uncovered that glucose is a critical activator of sterol regulatory element-binding proteins (SREBPs). Glucose promotes SREBP-cleavage activating protein (SCAP)/SREBP complex trafficking from the ER to the Golgi and subsequent SREBP activation via N-glycosylation of SCAP. Our study also demonstrated that SCAP plays a critical role in tumor growth.

  15. Ptpmt1 induced by HIF-2α regulates the proliferation and glucose metabolism in erythroleukemia cells.

    Xu, Qin-Qin; Xiao, Feng-Jun; Sun, Hui-Yan; Shi, Xue-Feng; Wang, Hua; Yang, Yue-Feng; Li, Yu-Xiang; Wang, Li-Sheng; Ge, Ri-Li

    2016-03-18

    Hypoxia provokes metabolism misbalance, mitochondrial dysfunction and oxidative stress in both human and animal cells. However, the mechanisms which hypoxia causes mitochondrial dysfunction and energy metabolism misbalance still remain unclear. In this study, we presented evidence that mitochondrial phosphatase Ptpmt1 is a hypoxia response molecule that regulates cell proliferation, survival and glucose metabolism in human erythroleukemia TF-1 cells. Exposure to hypoxia or DFO treatment results in upregulation of HIF1-α, HIF-2α and Ptpmt1. Only inhibition of HIF-2α by shRNA transduction reduces Ptpmt1 expression in TF-1 cells under hypoxia. Ptpmt1 inhibitor suppresses the growth and induces apoptosis of TF-1 cells. Furthermore, we demonstrated that Ptpmt1 inhibition reduces the Glut1 and Glut3 expression and decreases the glucose consumption in TF-1 cells. In additional, Ptpmt1 knockdown also results in the mitochondrial dysfunction determined by JC1 staining. These results delineate a key role for HIF-2α-induced Ptpmt1 upregulation in proliferation, survival and glucose metabolism of erythroleukemia cells. It is indicated that Ptpmt1 plays important roles in hypoxia-induced cell metabolism and mitochondrial dysfunction. PMID:26898802

  16. 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...

  17. Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

    Lee, Mi Jin; Lee, Seung Jun; Yun, Su Jin; Jang, Ji-Young; Kang, Hangoo; Kim, Kyongmin; Choi, In-Hong; Park, Sun

    2016-01-01

    The silver nanoparticle (AgNP) is a candidate for anticancer therapy because of its effects on cell survival and signaling. Although numerous reports are available regarding their effect on cell death, the effect of AgNPs on metabolism is not well understood. In this study, we investigated the effect of AgNPs on glucose metabolism in hepatoma cell lines. Lactate release from both HepG2 and Huh7 cells was reduced with 5 nm AgNPs as early as 1 hour after treatment, when cell death did not occur. Treatment with 5 nm AgNPs decreased glucose consumption in HepG2 cells but not in Huh7 cells. Treatment with 5 nm AgNPs reduced nuclear factor erythroid 2-like 2 expression in both cell types without affecting its activation at the early time points after AgNPs treatment. Increased reactive oxygen species (ROS) production was detected 1 hour after 5 nm AgNPs treatment, and lactate release was restored in the presence of an ROS scavenger. Our results suggest that 5 nm AgNPs affect glucose metabolism by producing ROS. PMID:26730190

  18. 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

  19. Retinoblastoma Protein Knockdown Favors Oxidative Metabolism and Glucose and Fatty Acid Disposal in Muscle Cells.

    Petrov, Petar D; Ribot, Joan; Lpez-Meja, Isabel C; Fajas, Llus; Palou, Andreu; Bonet, M Luisa

    2016-03-01

    Deficiency in the retinoblastoma protein (Rb) favors leanness and a healthy metabolic profile in mice largely attributed to activation of oxidative metabolism in white and brown adipose tissues. Less is known about Rb modulation of skeletal muscle metabolism. This was studied here by transiently knocking down Rb expression in differentiated C2C12 myotubes using small interfering RNAs. Compared with control cells transfected with non-targeting RNAs, myotubes silenced for Rb (by 80-90%) had increased expression of genes related to fatty acid uptake and oxidation such as Cd36 and Cpt1b (by 61% and 42%, respectively), increased Mitofusin 2 protein content (?2.5-fold increase), increased mitochondrial to nuclear DNA ratio (by 48%), increased oxygen consumption (by 65%) and decreased intracellular lipid accumulation. Rb silenced myotubes also displayed up-regulated levels of glucose transporter type 4 expression (?5-fold increase), increased basal glucose uptake, and enhanced insulin-induced Akt phosphorylation. Interestingly, exercise in mice led to increased Rb phosphorylation (inactivation) in skeletal muscle as evidenced by immunohistochemistry analysis. In conclusion, the silencing of Rb enhances mitochondrial oxidative metabolism and fatty acid and glucose disposal in skeletal myotubes, and changes in Rb status may contribute to muscle physiological adaptation to exercise. J. Cell. Physiol. 231: 708-718, 2016. 2015 Wiley Periodicals, Inc. PMID:26241807

  20. Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

    Lee MJ

    2015-12-01

    Full Text Available Mi Jin Lee,1 Seung Jun Lee,1,2,* Su Jin Yun,1,2,* Ji-Young Jang,3 Hangoo Kang,3 Kyongmin Kim,1,2 In-Hong Choi,3,4 Sun Park1,2 1Department of Microbiology, Ajou University School of Medicine, 2Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, 3Department of Microbiology, The Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea; 4Brain Korea 21 Plus Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea *These authors contributed equally tothis work Abstract: The silver nanoparticle (AgNP is a candidate for anticancer therapy because of its effects on cell survival and signaling. Although numerous reports are available regarding their effect on cell death, the effect of AgNPs on metabolism is not well understood. In this study, we investigated the effect of AgNPs on glucose metabolism in hepatoma cell lines. Lactate release from both HepG2 and Huh7 cells was reduced with 5 nm AgNPs as early as 1 hour after treatment, when cell death did not occur. Treatment with 5 nm AgNPs decreased glucose consumption in HepG2 cells but not in Huh7 cells. Treatment with 5 nm AgNPs reduced nuclear factor erythroid 2-like 2 expression in both cell types without affecting its activation at the early time points after AgNPs treatment. Increased reactive oxygen species (ROS production was detected 1 hour after 5 nm AgNPs treatment, and lactate release was restored in the presence of an ROS scavenger. Our results suggest that 5 nm AgNPs affect glucose metabolism by producing ROS. Keywords: metal nanoparticles, carbohydrate metabolism, lactic acid, cytotoxicity

  1. Interactions between the metabolism of L-leucine and D-glucose in the pancreatic ?-cells

    ?-cell-rich pancreatic islets microdissected from obese-hyperglycemic mice were used to study interactions between the metabolism of L-leucine and D-glucose. L-leucine reduced the islet content of aspartic acid whereas D-glucose, when added to L-leucine-incubated islets, increased the contents of aspartic acid and ?-aminobutyric acid (GABA). D-glucose also increased the incorporation of L-leucine carbon into aspartic acid, GABA and glutamic acid, suggesting stimulation of a malate shuttle mechanism. When expressed per mole of the individual amino acids, the incorporation of L-leucine carbon into GABA was 2.5 - 4 times higher than into glutamic acid indicating intracellular compartmentation of the latter amino acid. Both L-leucine and D-leucine stimulated 14CO2 production from 14C-labelled D-glucose. L-leucine did not affect 3H2O production from tritiated D-glucose. The present data do not indicate a role of other amino acids or D-glucose in L-leucine-stimulated insulin release. (orig.)

  2. 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

  3. 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.

  4. 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.)

  5. 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)

  6. Osteocalcin, energy and glucose metabolism

    Leila C. B. Zanatta

    2014-07-01

    Full Text Available Osteocalcin is a bone matrix protein that has been associated with several hormonal actions on energy and glucose metabolism. Animal and experimental models have shown that osteocalcin is released into the bloodstream and exerts biological effects on pancreatic beta cells and adipose tissue. Undercarboxylated osteocalcin is the hormonally active isoform and stimulates insulin secretion and enhances insulin sensitivity in adipose tissue and muscle. Insulin and leptin, in turn, act on bone tissue, modulating the osteocalcin secretion, in a traditional feedback mechanism that places the skeleton as a true endocrine organ. Further studies are required to elucidate the role of osteocalcin in the regulation of glucose and energy metabolism in humans and its potential therapeutic implications in diabetes, obesity and metabolic syndrome.

  7. Effects of SH-reagents of different molecular size upon glucose metabolism in isolated rat fat cells

    To study the role of membrane SH-groups in glucose transport of isolated rat fat cells we compared the effects of a small organic mercurial reagent p-CMB with those of a large p-CMB-derivative - p-CMB-Dextran, MW approximately 10,000 -. It could be shown that both compounds were of almost identical reactivity on fat cell homogenate metabolism. When applied to intact fat cells uncoupled p-CMB showed an 1) insulin-like enhancement of 14C incorporation from (U-14C) glucose into CO2 and triglyceride, 2) inhibition of the insulin-stimulatory effect on these parameters and 3) inhibition of basal glucose uptake dependent on the concentrations used. Identical concentrations of p-CMB-Dextran, however, failed to influence basal glucose uptake as well as the insulin mediated increase in glucose metabolism. (orig.)

  8. Effects of Salmonella typhimurium Infection and Ofloxacin Treatment on Glucose and Glutamine Metabolism in Caco-2/TC-7 Cells

    Posho, Leta; Delbos-Bocage, Laurence; Gueylard, Delphine; Farinotti, Robert; Carbon, Claude

    1998-01-01

    The effects of both Salmonella typhimurium infection and 5 mM ofloxacin treatment on 2 mM glutamine and 5 mM glucose metabolism in the enterocyte-like Caco-2/TC-7 cell line were studied. These cells utilized glutamine (212.07 ± 16.75 [mean ± standard deviation] nmol per h per 106 viable cells) and, to a lesser extent, glucose (139.63 ± 11.52 nmol per h per 106 viable cells). Metabolism of these substrates in Caco-2/TC-7 cells resembled that in rat, pig, or human enterocytes. Infection by S. t...

  9. 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.

  10. 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

  11. Protective effects of epoxypukalide on pancreatic β-cells and glucose metabolism in STZ-induced diabetic mice.

    López-Acosta, Jose F; Villa-Pérez, Pablo; Fernández-Díaz, Cristina M; Román, Daniel de Luis; Díaz-Marrero, Ana R; Cueto, Mercedes; Perdomo, Germán; Cózar-Castellano, Irene

    2015-01-01

    Diabetes is a consequence of a decrease on functional β-cell mass. We have recently demonstrated that epoxypukalide (Epoxy) is a natural compound with beneficial effects on primary cultures of rat islets. In this study, we extend our previous investigations to test the hypothesis that Epoxy protects β-cells and improves glucose metabolism in STZ-induced diabetic mice. We used 3-months old male mice that were treated with Epoxy at 200 μg/kg body weight. Glucose intolerance was induced by multiple intraperitoneal low-doses of streptozotocin (STZ) on 5 consecutive days. Glucose homeostasis was evaluated measuring plasma insulin levels and glucose tolerance. Histomorphometry was used to quantify the number of pancreatic β-cells per islet. β-cell proliferation was assessed by BrdU incorporation, and apoptosis by TUNEL staining. Epoxy treatment significantly improved glucose tolerance and plasma insulin levels. These metabolic changes were associated with increased β-cell numbers, as a result of a two-fold increase in β-cell proliferation and a 50% decrease in β-cell death. Our results demonstrate that Epoxy improves whole-body glucose homeostasis by preventing pancreatic β-cell death due to STZ-induced toxicity in STZ-treated mice. PMID:26406478

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

    Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian; Wagtberg Sen, Jette; Rasmussen, Søren Kofoed; Kontoravdi, Cleo; Weilguny, Dietmar; Andersen, Mikael Rørdam

    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 process...

  13. 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.

  14. TRIM24 links glucose metabolism with transformation of human mammary epithelial cells.

    Pathiraja, T N; Thakkar, K N; Jiang, S; Stratton, S; Liu, Z; Gagea, M; Shi, X; Shah, P K; Phan, L; Lee, M-H; Andersen, J; Stampfer, M; Barton, M C

    2015-05-28

    Tripartite motif 24 protein (TRIM24) is a plant homeodomain/bromodomain histone reader, recently associated with poor overall survival of breast-cancer patients. At a molecular level, TRIM24 is a negative regulator of p53 levels and a co-activator of estrogen receptor. However, the role of TRIM24 in breast tumorigenesis remains largely unknown. We used an isogenic human mammary epithelial cell (HMEC) culture model, derived from reduction mammoplasty tissue, and found that ectopic expression of TRIM24 in immortalized HMECs (TRIM24 iHMECs) greatly increased cellular proliferation and induced malignant transformation. Subcutaneous injection of TRIM24 iHMECs in nude mice led to growth of intermediate to high-grade tumors in 60-70% of mice. Molecular analysis of TRIM24 iHMECs revealed a glycolytic and tricarboxylic acid cycle gene signature, alongside increased glucose uptake and activated aerobic glycolysis. Collectively, these results identify a role for TRIM24 in breast tumorigenesis through reprogramming of glucose metabolism in HMECs, further supporting TRIM24 as a viable therapeutic target in breast cancer. PMID:25065590

  15. 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.

  16. 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...

  17. 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

  18. 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.

  19. 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.)

  20. 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

  1. Procyanidin effects on an impaired glucose metabolism: a further insight into procyanidin signalling in adipose cells

    Montagut Pino, Gemma

    2009-01-01

    ANGLS A grape-seed derived procyanidins extract (GSPE) was reported to mimic some of the physiological effects of insulin. However, GSPE showed some divergences when compared to insulin action, which suggests that procyanidins could be useful on a state of impaired insulin action. Therefore, the main purpose of this thesis was to understand how dietary procyanidins modulate glucose metabolism, mainly in adipose tissue and under an insulin resistant condition.Results show that a treatment of ...

  2. 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

  3. 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...

  4. Study on the insulin resistance and β-cell function in individuals with normal and those with abnormal glucose metabolism

    Objective: To study the insulin resistance and β-cell function in individuals with normal glucose tolerance (NGT) and those with glucose metabolism dysfunction. Methods: Insulin resistance and β-cell function were studied with oral glucose tolerance test and the following parameters: 2h insulin/2h plasma glucose (2hIns/2hPG), insulin resistance index (IRI), insulin sensitivity index (ISI) and 30 min net increment of insulin/30min net increment of glucose (AI30/AG30) were examined in 44 individuals with NGT, 45 subjects with impaired glucose tolerance (IGT), 66 recently diagnosed diabetics and 175 well-established diabetics. Results: The insulin resistance index (IRI) increased progressively from that in NGT individuals to that in recently diabetics (20 ± 1. 5→3.1 ± 1.6→4.1 ± 1.8), while the 2hIns/2hPG, ΔI30/ΔG30 and ISI decreased progressively with significant differences between those in successive groups (P30/ΔG30 and ISI kept decreasing (values in patients with disease history less than 3 yrs vs those in patients with disease over 3yrs: 2.9 ± 3.2 vs 2.4 + 2.3, 30.2 + 1.1 vs 23.4 ± 2.3, P30/ΔG30 were significantly correlated with ISI (F =96.3, 58.4 and 47.5 respectively). For principal component analysis display, the cumulative contribution rate of four parameters (2hIns/2hPG, ISI, ΔI30/ΔG30 and 2h C-peptide) exceeded 85% (86.5%). Conclusion: As the dysfunction of glucose metabolism proceeded from IGT to well established diabetes, the IR increased first with decrease of β-cell secretion followed. The parameters 2hIns/2hPG, ISI, 2h C-peptide ΔI30/ΔG30 were especially useful for the investigation . (authors)

  5. 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)

  6. The effect of Fe2O3 and ZnO nanoparticles on cytotoxicity and glucose metabolism in lung epithelial cells.

    Lai, Xiaofeng; Wei, Yifang; Zhao, Hu; Chen, Suning; Bu, Xin; Lu, Fan; Qu, Dingding; Yao, Libo; Zheng, Jianyong; Zhang, Jian

    2015-06-01

    Metallic nanoparticles (NPs) have potential applications in industry and medicine, but they also have the potential to cause many chronic pulmonary diseases. Mechanisms for their cytotoxicity, glucose and energy metabolism responses need to be fully explained in lung epithelial cells after treatment with metallic nanoparticles. In our study, two different metallic nanoparticles (Fe2 O3 and ZnO) and two cell-based assays (BEAS-2B and A549 cell lines) were used. Our findings demonstrate that ZnO nanoparticles, but not Fe2 O3 nanoparticles, induce cell cycle arrest, cell apoptosis, reactive oxygen species (ROS) production, mitochondrial dysfunction and glucose metabolism perturbation, which are responsible for cytotoxicity. These results also suggest that the glucose metabolism and bioenergetics had a great potential in evaluating the cytotoxicity and thus were very helpful in understanding their underlying molecular mechanisms. PMID:25727528

  7. Comparison of Cell Proliferation, Protein, and Glucose Metabolism in Musculoskeletal Tumors in a PET Study

    Mei Tian; Hong Zhang; Keigo Endo

    2011-01-01

    11C-choline and 18F-FAMT are known to correlate with tumor cell proliferation and amino acid metabolism. We investigated the ability of 11C-Choline and 18F-FAMT PET in diagnosis of musculoskeletal tumors in thirty-six patients in comparison of 18F-FDG PET. 11C-Choline and 18F-FDG PET were positive in all the malignant tumors (n = 13), whereas 18F-FAMT was positive in 11 tumors. The mean SUVs for malignant tumors were significantly higher than those for benign lesions in all three tracers imag...

  8. Sex steroids and glucose metabolism

    Carolyn A Allan

    2014-04-01

    Full Text Available Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus (T2DM and also predict the onset of these adverse metabolic states. Body composition (body mass index, waist circumference is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter's syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.

  9. 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; Windeløv, Johanne Agerlin; Grunddal, Kaare Villum; Schwartz, T W; Füchtbauer, Ernst-Martin; Poulsen, S S; Holst, P J; Holst, J J

    2013-01-01

    glucagon in pancreas in TgN(GCG.DTR) compared with wild-type mice. GIP response to oral glucose was attenuated following K cell loss, but oral and intraperitoneal glucose tolerances were unaffected. Intraperitoneal glucose tolerance was impaired following combined L cell and α-cell loss and normal...

  10. 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

  11. 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)

  12. Metabolic pathways for glucose in astrocytes.

    Wiesinger, H; Hamprecht, B; Dringen, R

    1997-09-01

    Cultured astroglial cells are able to utilize the monosaccharides glucose, mannose, or fructose as well as the sugar alcohol sorbitol as energy fuel. Astroglial uptake of the aldoses is carrier-mediated, whereas a non-saturable transport mechanism is operating for fructose and sorbitol. The first metabolic step for all sugars, including fructose being generated by enzymatic oxidation of sorbitol, is phosphorylation by hexokinase. Besides glucose only mannose may serve as substrate for build-up of astroglial glycogen. Whereas glycogen synthase appears to be present in astrocytes as well as neurons, the exclusive localization of glycogen phosphorylase in astrocytes and ependymal cells of central nervous tissue correlates well with the occurrence of glycogen in these cells. The identification of lactic acid rather than glucose as degradation product of astroglial glycogen appears to render the presence of glucose-6-phosphatase in cultured astrocytes an enigma. The colocalization of pyruvate carboxylase, phosphenolpyruvate carboxykinase and fructose-1,6-bisphosphatase points to astrocytes as being the gluconeogenic cell type of the CNS. PMID:9298844

  13. 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.

  14. 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 phosphorylation of protein kinase C-? (PKC?). Chelation of calcium with BAPTA-AM blocked isoeugenol-induced AMPK phosphorylation and glucose uptake. Isoeugenol stimulated p38MAPK phosphorylation that was inhibited after pretreatment with compound C, an AMPK inhibitor. Isoeugenol also increased glucose transporter type 4 (GLUT4) expression and its translocation to the plasma membrane. GLUT4 translocation was not observed after the inhibition of AMPK and CaMKK. In addition, isoeugenol activated the Akt substrate 160 (AS160) pathway, which is downstream of the p38MAPK pathway. Knockdown of the gene encoding AS160 inhibited isoeugenol-induced glucose uptake. Together, these results indicate that isoeugenol exerts beneficial health effects by activating the AMPK/p38MAPK/AS160 pathways in skeletal muscle. PMID:26585419

  15. The Acute Effects of Low-Dose TNF-? on Glucose Metabolism and ?-Cell Function in Humans

    Ibfelt, Tobias; Fischer, Christian Philip; Plomgaard, Peter; van Hall, Gerrit; Pedersen, Bente Klarlund

    2014-01-01

    in vivo. However, it is unclear whether TNF-? may also affect endogenous glucose production (EGP) during fasting and glucose-stimulated insulin secretion (GSIS) in vivo. We hypothesized that low-dose TNF- ? would increase EGP and attenuate GSIS. Recombinant human TNF-? or placebo was infused in...... healthy, nondiabetic young men (n = 10) during a 4-hour basal period followed by an intravenous glucose tolerance test (IVGTT). TNF-? lowered insulin levels by 12% during the basal period (P < 0.05). In response to the IVGTT, insulin levels increased markedly in both trials, but there was no difference...... between trials. Compared to placebo, TNF-? did not affect EGP during the basal period. Our results indicate that TNF-? acutely lowers basal plasma insulin levels but does not impair GSIS. The mechanisms behind this are unknown but we suggest that it may be due to TNF-? increasing clearance of insulin from...

  16. 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.

  17. Visfatin, glucose metabolism and vascular disease: a review of evidence

    Saddi-Rosa Pedro

    2010-03-01

    Full Text Available Abstract The adipose tissue is an endocrine organ producing substances called adipocytokines that have different effects on lipid metabolism, metabolic syndrome, and cardiovascular risk. Visfatin was recently described as an adipocytokine with potentially important effects on glucose metabolism and atherosclerosis. Visfatin has been linked to several inflammatory conditions, beta cell function, and cardiovascular disease. The growing number of publications on the subject shall bring further evidence about this adipocytokine. Its findings may contribute in the identification of higher risk individuals for diabetes and cardiovascular disease with a better comprehension about the complex intercorrelation between adiposity, glucose metabolism and vascular disease.

  18. Cancer-specific interruption of glucose metabolism by resveratrol is mediated through inhibition of Akt/GLUT1 axis in ovarian cancer cells.

    Gwak, HyeRan; Haegeman, Guy; Tsang, Benjamin K; Song, Yong Sang

    2015-12-01

    The metabolic phenotype of cancer is considered an ideal target for anticancer therapy. In ovarian cancer, glucose transporter 1 (GLUT1) is overexpressed and positron emission tomography (PET) using [18(F)] fluorodeoxyglucose (FDG), as a metabolic tumor parameter, has been found to be an effective diagnostic tool. In this study, we have characterized the selective cytotoxicity of resveratrol (RSV) in ovarian cancer cells through glucose metabolism regulation via GLUT1 modulation. We have demonstrated that, in contrast to primary normal ovarian epithelial cells, RSV selectively inhibited glucose uptake and induced apoptosis irrespective of p53 status in vitro. RSV had no affect on GLUT1 mRNA and protein expressions but interrupted intracellular GLUT1 trafficking to the plasma membrane. Suppressed plasma membrane GLUT1 localization in ovarian cancer was found to be associated with the inhibition of Akt activity by RSV, as confirmed by the action of the Akt inhibitors (LY294002 and Akt inhibitor IV), as well as overexpression of a constitutive active form of Akt. Taken together, these findings suggested that RSV induced apoptosis in ovarian cancer cells by impairing glucose uptake, a process involving Akt-regulated plasma membrane GLUT1 trafficking. PMID:25307508

  19. Hepatic glucose sensing is required to preserve ? cell glucose competence.

    Seyer, Pascal; Vallois, David; Poitry-Yamate, Carole; Schtz, Frdric; Metref, Salima; Tarussio, David; Maechler, Pierre; Staels, Bart; Lanz, Bernard; Grueter, Rolf; Decaris, Julie; Turner, Scott; da Costa, Anabela; Preitner, Frdric; Minehira, Kaori; Foretz, Marc; Thorens, Bernard

    2013-04-01

    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 expenditure, and insulin sensitivity were identical in LG2KO and control mice. Glucose tolerance was initially normal after Glut2 inactivation, but LG2KO mice exhibited progressive impairment of glucose-stimulated insulin secretion even though ? cell mass and insulin content remained normal. Liver transcript profiling revealed a coordinated downregulation of cholesterol biosynthesis genes in LG2KO mice that was associated with reduced hepatic cholesterol in fasted mice and reduced bile acids (BAs) in feces, with a similar trend in plasma. We showed that chronic BAs or farnesoid X receptor (FXR) agonist treatment of primary islets increases glucose-stimulated insulin secretion, an effect not seen in islets from Fxr(-/-) mice. Collectively, our data show that glucose sensing by the liver controls ? cell glucose competence and suggest BAs as a potential mechanistic link. PMID:23549084

  20. Growth Factors Can Influence Cell Growth and Survival through Effects on Glucose Metabolism

    Vander Heiden, Matthew G.; Plas, David R.; Rathmell, Jeffrey C.; Fox, Casey J.; Harris, Marian H; Thompson, Craig B

    2001-01-01

    Cells from multicellular organisms are dependent upon exogenous signals for survival, growth, and proliferation. The relationship among these three processes was examined using an interleukin-3 (IL-3)-dependent cell line. No fixed dose of IL-3 determined the threshold below which cells underwent apoptosis. Instead, increasing growth factor concentrations resulted in progressive shortening of the G1 phase of the cell cycle and more rapid proliferative expansion. Increased growth factor concent...

  1. 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...

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

    Simons Andrean

    2009-09-01

    Full Text Available 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 (from glycolysis and NADPH (from the pentose cycle. Furthermore, in cancer cells, glucose deprivation as well as treatment with 2-deoxyglucose (2 DG has been shown to induce oxidative stress and cytotoxicity. Additionally, transformed cells have been shown to be more susceptible to glucose deprivation (and 2DG--induced cytotoxicity and oxidative stress than untransformed cells. These results support the hypothesis that cancer cells have a defect in mitochondrial respiration leading to increased steady state levels of O 2· - and H 2 O2 , and glucose metabolism is increased to compensate for this defect. The application of these findings to developing cancer therapies using 2DG combined with inhibitors of hydroperoxide metabolism to induce radio/chemosensitization is discussed, as well as the possibility that FDG-PET imaging may predict tumor responses to these therapies.

  3. 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

  4. 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)

  5. Visfatin, glucose metabolism and vascular disease: a review of evidence

    Saddi-Rosa Pedro; Oliveira Carolina SV; Giuffrida Fernando MA; Reis André F.

    2010-01-01

    Abstract The adipose tissue is an endocrine organ producing substances called adipocytokines that have different effects on lipid metabolism, metabolic syndrome, and cardiovascular risk. Visfatin was recently described as an adipocytokine with potentially important effects on glucose metabolism and atherosclerosis. Visfatin has been linked to several inflammatory conditions, beta cell function, and cardiovascular disease. The growing number of publications on the subject shall bring further e...

  6. Texture analysis of non-small cell lung cancer on unenhanced computed tomography: initial evidence for a relationship with tumour glucose metabolism and stage

    Ganeshan, Balaji; Abaleke, Sandra; Young, Rupert C.D.; Chatwin, Christopher R.; Miles, Kenneth A.

    2010-01-01

    Abstract The aim was to undertake an initial study of the relationship between texture features in computed tomography (CT) images of non-small cell lung cancer (NSCLC) and tumour glucose metabolism and stage. This retrospective pilot study comprised 17 patients with 18 pathologically confirmed NSCLC. Non-contrast-enhanced CT images of the primary pulmonary lesions underwent texture analysis in 2 stages as follows: (a) image filtration using Laplacian of Gaussian filter to differentially high...

  7. 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. • DCA augments BMC cellularity, differentiation and repolarization of macrophages.

  8. 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. • DCA augments BMC cellularity, differentiation and repolarization of macrophages

  9. Regulation of the expression and activity of glucose and lactic acid metabolism-related genes by protein kinase C in skeletal muscle cells.

    Otake, Sho; Kobayashi, Masaki; Narumi, Katsuya; Sasaki, Shotaro; Kikutani, Yurika; Furugen, Ayako; Watanabe, Meguho; Takahashi, Natsuko; Ogura, Jiro; Yamaguchi, Hiroaki; Iseki, Ken

    2013-01-01

    Protein kinase C (PKC) modulators are very attractive therapeutic targets in cancer. Since most cancer cells display increased glycolysis, elucidations of the effects of PKC activation on glycolysis is necessary for the development of effective medicine. In the present study, to clarify the role of PKC in the regulation of glycolysis, we examined the effect of phorbol 12-myristate 13-acetate (PMA), a PKC activator, on the expression and activity of glucose and lactic acid metabolism-related genes in human rhabdomyosarcoma cells (RD cells). In parallel to increases in glucose uptake and mRNA levels of glucose transporters (GLUTs) induced by PMA treatment for 6 h, the hexokinase (HK) mRNA level and activity were also significantly increased in RD cells. On the other hand, a significant increase in lactate dehydrogenase (LDH) mRNA level and activity was seen when the cells were incubated with PMA for 24 h, but not for 6 or 12 h, and was associated with lactic acid production. These effects by PMA treatment were markedly suppressed by Bisindolylmaleimide (BIM), a PKC inhibitor. Furthermore, chetomin, a hypoxia-inducible factor 1 (HIF-1) inhibitor, completely abrogated the increment of LDH mRNA level and activity as well as monocarboxylate transporter (MCT) 4, a lactic acid efflux transporter. In conclusion, we found that HK and LDH activity induced by PKC activation was associated with the glucose uptake and lactic acid level and that LDH and MCT4 are modulated by a common factor, HIF-1. PMID:23995654

  10. 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

  11. 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)

  12. 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 Roden (DOI: 10.1007/s00125-016-3911-x ). PMID:27048250

  13. In vitro expansion of U87-MG human glioblastoma cells under hypoxic conditions affects glucose metabolism and subsequent in vivo growth.

    Lemaire, L; Franconi, F; Siegler, B; Legendre, C; Garcion, E

    2015-09-01

    Hypoxia is a characteristic feature of solid tumors leading to the over expression of hypoxia-inducible factor (HIF)-1? protein and therefore to a specific cellular behavior. However, even though the oxygen tension in tumors is low (<5 %), most of the cell lines used in cancer studies are grown under 21 % oxygen tension. This work focuses on the impact of oxygen conditions during in vitro cell culture on glucose metabolism using 1-(13)C-glucose. Growing U87-MG glioma cells under hypoxic conditions leads to a two- to threefold reduction of labeled glutamine and an accumulation of fructose. However, under both hypoxic and normoxic conditions, glucose is used for de novo synthesis of pyrimidine since the (13)C label is found both in the uracil and ribose moieties. Labeling of the ribose ring demonstrates that U87-MG glioma cells use the reversible branch of the non-oxidative pentose phosphate pathway. Interestingly, stereotactic implantation of U87-MG cells grown under normoxia or mild hypoxia within the striatum of nude mice led to differential growth; the cells grown under hypoxia retaining an imprint of the oxygen adaptation as their development is then slowed down. PMID:25934335

  14. Deletion of Cyclophilin D Impairs ?-Oxidation and Promotes Glucose Metabolism.

    Tavecchio, Michele; Lisanti, Sofia; Bennett, Michael J; Languino, Lucia R; Altieri, Dario C

    2015-01-01

    Cyclophilin D (CypD) is a mitochondrial matrix protein implicated in cell death, but a potential role in bioenergetics is not understood. Here, we show that loss or depletion of CypD in cell lines and mice induces defects in mitochondrial bioenergetics due to impaired fatty acid ?-oxidation. In turn, CypD loss triggers a global compensatory shift towards glycolysis, with transcriptional upregulation of effectors of glucose metabolism, increased glucose consumption and higher ATP production. In vivo, the glycolytic shift secondary to CypD deletion is associated with expansion of insulin-producing ?-cells, mild hyperinsulinemia, improved glucose tolerance, and resistance to high fat diet-induced liver damage and weight gain. Therefore, CypD is a novel regulator of mitochondrial bioenergetics, and unexpectedly controls glucose homeostasis, in vivo. PMID:26515038

  15. Mulberry anthocyanin extract regulates glucose metabolism by promotion of glycogen synthesis and reduction of gluconeogenesis in human HepG2 cells.

    Yan, Fujie; Zhang, Ji; Zhang, Lingxia; Zheng, Xiaodong

    2016-01-20

    Mulberry has been demonstrated to possess important biological activities such as antioxidation and antiinflammation. However, research on the ability of mulberry for diabetes improvement mainly focuses on the leaves and less on the fruit. This study showed that a mulberry anthocyanin extract (MAE) had a significant effect on increasing the glucose consumption in HepG2 cells. The MAE enhanced the glycogen content and suppressed levels of glucose production. The enzyme activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were decreased in HepG2 cells after MAE treatment due to PPAR? coactivator 1? (PGC-1?) and forkhead box protein O1 (FOXO1) inhibition. Moreover, the phosphorylation of protein kinase B (AKT) and glycogen synthase kinase-3? (GSK-3?) was increased by the MAE, leading to an expression enhancement of glycogen synthase 2 (GYS2). And this effect was blocked by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002. In summary, our results suggested that the MAE regulates glucose metabolism by activating the PI3K/AKT pathway that relates to glycogen synthesis as well as through the inhibition of key molecules that promote gluconeogenesis. PMID:26467565

  16. Single Cell "Glucose Nanosensor" Verifies Elevated Glucose Levels in Individual Cancer Cells.

    Nascimento, Raphael A S; zel, R?fat Emrah; Mak, Wai Han; Mulato, Marcelo; Singaram, Bakthan; Pourmand, Nader

    2016-02-10

    Because the transition from oxidative phosphorylation to anaerobic glycolytic metabolism is a hallmark of cancer progression, approaches to identify single living cancer cells by their unique glucose metabolic signature would be useful. Here, we present nanopipettes specifically developed to measure glucose levels in single cells with temporal and spatial resolution, and we use this technology to verify the hypothesis that individual cancer cells can indeed display higher intracellular glucose levels. The nanopipettes were functionalized as glucose nanosensors by immobilizing glucose oxidase (GOx) covalently to the tip so that the interaction of glucose with GOx resulted in a catalytic oxidation of ?-d-glucose to d-gluconic acid, which was measured as a change in impedance due to drop in pH of the medium at the nanopipette tip. Calibration studies showed a direct relationship between impedance changes at the tip and glucose concentration in solution. The glucose nanosensor quantified single cell intracellular glucose levels in human fibroblasts and the metastatic breast cancer lines MDA-MB-231 and MCF7 and revealed that the cancer cells expressed reproducible and reliable increases in glucose levels compared to the nonmalignant cells. Nanopipettes allow repeated sampling of the same cell, as cells remain viable during and after measurements. Therefore, nanopipette-based glucose sensors provide an approach to compare changes in glucose levels with changes in proliferative or metastatic state. The platform has great promise for mechanistic investigations, as a diagnostic tool to distinguish cancer cells from nonmalignant cells in heterogeneous tissue biopsies, as well as a tool for monitoring cancer progression in situ. PMID:26752097

  17. Glucose metabolism in gastric cancer: The cutting-edge

    Yuan, Lian-Wen; Yamashita, Hiroharu; Seto, Yasuyuki

    2016-01-01

    Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis (Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for e...

  18. Glucose availability and glycolytic metabolism dictate glycosphingolipid levels

    Stathem, Morgan; Marimuthu, Subathra; O'Neal, Julie; Rathmell, Jeffrey C.; Chesney, Jason A.; Beverly, Levi J.; Siskind, Leah J.

    2014-01-01

    Cancer therapeutics has seen an emergence and re-emergence of two metabolic fields in recent years, those of bioactive sphingolipids and glycolytic metabolism. Anaerobic glycolysis and its implications in cancer have been at the forefront of cancer research for over 90 years. More recently, the role of sphingolipids in cancer cell metabolism has gained recognition, notably ceramide's essential role in programmed cell death and the role of the glucosylceramide synthase (GCS) in chemotherapeutic resistance. Despite this knowledge, a direct link between these two fields has yet to be definitively drawn. Herein, we show that in a model of highly glycolytic cells, generation of the glycosphingolipid (GSL) glucosylceramide (GlcCer) by GCS was elevated in response to increased glucose availability, while glucose deprivation diminished GSL levels. This effect was likely substrate dependent, independent of both GCS levels and activity. Conversely, leukemia cells with elevated GSLs showed a significant change in GCS activity, but no change in glucose uptake or GCS expression. In a leukemia cell line with elevated GlcCer, treatment with inhibitors of glycolysis or the pentose phosphate pathway (PPP) significantly decreased GlcCer levels. When combined with pre-clinical inhibitor ABT-263, this effect was augmented and production of pro-apoptotic sphingolipid ceramide increased. Taken together, we have shown that there exists a definitive link between glucose metabolism and GSL production, laying the groundwork for connecting two distinct yet essential metabolic fields in cancer research. Furthermore, we have proposed a novel combination therapeutic option targeting two metabolic vulnerabilities for the treatment of leukemia. PMID:25145677

  19. Correlation of hypoxic cell fraction with glucose metabolic rate in gliomas with 18F-Fluoromisonidazole (FMISO) and 18F- Fluorodeoxyglucose (FDG) positron emission tomography (PET)

    Full text: FDG-PET studies of brain tumours to measure tumour activity are well established, with regions of higher grade tumour utilising more glucose compared to lower grade tumour tissue and normal tissue. FDG uptake in tumour cells may reflect anaerobic glycolysis, but this has not been proven in- vivo. FMISO is a novel positron-emitting compound that has been shown to selectively identify hypoxic but viable tissue, which may contribute to chemoradiotherapy resistance in tumour cells. Studies correlating measurements of regional hypoxia and glucose activity within brain tumours prior to therapy may help gain further insight into the relationship between hypoxic tumour tissue and resistance to chemoradiotherapy. Three patients with newly diagnosed primary brain tumours have been prospectively studied with FMISO-PET, FDG-PET and MRI, prior to surgery. Each patient presented with a suspected primary brain glioma on MRI, which were all confirmed to be high grade glioma on subsequent histology at surgery FMISO-PET, FDG-PET and MRI images of all patients were co-registered to precisely identify the areas of metabolic activity within tumour and surrounding cortical tissue. All gliomas demonstrated areas of FMISO uptake, which corresponded to areas of maximal FDG uptake, indicating a correlation between hypoxic areas within tumour with areas of increased glucose metabolic activity. This supports the hypothesis that hypoxic areas within tumour tissue may be associated with increased FDG uptake, although whether hypoxia itself increases FDG uptake remains controversial. These correlative studies characterising areas of hypoxia and glucose activity should hopefully assist in future therapeutic manipulations to improve the outcome from treatment of primary brain tumours

  20. Circadian control of glucose metabolism

    Kalsbeek, A.; la Fleur, Susanne; Fliers, Eric

    2014-01-01

    The incidence of obesity and type 2 diabetes mellitus (T2DM) has risen to epidemic proportions. The pathophysiology of T2DM is complex and involves insulin resistance, pancreatic ?-cell dysfunction and visceral adiposity. It has been known for decades that a disruption of biological rhythms (which happens the most profoundly with shift work) increases the risk of developing obesity and T2DM. Recent evidence from basal studies has further sparked interest in the involvement of daily rhythms (a...

  1. Enhanced muscle glucose metabolism after exercise

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

    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...

  2. [Major risk factors of glucose metabolism abnormalities].

    Misnikova, I V; Dreval', A V; Barsukov, I A; Dzebisashvili, T G

    2011-01-01

    Using the data of population base study of adult residents of 2 districts of Moscow Region (2638 persons), prevalence is studied and influence on occurrence of glucose metabolism abnormalities of major risk factors is estimated. Influence of risk factors was estimated with Cox regression analyses. High prevalence undiagnosed glucose metabolism abnormalities among persons (24,9%) is taped; it is established that relative risk of diabetes mellitus type 2 significantly raised at persons is more than 50 years of age independently of BMI, at the same time first-degree obesity increased relative risk of diabetes mellitus type 2 in 4,3 times and third-degree obesity--in 9,0 times independently of age. PMID:22232886

  3. 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

  4. Systemic chemotherapy decreases brain glucose metabolism

    Horky, Laura L; Gerbaudo, Victor H; Zaitsev, Alexander; Plesniak, Wen; Hainer, Jon; Govindarajulu, Usha; Kikinis, Ron; Dietrich, Jrg

    2014-01-01

    Objective: Cancer patients may experience neurologic adverse effects, such as alterations in neurocognitive function, as a consequence of chemotherapy. The mechanisms underlying such neurotoxic syndromes remain poorly understood. We here describe the temporal and regional effects of systemically administered platinum-based chemotherapy on glucose metabolism in the brain of cancer patients. Methods: Using sequential FDG-PET/CT imaging prior to and after administration of chemotherapy, we retro...

  5. Hepatic glucose sensing is required to preserve ? cell glucose competence

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

  6. Effects of different metabolic states and surgical models on glucose metabolism and secretion of ileal L-cell peptides: protocol for a cross-sectional study

    Celik, Alper; Dixon, John B; Pouwels, Sjaak; Celik, Bahri Onur; Karaca, Fatih Can; Gupta, Adarsh; Santoro, Sergio; Ugale, Surendra

    2016-01-01

    Introduction Obesity and type 2 diabetes mellitus are increasing worldwide, reaching pandemic proportions. The understanding of the role of functional restriction and gut hormones can be a beneficial tool in treating obesity and diabetes. However, the exact hormonal profiles in different metabolic states and surgical models are not known. Methods and analysis The HIPER-1 Study is a single-centre cross-sectional study in which 240 patients (in different metabolic states and surgical models) will receive an oral mixed-meal tolerance test (OMTT). At baseline and after 30, 60 and 120 min, peptide YY and glucagon-like peptide 1 levels and glucose and insulin sensitivity will be measured. The primary end point of the study will be the area under the glucagon-like peptide 1 and peptide YY curves after the OMTT. Secondary study end points will include examination of the difference in plasma levels of the distal ileal hormones in subjects with various health statuses and in patients who have been treated with different surgical techniques. Ethics and dissemination An independent ethics committee, the Institutional Review Board of Istanbul Sisli Kolan International Hospital, Turkey, has approved the study protocol. Dissemination will occur via publication, national and international conference presentations, and exchanges with regional, provincial and national stakeholders. Trial registration number NCT02532829; Pre-results. PMID:26975937

  7. No correlation between glucose metabolism and apparent diffusion coefficient in diffuse large B-cell lymphoma: A PET/CT and DW-MRI study

    Purpose: Both positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) are oncologic feasible techniques for evaluating the malignancy of tumors. Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by PET/CT. Apparent diffusion coefficient (ADC) measured by DWI can provide information about tissue cellularity. The aim of the study was to evaluate the correlation between SUV and ADC in untreated diffuse large B-cell lymphoma (DLBCL). Materials and methods: Fifteen pre-therapy patients with histologically proven DLBCL underwent PET/CT and DWI examinations within two days. Tumor glucose metabolism was evaluated by the maximum and mean SUV (SUVmax and SUVmean) on the PET/CT images. The mean ADC value was measured directly on the parametric ADC maps. Results: In total, 28 lymphoma lesions with best match PET/CT and DWI were identified and evaluated. The mean SUVmax and SUVmean were 16.8 and 11.1, respectively; the mean ADC was 0.74 x 10-3 mm2/s. There was no correlation between the mean ADC and the SUVmax or SUVmean. Conclusion: SUV determined from PET/CT and ADC value measured from DWI are different indices for the diagnosis of tumor malignancy, they may provide complimentary functional information of tumor tissue.

  8. No correlation between glucose metabolism and apparent diffusion coefficient in diffuse large B-cell lymphoma: A PET/CT and DW-MRI study

    Wu Xingchen, E-mail: Xingchen.Wu@uta.fi [Department of Oncology, Tampere University Hospital, Tampere (Finland); Medical Imaging Centre, Department of Radiology, Tampere University Hospital, Tampere (Finland); Korkola, Pasi [Medical Imaging Centre, Department of Nuclear Medicine, Tampere University Hospital, Tampere (Finland); Pertovaara, Hannu [Department of Oncology, Tampere University Hospital, Tampere (Finland); Eskola, Hannu [Medical Imaging Centre, Department of Radiology, Tampere University Hospital, Tampere (Finland); Department of Biomedical Engineering, Tampere University of Technology, Tampere (Finland); Jaervenpaeae, Ritva [Medical Imaging Centre, Department of Radiology, Tampere University Hospital, Tampere (Finland); Kellokumpu-Lehtinen, Pirkko-Liisa [Department of Oncology, Tampere University Hospital, Tampere (Finland); Medical School, University of Tampere (Finland)

    2011-08-15

    Purpose: Both positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) are oncologic feasible techniques for evaluating the malignancy of tumors. Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by PET/CT. Apparent diffusion coefficient (ADC) measured by DWI can provide information about tissue cellularity. The aim of the study was to evaluate the correlation between SUV and ADC in untreated diffuse large B-cell lymphoma (DLBCL). Materials and methods: Fifteen pre-therapy patients with histologically proven DLBCL underwent PET/CT and DWI examinations within two days. Tumor glucose metabolism was evaluated by the maximum and mean SUV (SUV{sub max} and SUV{sub mean}) on the PET/CT images. The mean ADC value was measured directly on the parametric ADC maps. Results: In total, 28 lymphoma lesions with best match PET/CT and DWI were identified and evaluated. The mean SUV{sub max} and SUV{sub mean} were 16.8 and 11.1, respectively; the mean ADC was 0.74 x 10{sup -3} mm{sup 2}/s. There was no correlation between the mean ADC and the SUV{sub max} or SUV{sub mean}. Conclusion: SUV determined from PET/CT and ADC value measured from DWI are different indices for the diagnosis of tumor malignancy, they may provide complimentary functional information of tumor tissue.

  9. Cancer metabolism: Is glutamine sweeter than glucose?

    Lu, Weiqin; PELICANO, HELENE; HUANG, PENG

    2010-01-01

    Glutamine is an essential nutrient for cancer cells. In this issue of Cancer Cell, Wang et al. show that malignant transformation by Rho GTPases leads to activation of glutaminase, which converts glutamine to glutamate to fuel cancer cell metabolism. Inhibition of glutaminase by a small compound effectively suppresses oncogenic transformation.

  10. 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)

  11. Effects of Glucose on Differentiation and Fat Metabolism of Chicken Preadipocytes

    Zhao Taotao

    2012-01-01

    Full Text Available The present study was carried out to illustrate the effect of glucose on chicken (Gallus gallus preadipocyte differentiation and fat metabolism. Adipocyte differentiation was initiated by maintaining confluent cells in a glucose-free medium supplemented with different concentrations of glucose. Upon exposure to high concentrations of glucose (25 mmol L-1, Peroxisome Proliferator-Activated Receptor ? (PPAR? and CCAAT/Enhancer-Binding Protein ? (C/EBP? as adipocyte differentiation markers were significantly increased compared with control cells. The morphology of the glucose-treated cells changed from fibroblast-like to polygonal and cells treated with moderate concentrations of glucose (15 mmol L-1 accumulated the most number of cytoplasmic lipid droplets as estimated by Oil red O staining. Compared with control cells varying concentrations of glucose affected the mRNA expression and protein levels for Fatty Acid Synthesis (FAS and Adipose Triglyceride Lipase (ATGL, the master regulators of fat metabolism. Moreover, the mRNA expression levels and protein contents of fatty acid transporters in glucose-treated cells were higher than in untreated cells. These results indicated that glucose is essential material for chick adipocytes differentiation. Moreover, overhigh concentrations of glucose maybe stimulate lipolysis in the cells.

  12. 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-responders. Conclusions: pre-therapeutic glucose metabolism was predictive of tumor response; higher glucose metabolism corresponded to poorer tumor response. There was a positive correlation between glucose metabolism and anti-CD20 antibody distribution, and heterogeneity rather than the absolute levels of anti-CD20 antibody correlated well with tumor response. (authors)

  13. 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 have a greater adverse effect on neuronal cell energy regulation mechanisms than either sustained high or low glucose levels. PMID:22565596

  14. 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

    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...

  15. 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.

  16. Decaffeinated Coffee and Glucose Metabolism in Young Men

    Greenberg, James A; Owen, David R; Geliebter, Allan

    2009-01-01

    OBJECTIVE The epidemiological association between coffee drinking and decreased risk of type 2 diabetes is strong. However, caffeinated coffee acutely impairs glucose metabolism. We assessed acute effects of decaffeinated coffee on glucose and insulin levels. RESEARCH DESIGN AND METHODS This was a randomized, cross-over, placebo-controlled trial of the effects of decaffeinated coffee, caffeinated coffee, and caffeine on glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) ...

  17. Osteoid osteoma is an osteocalcinoma affecting glucose metabolism.

    Confavreux, C B; Borel, O; Lee, F; Vaz, G; Guyard, M; Fadat, C; Carlier, M-C; Chapurlat, R; Karsenty, G

    2012-05-01

    Osteocalcin is a hormone secreted by osteoblasts, which regulates energy metabolism by increasing β-cell proliferation, insulin secretion, insulin sensitivity, and energy expenditure. This has been demonstrated in mice, but to date, the evidence implicating osteocalcin in the regulation of energy metabolism in humans are indirect. To address this question more directly, we asked whether a benign osteoblastic tumor, such as osteoma osteoid in young adults, may secrete osteocalcin. The study was designed to assess the effect of surgical resection of osteoid osteoma on osteocalcin and blood glucose levels in comparison with patients undergoing knee surgery and healthy volunteers. Blood collections were performed the day of surgery and the following morning after overnight fasting. Patients and controls were recruited in the orthopedic surgery department of New York Presbiterian Hospital, NY-USA and Hospices Civils de Lyon, France. Seven young males were included in the study: two had osteoid osteoma, two underwent knee surgery, and three were healthy volunteers. After resection of the osteoid osteomas, we observed a decrease of osteocalcin by 62% and 30% from the initial levels. Simultaneously, blood glucose increased respectively by 32% and 15%. Bone turnover markers were not affected. This case study shows for the first time that osteocalcin in humans affects blood glucose level. This study also suggests that ostoid osteoma may be considered, at least in part, as an osteocalcinoma. PMID:21681611

  18. 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

  19. Osteocalcin and the Regulation of Glucose Metabolism

    Vella, Adrian; Kumar, Rajiv

    2012-01-01

    Uncarboxylated osteocalcin enhances insulin and adiponectin release and improves glucose tolerance in mice. Data in humans do not unequivocally support a role for osteocalcin in glucose homeostasis. Changes in the amount of uncarboxylated osteocalcin induced by vitamin K or warfarin treatment are not associated with changes in glucose and insulin concentrations. Interventional studies in humans, designed to detect small changes in insulin secretion and action attributable to changes in uncarb...

  20. 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

  1. 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.

  2. IL4 receptor α mediates enhanced glucose and glutamine metabolism to support breast cancer growth.

    Venmar, Katherine T; Kimmel, Danielle W; Cliffel, David E; Fingleton, Barbara

    2015-05-01

    The type II interleukin-4 receptor (IL4R) is expressed in human breast cancer, and in murine models thereof. It is activated by interleukin-4 (IL4), a cytokine produced predominantly by immune cells. Previously, we showed that expression of IL4Rα, a signaling component of IL4R, mediates enhanced metastatic growth through promotion of tumor cell survival and proliferation. In lymphocytes, these processes are supported by increased glucose and glutamine metabolism, and B lymphocyte survival is dependent upon IL4/IL4R-induced glucose metabolism. However, it is unknown whether IL4R-mediated metabolic reprogramming could support tumor growth. Here, we show that IL4Rα expression increases proliferation thus enhancing primary mammary tumor growth. In vitro, IL4-enhanced glucose consumption and lactate production in 4T1 cells was mediated by IL4Rα. Expression of the glucose transporter GLUT1 increased in response to IL4 in vitro, and enhanced GLUT1 expression was associated with the presence of IL4Rα in 4T1 mammary tumors in vivo. Although IL4 treatment did not induce changes in glucose metabolism in MDA-MB-231 human breast cancer cells, it increased expression of the main glutamine transporter, ASCT2, and enhanced glutamine consumption in both MDA-MB-231 and 4T1 cells. Pharmacologic inhibition of glutamine metabolism with compound 968 blocked IL4/IL4Rα-increased cell number in both cell lines. Our results demonstrate that IL4R mediates enhanced glucose and glutamine metabolism in 4T1 cancer cells, and that IL4-induced growth is supported by IL4/IL4R-enhanced glutamine metabolism in both human and murine mammary cancer cells. This highlights IL4Rα as a possible target for effective breast cancer therapy. PMID:25746764

  3. Abnormal glucose metabolism in patients treated with antipsychotics.

    SCHEEN, Andr; De Hert, M. A.

    2007-01-01

    Second-generation (atypical) antipsychotic medications are of great benefit to a wide variety of people with psychiatric disorders, especially patients with schizophrenia. However, one constellation of adverse effects is an increased risk of obesity, diabetes, and metabolic syndrome. Increasing numbers of reports concerning impaired glucose tolerance, diabetes, and ketoacidosis have raised concerns about a possible association between abnormal glucose metabolism and treatment with atypical an...

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

    Frost, M; Petersen, I; Brixen, K; Beck-Nielsen, Henning; Holst, Jens Juul; Christiansen, L; Højlund, Kurt; Christensen, 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....

  5. 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.; Jensen, Pernille Rose; Lerche, Mathilde H.

    2014-01-01

    +]/[NADH] ratio determined in prostate cancer cells was 4 times higher than in breast cancer cells. This higher ratio reflects a distinct metabolic phenotype of prostate cancer cells consistent with previously reported alterations in the energy metabolism of these cells. As a reporter on free cytosolic [NAD...... death and oxidative stress. It has been suggested that changes in the ratio of free cytosolic [NAD+]/[NADH] reflects metabolic alterations leading to, or correlating with, pathological states. We have designed an isotopically labelled metabolic bioprobe of free cytosolic [NAD+]/[NADH] by combining a...... magnetic enhancement technique (hyperpolarization) with cellular glycolytic activity. The bioprobe reports free cytosolic [NAD+]/[NADH] ratios based on dynamically measured in-cell [pyruvate]/ [lactate] ratios. We demonstrate its utility in breast and prostate cancer cells. The free cytosolic [NAD...

  6. Degranulation effect of ferric nitrilotriacetate (Fe3+-NTA on the pancreatic islet beta-cells: its acute toxic effect on glucose metabolism.

    Yamanoi,Yasuhiro

    1984-10-01

    Full Text Available A single injection of ferric nitrilotriacetate (Fe3+-NTA caused a transitory increase in plasma immunoreactive insulin (IRI and plasma immunoreactive glucagon (IRG in rats. They reached maximum levels at 2 days after injection and returned to the normal range at 10 days. At 2 days after Fe3+-NTA injection, blood glucose level was normal but the glucose tolerance test (GTT was impaired. There was a further increase in plasma IRI level and IRG level was suppressed after glucose loading. At 10 days after Fe3+-NTA injection, glucose tolerance was normal and IRI also returned to the normal range. No degenerative changes were found on H.E.-stained rat pancreatic tissue sections after Fe3+-NTA injection. Histochemical staining, however, showed a reduction in beta-granules and heavy metals (Timm's granules from islet cells in the central area of the rat pancreatic islet 1 to 3 days after injection of Fe3+-NTA. The fading remained in some islets even at 10 days after injection, but by then the beta-granule distribution was restored in most islet cells. The results indicate a single Fe3+-NTA injection induced transitory instability of the pancreatic islet beta-cell granules and the glucose intolerance with a hyperresponse of IRI.

  7. 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.)

  8. 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.)

  9. 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 inflammation and the development of the metabolic syndrome

  10. Osteocalcin as a hormone regulating glucose metabolism

    Kanazawa, Ippei

    2015-01-01

    The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, regulates glucose homeostasis by stimulating insulin expression in pancreas and adiponectin expression in adipocytes, resulting in improving glucose intolerance. On the other hand, insulin and adiponectin stimulate ost...

  11. Aerobic glucose metabolism of Saccharomyces kluyveri: Growth, metabolite production, and quantification of metabolic fluxes

    Mller, Kasper; Christensen, B.; Frster, Jochen; Piskur, Jure; Nielsen, Jens; Olsson, Lisbeth

    2002-01-01

    constant specific rate of 0.12 g ethyl acetate per g dry weight per hour. The aerobic glucose metabolism in S. kluyveri was found to be less fermentative than in S. cerevisiae, as illustrated by the comparably low yield of ethanol on glucose (0.08 +/- 0.02 g/g), and high yield of biomass on glucose (0.......29 +/- 0.01 g/g). The glucose metabolism of S. kluyveri was further characterized by the new and powerful techniques of metabolic network analysis. Flux distributions in the central carbon metabolism were estimated for respiro-fermentative growth in aerobic batch cultivation on glucose and respiratory...... previously been observed in S. cerevisiae at the same growth conditions, where the tricarboxylic acid cycle operates as two branches. This indicates that the respiratory system was not significantly repressed in S. kluyveri during batch cultivation on glucose....

  12. 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

  13. 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

  14. Cerebral glucose metabolism in Wernicke's, Broca's, and conduction aphasia

    Cerebral glucose metabolism was evaluated in patients with either Wernicke's (N = 7), Broca's (N = 11), or conduction (N = 10) aphasia using 18F-2-fluoro-2-deoxy-D-glucose with positron emission tomography. The three aphasic syndromes differed in the degree of left-to-right frontal metabolic asymmetry, with Broca's aphasia showing severe asymmetry and Wernicke's aphasia mild-to-moderate metabolic asymmetry, while patients with conduction aphasia were metabolically symmetric. On the other hand, the three syndromes showed the same degree of metabolic decline in the left temporal region. The parietal region appeared to separate conduction aphasia from both Broca's and Wernicke's aphasias. Common aphasic features in the three syndromes appear to be due to common changes in the temporal region, while unique features were associated with frontal and parietal metabolic differences

  15. Muscle glucose metabolism following exercise in the rat

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

    1982-01-01

    Muscle glycogen stores are depleted during exercise and are rapidly repleted during the recovery period. To investigate the mechanism for this phenomenon, untrained male rats were run for 45 min on a motor-driven treadmill and the ability of their muscles to utilize glucose was then assessed during...... 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....... Prior exercise did not enhance the ability of insulin to convert glycogen synthase from its glucose-6-phosphate-dependent (D) to its glucose-6-phosphate-independent (1) form. On the other hand, following exercise, insulin prevented a marked decrease in muscle glucose-6-phosphate, which could have...

  16. Metabolism of tritiated D-glucose in rat erythrocytes

    The metabolism of D-[U-14C]glucose, D-[1-14C]glucose, D-[6-14C]glucose, D-[1-3H]glucose, D-[2-3H]glucose, D-[3-3H]glucose, D-[3,4-3H]glucose, D-[5-3H]glucose, and D-[6-3H]glucose was examined in rat erythrocytes. There was a fair agreement between the rate of 3HOH production from either D-[3-3H]glucose and D-[5-3H]glucose, the decrease in the 2,3-diphosphoglycerate pool, its fractional turnover rate, the production of 14C-labeled lactate from D-[U-14C]glucose, and the total lactate output. The generation of both 3HOH and tritiated acidic metabolites from D-[3,4-3H]glucose indicated incomplete detritiation of the C4 during interconversion of fructose-1,6-bisphosphate and triose phosphates. Erythrocytes unexpectedly generated 3HOH from D-[6-3H]glucose, a phenomenon possibly attributable to the detritiation of [3-3H]pyruvate in the reaction catalyzed by glutamate pyruvate transaminase. The production of 3HOH from D-[2-3H]glucose was lower than that from D-[5-3H]glucose, suggesting enzyme-to-enzyme tunneling of glycolytic intermediates in the hexokinase/phosphoglucoisomerase/phosphofructokinase sequence. The production of 3HOH from D-[1-3H]glucose largely exceeded that of 14CO2 from D-[1-14C]glucose, a situation tentatively ascribed to the generation of 3HOH in the phosphomannoisomerase reaction. It is further speculated that the adjustment in specific radioactivity of D-[1-3H]glucose-6-phosphate cannot simultaneously match the vastly different degrees of isotopic discrimination in velocity at the levels of the reactions catalyzed by either glucose-6-phosphate dehydrogenase or phosphoglucoisomerase. The interpretation of the present findings thus raises a number of questions, which are proposed as a scope for further investigations

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

    H.G., Padilha; C.A., Crispim; I.Z., Zimberg; D.A., De-Souza; J., Waterhouse; S., Tufik; M.T, de-Mello.

    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 l [...] iterature 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-? (TNF-?) 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.

  18. Relationships Between Osteocalcin, Glucose Metabolism, and Adiponectin in Obese Children: Is there Crosstalk Between Bone Tissue and Glucose Metabolism?

    Abseyi, Nilay; Şıklar, Zeynep; BERBEROĞLU, Merih; Hacıhamdioğlu, Bülent; Savaş Erdeve, Şenay; Öçal, Gönül

    2012-01-01

    Objective: Recently, scientific interest has focused on the association between osteocalcin, which originates from the skeletal system, and glucose metabolism. Although the association between lipid metabolism, adiponectin, and metabolic syndrome is well known, that between obesity, insulin resistance, and osteocalcin have not been clarified yet in children. The aim of this study was to assess the prevalence of insulin resistance in obese children and adolescents, as well as to investigate th...

  19. Glucose Metabolism in Critically Ill Patients

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

    2015-01-01

    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...

  20. Glucose, pyruvate, and acetate metabolism by developing soybean seeds

    Developing soybean cotyledons were incubated with glucose-14C, pyruvate-14C, and acetate-14C. Glucose was metabolized by both the Embden-Meyerhof-parnas pathway and the pentose phosphate pathway. Developing soybean cotyledons also have the capacity to synthesize sucrose since 14C was found in fructose and sucrose from glucose incubations. Complete analysis showed that the carbons from glucose were directed into CO2, lipid, and solids. Pyruvate was metabolised to a C-2 unit which is presumably acetyl CoA. After conversion to the C-2 unit, the carbons of pyruvate were metabolized in the same manner as acetate. Both pyruvate and acetate carbons were directed predominately into lipids. (auth.)

  1. 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...

  2. 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

  3. Antilipolytic drug boosts glucose metabolism in prostate cancer

    Andersen, Kim Francis; Divilov, Vadim; Koziorowski, Jacek; Pillarsetty, NagaVaraKishore; Lewis, Jason S

    2013-01-01

    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.......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....

  4. Glucose-induced remodeling of intermediary and energy metabolism in procyclic Trypanosoma brucei.

    Coustou, Virginie; Biran, Marc; Breton, Marc; Guegan, Fabien; Rivire, Loc; Plazolles, Nicolas; Nolan, Derek; Barrett, Michael P; Franconi, Jean-Michel; Bringaud, Frdric

    2008-06-13

    The procyclic form of Trypanosoma brucei is a parasitic protozoan that normally dwells in the midgut of its insect vector. In vitro, this parasite prefers d-glucose to l -proline as a carbon source, although this amino acid is the main carbon source available in its natural habitat. Here, we investigated how l -proline is metabolized in glucose-rich and glucose-depleted conditions. Analysis of the excreted end products of (13)C-enriched l -proline metabolism showed that the amino acid is converted into succinate or l -alanine depending on the presence or absence of d-glucose, respectively. The fact that the pathway of l -proline metabolism was truncated in glucose-rich conditions was confirmed by the analysis of 13 separate RNA interference-harboring or knock-out cell lines affecting different steps of this pathway. For instance, RNA interference studies revealed the loss of succinate dehydrogenase activity to be conditionally lethal only in the absence of d-glucose, confirming that in glucose-depleted conditions, l -proline needs to be converted beyond succinate. In addition, depletion of the F(0)/F(1)-ATP synthase activity by RNA interference led to cell death in glucose-depleted medium, but not in glucose-rich medium. This implies that, in the presence of d-glucose, the importance of the F(0)/F(1)-ATP synthase is diminished and ATP is produced by substrate level phosphorylation. We conclude that trypanosomes develop an elaborate adaptation of their energy production pathways in response to carbon source availability. PMID:18430732

  5. 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...

  6. Effects of Pollen Typhae total flavone on glucose and lipid metabolism in 3T3-L1 adipocytes

    Yan-ming HE; Wang, Wen-Jian

    2006-01-01

    Objective: To observe the effects of Pollen Typhae total flavone (PTF) on glucose and lipid metabolism in 3T3-L1 adipocytes. Methods: The content of glucose which disappeared from the culture medium after incubation with drugs for 24 hours was determined as glucose consumption of the cells. The activity of cells was detected by XTT method. The transport of glucose was observed by 3H-glucose uptake method. The efflux of free fatty acid (FFA) from adipocytes was observed by the concentration of...

  7. A distinct metabolic signature predicts development of fasting plasma glucose

    Hische Manuela

    2012-02-01

    Full Text Available Abstract Background High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called 'omics' approaches in the recent years promises to identify molecular markers and to further understand the molecular basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high-throughput methods. Methods We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up. We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS, and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort. Results We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross-validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis. Conclusions We demonstrate that metabolites identified using a high-throughput method (GC-MS perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by high-throughput methods.

  8. Gastric emptying, glucose metabolism and gut hormones

    Vermeulen, Mechteld A R; Richir, Milan C; Garretsen, Martijn K; van Schie, Annelies; Ghatei, Mohammed A; Holst, Jens Juul; Heijboer, Annemieke C; Uitdehaag, Bernard M J; Diamant, Michaela; Eekhoff, E Marelise W; van Leeuwen, Paul A M; Ligthart-Melis, Gerdien C

    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...

  9. 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

  10. 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.

  11. 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

  12. 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 key enzymes. This results in enhanced glucose dependency and leads to cell death under low-glucose conditions. On the other hand, the reduced requirements for oxygen and nutrients from the surrounding environment, might confer the resistance to cell death induced by hypoxia and malnutrition.

  13. 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. This results in enhanced glucose dependency and leads to cell death under low-glucose conditions. On the other hand, the reduced requirements for oxygen and nutrients from the surrounding environment, might confer the resistance to cell death induced by hypoxia and malnutrition

  14. 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...

  15. 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)

  16. Nicotinamide nucleotide transhydrogenase: a link between insulin secretion, glucose metabolism and oxidative stress.

    Freeman, H; Shimomura, K; Cox, R D; Ashcroft, F M

    2006-11-01

    This paper reviews recent studies on the role of Nnt (nicotinamide nucleotide transhydrogenase) in insulin secretion and detoxification of ROS (reactive oxygen species). Glucose-stimulated insulin release from pancreatic beta-cells is mediated by increased metabolism. This elevates intracellular [ATP], thereby closing KATP channels (ATP-sensitive potassium channels) and producing membrane depolarization, activation of voltage-gated Ca2+ channels, Ca2+ influx and, consequently, insulin secretion. The C57BL/6J mouse displays glucose intolerance and reduced insulin secretion, which results from a naturally occurring deletion in the Nnt gene. Transgenic expression of the wild-type Nnt gene in C57BL/6J mice rescues the phenotype. Knockdown of Nnt in the insulin-secreting cell line MIN6 with small interfering RNA dramatically reduced Ca2+ influx and insulin secretion. Similarly, mice carrying ENU (N-ethyl-N-nitrosourea)-induced loss-of-function mutations in Nnt were glucose intolerant and secreted less insulin during a glucose tolerance test. Islets isolated from these mice showed impaired insulin secretion in response to glucose, but not to the KATP channel blocker tolbutamide. This is explained by the fact that glucose failed to elevate ATP in Nnt mutant islets. Nnt is a nuclear-encoded mitochondrial protein involved in detoxification of ROS. beta-Cells isolated from Nnt mutant mice showed increased ROS production on glucose stimulation. We hypothesize that Nnt mutations enhance glucose-dependent ROS production and thereby impair beta-cell mitochondrial metabolism, possibly via activation of uncoupling proteins. This reduces ATP production and lowers KATP channel activity. Consequently, glucose-dependent electrical activity and insulin secretion are impaired. PMID:17052203

  17. Cerebral glucose metabolism in the course of subacute sclerosing panencephalitis

    Huber, M.; Herholz, K.; Pawlik, G.; Szelies, B.; Juergens, R.H.; Heiss, W.D.

    1989-01-01

    Regional cerebral glucose metabolism was studied in a 15-year-old boy with subacute sclerosing panencephalitis before and after therapy with human interferon beta, using positron emission tomography of fluorine 18-2-fluoro-2-deoxyglucose. At first examination, metabolism was symmetrically decreased in the thalamus, cerebellum, and all cortical areas except prerolandic motor cortex, but increased in lentiform nucleus. A computed tomographic scan was normal. Six months later, bilateral focal necrosis centered in the previously hypermetabolic putamen was demonstrated by computed tomography and magnetic resonance imaging. The caudate nucleus and the superoposterior part of the putamen were spared, still showing increased metabolism. Corresponding with some clinical improvement, cortical glucose consumption rates had returned to a normal level.

  18. Cerebral glucose metabolism in the course of subacute sclerosing panencephalitis

    Regional cerebral glucose metabolism was studied in a 15-year-old boy with subacute sclerosing panencephalitis before and after therapy with human interferon beta, using positron emission tomography of fluorine 18-2-fluoro-2-deoxyglucose. At first examination, metabolism was symmetrically decreased in the thalamus, cerebellum, and all cortical areas except prerolandic motor cortex, but increased in lentiform nucleus. A computed tomographic scan was normal. Six months later, bilateral focal necrosis centered in the previously hypermetabolic putamen was demonstrated by computed tomography and magnetic resonance imaging. The caudate nucleus and the superoposterior part of the putamen were spared, still showing increased metabolism. Corresponding with some clinical improvement, cortical glucose consumption rates had returned to a normal level

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

    Michael Lawrence James Ashford

    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.

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

    Dalgaard, Louise T

    2012-01-01

    Uncoupling Protein 2 (UCP2) is expressed in the pancreatic ?-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. PMID:22177951

  1. Glucose Metabolism in Sheep Fed Grass Supplemented with Gliricidia Sepium

    Y. Widiawati

    2014-12-01

    Full Text Available 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 nutritivefeed 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 propionat 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. Fifteen sheeps (18 months old were used in the experiment. Theseare 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]glucoseinfusate was infused continuously through the left jugular venous catheter of each animal to measure glucose metabolism in those sheeps. The 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 theutilization 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.

  2. Role of sodium and potassium ions in regulation of glucose metabolism in cultured astroglia.

    Takahashi, S.; Driscoll, B F; Law, M J; Sokoloff, L

    1995-01-01

    Effects of increasing extracellular K+ or intracellular Na+ concentrations on glucose metabolism in cultures of rat astroglia and neurons were examined. Cells were incubated in bicarbonate buffer, pH 7.2, containing 2 mM glucose, tracer amounts of [14C]deoxyglucose ([14C]dGlc), and 5.4, 28, or 56 mM KCl for 10, 15, or 30 min, and then for 5 min in [14C]dGlc-free buffer to allow efflux of unmetabolized [14C]dGlc. Cells were then digested and assayed for labeled products, which were shown to co...

  3. Cerebral glucose metabolic differences in patients with panic disorder

    Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer [F-18]-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al., we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings that would have been noted in a study performed without task

  4. Glucose availability and glycolytic metabolism dictate glycosphingolipid levels

    Stathem, Morgan; Marimuthu, Subathra; O'Neal, Julie; Rathmell, Jeffrey C.; Chesney, Jason A.; Beverly, Levi J.; Siskind, Leah J.

    2015-01-01

    Cancer therapeutics has seen an emergence and re-emergence of two metabolic fields in recent years, those of bioactive sphingolipids and glycolytic metabolism. Anaerobic glycolysis and its implications in cancer have been at the forefront of cancer research for over 90 years. More recently, the role of sphingolipids in cancer cell metabolism has gained recognition, notably ceramide's essential role in programmed cell death and the role of the glucosylceramide synthase (GCS) in chemotherapeuti...

  5. 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

  6. 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 sistmicos da imobilizao por desnervao do msculo esqueltico sobre o metabolismo glicidico. Ratos foram submetidos seco do nervo citico da pata direita. Observou-se reduo da captao de glicose pelo msculo sleo isolado da pata desnervada aps 3 e 7 mas no aps 28 dias em relao a animais controle. No houve diferena aps 3 e 7 dias na captao de glicose pelo msculo sleo da pata contralateral intacta em relao ao controle. Houve aumento da captao de glicose nesta mesma pata 28 dias aps a desnervao. A taxa de remoo da glicose em resposta insulina exgena aps 28 dias de desnervao foi significantemente superior do controle e quelas observadas aps 3 e 7 dias da desnervao. Esses resultados sugerem que a imobilizao por desnervao interfere no s no metabolismo da glicose no msculo esqueltico envolvido como tambm em outros tecidos.

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

    Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost; Tvede, Michael; Hansen, Torben; Pedersen, Oluf Borbye; Holst, Jens Juul; Vilsbøll, Tina; Knop, Filip Krag

    2013-01-01

    New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gut microbiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gut microbiota and that...... 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....

  8. 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 ...

  9. 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...

  10. 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

  11. Molecular mechanism of hepatitis C virus-induced glucose metabolic disorders

    IkuoShoji

    2012-01-01

    Full Text Available Hepatitis C virus (HCV infection causes not only intrahepatic diseases but also extrahepatic manifestations, including metabolic disorders. Chronic HCV infection is often associated with type 2 diabetes. However, the precise mechanism underlying this association is still unclear. Glucose is transported into hepatocytes via glucose transporter 2 (GLUT2. Hepatocytes play a crucial role in maintaining plasma glucose homeostasis via the gluconeogenic and glycolytic pathways. We have been investigating the molecular mechanism of HCV-related type 2 diabetes using HCV RNA replicon cells and HCV J6/JFH1 system. We found that HCV replication down-regulates cell surface expression of GLUT2 at the transcriptional level. We also found that HCV infection promotes hepatic gluconeogenesis in HCV J6/JFH1-infected Huh-7.5 cells. HCV infection transcriptionally up-regulated the genes for PEPCK and G6Pase, the rate-limiting enzymes for hepatic gluconeogenesis. Gene expression of PEPCK and G6Pase was regulated by the transcription factor forkhead box O1 (FoxO1 in HCV-infected cells. Phosphorylation of FoxO1 at Ser319 was markedly diminished in HCV-infected cells, resulting in increased nuclear accumulation of FoxO1. HCV NS5A protein was directly linked with the FoxO1-dependent increased gluconeogenesis. This paper will discuss the current model of HCV-induced glucose metabolic disorders.

  12. 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. Overall, extracellular glucose makes only a minor contribution to ATP production but a sustained glycolysis may be necessary to support Ca(2+) transport mechanisms at either the sarcoplasmic reticulum or the sarcolemmal membrane. PMID:26944490

  13. Seasonal Temperature Changes Do Not Affect Cardiac Glucose Metabolism

    Schildt, Jukka; Loimaala, Antti; Hippeläinen, Eero; Nikkinen, Päivi; Ahonen, Aapo

    2015-01-01

    FDG-PET/CT is widely used to diagnose cardiac inflammation such as cardiac sarcoidosis. Physiological myocardial FDG uptake often creates a problem when assessing the possible pathological glucose metabolism of the heart. Several factors, such as fasting, blood glucose, and hormone levels, influence normal myocardial glucose metabolism. The effect of outdoor temperature on myocardial FDG uptake has not been reported before. We retrospectively reviewed 29 cancer patients who underwent PET scans in warm summer months and again in cold winter months. We obtained myocardial, liver, and mediastinal standardized uptake values (SUVs) as well as quantitative cardiac heterogeneity and the myocardial FDG uptake pattern. We also compared age and body mass index to other variables. The mean myocardial FDG uptake showed no significant difference between summer and winter months. Average outdoor temperature did not correlate significantly with myocardial SUVmax in either summer or winter. The heterogeneity of myocardial FDG uptake did not differ significantly between seasons. Outdoor temperature seems to have no significant effect on myocardial FDG uptake or heterogeneity. Therefore, warming the patients prior to attending cardiac PET studies in order to reduce physiological myocardial FDG uptake seems to be unnecessary. PMID:26858844

  14. Interaction between Glucose and Lipid Metabolism: More than Diabetic Dyslipidemia.

    Parhofer, Klaus G

    2015-10-01

    Glucose and lipid metabolism are linked to each other in many ways. The most important clinical manifestation of this interaction is diabetic dyslipidemia, characterized by elevated triglycerides, low high density lipoprotein cholesterol (HDL-C), and predominance of small-dense LDL particles. However, in the last decade we have learned that the interaction is much more complex. Hypertriglyceridemia and low HDL-C cannot only be the consequence but also the cause of a disturbed glucose metabolism. Furthermore, it is now well established that statins are associated with a small but significant increase in the risk for new onset diabetes. The underlying mechanisms are not completely understood but modulation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA)-reductase may play a central role as genetic data indicate that mutations resulting in lower HMG CoA-reductase activity are also associated with obesity, higher glucose concentrations and diabetes. Very interestingly, this statin induced increased risk for new onset type 2 diabetes is not detectable in subjects with familial hypercholesterolemia. Furthermore, patients with familial hypercholesterolemia seem to have a lower risk for type 2 diabetes, a phenomenon which seems to be dose-dependent (the higher the low density lipoprotein cholesterol, the lower the risk). Whether there is also an interaction between lipoprotein(a) and diabetes is still a matter of debate. PMID:26566492

  15. 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.

  16. 2-Deoxy-2-fluoro-d-glucose metabolism in Arabidopsis thaliana.

    Fatangare, Amol; Paetz, Christian; Saluz, Hanspeter; Svato, Ale

    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 FDG in the model plant species Arabidopsis thaliana. We fed FDG to leaf tissue and analyzed leaf extracts using MS and NMR. On the basis of exact mono-isotopic masses, MS/MS fragmentation, and NMR data, we identified 2-deoxy-2-fluoro-gluconic acid, FDG-6-phosphate, 2-deoxy-2-fluoro-maltose, and uridine-diphosphate-FDG as four major end products of FDG metabolism. Glycolysis and starch degradation seemed to be the important pathways for FDG metabolism. We showed that FDG metabolism in plants is considerably different than animal cells and goes beyond FDG-phosphate as previously presumed. PMID:26579178

  17. 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)

  18. 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...

  19. 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....

  20. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with adolescent idiopathic scoliosis. The mean mini-mental status exam score in the congenital scoliosis group was significantly lower than that in the adolescent idiopathic scoliosis group. Group analysis found that various brain areas of patients with congenital scoliosis showed glucose hypometabolisms in the left prefrontal cortex (Brodmann area 10), right orbitofrontal cortex (Brodmann area 11), left dorsolateral prefrontal cortex (Brodmann area 9), left anterior cingulate gyrus (Brodmann area 24) and pulvinar of the left thalamus. From this study, we could find the metabolic abnormalities of brain in patients with congenital scoliosis and suggest the possible role of voxel-based analysis of brain fluorodeoxyglucose positron emission tomography

  1. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

    Nam, H. Y.; Seo, G. T.; Lee, J. S.; Kim, S. C.; Kim, I. J.; Kim, Y. K.; Jeon, S. M. [Pusan National University Hospital, Pusan (Korea, Republic of)

    2007-07-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with adolescent idiopathic scoliosis. The mean mini-mental status exam score in the congenital scoliosis group was significantly lower than that in the adolescent idiopathic scoliosis group. Group analysis found that various brain areas of patients with congenital scoliosis showed glucose hypometabolisms in the left prefrontal cortex (Brodmann area 10), right orbitofrontal cortex (Brodmann area 11), left dorsolateral prefrontal cortex (Brodmann area 9), left anterior cingulate gyrus (Brodmann area 24) and pulvinar of the left thalamus. From this study, we could find the metabolic abnormalities of brain in patients with congenital scoliosis and suggest the possible role of voxel-based analysis of brain fluorodeoxyglucose positron emission tomography.

  2. Effect of Plasma Membrane Cholesterol Depletion on Glucose Transport Regulation in Leukemia Cells

    Caliceti, Cristiana; Zambonin, Laura; Prata, Cecilia; Vieceli Dalla Sega, Francesco; Hakim, Gabriele; Hrelia, Silvana; Fiorentini, Diana

    2012-01-01

    GLUT1 is the predominant glucose transporter in leukemia cells, and the modulation of glucose transport activity by cytokines, oncogenes or metabolic stresses is essential for their survival and proliferation. However, the molecular mechanisms allowing to control GLUT1 trafficking and degradation are still under debate. In this study we investigated whether plasma membrane cholesterol depletion plays a role in glucose transport activity in M07e cells, a human megakaryocytic leukemia line. To ...

  3. Glucose metabolism alterations in patients with bipolar disorder.

    Rosso, Gianluca; Cattaneo, Annamaria; Zanardini, Roberta; Gennarelli, Massimo; Maina, Giuseppe; Bocchio-Chiavetto, Luisella

    2015-09-15

    Patients with bipolar disorder (BD) are more frequently affected by metabolic syndrome (MetS) than the general population, but the neurobiological correlates underlying such association are still not clarified and few studies in BD have evaluated the role of regulators of lipid and glucose metabolism. The present study was aimed to investigate putative alterations in markers linked to metabolic dysfunctions as C-peptide, Ghrelin, GIP, GLP-1, Glucagon, Insulin, Leptin, PAI-1 (total), Resistin and Visfatin in a sample of BD patients compared to controls. Furthermore, associations between changes of metabolic markers and relevant clinical features, such as severity of symptomatology, number and type of past mood episodes, drug treatments and presence/absence of metabolic alterations (MetS, diabetes and cardiovascular disease) were analyzed. A total of 57 patients with BD and 49 healthy controls were recruited. The main results showed lower serum levels of Glucagon, GLP-1, Ghrelin, and higher levels of GIP in BD patients as compared to controls (p = 0.018 for Ghrelin; p < 0.0001 for Glucagon; p < 0.0001 for GLP-1; p < 0.0001 for GIP). Further, Glucagon and GLP-1 levels were significantly associated with the number of past mood episodes. These findings support the hypothesis that alterations in Glucagon, GLP-1, GIP and Ghrelin might be involved in BD pathogenesis and might represent useful biomarkers for the development of preventive and personalized therapies in this disorder. PMID:26120808

  4. 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

  5. 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

  6. 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....

  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. Carbon balance studies of glucose metabolism in rat cerebral cortical synaptosomes

    Bauer, U.; Brand, K.

    1982-07-01

    Synaptosomes were isolated from rat cerebral cortex and incubated with (U-/sup 14/C)-, (1-/sup 14/C)- or (6-/sup 14/C)glucose. Glucose utilization and the metabolic partitioning of glucose carbon in products were determined by isotopic methods. From the data obtained a carbon balance was constructed, showing lactate to be the main product of glucose metabolism, followed by CO/sup 2/, amino acids and pyruvate. Measuring the release of /sup 14/CO/sup 2/ from glucose labelled in three different positions allowed the construction of a flow diagram of glucose carbon atoms in synaptosomes, which provides information about the contribution of the various pathways of glucose metabolism. Some 2% of glucose utilized was calculated to be degraded via the pentose phosphate pathway. Addition of chlorpromazine, imipramine or haloperidol at concentrations of 10(-5) M reduced glucose utilisation by 30% without changing the distribution pattern of radioactivity in the various products.

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

    Nugent Scott; Courchesne-Loyer Alexandre; St-Pierre Valerie; Vandenberghe Camille; Castellano Christian-Alexandre; Cunnane Stephen C.

    2016-01-01

    Brain energy metabolism in Alzheimers 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) c...

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

    Pei Dee

    2007-01-01

    Full Text Available Background: 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. Subjects and Methods: All participants received a standard 75-g 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. Results: 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. Conclusion: 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.

  11. 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)

  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. Glucose metabolism, enzymic analysis and product formation in chemostat culture of Hanseniaspora uvarum.

    Venturin, C; Boze, H; Moulin, G; Galzy, P

    1995-04-15

    The physiology of Hanseniaspora uvarum K5 was studied in glucose-limited chemostat cultures and upon glucose pulse. Up to a dilution rate of 0.28 h-1, glucose was completely metabolized in biomass and CO2. Above this value, increase in the dilution rate was accompanied by sequential production of metabolites (glycerol, acetate and ethanol) and decrease in cell yield. Similar results were observed upon glucose pulse. From the enzyme activities (pyruvate dehydrogenase, pyruvate decarboxylase, NAD and NADP-dependent acetaldehyde dehydrogenases, acetyl coenzyme A synthetase and alcohol dehydrogenase) and substrate affinities, the following conclusions were drawn with respect to product formation of cells: (1) pyruvate was preferentially metabolized via pyruvate dehydrogenase, when biomass and CO2 were the only products formed; (2) acetaldehyde formed by pyruvate decarboxylase was preferentially oxidized in acetate by NADP-dependent aldehyde dehydrogenase; acetate accumulation results from insufficient activity of acetyl-CoA synthetase required for the complete oxidation of acetate; (3) acetaldehyde was oxidized in ethanol by alcohol dehydrogenase, in addition to acetate production. PMID:7785333

  14. Glucose: an Energy Currency and Structural Precursor in Articular Cartilage and Bone with Emerging Roles as an Extracellular Signalling Molecule and Metabolic Regulator

    AliMobasheri

    2012-12-01

    Full Text Available In the musculoskeletal system glucose serves as an essential source of energy for the development, growth and maintenance of bone and articular cartilage. It is particularly needed for skeletal morphogenesis during embryonic growth and foetal development. Glucose is vital for osteogenesis and chondrogenesis, and is used as a precursor for the synthesis of glycosaminoglycans, glycoproteins and glycolipids. Glucose sensors are present in tissues and organs that carry out bulk glucose fluxes (i.e. intestine, kidney and liver. The beta cells of the pancreatic islets of Langerhans respond to changes in glucose concentration by varying the rate of insulin synthesis and secretion. Neuronal cells in the hypothalamus are also capable of sensing extracellular glucose. Glucosensing neurons use glucose as a signalling molecule to alter their action potential frequency in response to variations in ambient glucose levels. Skeletal muscle and adipose tissue can respond to changes in circulating glucose but much less is known about glucosensing in bone and cartilage. Recent research suggests that bone cells can influence (and be influenced by systemic glucose metabolism. This focused review article discusses what we know about glucose transport and metabolism in bone and cartilage and highlights recent studies that have linked glucose metabolism, insulin signalling and osteocalcin activity in bone and cartilage. These new findings in bone cells raise important questions about nutrient sensing, uptake, storage and processing mechanisms and how they might contribute to overall energy homeostasis in health and disease. The role of glucose in modulating anabolic and catabolic gene expression in normal and osteoarthritic chondrocytes is also discussed. In summary, cartilage and bone cells are sensitive to extracellular glucose and adjust their gene expression and metabolism in response to varying extracellular glucose concentrations.

  15. Cell cycle regulators in the control of metabolism. : Cell cycle and metabolism.

    Blanchet, Emilie; Annicotte, Jean-Sébastien; Fajas, Lluis

    2009-01-01

    We recently showed that the CDK4-pRB-E2F1 cell cycle regulators directly regulate the expression of Kir6.2, which is a key component of the K(ATP) channel involved in the regulation of glucose-induced insulin secretion. There is enough evidence to indicate that the CDK4-pRB-E2F1 regulatory pathway is involved in general glucose homeostasis, and metabolism. In this article we discuss which are the metabolic implications of these findings.

  16. [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

  17. Effect of naproxen on glucose metabolism and tolbutamide kinetics and dynamics in maturity onset diabetics.

    Whiting, B.; Williams, R. L.; Lorenzi, M.; Varady, J C; Robins, D S

    1981-01-01

    1 The influence of the nonsteroidal anti-inflammatory drug naproxen on glucose metabolism and on tolbutamide pharmacokinetics and pharmacodynamics has been studied in ten maturity-onset diabetics. 2 Comparison of both plasma glucose decay curves and insulin responses during an intravenous glucose tolerance test before and after eight 12 hourly doses of naproxen revealed that naproxen had no significant influence on fasting glucose levels or on rates of glucose elimination. 3 When the subjects...

  18. 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.)

  19. 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 energy metabolism.

  20. 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 improvements in tumor-to-background ratios. Data indicate that administration of Acipimox prior to 18 F-FDG PET scans has potential to improve sensitivity and specificity in patients with castration-resistant advanced PCa

  1. 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 ...

  2. 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

    OBJECTIVES: Lipodystrophy and insulin resistance are prevalent among human immunodeficiency virus (HIV)-infected patients on combined antiretroviral therapy (HAART). Aiming to provide a detailed description of the metabolic adverse effects of HIV-lipodystrophy, we investigated several aspects of ...

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

    2005-01-01

    OBJECTIVES: Lipodystrophy and insulin resistance are prevalent among human immunodeficiency virus (HIV)-infected patients on combined antiretroviral therapy (HAART). Aiming to provide a detailed description of the metabolic adverse effects of HIV-lipodystrophy, we investigated several aspects of...

  4. 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

  5. Metabolic flux profiling of recombinant protein secreting Pichia pastoris growing on glucose:methanol mixtures

    Jordà Joel

    2012-05-01

    Full Text Available Abstract Background The methylotrophic yeast Pichia pastoris has emerged as one of the most promising yeast hosts for the production of heterologous proteins. Mixed feeds of methanol and a multicarbon source instead of methanol as sole carbon source have been shown to improve product productivities and alleviate metabolic burden derived from protein production. Nevertheless, systematic quantitative studies on the relationships between the central metabolism and recombinant protein production in P. pastoris are still rather limited, particularly when growing this yeast on mixed carbon sources, thus hampering future metabolic network engineering strategies for improved protein production. Results The metabolic flux distribution in the central metabolism of P. pastoris growing on a mixed feed of glucose and methanol was analyzed by Metabolic Flux Analysis (MFA using 13C-NMR-derived constraints. For this purpose, we defined new flux ratios for methanol assimilation pathways in P. pastoris cells growing on glucose:methanol mixtures. By using this experimental approach, the metabolic burden caused by the overexpression and secretion of a Rhizopus oryzae lipase (Rol in P. pastoris was further analyzed. This protein has been previously shown to trigger the unfolded protein response in P. pastoris. A series of 13C-tracer experiments were performed on aerobic chemostat cultivations with a control and two different Rol producing strains growing at a dilution rate of 0.09 h−1 using a glucose:methanol 80:20 (w/w mix as carbon source. The MFA performed in this study reveals a significant redistristribution of carbon fluxes in the central carbon metabolism when comparing the two recombinant strains vs the control strain, reflected in increased glycolytic, TCA cycle and NADH regeneration fluxes, as well as higher methanol dissimilation rates. Conclusions Overall, a further 13C-based MFA development to characterise the central metabolism of methylotrophic yeasts when growing on mixed methanol:multicarbon sources has been implemented, thus providing a new tool for the investigation of the relationships between central metabolism and protein production. Specifically, the study points at a limited but significant impact of the conformational stress associated to secretion of recombinant proteins on the central metabolism, occurring even at modest production levels.

  6. 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

  7. A Regulatory Mutant of Hansenula polymorpha Exhibiting Methanol Utilization Metabolism and Peroxisome Proliferation in Glucose

    Parpinello, Giuseppinia; Berardi, Enrico; Strabbioli, Rosanna

    1998-01-01

    Mutant LGM-128 of Hansenula polymorpha harbors the recessive mutation glr2-1 which confers a complex pleiotropic phenotype, the major feature of which is the metabolically unnecessary induction of methanol utilization metabolism (C1 metabolism) during growth on glucose, whether or not methanol is in the medium. Therefore, in this mutant, peroxisomes are formed and proliferate upon cultivation in glucose-containing media. In these media, LGM-128 shows induction levels of C1 metabolism that are...

  8. Effects of Pollen Typhae total flavone on glucose and lipid metabolism in 3T3-L1 adipocytes

    Yan-Ming HE

    2006-11-01

    Full Text Available Objective: To observe the effects of Pollen Typhae total flavone (PTF on glucose and lipid metabolism in 3T3-L1 adipocytes. Methods: The content of glucose which disappeared from the culture medium after incubation with drugs for 24 hours was determined as glucose consumption of the cells. The activity of cells was detected by XTT method. The transport of glucose was observed by 3H-glucose uptake method. The efflux of free fatty acid (FFA from adipocytes was observed by the concentration of FFA in the culture medium. Results: The glucose concentration in culture medium was significantly decreased with a concentration-dependent effect, when PTF concentrations were from 0.025 g/L to 0.4 g/L. The toxic effect on cells appeared while PTF concentration was 0.4 g/L, and the MTT value decreased. PTF also significantly increased glucose transportation in the 3T3-L1 adipocytes as rosiglitazone (ROS did. At the same time, FFA concentration in culture medium was significantly decreased as compared to the normal control group, while ROS-treated group did not show any difference. Conclusion: PTF can increase insulin sensitivity by increasing glucose transportation and consumption in the 3T3-L1 adipocytes as well as decreasing the FFA efflux from the cells.

  9. Does overnight normalization of plasma glucose by insulin infusion affect assessment of glucose metabolism in Type 2 diabetes?

    Staehr, P; Højlund, Kurt; Hother-Nielsen, O; Holst, J J; Beck-Nielsen, H

    2003-01-01

    AIMS: In order to perform euglycaemic clamp studies in Type 2 diabetic patients, plasma glucose must be reduced to normal levels. This can be done either (i) acutely during the clamp study using high-dose insulin infusion, or (ii) slowly overnight preceding the clamp study using a low-dose insulin...... infusion. We assessed whether the choice of either of these methods to obtain euglycaemia biases subsequent assessment of glucose metabolism and insulin action. METHODS: We studied seven obese Type 2 diabetic patients twice: once with (+ ON) and once without (- ON) prior overnight insulin infusion. Glucose...... turnover rates were quantified by adjusted primed-constant 3-3H-glucose infusions, and insulin action was assessed in 4-h euglycaemic, hyperinsulinaemic (40 mU m-2 min-1) clamp studies using labelled glucose infusates (Hot-GINF). RESULTS: Basal plasma glucose levels (mean +/- sd) were 5.5 +/- 0.5 and 10...

  10. Reciprocal effects of 2-fluoro-2-deoxy-D-glucose and glucose on their metabolism in Saccharomyces cerevisiae studied by multi-nuclear NMR spectroscopy

    The effects of various concentrations of 2-fluoro-2-deoxy-D-glucose (FDG) on the aerobic metabolism of glucose and the reciprocal effect of glucose on the metabolism of FDG in glucose-grown repressed Saccharomyces cerevisiae cells were studied at 30 deg C in a standard pyrophosphate medium containing 5 x 107 cells/ml by 1H-, 19F-, 31P-NMR and biochemical techniques. The glucose consumption rate is reduced by about 57% and 71% in the presence of 5 mM FDG and 10 mM FDG respectively. Under the same conditions, the ethanol production rate also decreases about 54% and 68%, respectively. When FDG is the unique carbon source, the ?- and ?-anomers of 2-fluoro-2-deoxy-D-glucose-6-phosphate (FDG6P) and a much smaller quantity of 2-fluoro-2-deoxy-gluconic acid (FDGA) were observed. The quantities of ? and ?-FDG6P reach their maximum values within 1 h of incubation and then decrease continuously. In contrast, Glc favors the consumption of FDG and the synthesis of FDG6P and uridine-5'-diphosphate fluoro-deoxy-glucose (UDP-FDG). In the presence of GLC, FDG6P reaches a plateau after 1 h or 2 h of incubation while UDP-FDG increases regularly with time. Apart from trehalose, no other disaccharide such as fluoro-dideoxy-trehalose (FDG-FDG) or fluoro-deoxy-trehalose (FDG-Glc) were observed. Thus, in contrast to UDP-Glc, UDP-DG, Glc6P and DG6P, UDP-FDG and FDG6P are not good substrates for trehalose-6-P synthetase. The effect of DG and FDG on the cell growth in standard nutrient media was also investigated at 37 deg C. The cell growth was found to be completely inhibited upon addition of 1 mM FDG and only slowed down in the presence of 1 mM DG. In the latter case, the doubling time ? is about 3 h instead of 1 h 25' in the absence of DG and FDG. The reciprocal effects of FDG and Glc on their metabolism, the toxicity of FDG and the blockage level of enzymes induced by FDG are discussed in comparison with 2-deoxy-D-glucose (DG) and Glc. The above results clearly show that the metabolism and the toxicity of a drug strongly depend on the physiological state of cells. (authors). 17 refs., 6 figs., 1 scheme

  11. Correlations Between Abnormal Glucose Metabolism and Bone Mineral Density or Bone Metabolism.

    Qu, Yang; Kang, Ming-Yang; Dong, Rong-Peng; Zhao, Jian-Wu

    2016-01-01

    BACKGROUND The aim of this meta-analysis was to explore the correlations of abnormal glucose metabolism (AGM) with bone mineral density (BMD) and bone metabolism. MATERIAL AND METHODS Relevant studies were identified using computerized and manual search strategies. The included studies were in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted with the Comprehensive Meta-analysis 2.0 (Biostat Inc., Englewood, NJ, USA). RESULTS Our present meta-analysis initially searched 844 studies, and 7 studies were eventually incorporated in the present meta-analysis. These 7 cohort studies included 1123 subjects altogether (560 patients with AGM and 563 healthy controls). The results showed that bone mass index (BMI), insulin, and insulin resistance (IR) of patients with AGM were significantly higher than that of the population with normal glucose metabolism (BMI: SMD=1.658, 95% CI=0.663~2.654, P=0.001; insulin: SMD=0.544, 95% CI=0.030~1.058, P=0.038; IR: SMD=8.767, 95% CI=4.178~13.356, Posteocalcin (OC) and BMD in patients with AGM and the population with normal glucose metabolism (OC: SMD=0.293, 95% CI=-0.023~0.609, P=0.069; BMD: SMD=0.805, 95% CI=-0. 212~1.821, P=0.121). CONCLUSIONS Our meta-analysis results suggest that AGM might lead to increased BMI, insulin, and IR, while it has no significant correlation with BMD or bone metabolism. PMID:26970713

  12. 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)

  13. 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.

  14. Alleviation of glucose repression of maltose metabolism by MIG1 disruption in Saccharomyces cerevisiae

    Klein, Christopher; Olsson, Lisbeth; Rønnow, B.; Mikkelsen, J.D.; Nielsen, Jens Bredal

    1996-01-01

    The MIG1 gene was disrupted in a haploid laboratory strain (B224) and in an industrial polyploid strain (DGI 342) of Saccharomyces cerevisiae. The alleviation of glucose repression of the expression of MAL genes and alleviation of glucose control of maltose metabolism were investigated in batch...... cultivations on glucose-maltose mixtures. In the MIG1-disrupted haploid strain, glucose repression was partly alleviated; i.e., maltose metabolism was initiated at higher glucose concentrations than in the corresponding wild-type strain. In contrast, the polyploid Delta mig1 strain exhibited an even more...... stringent glucose control of maltose metabolism than the corresponding wild-type strain, which could be explained by a more rigid catabolite inactivation of maltose permease, affecting the uptake of maltose. Growth on the glucose-sucrose mixture showed that the polyploid Delta mig1 strain was relieved of...

  15. Acclimation of metabolism to light in Arabidopsis thaliana: the glucose 6-phosphate/phosphate translocator GPT2 directs metabolic acclimation.

    Dyson, Beth C; Allwood, J William; Feil, Regina; Xu, Yun; Miller, Matthew; Bowsher, Caroline G; Goodacre, Royston; Lunn, John E; Johnson, Giles N

    2015-07-01

    Mature leaves of plants transferred from low to high light typically increase their photosynthetic capacity. In Arabidopsis thaliana, this dynamic acclimation requires expression of GPT2, a glucose 6-phosphate/phosphate translocator. Here, we examine the impact of GPT2 on leaf metabolism and photosynthesis. Plants of wild type and of a GPT2 knockout (gpt2.2) grown under low light achieved the same photosynthetic rate despite having different metabolic and transcriptomic strategies. Immediately upon transfer to high light, gpt2.2 plants showed a higher rate of photosynthesis than wild-type plants (35%); however, over subsequent days, wild-type plants acclimated photosynthetic capacity, increasing the photosynthesis rate by 100% after 7 d. Wild-type plants accumulated more starch than gpt2.2 plants throughout acclimation. We suggest that GPT2 activity results in the net import of glucose 6-phosphate from cytosol to chloroplast, increasing starch synthesis. There was clear acclimation of metabolism, with short-term changes typically being reversed as plants acclimated. Distinct responses to light were observed in wild-type and gpt2.2 leaves. Significantly higher levels of sugar phosphates were observed in gpt2.2. We suggest that GPT2 alters the distribution of metabolites between compartments and that this plays an essential role in allowing the cell to interpret environmental signals. PMID:25474495

  16. The Relationship between Serum Osteocalcin Concentration and Glucose Metabolism in Patients with Type 2 Diabetes Mellitus

    Qingqing Wang; Beibei Zhang; Yulan Xu; Hongdi Xu; Nan Zhang

    2013-01-01

    To study the correlations between serum osteocalcin and glucose metabolism in patients with type 2 diabetes, 66 cases were collected to determine total osteocalcin, undercarboxylated osteocalcin, fasting blood glucose, fasting insulin, and HbA1c. Osteocalcin concentrations were compared between groups of different levels of HbA1c, and parameters of glucose metabolism were compared between groups of different levels of total osteocalcin and undercarboxylated osteocalcin. The relationship betwe...

  17. 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...

  18. Transport and Metabolism of Lactose, Glucose, and Galactose in Homofermentative Lactobacilli

    Hickey, Malcolm W.; Hillier, Alan J.; Jago, G. Richard

    1986-01-01

    A number of species of lactobacilli were examined for their ability to ferment both the glucose and galactose moieties of lactose. Lactobacillus helveticus strains metabolized both the glucose and galactose moieties, whereas L. bulgaricus, L. lactis, and L. acidophilus strains metabolized only the glucose moiety and released galactose into the growth medium. All four species tested contained β-galactosidase activity, and no significant phospho-β-galactosidase activity was observed. L. bulgari...

  19. 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...

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

    Sonne, David P; Hare, Kristine J; Martens, Pernille; Rehfeld, Jens F; Holst, Jens Juul; Vilsbøll, Tina; Knop, Filip K

    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...

  1. Thyroid volume in patients with glucose metabolism disorders

    Ayse Ocak Duran

    2014-11-01

    Full Text Available Objective Thyroid volume and the prevalence of thyroid nodules are higher in patients with insulin resistance. A relationship between thyroid volume and glucose metabolism disorders (GMD has not as yet been clarified. The present retrospective study aimed to investigate the association between GMD and thyroid volume. Subjects and methods: We investigated the data of 2,630 patients who were evaluated for thyroid biopsy in our hospital. The study population included 602 patients with GMD, 554 patients with diabetes mellitus (DM and 1,474 patients with normal glucose metabolism as a control group. We obtained the levels of serum thyroid stimulating hormone (TSH and the thyroid volumes of those patients retrospectively. Results The median ages for the control group, GMD group and DM group were 55 (15‐91 years, 60 (27‐97 years, and 65 (27‐91 years respectively and there was a statistically significant difference between the groups with regard to age and gender (p<0.001. Levels of TSH were similar in all groups. The median total thyroid volumes for patients with DM and GMD were significantly higher than that of the control group [22.5 (3‐202 mL, 20.2 (4‐190 mL, and 19.2 (3‐168 mL respectively, p≤0.001 for all parameters]. Also the median total thyroid volume for patients with DM was significantly higher than that of the GMD group (p<0.001. According to the correlation analysis, thyroid volume was significantly correlated with age (r=0.92, p<0.001 and TSH (r=0.435, p<0.001. Age, gender, TSH levels, GMD and DM diagnosis were independently correlated with thyroid volume. Conclusion The thyroid gland is one of the target tissues of metabolic disorders. We reported a positive correlation between GMD/type 2 DM and thyroid volume. Further controlled, prospective, randomized studies on this subject are required to gain more information.

  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 are associated and that these associations are partially BMI-dependent. Furthermore, the interaction of ABCG1 with glucose metabolism is modulated by epigenetic processes. PMID:27019061

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

    Hasselbalch, Steen; Paulson, Olaf Bjarne

    metabolism was originally performed using the Kety-Schmidt method and this method still represent the gold standard by which subsequent methods have been evaluated. However, in its classical setting, the method overestimates cerebral blood flow. Studies of metabolic changes during activation must take this...... 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...

  4. Insulin regulation of renal glucose metabolism in conscious dogs.

    Cersosimo, E; Judd, R L; Miles, J M

    1994-01-01

    Previous studies indicating that postabsorptive renal glucose production is negligible used the net balance technique, which cannot partition simultaneous renal glucose production and glucose uptake. 10 d after surgical placement of sampling catheters in the left renal vein and femoral artery and a nonobstructive infusion catheter in the left renal artery of dogs, systemic and renal glucose and glycerol kinetics were measured with peripheral infusions of [3-3H]glucose and [2-14C]glycerol. Aft...

  5. 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 Aspergillus niger, to examine whether it would be capable of 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

  6. Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine

    Leke, Renata; Bak, Lasse Kristoffer; Anker, Malene; Melø, Torun M; Sørensen, Michael; Keiding, Susanne; Vilstrup, Hendrik; Ott, Peter; Portela, Luis V; Sonnewald, Ursula; Schousboe, Arne; Waagepetersen, Helle S

    2011-01-01

    mouse neuronal-astrocytic co-culture model of the GABAergic system. We found that 5 mM ammonium chloride affected energy metabolism by increasing the neuronal TCA cycle activity and switching the astrocytic TCA cycle toward synthesis of substrate for glutamine synthesis. Furthermore, ammonia exposure......Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme...

  7. Effects of sodium benzoate, a widely used food preservative, on glucose homeostasis and metabolic profiles in humans.

    Lennerz, Belinda S; Vafai, Scott B; Delaney, Nigel F; Clish, Clary B; Deik, Amy A; Pierce, Kerry A; Ludwig, David S; Mootha, Vamsi K

    2015-01-01

    Sodium benzoate is a widely used preservative found in many foods and soft drinks. It is metabolized within mitochondria to produce hippurate, which is then cleared by the kidneys. We previously reported that ingestion of sodium benzoate at the generally regarded as safe (GRAS) dose leads to a robust excursion in the plasma hippurate level [1]. Since previous reports demonstrated adverse effects of benzoate and hippurate on glucose homeostasis in cells and in animal models, we hypothesized that benzoate might represent a widespread and underappreciated diabetogenic dietary exposure in humans. Here, we evaluated whether acute exposure to GRAS levels of sodium benzoate alters insulin and glucose homeostasis through a randomized, controlled, cross-over study of 14 overweight subjects. Serial blood samples were collected following an oral glucose challenge, in the presence or absence of sodium benzoate. Outcome measurements included glucose, insulin, glucagon, as well as temporal mass spectrometry-based metabolic profiles. We did not find a statistically significant effect of an acute oral exposure to sodium benzoate on glucose homeostasis. Of the 146 metabolites targeted, four changed significantly in response to benzoate, including the expected rise in benzoate and hippurate. In addition, anthranilic acid, a tryptophan metabolite, exhibited a robust rise, while acetylglycine dropped. Although our study shows that GRAS doses of benzoate do not have an acute, adverse effect on glucose homeostasis, future studies will be necessary to explore the metabolic impact of chronic benzoate exposure. PMID:25497115

  8. Decreased Insulin Receptors but Normal Glucose Metabolism in Duchenne Muscular Dystrophy

    de Pirro, Roberto; Lauro, Renato; Testa, Ivano; Ferretti, Ginofabrizio; de Martinis, Carlo; Dellantonio, Renzo

    1982-04-01

    Compared to matched controls, 17 patients with Duchenne muscular dystrophy showed decreased insulin binding to monocytes due to decreased receptor concentration. These patients showed no signs of altered glucose metabolism and retrospective analysis of the clinical records of a further 56 such patients revealed no modification in carbohydrate metabolism. These data suggest that reduced insulin receptor number does not produce overt modifications of glucose metabolism in Duchenne muscular dystrophy.

  9. 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

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

    Andersen, Ove; Eugen-Olsen, Jesper; Kofoed, Kristian; Iversen, Johan; Haugaard, Steen B

    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 correlated inversely with ISI(composite) and positively with 2h plasma glucose, fasting insulin secretion, fasting intact proinsulin and FFA level during the OGTT (all P<0.05). In multiple regression analyses, in which anthropometric measures (BMI, limbadiposity and fat mass), immune markers (CD4, HIV......-RNA, duration of HIV infection), and dyslipidemia (plasma total cholesterol, triglyceride and free fatty acid level during the OGTT) were included, suPAR remained a significant marker of glucose tolerance and insulin sensitivity. Plasma suPAR exhibited a small CV (11%) during the 3h OGTT. CONCLUSIONS: su...

  11. 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

  12. 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

  13. Glucose metabolism and kinetics of phosphorus removal by the fermentative bacterium Microlunatus phosphovorus.

    Santos, M M; Lemos, P C; Reis, M A; Santos, H

    1999-09-01

    Phosphorus and carbon metabolism in Microlunatus phosphovorus was investigated by using a batch reactor to study the kinetics of uptake and release of extracellular compounds, in combination with (31)P and (13)C nuclear magnetic resonance (NMR) to characterize intracellular pools and to trace the fate of carbon substrates through the anaerobic and aerobic cycles. The organism was subjected to repetitive anaerobic and aerobic cycles to induce phosphorus release and uptake in a sequential batch reactor; an ultrafiltration membrane module was required since cell suspensions did not sediment. M. phosphovorus fermented glucose to acetate via an Embden-Meyerhof pathway but was unable to grow under anaerobic conditions. A remarkable time shift was observed between the uptake of glucose and excretion of acetate, resulting in an intracellular accumulation of acetate. The acetate produced was oxidized in the subsequent aerobic stage. Very high phosphorus release and uptake rates were measured, 3.34 mmol g of cell(-1) h(-1) and 1.56 mmol g of cell(-1) h(-1), respectively, values only comparable with those determined in activated sludge. In the aerobic period, growth was strictly dependent on the availability of external phosphate. Natural abundance (13)C NMR showed the presence of reserves of glutamate and trehalose in cell suspensions. Unexpectedly, [1-(13)C]glucose was not significantly channeled to the synthesis of internal reserves in the anaerobic phase, and acetate was not during the aerobic stage, although the glutamate pool became labeled via the exchange with intermediates of the tricarboxylic acid cycle at the level of glutamate dehydrogenase. The intracellular pool of glutamate increased under anaerobic conditions and decreased during the aerobic period. The contribution of M. phosphovorus for phosphorus removal in wastewater treatment plants is discussed on the basis of the metabolic features disclosed by this study. PMID:10473396

  14. Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

    Shimoyama, I.; Dauth, G.W.; Gilman, S.; Frey, K.A.; Penney, J.B. Jr.

    1988-12-01

    Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.

  15. Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

    Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated

  16. High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus

    Drew, Brian G; Duffy, Stephen J; Formosa, Melissa F; Natoli, Alaina K; Henstridge, Darren C; Penfold, Sally A; Thomas, Walter G; Mukhamedova, Nigora; de Courten, Barbora; Forbes, Josephine M; Yap, Felicia Y; Kaye, David M; Van Hall, Gerrit; Febbraio, Mark A; Kemp, Bruce E; Sviridov, Dmitri; Steinberg, Gregory R; Kingwell, Bronwyn A

    2009-01-01

    BACKGROUND: Low plasma high-density lipoprotein (HDL) is associated with elevated cardiovascular risk and aspects of the metabolic syndrome. We hypothesized that HDL modulates glucose metabolism via elevation of plasma insulin and through activation of the key metabolic regulatory enzyme, AMP......-activated protein kinase, in skeletal muscle. METHODS AND RESULTS: Thirteen patients with type 2 diabetes mellitus received both intravenous reconstituted HDL (rHDL: 80 mg/kg over 4 hours) and placebo on separate days in a double-blind, placebo-controlled crossover study. A greater fall in plasma glucose from...... baseline occurred during rHDL than during placebo (at 4 hours rHDL=-2.6+/-0.4; placebo=-2.1+/-0.3 mmol/L; P=0.018). rHDL increased plasma insulin (at 4 hours rHDL=3.4+/-10.0; placebo= -19.2+/-7.4 pmol/L; P=0.034) and also the homeostasis model assessment beta-cell function index (at 4 hours rHDL=18...

  17. AICAR administration affects glucose metabolism by upregulating the novel glucose transporter, GLUT8, in equine skeletal muscle.

    de Laat, M A; Robinson, M A; Gruntmeir, K J; Liu, Y; Soma, L R; Lacombe, V A

    2015-09-01

    Equine metabolic syndrome is characterized by obesity and insulin resistance (IR). Currently, there is no effective pharmacological treatment for this insidious disease. Glucose uptake is mediated by a family of glucose transporters (GLUT), and is regulated by insulin-dependent and -independent pathways, including 5-AMP-activated protein kinase (AMPK). Importantly, the activation of AMPK, by 5-aminoimidazole-4-carboxamide-1-D-ribofuranoside (AICAR) stimulates glucose uptake in both healthy and diabetic humans. However, whether AICAR promotes glucose uptake in horses has not been established. It is hypothesized that AICAR administration would enhance glucose transport in equine skeletal muscle through AMPK activation. In this study, the effect of an intravenous AICAR infusion on blood glucose and insulin concentrations, as well as on GLUT expression and AMPK activation in equine skeletal muscle (quantified by Western blotting) was examined. Upon administration, plasma AICAR rapidly reached peak concentration. Treatment with AICAR resulted in a decrease (P?equine muscle glucose transport. In addition, the data suggest that AMPK activation enhances pancreatic insulin secretion. Collectively, the findings suggest that AICAR acutely promotes muscle glucose uptake in healthy horses and thus its therapeutic potential for managing IR requires investigation. PMID:26116041

  18. 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.

  19. 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

  20. Transcriptional Regulation of Glucose Sensors in Pancreatic β-Cells and Liver: An Update

    Jin-Sik Bae

    2010-05-01

    Full Text Available Pancreatic β-cells and the liver play a key role in glucose homeostasis. After a meal or in a state of hyperglycemia, glucose is transported into the β-cells or hepatocytes where it is metabolized. In the β-cells, glucose is metabolized to increase the ATP:ADP ratio, resulting in the secretion of insulin stored in the vesicle. In the hepatocytes, glucose is metabolized to CO2, fatty acids or stored as glycogen. In these cells, solute carrier family 2 (SLC2A2 and glucokinase play a key role in sensing and uptaking glucose. Dysfunction of these proteins results in the hyperglycemia which is one of the characteristics of type 2 diabetes mellitus (T2DM. Thus, studies on the molecular mechanisms of their transcriptional regulations are important in understanding pathogenesis and combating T2DM. In this paper, we will review a recent update on the progress of gene regulation of glucose sensors in the liver and β-cells.

  1. The concentration of phosphatidylethanolamine in mitochondria can modulate ATP production and glucose metabolism in mice.

    van der Veen, Jelske N; Lingrell, Susanne; da Silva, Robin P; Jacobs, Ren L; Vance, Dennis E

    2014-08-01

    Phosphatidylethanolamine (PE) N-methyltransferase (PEMT) catalyzes the synthesis of phosphatidylcholine (PC) in the liver. Mice lacking PEMT are protected against diet-induced obesity and insulin resistance. We investigated the role of PEMT in hepatic carbohydrate metabolism in chow-fed mice. A pyruvate tolerance test revealed that PEMT deficiency greatly attenuated gluconeogenesis. The reduction in glucose production was specific for pyruvate; glucose production from glycerol was unaffected. Mitochondrial PC levels were lower and PE levels were higher in livers from Pemt(-/-) compared with Pemt(+/+) mice, resulting in a 33% reduction of the PC-to-PE ratio. Mitochondria from Pemt(-/-) mice were also smaller and more elongated. Activities of cytochrome c oxidase and succinate reductase were increased in mitochondria of Pemt(-/-) mice. Accordingly, ATP levels in hepatocytes from Pemt(-/-) mice were double that in Pemt(+/+) hepatocytes. We observed a strong correlation between mitochondrial PC-to-PE ratio and cellular ATP levels in hepatoma cells that expressed various amounts of PEMT. Moreover, mitochondrial respiration was increased in cells lacking PEMT. In the absence of PEMT, changes in mitochondrial phospholipids caused a shift of pyruvate toward decarboxylation and energy production away from the carboxylation pathway that leads to glucose production. PMID:24677714

  2. Cerebrospinal fluid ionic regulation, cerebral blood flow, and glucose use during chronic metabolic alkalosis

    Schroeck, H.K.; Kuschinsky, W. (Univ. of Bonn (Germany, F.R.))

    1989-10-01

    Chronic metabolic alkalosis was induced in rats by combining a low K+ diet with a 0.2 M NaHCO3 solution as drinking fluid for either 15 or 27 days. Local cerebral blood flow and local cerebral glucose utilization were measured in 31 different structures of the brain in conscious animals by means of the iodo-(14C)antipyrine and 2-(14C)deoxy-D-glucose method. The treatment induced moderate (15 days, base excess (BE) 16 mM) to severe (27 days, BE 25 mM) hypochloremic metabolic alkalosis and K+ depletion. During moderate metabolic alkalosis no change in cerebral glucose utilization and blood flow was detectable in most brain structures when compared with controls. Cerebrospinal fluid (CSF) K+ and H+ concentrations were significantly decreased. During severe hypochloremic alkalosis, cerebral blood flow was decreased by 19% and cerebral glucose utilization by 24% when compared with the control values. The decrease in cerebral blood flow during severe metabolic alkalosis is attributed mainly to the decreased cerebral metabolism and to a lesser extent to a further decrease of the CSF H+ concentration. CSF K+ concentration was not further decreased. The results show an unaltered cerebral blood flow and glucose utilization together with a decrease in CSF H+ and K+ concentrations at moderate metabolic alkalosis and a decrease in cerebral blood flow and glucose utilization together with a further decreased CSF H+ concentration at severe metabolic alkalosis.

  3. Cerebrospinal fluid ionic regulation, cerebral blood flow, and glucose use during chronic metabolic alkalosis

    Chronic metabolic alkalosis was induced in rats by combining a low K+ diet with a 0.2 M NaHCO3 solution as drinking fluid for either 15 or 27 days. Local cerebral blood flow and local cerebral glucose utilization were measured in 31 different structures of the brain in conscious animals by means of the iodo-[14C]antipyrine and 2-[14C]deoxy-D-glucose method. The treatment induced moderate [15 days, base excess (BE) 16 mM] to severe (27 days, BE 25 mM) hypochloremic metabolic alkalosis and K+ depletion. During moderate metabolic alkalosis no change in cerebral glucose utilization and blood flow was detectable in most brain structures when compared with controls. Cerebrospinal fluid (CSF) K+ and H+ concentrations were significantly decreased. During severe hypochloremic alkalosis, cerebral blood flow was decreased by 19% and cerebral glucose utilization by 24% when compared with the control values. The decrease in cerebral blood flow during severe metabolic alkalosis is attributed mainly to the decreased cerebral metabolism and to a lesser extent to a further decrease of the CSF H+ concentration. CSF K+ concentration was not further decreased. The results show an unaltered cerebral blood flow and glucose utilization together with a decrease in CSF H+ and K+ concentrations at moderate metabolic alkalosis and a decrease in cerebral blood flow and glucose utilization together with a further decreased CSF H+ concentration at severe metabolic alkalosis

  4. Glucose homeostasis and the enteroinsular axis in the horse: a possible role in equine metabolic syndrome.

    de Graaf-Roelfsema, Ellen

    2014-01-01

    One of the principal components of equine metabolic syndrome (EMS) is hyperinsulinaemia combined with insulin resistance. It has long been known that hyperinsulinaemia occurs after the development of insulin resistance. But it is also known that hyperinsulinaemia itself can induce insulin resistance and obesity and might play a key role in the development of metabolic syndrome. This review focuses on the physiology of glucose and insulin metabolism and the pathophysiological mechanisms in glucose homeostasis in the horse (compared with what is already known in humans) in order to gain insight into the pathophysiological principles underlying EMS. The review summarizes new insights on the oral uptake of glucose by the gut and the enteroinsular axis, the role of diet in incretin hormone and postprandial insulin responses, the handling of glucose by the liver, muscle and fat tissue, and the production and secretion of insulin by the pancreas under healthy and disrupted glucose homeostatic conditions in horses. PMID:24287206

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

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

    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...... essentially effected via increased blood flow, significantly contributes to stimulate glucose uptake. Again, however, increased glucose delivery appears to be a more potent stimulus of muscle glucose uptake as the circulating insulin level is increased. Furthermore, contractions and elevated flow prove to be...

  6. 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)

  7. Changes in serum metabolic hormone levels after glucose infusion during lactation cycles in Holstein cows

    Aliasghar Chalmeh

    2015-02-01

    Full Text Available Negative energy balance can impair the metabolism of high producing dairy cows and supplying the glucose, as an energy source; can prevent the metabolic disorders in these animals. Hence, we hypothesized that bolus intravenous glucose administration may change the concentrations of metabolic hormones in order to prevent and control of metabolic dysfunctions of dairy cows. Twenty five multiparous Holstein dairy cows were divided to 5 equal groups containing early, mid and late lactations, far-off and close-up dry periods. All cows were received dextrose 50% intravenously at 500 mg/kg, 10 mL/kg/h. Blood samples were collected from all animals prior to and 1, 2, 3 and 4 after dextrose 50% infusion and sera were separated to determine glucose, triiodothyronine (T3, thyroxine (T4, serum free T3 (fT3, free T4 (fT4, cortisol and insulin like growth factor-1 (IGF-1. The decreasing pattern of T3 concentration was detected in all studied animals following intravenous glucose infusion (P<0.05. The significant increasing pattern of T4 levels was seen in early and mid lactation cows after glucose administration (P<0.05. The significant decreasing pattern of IGF-1 was detected in mid and late lactations and far-off dry groups (P<0.05. There were no significant alterations in fT3, fT4 and cortisol concentrations following glucose infusion in all experimental groups. In conclusion, bolus intravenous glucose infusion could influence the metabolic hormones in high producing Holstein dairy cows. Alterations of metabolic hormones following bolus intravenous glucose administration indicated that glucose is an important direct controller of metabolic interactions and responses in dairy cows during different physiological states.

  8. Subcellular Localization of Hexokinases I and II Directs the Metabolic Fate of Glucose

    John, Scott; Weiss, James N.; Ribalet, Bernard

    2011-01-01

    Background The first step in glucose metabolism is conversion of glucose to glucose 6-phosphate (G-6-P) by hexokinases (HKs), a family with 4 isoforms. The two most common isoforms, HKI and HKII, have overlapping tissue expression, but different subcellular distributions, with HKI associated mainly with mitochondria and HKII associated with both mitochondrial and cytoplasmic compartments. Here we tested the hypothesis that these different subcellular distributions are associated with differen...

  9. 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...

  10. Trophic relationships between Saccharomyces cerevisiae and Lactobacillus plantarum and their metabolism of glucose and citrate.

    Veiga, María C.; Kennes, Christian; DUBOURGUIER, H.C.; Touzel, J P; Albagnac, G.; Naveau, H; Nyns, E J

    1991-01-01

    Glucose and citrate are two major carbon sources in fruits or fruit juices such as orange juice. Their metabolism and the microorganisms involved in their degradation were studied by inoculating with an aliquot of fermented orange juice a synthetic model medium containing glucose and citrate. At pH 3.6, their degradation led, first, to the formation of ethanol due to the activity of yeasts fermenting glucose and, eventually, to the formation of acetate resulting from the activity of lactobaci...

  11. Halofuginone inhibits colorectal cancer growth through suppression of Akt/mTORC1 signaling and glucose metabolism

    Chen, Guo-Qing; Tang, Cheng-Fang; Shi, Xiao-Ke; Lin, Cheng-Yuan; Fatima, Sarwat; Pan, Xiao-Hua; Yang, Da-Jian; Zhang, Ge; Lu, Ai-Ping; Lin, Shu-Hai; Bian, Zhao-Xiang

    2015-01-01

    The Akt/mTORC1 pathway plays a central role in the activation of Warburg effect in cancer. Here, we present for the first time that halofuginone (HF) treatment inhibits colorectal cancer (CRC) growth both in vitro and in vivo through regulation of Akt/mTORC1 signaling pathway. Halofuginone treatment of human CRC cells inhibited cell proliferation, induced the generation of reactive oxygen species and apoptosis. As expected, reduced level of NADPH was also observed, at least in part due to inactivation of glucose-6-phosphate dehydrogenase in pentose phosphate pathway upon HF treatment. Given these findings, we further investigated metabolic regulation of HF through Akt/mTORC1-mediated aerobic glycolysis and found that HF downregulated Akt/mTORC1 signaling pathway. Moreover, metabolomics delineated the slower rates in both glycolytic flux and glucose-derived tricarboxylic acid cycle flux. Meanwhile, both glucose transporter GLUT1 and hexokinase-2 in glycolysis were suppressed in CRC cells upon HF treatment, to support our notion that HF regulates Akt/mTORC1 signaling pathway to dampen glucose uptake and glycolysis in CRC cells. Furthermore, HF retarded tumor growth in nude mice inoculated with HCT116 cells, showing the anticancer activity of HF through metabolic regulation of Akt/mTORC1 in CRC. PMID:26160839

  12. 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.

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

    Dalgaard, Louise Torp

    2012-01-01

    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...

  14. 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

  15. 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...

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

    Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Shima, Fumio; Kato, Motohiro (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine)

    1992-12-01

    The nigrostriatal dopaminergic function and glucose metabolism were evaluated in 34 patients with various movement disorders by using positron emission tomography with [sup 18]F-Dopa and [sup 18]F-FDG respectively. The [sup 18]F-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 [sup 18]F-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 [sup 18]F-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 [sup 18]F-Dopa uptake in the striatum increased and the glucose metabolism was normal in cases of idiopathic dystonia. Various patterns of [sup 18]F-Dopa uptake and glucose metabolism were thus observed in the various movement disorders. These results suggest that the measurements of the [sup 18]F-Dopa uptake and the cerebral glucose metabolism would be useful for the evaluation of the striatal function in various movement disorders. (author).

  17. Plant Oils Were Associated with Low Prevalence of Impaired Glucose Metabolism in Japanese Workers

    Kurotani, Kayo; Kochi, Takeshi; Nanri, Akiko; Tsuruoka, Hiroko; Kuwahara, Keisuke; Pham, Ngoc Minh; Kabe, Isamu; Mizoue, Tetsuya

    2013-01-01

    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...

  18. 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)....

  19. Glucose Metabolism Gene Expression Patterns and Tumor Uptake of 18F-Fluorodeoxyglucose After Radiation Treatment

    Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of 18F-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 mm3 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: 18F-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

  20. 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

  1. 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

  2. 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

  3. Calcium Co-regulates Oxidative Metabolism and ATP Synthase-dependent Respiration in Pancreatic Beta Cells

    De Marchi, Umberto; Thevenet, Jonathan; Hermant, Aurelie; Dioum, Elhadji; Wiederkehr, Andreas

    2014-01-01

    Mitochondrial energy metabolism is essential for glucose-induced calcium signaling and, therefore, insulin granule exocytosis in pancreatic beta cells. Calcium signals are sensed by mitochondria acting in concert with mitochondrial substrates for the full activation of the organelle. Here we have studied glucose-induced calcium signaling and energy metabolism in INS-1E insulinoma cells and human islet beta cells. In insulin secreting cells a surprisingly large fraction of total respiration un...

  4. 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.

  5. 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

  6. 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)

  7. Roles of microRNA on cancer cell metabolism

    Chen Bing

    2012-11-01

    Full Text Available Abstract Advanced studies of microRNAs (miRNAs have revealed their manifold biological functions, including control of cell proliferation, cell cycle and cell death. However, it seems that their roles as key regulators of metabolism have drawn more and more attention in the recent years. Cancer cells display increased metabolic autonomy in comparison to non-transformed cells, taking up nutrients and metabolizing them in pathways that support growth and proliferation. MiRNAs regulate cell metabolic processes through complicated mechanisms, including directly targeting key enzymes or transporters of metabolic processes and regulating transcription factors, oncogenes / tumor suppressors as well as multiple oncogenic signaling pathways. MiRNAs like miR-375, miR-143, miR-14 and miR-29b participate in controlling cancer cell metabolism by regulating the expression of genes whose protein products either directly regulate metabolic machinery or indirectly modulate the expression of metabolic enzymes, serving as master regulators, which will hopefully lead to a new therapeutic strategy for malignant cancer. This review focuses on miRNA regulations of cancer cell metabolism,including glucose uptake, glycolysis, tricarboxylic acid cycle and insulin production, lipid metabolism and amino acid biogenesis, as well as several oncogenic signaling pathways. Furthermore, the challenges of miRNA-based strategies for cancer diagnosis, prognosis and therapeutics have been discussed.

  8. Human myotubes from myoblast cultures undergoing senescence exhibit defects in glucose and lipid metabolism

    Nehlin, Jan O; Just, Marlene; Rustan, Arild C; Gaster, Michael

    2011-01-01

    Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways. As the...... acid β-oxidation became gradually impaired. Upon insulin stimulation, glucose uptake and glycogen synthesis increased but as the cellular proliferative capacity became gradually exhausted, the response dropped concomitantly. Palmitic acid incorporation into lipids in myotubes decreased with passage...... number and could be explained by reduced incorporation into diacyl- and triacylglycerols. The levels of long-chain acyl-CoA esters decreased with increased passage number. Late-passage, non-proliferating, myoblast cultures showed strong senescence-associated β-galactosidase activity indicating that the...

  9. 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

  10. Compartmentalized acyl-CoA metabolism in skeletal muscle regulates systemic glucose homeostasis

    Li, Lei O; Grevengoed, Trisha J; Paul, David S; Ilkayeva, Olga; Koves, Timothy R; Pascual, Florencia; Newgard, Christopher B; Muoio, Deborah M; Coleman, Rosalind A

    2015-01-01

    The impaired capacity of skeletal muscle to switch between the oxidation of fatty acid (FA) and glucose is linked to disordered metabolic homeostasis. To understand how muscle FA oxidation affects systemic glucose, we studied mice with a skeletal muscle-specific deficiency of long-chain acyl......, indicating that acyl-CoAs synthesized by other ACSL isoforms were not available for β-oxidation. This compartmentalization of acyl-CoAs resulted in both an excessive glucose requirement and severely compromised systemic glucose homeostasis....

  11. 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

  12. The role of osteocalcin in human glucose metabolism: marker or mediator?

    Increasing evidence supports an association between the skeleton and energy metabolism. These interactions are mediated by a variety of hormones, cytokines, and nutrients. Here, the evidence for a role of osteocalcin in the regulation of glucose metabolism in humans is reviewed. Osteocalcin is a bon...

  13. Glucose inhibits GABA release by pancreatic beta-cells through an increase in GABA shunt activity.

    Wang, Chen; Kerckhofs, Karen; Van de Casteele, Mark; Smolders, Ilse; Pipeleers, Daniel; Ling, Zhidong

    2006-03-01

    GABA is the major inhibitory neurotransmitter in the nervous system. It is also released by the insulin-producing beta-cells, providing them with a potential paracrine regulator. Because glucose was found to inhibit GABA release, we investigated whether extracellular GABA can serve as a marker for glucose-induced mitochondrial activity and thus for the functional state of beta-cells. GABA release by rat and human beta-cells was shown to reflect net GABA production, varying with the functional state of the cells. Net GABA production is the result of GABA formation through glutamate decarboxylase (GAD) and GABA catabolism involving a GABA-transferase (GABA-T)-mediated shunt to the TCA cycle. GABA-T exhibits K(m) values for GABA (1.25 mM) and for alpha-ketoglutarate (alpha-KG; 0.49 mM) that are, respectively, similar to and lower than those in brain. The GABA-T inhibitor gamma-vinyl GABA was used to assess the relative contribution of GABA formation and catabolism to net production and release. The nutrient status of the beta-cells was found to regulate both processes. Glutamine dose-dependently increased GAD-mediated formation of GABA, whereas glucose metabolism shunts part of this GABA to mitochondrial catabolism, involving alpha-KG-induced activation of GABA-T. In absence of extracellular glutamine, glucose also contributed to GABA formation through aminotransferase generation of glutamate from alpha-KG; this stimulatory effect increased GABA release only when GABA-T activity was suppressed. We conclude that GABA release from beta-cells is regulated by glutamine and glucose. Glucose inhibits glutamine-driven GABA formation and release through increasing GABA-T shunt activity by its cellular metabolism. Our data indicate that GABA release by beta-cells can be used to monitor their metabolic responsiveness to glucose irrespective of their insulin-secretory activity. PMID:16249254

  14. 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 ismediated by cAMP signaling, but the mechanismlinking 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 ? 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.

  15. d-Glucose and d-mannose-based metabolic probes. Part 3: Synthesis of specifically deuterated d-glucose, d-mannose, and 2-deoxy-d-glucose

    Fokt, Izabela; Skora, Stanislaw; Conrad, Charles; Madden, Timothy; Emmett, Mark; Priebe, Waldemar

    2012-01-01

    Altered carbohydrate metabolism in cancer cells was first noted by Otto Warburg more than 80 years ago. Upregulation of genes controlling the glycolytic pathway under normoxia, known as the Warburg effect, clearly differentiates malignant from non-malignant cells. The resurgence of interest in cancer metabolism aims at a better understanding of the metabolic differences between malignant and non-malignant cells and the creation of novel therapeutic and diagnostic agents exploiting these diffe...

  16. 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

  17. ?-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes

    Shi, Chang-Xiang; Zhao, Ming-Xia; Shu, Xiao-Dong; Xiong, Xiao-Qing; Wang, Jue-Jin; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-01-01

    ?-aminoisobutyric acid (BAIBA) is a nature thymine catabolite, and contributes to exercise-induced protection from metabolic diseases. Here we show the therapeutical effects of BAIBA on hepatic endoplasmic reticulum (ER) stress and glucose/lipid metabolic disturbance in diabetes. Type 2 diabetes was induced by combined streptozotocin (STZ) and high-fat diet (HFD) in mice. Oral administration of BAIBA for 4 weeks reduced blood glucose and lipids levels, hepatic key enzymes of gluconeogenesis and lipogenesis expressions, attenuated hepatic insulin resistance and lipid accumulation, and improved insulin signaling in type 2 diabetic mice. BAIBA reduced hepatic ER stress and apoptosis in type 2 diabetic mice. Furthermore, BAIBA alleviated ER stress in human hepatocellular carcinoma (HepG2) cells with glucosamine-induced insulin resistance. Hepatic AMPK phosphorylation was reduced in STZ/HFD mice and glucosamine-treated HepG2 cells, which were restored by BAIBA treatment. The suppressive effects of BAIBA on glucosamine-induced ER stress were reversed by knockdown of AMPK with siRNA. In addition, BAIBA prevented thapsigargin- or tunicamycin-induced ER stress, and tunicamycininduced apoptosis in HepG2 cells. These results indicate that BAIBA attenuates hepatic ER stress, apoptosis and glucose/lipid metabolic disturbance in mice with type 2 diabetes. AMPK signaling is involved to the role of BAIBA in attenuating ER stress. PMID:26907958

  18. ?-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes.

    Shi, Chang-Xiang; Zhao, Ming-Xia; Shu, Xiao-Dong; Xiong, Xiao-Qing; Wang, Jue-Jin; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-01-01

    ?-aminoisobutyric acid (BAIBA) is a nature thymine catabolite, and contributes to exercise-induced protection from metabolic diseases. Here we show the therapeutical effects of BAIBA on hepatic endoplasmic reticulum (ER) stress and glucose/lipid metabolic disturbance in diabetes. Type 2 diabetes was induced by combined streptozotocin (STZ) and high-fat diet (HFD) in mice. Oral administration of BAIBA for 4 weeks reduced blood glucose and lipids levels, hepatic key enzymes of gluconeogenesis and lipogenesis expressions, attenuated hepatic insulin resistance and lipid accumulation, and improved insulin signaling in type 2 diabetic mice. BAIBA reduced hepatic ER stress and apoptosis in type 2 diabetic mice. Furthermore, BAIBA alleviated ER stress in human hepatocellular carcinoma (HepG2) cells with glucosamine-induced insulin resistance. Hepatic AMPK phosphorylation was reduced in STZ/HFD mice and glucosamine-treated HepG2 cells, which were restored by BAIBA treatment. The suppressive effects of BAIBA on glucosamine-induced ER stress were reversed by knockdown of AMPK with siRNA. In addition, BAIBA prevented thapsigargin- or tunicamycin-induced ER stress, and tunicamycin-induced apoptosis in HepG2 cells. These results indicate that BAIBA attenuates hepatic ER stress, apoptosis and glucose/lipid metabolic disturbance in mice with type 2 diabetes. AMPK signaling is involved to the role of BAIBA in attenuating ER stress. PMID:26907958

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

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-05-01

    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.

  20. 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

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

    Phillips, R.L.; London, E.D.; Links, J.M.; Cascella, N.G. (NIDA Addiction Research Center, Baltimore, MD (USA))

    1990-12-01

    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.

  2. 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

  3. Osteocalcin, energy and glucose metabolism / Osteocalcina, metabolismo energtico e da glicose

    Leila C. B., Zanatta; Cesar L., Boguszewski; Victoria Z. C., Borba; Carolina A. M., Kulak.

    2014-07-01

    Full Text Available A osteocalcina uma protena da matriz ssea que tem sido implicada com vrias aes hormonais relacionadas homeostase de glicose e ao metabolismo energtico. Modelos animais e experimentais tm demonstrado que a osteocalcina liberada do osso para a circulao sangunea e age nas clulas betapa [...] ncreticas e no tecido adiposo. A osteocalcina decarboxilada a isoforma hormonalmente ativa e estimula a secreo e sensibilidade insulina no tecido adiposo e muscular. A insulina e a leptina, por sua vez, atuam no tecido sseo modulando a secreo da osteocalcina, formando uma ala de retroalimentao tradicional em que o esqueleto torna-se um rgo endcrino. Novos estudos ainda so necessrios para elucidar o papel da osteocalcina na regulao glicmica e no metabolismo energtico em humanos, com potenciais implicaes teraputicas no tratamento de diabetes, obesidade e sndrome metablica. Abstract in english Osteocalcin is a bone matrix protein that has been associated with several hormonal actions on energy and glucose metabolism. Animal and experimental models have shown that osteocalcin is released into the bloodstream and exerts biological effects on pancreatic beta cells and adipose tissue. Underca [...] rboxylated osteocalcin is the hormonally active isoform and stimulates insulin secretion and enhances insulin sensitivity in adipose tissue and muscle. Insulin and leptin, in turn, act on bone tissue, modulating the osteocalcin secretion, in a traditional feedback mechanism that places the skeleton as a true endocrine organ. Further studies are required to elucidate the role of osteocalcin in the regulation of glucose and energy metabolism in humans and its potential therapeutic implications in diabetes, obesity and metabolic syndrome.

  4. 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.

  5. 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.

  6. Linking neuronal brain activity to the glucose metabolism

    Gbel, Britta; Oltmanns, Kerstin M.; Chung, Matthias

    2013-01-01

    Abstract Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying...

  7. 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

  8. 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

  9. 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)

  10. Variations in insulin responsiveness in rat fat cells are due to metabolic differences rather than insulin binding

    Hansen, Finn Mølgård; Nilsson, Poul; Sonne, Ole; Hustvedt, B E; Nilsson-Ehle, P; Løvø, A; Nielsen, Jens Høiriis

    1983-01-01

    Insulin resistance was studied by comparing insulin response and insulin binding in four groups of rats. Glucose metabolism in isolated fat cells from male Wistar rats weighing 340 g was less responsive to a supramaximal dose of insulin than glucose metabolism in fat cells from rats weighing 200 ...

  11. 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

  12. Responses of the Central Metabolism in Escherichia coli to Phosphoglucose Isomerase and Glucose-6-Phosphate Dehydrogenase Knockouts

    Hua, Qiang; Yang, Chen; BABA, Tomoya; Mori, Hirotada; Shimizu, Kazuyuki

    2003-01-01

    The responses of Escherichia coli central carbon metabolism to knockout mutations in phosphoglucose isomerase and glucose-6-phosphate (G6P) dehydrogenase genes were investigated by using glucose- and ammonia-limited chemostats. The metabolic network structures and intracellular carbon fluxes in the wild type and in the knockout mutants were characterized by using the complementary methods of flux ratio analysis and metabolic flux analysis based on [U-13C]glucose labeling and two-dimensional n...

  13. Correlation of regional glucose metabolism with gender, health status, and aging as determined by PET-FDG technique

    The present study presents the findings in a series of 85 volunteers who participated in a protocol to evaluate the effects of aging and dementia on brain glucose metabolism. Positron emission tomography permits noninvasive assessment of both whole brain and regional glucose metabolism and other biochemical functions. Absolute regional and whole brain glucose metabolism can be determined by using the fluorine deoxyglucose (FDG) method. (author). 3 refs

  14. 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.

  15. Glucose Deprivation Regulates KATP Channel Trafficking via AMP-Activated Protein Kinase in Pancreatic β-Cells

    Lim, Ajin; Park, Sun-Hyun; Sohn, Jong-Woo; Jeon, Ju-Hong; Park, Jae-Hyung; Song, Dae-Kyu; Lee, Suk-Ho; Ho, Won-Kyung

    2009-01-01

    OBJECTIVE AMP-activated protein kinase (AMPK) and the ATP-sensitive K+ (KATP) channel are metabolic sensors that become activated during metabolic stress. AMPK is an important regulator of metabolism, whereas the KATP channel is a regulator of cellular excitability. Cross talk between these systems is poorly understood. RESEARCH DESIGN AND METHODS Rat pancreatic β-cells or INS-1 cells were pretreated for 2 h at various concentrations of glucose. Maximum KATP conductance (Gmax) was monitored b...

  16. Glucose Metabolism in gcr Mutants of Saccharomyces cerevisiae

    Uemura, H.; Fraenkel, D G

    1999-01-01

    A gcr2 null mutant of Saccharomyces cerevisiae grows well on glucose in spite of its lower level of glycolytic enzymes between triose phosphates and pyruvate. A quantitative analysis shows that these levels are adequate to the flux but glycerate phosphates are elevated.

  17. 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...

  18. Time course of regional myocardial glucose metabolism after transient ischemia assessed by positron emission tomography

    The purpose of this study was to examine the significance of glucose metabolism in ischemic canine myocardium after reperfusion. Transient ischemia was induced by 90 or 180 minutes occlusion of the left anterior descending coronary artery. Twelve hours and 4 weeks after reperfusion, myocardial blood flow (MBF) and glucose metabolism were assessed (with H215O and 18F-FDG, respectively) by positron emission tomography (PET) under the fasting state, and the metabolic findings were compared with the histologic examination. Glucose metabolism in ischemic regions was inversely related to the amount of tissue necrosis 12 hours and 4 weeks after reperfusion (r=-0.89 and r=-0.82, respectively). The perfusion-metabolism mismatch pattern was seen in the area with less than 10 percent necrosis 12 hours after reperfusion, but this pattern disappeared after 4 weeks. The area with 10 to 50 percent necrosis showed the mismatch pattern until 4 weeks after reperfusion, and in the area with more than 50 percent necrosis, perfusion-metabolism concordantly decreased. Thus, metabolic index assessed early after reperfusion by PET identified myocardial viability, and the perfusion-metabolism mismatch pattern sustained in relation to the degree of ischemic injury. Since some regions estimated to be irreversible by PET were viable by the histologic examination, PET study might underestimate the myocardial viability. (author)

  19. 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...

  20. A potent glucose-platinum conjugate exploits glucose transporters and preferentially accumulates in cancer cells

    Patra, Malay; Johnstone, Timothy C.; Suntharalingam, Kogularamanan; Lippard*, Stephen J.

    2016-01-01

    Three rationally designed glucose-platinum conjugates (Glc-Pts) were synthesized and their biological activities evaluated. The Glc-Pts, 1-3, exhibit high levels of cytotoxicity toward a panel of cancer cells. The subcellular target and cellular uptake mechanism of the Glc-Pts were elucidated. For uptake into cells, Glc-Pt 1 exploits both glucose and organic cation transporters, both widely overexpressed in cancer. Compound 1 preferentially accumulates in and annihilates cancer, compared to n...

  1. 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...

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

    Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain; Licht, Tine Rask; Jensen, Ulrich S.; Rosenberg, Jacob; Pedersen, Oluf; Hansen, Torben; Rehfeld, Jens F.; Holst, Jens J.; Vilsbøll, Tina; Knop, Filip K.

    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....

  3. Elucidating the role of copper in CHO cell energy metabolism using (13)C metabolic flux analysis.

    Nargund, Shilpa; Qiu, Jinshu; Goudar, Chetan T

    2015-01-01

    (13)C-metabolic flux analysis was used to understand copper deficiency-related restructuring of energy metabolism, which leads to excessive lactate production in recombinant protein-producing CHO cells. Stationary-phase labeling experiments with U-(13)C glucose were conducted on CHO cells grown under high and limiting copper in 3 L fed-batch bioreactors. The resultant labeling patterns of soluble metabolites were measured by GC-MS and used to estimate metabolic fluxes in the central carbon metabolism pathways using OpenFlux. Fluxes were evaluated 300 times from stoichiometrically feasible random guess values and their confidence intervals calculated by Monte Carlo simulations. Results from metabolic flux analysis exhibited significant carbon redistribution throughout the metabolic network in cells under Cu deficiency. Specifically, glycolytic fluxes increased (25%-79% relative to glucose uptake) whereas fluxes through the TCA and pentose phosphate pathway (PPP) were lower (15%-23% and 74%, respectively) compared with the Cu-containing condition. Furthermore, under Cu deficiency, 33% of the flux entering TCA via the pyruvate node was redirected to lactate and malate production. Based on these results, we hypothesize that Cu deficiency disrupts the electron transport chain causing ATP deficiency, redox imbalance, and oxidative stress, which in turn drive copper-deficient CHO cells to produce energy via aerobic glycolysis, which is associated with excessive lactate production, rather than the more efficient route of oxidative phosphorylation. PMID:26097228

  4. Mechanisms Linking the Gut Microbiome and Glucose Metabolism.

    Utzschneider, Kristina M; Kratz, Mario; Damman, Chris J; Hullarg, Meredith

    2016-04-01

    This review details potential mechanisms linking gut dysbiosis to metabolic dysfunction, including lipopolysaccharide, bile acids, short chain fatty acids, gut hormones, and branched-chain amino acids. PMID:26938201

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

    Borghammer, Per; Hansen, Søren B; Eggers, Carsten; Chakravarty, Mallar; Vang, Kim; Aanerud, Joel; Hilker, Rüdiger; Heiss, Wolf-Dieter; Rodell, Anders; Munk, Ole L; Keator, David; Gjedde, Albert

    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 (PET...

  6. Effects of glucose metabolism during in vitro maturation on cytoplasmic maturation of mouse oocytes

    Xie, Hong-Li; Wang, Yan-Bo; Jiao, Guang-Zhong; Kong, De-Ling; Li, Qing; Li, Hong; Zheng, Liang-Liang; Tan, Jing-He

    2016-01-01

    Although there are many reports on the effect of glucose metabolism on oocyte nuclear maturation, there are few studies on its effect on ooplasmic maturation. By manipulating glucose metabolism pathways using a maturation medium that could support oocyte nuclear maturation but only a limited blastocyst formation without glucose, this study determined effects of glucose metabolism pathways on ooplasmic maturation. During maturation of cumulus-oocyte-complexes (COCs) with glucose, the presence of PPP inhibitor, DHEA or glycolysis inhibitor, iodoacetate significantly decreased blastocyst rates, intraoocyte glutathione and ATP. While blastocyst rates, GSH/GSSG ratio and NADPH were higher, ROS was lower significantly in COCs matured with iodoacetate than with DHEA. Fructose-6-phosphate overcame the inhibitory effect of DHEA on PPP. During maturation of COCs with pyruvate, electron transport inhibitor, rotenone or monocarboxylate transfer inhibitor, 4-CIN significantly decreased blastocyst rates. Cumulus-denuded oocytes had a limited capacity to use glucose or lactate, but they could use pyruvate to support maturation. In conclusion, whereas glycolysis promoted ooplasmic maturation mainly by supplying energy, PPP facilitated ooplasmic maturation to a greater extent by both reducing oxidative stress and supplying energy through providing fructose-6-phosphate for glycolysis. Pyruvate was transferred by monocarboxylate transporters and utilized through mitochondrial electron transport to sustain ooplasmic maturation. PMID:26857840

  7. 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

  8. Effects of glucose metabolism during in vitro maturation on cytoplasmic maturation of mouse oocytes.

    Xie, Hong-Li; Wang, Yan-Bo; Jiao, Guang-Zhong; Kong, De-Ling; Li, Qing; Li, Hong; Zheng, Liang-Liang; Tan, Jing-He

    2016-01-01

    Although there are many reports on the effect of glucose metabolism on oocyte nuclear maturation, there are few studies on its effect on ooplasmic maturation. By manipulating glucose metabolism pathways using a maturation medium that could support oocyte nuclear maturation but only a limited blastocyst formation without glucose, this study determined effects of glucose metabolism pathways on ooplasmic maturation. During maturation of cumulus-oocyte-complexes (COCs) with glucose, the presence of PPP inhibitor, DHEA or glycolysis inhibitor, iodoacetate significantly decreased blastocyst rates, intraoocyte glutathione and ATP. While blastocyst rates, GSH/GSSG ratio and NADPH were higher, ROS was lower significantly in COCs matured with iodoacetate than with DHEA. Fructose-6-phosphate overcame the inhibitory effect of DHEA on PPP. During maturation of COCs with pyruvate, electron transport inhibitor, rotenone or monocarboxylate transfer inhibitor, 4-CIN significantly decreased blastocyst rates. Cumulus-denuded oocytes had a limited capacity to use glucose or lactate, but they could use pyruvate to support maturation. In conclusion, whereas glycolysis promoted ooplasmic maturation mainly by supplying energy, PPP facilitated ooplasmic maturation to a greater extent by both reducing oxidative stress and supplying energy through providing fructose-6-phosphate for glycolysis. Pyruvate was transferred by monocarboxylate transporters and utilized through mitochondrial electron transport to sustain ooplasmic maturation. PMID:26857840

  9. 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.

  10. Sex-Specific Differences in Lipid and Glucose Metabolism

    Varlamov, Oleg; Bethea, Cynthia L.; Roberts, Charles T

    2015-01-01

    Energy metabolism in humans is tuned to distinct sex-specific functions that potentially reflect the unique requirements in females for gestation and lactation, whereas male metabolism may represent a default state. These differences are the consequence of the action of sex chromosomes and sex-specific hormones, including estrogens and progesterone in females and androgens in males. In humans, sex-specific specialization is associated with distinct body-fat distribution and energy substrate-u...

  11. Regulation of beta-cell glucose transporter gene expression.

    Chen, L; Alam, T.; Johnson, J. H.; Hughes, S.; Newgard, C. B.; Unger, R H

    1990-01-01

    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, we 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 (glucose at 29 +/- 5 mg/dl), GLUT-2 and proinsulin mRNA signal densities were reduced by 25% of the level i...

  12. 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...

  13. 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

    (HI), 40 mU/m(2) x min], 3-(3)H-glucose, indirect calorimetry, and iv glucose tolerance test. Free fatty acid concentrations were similar during basal steady state but 3.7- to 13-fold higher during clamps. P-glucagon increased and the insulin/glucagon ratio decreased at both LI and HI during...... 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....

  14. 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)

  15. Parameters of glucose metabolism and the aging brain

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild; Jansen, Steffy W; van Buchem, Mark A; Slagboom, P Eline; Westendorp, Rudi G; van Heemst, Diana; van der Grond, Jeroen

    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...... was significantly associated with white matter atrophy (P = 0.028). Micro-structurally, decreased magnetization transfer ratio (MTR) peak height in gray matter was associated with higher fasted insulin (P = 0.010), AUCinsulin (P = 0.001), insulinogenic index (P = 0.008) and lower HOMA-IS index (P < 0.......001). Similar significant associations were found for white matter. Thus, while higher glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association...

  16. 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

  17. Glucose and lactate biosensors for scanning electrochemical microscopy imaging of single live cells.

    Ciobanu, Madalina; Taylor, Dale E; Wilburn, Jeremy P; Cliffel, David E

    2008-04-15

    We have developed glucose and lactate ultramicroelectrode (UME) biosensors based on glucose oxidase and lactate oxidase (with enzymes immobilized onto Pt UMEs by either electropolymerization or casting) for scanning electrochemical microscopy (SECM) and have determined their sensitivity to glucose and lactate, respectively. The results of our evaluations reveal different advantages for sensors constructed by each method: improved sensitivity and shorter manufacturing time for hand-casting, and increased reproducibility for electropolymerization. We have acquired amperometric approach curves (ACs) for each type of manufactured biosensor UME, and these ACs can be used as a means of positioning the UME above a substrate at a known distance. We have used the glucose biosensor UMEs to record profiles of glucose uptake above individual fibroblasts. Likewise, we have employed the lactate biosensor UMEs for recording the lactate production above single cancer cells with the SECM. We also show that oxygen respiration profiles for single cancer cells do not mimic cell topography, but are rather more convoluted, with a higher respiration activity observed at the points where the cell touches the Petri dish. These UME biosensors, along with the application of others already described in the literature, could prove to be powerful tools for mapping metabolic analytes, such as glucose, lactate, and oxygen, in single cancer cells. PMID:18345647

  18. 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...

  19. 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)

  20. 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 metabolism during Aedes aegypti embryogenesis. Furthermore, the results also suggest a role for GSK3 in glycogen balance/distribution during morphological modifications.

  1. 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

  2. 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.

  3. [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

  4. [{sup 18}F]-2-fluoro-2-deoxyglucose transport kinetics as a function of extracellular glucose concentration in malignant glioma, fibroblast and macrophage cells in vitro

    Burrows, Robert C.; Freeman, Scott D.; Charlop, Aaron W.; Wiseman, Robert W.; Adamsen, Tom C.H.; Krohn, Kenneth A.; Spence, Alexander M. E-mail: aspence@u.washington.edu

    2004-01-01

    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.

  5. Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism.

    Belgardt, Bengt F; Mauer, Jan; Wunderlich, F Thomas; Ernst, Marianne B; Pal, Martin; Spohn, Gabriele; Brönneke, Hella S; Brodesser, Susanne; Hampel, Brigitte; Schauss, Astrid C; Brüning, Jens C

    2010-03-30

    c-Jun N-terminal kinase (JNK) 1-dependent signaling plays a crucial role in the development of obesity-associated insulin resistance. Here we demonstrate that JNK activation not only occurs in peripheral tissues, but also in the hypothalamus and pituitary of obese mice. To resolve the importance of JNK1 signaling in the hypothalamic/pituitary circuitry, we have generated mice with a conditional inactivation of JNK1 in nestin-expressing cells (JNK1(DeltaNES) mice). JNK1(DeltaNES) mice exhibit improved insulin sensitivity both in the CNS and in peripheral tissues, improved glucose metabolism, as well as protection from hepatic steatosis and adipose tissue dysfunction upon high-fat feeding. Moreover, JNK1(DeltaNES) mice also show reduced somatic growth in the presence of reduced circulating growth hormone (GH) and insulin-like growth factor 1 (IGF1) concentrations, as well as increased thyroid axis activity. Collectively, these experiments reveal an unexpected, critical role for hypothalamic/pituitary JNK1 signaling in the coordination of metabolic/endocrine homeostasis. PMID:20231445

  6. Enhanced muscle glucose metabolism after exercise in the rat

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

    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 gl...... 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....

  7. Experimental Identification and Quantification of Glucose Metabolism in Seven Bacterial Species†

    Fuhrer, Tobias; Fischer, Eliane; Sauer, Uwe

    2005-01-01

    The structurally conserved and ubiquitous pathways of central carbon metabolism provide building blocks and cofactors for the biosynthesis of cellular macromolecules. The relative uses of pathways and reactions, however, vary widely among species and depend upon conditions, and some are not used at all. Here we identify the network topology of glucose metabolism and its in vivo operation by quantification of intracellular carbon fluxes from 13C tracer experiments. Specifically, we investigate...

  8. 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.

  9. Comparison of dietary energy and macronutrient intake at different levels of glucose metabolism

    Yan, Li-Jun; JIANG, SHENG; Sun, Shi-An; Xie, Zi-Jing

    2015-01-01

    The aim of this study was to evaluate energy and glycolipid metabolism by determining the intake of energy and macronutrients in persons with differing glucose metabolisms. In total, 147 patients who were newly diagnosed with pre-diabetes, 177 patients with diabetes, 139 patients who were previously diagnosed with diabetes, and 140 patients with normal blood sugar were selected from the 103rd Regiment of Xinjiang. All patients had Han nationality and were over 30 years old. Their energy and m...

  10. The role of osteocalcin in human glucose metabolism: marker or mediator?

    Booth, Sarah L.; Centi, Amanda; Smith, Steven R.; Gundberg, Caren

    2012-01-01

    Increasing evidence supports an association between the skeleton and energy metabolism. These interactions are mediated by a variety of hormones, cytokines and nutrients. Here, the evidence for a role of osteocalcin in the regulation of glucose metabolism in humans is reviewed. Osteocalcin is a bone matrix protein that regulates hydroxyapatite size and shape through its vitamin-K-dependent γ-carboxylated form. In circulation, the concentration of osteocalcin is a measure of bone formation. Th...

  11. Effects of poor and short sleep on glucose metabolism and obesity risk

    Spiegel, Karine; TASALI, Esra; Leproult, Rachel; Van Cauter, Eve

    2009-01-01

    The importance of sleep to hormones and glucose metabolism was first documented more than four decades ago. Since then, sleep curtailment has become an endemic behavior in modern society. In addition, the prevalence of sleep disorders, particularly obstructive sleep apnea (OSA), has increased. OSA is very common in endocrine and metabolic disorders, but often remains undiagnosed. This Review summarizes the laboratory and epidemiologic evidence that suggests how sleep loss, either behavioral o...

  12. Oxidative stress in the etiology of age-associated decline in glucose metabolism

    Salmon, Adam B

    2012-01-01

    One of the most common pathologies in aging humans is the development of glucose metabolism dysfunction. The high incidence of metabolic dysfunction, in particular type 2 diabetes mellitus, is a significant health and economic burden on the aging population. However, the mechanisms that regulate this age-related physiological decline, and thus potential preventative treatments, remain elusive. Even after accounting for age-related changes in adiposity, lean mass, blood lipids, etc., aging is ...

  13. Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle

    Tsutsumi, Rie; Yoshida, Tomomi; Nii, Yoshitaka; Okahisa, Naoki; Iwata, Shinya; Tsukayama, Masao; Hashimoto, Rei; Taniguchi, Yasuko; Sakaue, Hiroshi; Hosaka, Toshio; Shuto, Emi; Sakai, Tohru

    2014-01-01

    Background Obesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulate...

  14. Increased T cell glucose uptake reflects acute rejection in lung grafts.

    Chen, D L; Wang, X; Yamamoto, S; Carpenter, D; Engle, J T; Li, W; Lin, X; Kreisel, D; Krupnick, A S; Huang, H J; Gelman, A E

    2013-10-01

    Although T cells are required for acute lung rejection, other graft-infiltrating cells such as neutrophils accumulate in allografts and are also high glucose utilizers. Positron emission tomography (PET) with the glucose probe [(18)F]fluorodeoxyglucose ([(18)F]FDG) has been employed to image solid organ acute rejection, but the sources of glucose utilization remain undefined. Using a mouse model of orthotopic lung transplantation, we analyzed glucose probe uptake in the grafts of syngeneic and allogeneic recipients with or without immunosuppression treatment. Pulmonary microPET scans demonstrated significantly higher [(18)F]FDG uptake in rejecting allografts when compared to transplanted lungs of either immunosuppressed or syngeneic recipients. [(18)F]FDG uptake was also markedly attenuated following T cell depletion therapy in lung recipients with ongoing acute rejection. Flow cytometric analysis using the fluorescent deoxyglucose analog 2-NBDG revealed that T cells, and in particular CD8(+) T cells, were the largest glucose utilizers in acutely rejecting lung grafts followed by neutrophils and antigen-presenting cells. These data indicate that imaging modalities tailored toward assessing T cell metabolism may be useful in identifying acute rejection in lung recipients. PMID:23927673

  15. DLK1 Regulates Whole-Body Glucose Metabolism

    Abdallah, Basem M; Ditzel, Nicholas; Laborda, Jorge; Karsenty, Gerard; Kassem, Moustapha

    2015-01-01

    metabolism. We show that Glu-OCN specifically stimulates Dlk1 expression by the pancreas. Conversely, Dlk1-deficient (Dlk1(-/-) ) mice exhibited increased circulating Glu-OCN levels and increased insulin sensitivity, whereas mice overexpressing Dlk1 in OB displayed reduced insulin secretion and sensitivity...

  16. 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.

  17. Changes in Cerebral Glucose Metabolism during Early Abstinence from Chronic Methamphetamine Abuse

    Berman, Steven M.; Voytek, Bradley; Mandelkern, Mark A.; Hassid, B. Daniel; Isaacson, Andrew; Monterosso, John; Miotto, Karen; Ling, Walter; London, Edythe D.

    2009-01-01

    Changes in brain function during the initial weeks of abstinence from chronic methamphetamine abuse may substantially affect clinical outcome, but are not well understood. We used positron emission tomography with [F-18]fluorodeoxyglucose (FDG) to quantify regional cerebral glucose metabolism, an index of brain function, during performance of a vigilance task. Ten methamphetamine-dependent subjects were tested after 5-9 days of abstinence, and after 4 additional weeks of supervised abstinence. Twelve healthy control subjects were tested at corresponding times. Global glucose metabolism increased between tests (p = .01), more in methamphetamine-dependent (10.9%, p = .02) than control subjects (1.9%, NS). Glucose metabolism did not change in subcortical regions of methamphetamine-dependent subjects, but increased in neocortex, with maximal increase (> 20%) in parietal regions. Changes in reaction time and self-reports of negative affect varied more in methamphetamine-dependent than in control subjects, and correlated both with the increase in parietal glucose metabolism, and decrease in relative activity (after scaling to the global mean) in some regions. A robust relationship between change in self-reports of depressive symptoms and relative activity in the ventral striatum may have great relevance to treatment success because of the role of this region in drug abuse-related behaviors. Shifts in cortical-subcortical metabolic balance either reflect new processes that occur during early abstinence, or the unmasking of effects of chronic methamphetamine abuse that are obscured by suppression of cortical glucose metabolism that continues for at least 5-9 days after cessation of methamphetamine self-administration. PMID:17938635

  18. 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.

  19. Intersections between mitochondrial sirtuin signaling and tumor cell metabolism.

    Gonzalez Herrera, Karina N; Lee, Jaewon; Haigis, Marcia C

    2015-01-01

    Cancer cells use glucose and glutamine to facilitate cell growth and proliferation, a process coined "metabolic reprograming" - an emerging hallmark of cancer. Inside the cell, these nutrients synergize to produce metabolic building blocks, such as nucleic acids, lipids and proteins, as well as energy (ATP), glutathione and reducing equivalents (NADPH), required for survival, growth and proliferation. Intense research aimed at understanding the underlying cause of the metabolic rewiring has revealed that established oncogenes and tumor suppressors involved in signaling alter cellular metabolism to contribute to the transition from a normal quiescent cell to a rapidly proliferating cancer cell. Likewise, bona fide metabolic sensors are emerging as regulators of tumorigenesis. This review will focus on one such family of sensors, sirtuins, which utilize NAD(+) as a cofactor to catalyze deacetylation, deacylation and ADP-ribosylation of their protein substrates. In this review, we will enumerate how cancer cell metabolism is different from a normal quiescent cell and highlight the emerging role of mitochondrial sirtuin signaling in the regulation of tumor metabolism. PMID:25898275

  20. Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle

    Yasuhiko Minokoshi

    2012-01-01

    Full Text Available 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 of glucose metabolism in insulin-deficient diabetes in rodents. We found that leptin increases glucose uptake and fatty acid oxidation in skeletal muscle in rats and mice in vivo. Leptin increases glucose uptake in skeletal muscle via the hypothalamic-sympathetic nervous system axis and ?-adrenergic mechanism, while leptin stimulates fatty acid oxidation in muscle via AMP-activated protein kinase (AMPK. Leptin-induced fatty acid oxidation results in the decrease of lipid accumulation in muscle, which can lead to functional impairments called as "lipotoxicity." Activation of AMPK occurs by direct action of leptin on muscle and through the medial hypothalamus-sympathetic nervous system and ?-adrenergic mechanism. Thus, leptin plays an important role in the regulation of glucose and fatty acid metabolism in skeletal muscle.

  1. 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 associated only with microvascular variables in the same way (functional capillary density, RBCV and RBCVmax. Fasting plasma glucose appeared to be related to principal component 4 and did not show any association with microvascular reactivity. Conclusions In non-diabetic female subjects, a multivariate scenario of associations between classic clinical variables strictly related to obesity and metabolic syndrome suggests a significant relationship between these diseases and microvascular reactivity.

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

    Hao, Qin; Yadav, Rachita; Basse, Astrid L; Petersen, Sidsel; Sonne, Si B; Rasmussen, Simon; Zhu, Qianhua; Lu, Zhike; Wang, Jun; Audouze, Karine; Gupta, Ramneek; Madsen, Lise; Kristiansen, Karsten; Hansen, Jacob B

    2015-03-01

    We applied digital gene expression profiling to determine the transcriptome of brown and white adipose tissues (BAT and WAT, respectively) during cold exposure. Male C57BL/6J mice were exposed to cold for 2 or 4 days. A notable induction of genes related to glucose uptake, glycolysis, glycogen metabolism, and the pentose phosphate pathway was observed in BAT from cold-exposed animals. In addition, glycerol-3-phosphate dehydrogenase 1 expression was induced in BAT from cold-challenged mice, suggesting increased synthesis of glycerol from glucose. Similarly, expression of lactate dehydrogenases was induced by cold in BAT. Pyruvate dehydrogenase kinase 2 (Pdk2) and Pdk4 were expressed at significantly higher levels in BAT than in WAT, and Pdk2 was induced in BAT by cold. Of notice, only a subset of the changes detected in BAT was observed in WAT. Based on changes in gene expression during cold 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 triacylglycerol synthesis/fatty acid re-esterification; 3) glycogen turnover and lactate production are increased; and 4) entry of glucose carbon into the tricarboxylic acid cycle is restricted by PDK2 and PDK4. In summary, our results demonstrate extensive and diverse gene expression changes related to glucose handling in activated BAT. PMID:25516548

  3. 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

  4. 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

  5. High glucose suppresses embryonic stem cell differentiation into neural lineage cells.

    Yang, Penghua; Shen, Wei-Bin; Albert Reece, E; Chen, Xi; Yang, Peixin

    2016-04-01

    Abnormal neurogenesis occurs during embryonic development in human diabetic pregnancies and in animal models of diabetic embryopathy. Our previous studies in a mouse model of diabetic embryopathy have implicated that high glucose of maternal diabetes delays neurogenesis in the developing neuroepithelium leading to neural tube defects. However, the underlying process in high glucose-impaired neurogenesis is uncharacterized. Neurogenesis from embryonic stem (ES) cells provides a valuable model for understanding the abnormal neural lineage development under high glucose conditions. ES cells are commonly generated and maintained in high glucose (approximately 25 mM glucose). Here, the mouse ES cell line, E14, was gradually adapted to and maintained in low glucose (5 mM), and became a glucose responsive E14 (GR-E14) line. High glucose induced the endoplasmic reticulum stress marker, CHOP, in GR-E14 cells. Under low glucose conditions, the GR-E14 cells retained their pluripotency and capability to differentiate into neural lineage cells. GR-E14 cell differentiation into neural stem cells (Sox1 and nestin positive cells) was inhibited by high glucose. Neuron (Tuj1 positive cells) and glia (GFAP positive cells) differentiation from GR-E14 cells was also suppressed by high glucose. In addition, high glucose delayed GR-E14 differentiation into neural crest cells by decreasing neural crest markers, paired box 3 (Pax3) and paired box 7 (Pax7). Thus, high glucose impairs ES cell differentiation into neural lineage cells. The low glucose adapted and high glucose responsive GR-E14 cell line is a useful in vitro model for assessing the adverse effect of high glucose on the development of the central nervous system. PMID:26940741

  6. Metabolic impact of an NADH-producing glucose-6-phosphate dehydrogenase in Escherichia coli

    Olavarria, K.; De Ingeniis, J.; Zielinski, D. C.; Fuentealba, M.; Muñoz, R.; McCloskey, D.; Feist, Adam; Cabrera, R.

    , we studied the metabolic response of this bacterium to the replacement of its glucose-6-phosphate dehydrogenase (G6PDH) by an NADH-producing variant. The homologous enzyme from Leuconostoc mesenteroides was studied by molecular dynamics and site-directed mutagenesis to obtain the NAD-preferring LmG6...

  7. Oolong tea does not improve glucose metabolism in non-diabetic adults

    Studies of the influence of tea on glucose metabolism have produced inconsistent results, possibly due to lack of dietary control and/or unclear characterization of tea products. Therefore, a double-blind crossover study was conducted in which healthy males (n=19) consumed each of three oolong tea ...

  8. PET-imaging of cerebral glucose metabolism during sleep and dreaming

    Positron emission tomography (PET) of (18F)-2-fluoro-2-deoxyglucose (FDG) affording non-invasive repeatable quantification of local cerebral glucose utilization was employed to determine possible differential effects of sleep, with and without dreaming, on regional brain metabolism of normal volunteers also measured during wakefulness. (author). 7 refs.; 1 tab

  9. 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

    2014-01-01

    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...

  10. Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Retardation and Down Syndrome.

    Haier, Richard J.; And Others

    1995-01-01

    Brain size and cerebral glucose metabolic rate were determined for 10 individuals with mild mental retardation (MR), 7 individuals with Down syndrome (DS), and 10 matched controls. MR and DS groups both had brain volumes of about 80% compared to controls, with variance greatest within the MR group. (SLD)

  11. 14C-carbaril metabolism in soils modified by organic matter oxidation and addition of glucose

    Carbaril behaviour is studied in samples of Brunizen and Dark Red Latosol soils from Parana, using radiometric techniques, with the objective of determining the role of oxidation fo its organic components, and enrichment with glucose, in the metabolism of the insecticide. Lots of autoclaved soils, oxidized and with no previous treatment, with and without glucose addition, are incubated with 14C-carbaril and analysed during eight weeks. Its was noted that, as a result of oxidation both soils showed a marked improvement in the metabolism of the agrochemical while addition of glucose exerted litlle influence on the degrading processes. Three metabolites were detected with R sub(f) 0.23, 0.40 and 0.70. (Author)

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

    Jin Shao; Zhi Wang; Tieyi Yang; Hui Ying; Yan Zhang; Shuyi Liu

    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...

  13. Recovery of glucose metabolism in reperfused canine myocardium demonstrated by positron-CT (PCT)

    Schwaiger, M.; Sochor, H.; Parodi, O.; Grover, M.; Hansen, H.W.; Selin, C.; Schelbert, H.R.

    1984-01-01

    The authors previously examined with PCT in chronic dogs the long term metabolic recovery during reperfusion after a 3 hr ischemic insult. Increased regional glucose utilization at 24 hrs of R accurately identified reversible tissue injury documented by late improvement in segmental function by ultrasonic crystals. To define the early metabolic events after a 3 hr LAD balloon occlusion, regional blood flow and glucose utilization was studied in 8 dogs with PCT, N-13 ammonia (NA) and F-18 deoxyglucose (FDG) at 2 hrs and at 24 hrs after R. The dogs were then thoracotomized and MBF by microspheres, arterio-venous differences for glucose, lactate and O/sub 2/ across the reperfused segment (LAD vein) and the left ventricle (coronary sinus) measured. Immediately after reperfusion, MBF and FDG uptake were 27 +- 24% and 21 +- 48% lower in the reperfused territory (RT) than in control myocardium (C). At 24 hrs, MBF by microspheres was and 22 +- 25% lower and FDG uptake 175 +- 73% higher in RT than in C. In the RT, consumption of glucose (by Fick method) was 202 +- 107% higher, of lactate 96 +- 85% lower and of O/sub 2/ 42 +- 26% lower than in the entire LV. PCT measured FDG uptake correlated with glucose consumption (r=0.94) and confirmed that the segmentally increased FDG uptake at 24 hrs reflected increased glucose utilization that, as indicated by the reduced lactate consumption, was partly anaerobic. The authors conclude that initially after R, glucose metabolism is depressed but increases above C within 24 hrs, a time course that now can be determined noninvasively with PCT and is useful for predicting functional recovery.

  14. A new application of electrical impedance spectroscopy for measuring glucose metabolism: a phantom study

    Dhurjaty, Sreeram; Qiu, Yuchen; Tan, Maxine; Liu, Hong; Zheng, Bin

    2015-03-01

    Glucose metabolism relates to biochemical processes in living organisms and plays an important role in diabetes and cancer-metastasis. Although many methods are available for measuring glucose metabolism-activities, from simple blood tests to positron emission tomography, currently there is no robust and affordable device that enables monitoring of glucose levels in real-time. In this study we tested feasibility of applying a unique resonance-frequency based electronic impedance spectroscopy (REIS) device that has been, recently developed to measure and monitor glucose metabolism levels using a phantom study. In this new testing model, a multi-frequency electrical signal sequence is applied and scanned through the subject. When the positive reactance of an inductor inside the device cancels out the negative reactance of the capacitance of the subject, the electrical impedance reaches a minimum value and this frequency is defined as the resonance frequency. The REIS system has a 24-bit analog-to-digital signal convertor and a frequency-resolution of 100Hz. In the experiment, two probes are placed inside a 100cc container initially filled with distilled water. As we gradually added liquid-glucose in increments of 1cc (250mg), we measured resonance frequencies and minimum electrical signal values (where A/D was normalized to a full scale of 1V). The results showed that resonance frequencies monotonously decreased from 243kHz to 178kHz, while the minimum voltages increased from 405mV to 793mV as the added amount of glucose increased from 0 to 5cc. The study demonstrated the feasibility of applying this new REIS technology to measure and/or monitor glucose levels in real-time in future.

  15. Response to dexamethasone is glucose-sensitive in multiple myeloma cell lines

    Turturro Francesco

    2011-09-01

    Full Text Available Abstract Background Hyperglycemia is among the major side effects of dexamethasone (DEX. Glucose or glucocorticoid (GC regulates the expression of thioredoxin-interacting protein (TXNIP that controls the production of reactive oxygen species (ROS through the modulation of thioredoxin (TRX activity. Methods Multiple myeloma (MM cells were grown in 5 or 20 mM/L glucose with or without 25 ?M DEX. Semiquantitative reverse transcription-PCR (RT-PCR was used to assess TXNIP RNA expression in response to glucose and DEX. ROS were detected by 5-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA. TRX activity was assayed by the insulin disulfide-reducing assay. Proliferation was evaluated using CellTiter96 reagent with 490-nm absorbtion and used to calculate the DEX IC50 in 20 mM/L glucose using the Chou's dose effect equation. Results TXNIP RNA level responded to glucose or DEX with the same order of magnitude ARH77 > NCIH929 > U266B1 in these cells. MC/CAR cells were resistant to the regulation. ROS level increased concurrently with reduced TRX activity. Surprisingly glucose increased TRX activity in MC/CAR cells keeping ROS level low. DEX and glucose were lacking the expected additive effect on TXNIP RNA regulation when used concurrently in sensitive cells. ROS level was significantly lower when DEX was used in conditions of hyperglycemia in ARH77/NCIH9292 cells but not in U266B1 cells. Dex-IC50 increased 10-fold when the dose response effect of DEX was evaluated with glucose in ARH && and MC/Car cells Conclusions Our study shows for the first time that glucose or DEX regulates important components of ROS production through TXNIP modulation or direct interference with TRX activity in MM cells. We show that glucose modulates the activity of DEX through ROS regualtion in MM cells. A better understanding of these pathways may help in improving the efficacy and reducing the toxicity of DEX, a drug still highly used in the treatment of MM. Our study also set the ground to study the relevance of the metabolic milieu in affecting drug response and toxicity in diabetic versus non-diabetic patients with MM.

  16. 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 [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. Results 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. Conclusion This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism. PMID:26959405

  17. 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 Embden...... - Meyerhof - Parnas (EMP) pathway is present in this organism. Moreover, Nonomuraea utilizes a PPi-dependent phosphofructokinase, an enzyme that has been connected with anaerobic metabolism in eukaryotes and higher plants, but recently has been recognized in several actinomycetes. In order to study its...

  18. 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)

  19. 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

  20. 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)

  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. 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

  3. 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

  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. 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

  6. 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.

  7. The influence of high ambient glucose level on the production of pericellular glycosaminoglycans by cultured endothelial cells.

    Yevdokimova, N Yu; Komisarenko, S V

    2003-01-01

    The 14C-acetate metabolic labeling of glycosaminoglycans (GAGs) was used to investigate the effect of high glucose level on the production of hyaluronic acid (HA), heparan sulphate (HS), chondroitin sulphate (CS) and dermatan sulphate (DS) by human immortalized umbilical vein endothelial cells. It is demonstrated that 30 mM glucose decreased the accumulation of HS and increased the accumulation of CS and DS in the cell layer, pericellular matrix and conditioned medium in 48 h of incubation. The modulation of the overall metabolism of sulphated GAGs by high glucose is in contrast to the observed redistribution of HA from the conditioned medium to the pericellular matrix of endothelial cells. The preincubation at 30 mM glucose increased also the attachment of hyaluronidase-treated endothelial cells to HA-coated surface and had no effect on the cell attachment to poly-D-lysine, indicating the alterations of CD44 binding to immobilized HA. The treatment of endothelial cells with p-nitrophenyl-beta-D-xylopyranoside, which inhibits the coupling of CS to the core protein, attenuated high glucose-induced pericellular HA accumulation and decreased cell attachment to HA-coated surface. It is supposed the implication of CD44-related CS in the accumulation of pericellular HA by endothelial cells exposed to high glucose level. PMID:14681993

  8. 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 metabolic effects are only slightly exacerbated in geriatric rats.

  9. 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 effects are only slightly exacerbated in geriatric rats

  10. 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.)

  11. Effects of fish oil on metabolic responses to oral fructose and glucose loads in healthy humans.

    Delarue, J; Couet, C; Cohen, R; Bréchot, J F; Antoine, J M; Lamisse, F

    1996-02-01

    This study examines the effect of the substitution of 6 g/day of fish oil in a saturated diet on glucose and fructose metabolism in healthy humans. Five subjects were submitted to two 3-wk controlled-diet periods (polyunsaturated/saturated = 0.21). During one period, 6 g/day of fat used for dressing were replaced by 6 g/day of fish oil [1.1 g/day of 20:5 (n-3) fatty acids and 0.7 g/day of 22:6 (n-3) fatty acids]. At the end of each period the subjects ingested a 1 g/kg fructose or glucose load 2 days apart. Plasma glucose fluxes were traced with the use of deuterated glucose and [U-13C]glucose. Substrate oxidation was measured by indirect calorimetry. Fish oil induced a 4% increase in basal and postload glycemia and a 40% decrease in insulinemia, whereas plasma C-peptide remained unaffected. Glucose fluxes were unaffected by fish oil, but carbohydrate (CHO) oxidation was reduced (fructose: 55.5 +/- 4.1 vs. 62.9 +/- 3.6 g/6 h; glucose: 36.7 +/- 4.7 vs. 50.5 +/- 4.7 g/6 h; all P Lipid oxidation was increased 35% by fish oil after both CHO loads. Nonoxidative glucose disposal was increased by fish oil (fructose: 9.4 +/- 2.5 vs. 2.9 +/- 1.1 g/6 h; glucose: 28.3 +/- 5.1 vs. 14.4 +/- 4.7 g/6 h; all P oxidation through the decrease in insulinemia and/or a specific effect on glycolytic pathway. PMID:8779959

  12. Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster.

    Wagner, Anika E; Piegholdt, Stefanie; Rabe, Doerte; Baenas, Nieves; Schloesser, Anke; Eggersdorfer, Manfred; Stocker, Achim; Rimbach, Gerald

    2015-10-13

    In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1?, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of ?-amylase and ?-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of ?-amylase and to a greater extent into ?-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies. PMID:26375250

  13. Effect of enoxacin, felbinac, and sparfloxacin on fatty acid metabolism and glucose concentrations in rat tissues.

    Kasuya, Fumiyo; Miwa, Yasushi; Kazumi, Maya; Inoue, Hiroyuki; Ohta, Hiroyuki

    2011-05-01

    Multiple changes in metabolic levels could be useful for understanding physiological toxicity. To explore further risk factors for the convulsions induced by the interaction of nonsteroidal anti-inflammatory and new quinolone antimicrobial drugs, the effect of sparfloxacin, enoxacin, and felbinac on fatty acid metabolism and glucose concentrations in the liver, brain, and blood of rats was investigated. The levels of long-chain acyl-CoAs (C(18:1) and C(20:4)) in the liver and brain were decreased at the onset of convulsions induced by the coadministration of enoxacin with felbinac. Then, glucose concentrations in the liver and blood were decreased, whereas they were increased in a dose-dependant manner in the brain. However, the formation of acyl-CoAs and glucose levels in the liver, brain, and blood was not significantly influenced by enoxacin, felbinac, and sparfloxacin alone, respectively. The disturbance of both fatty acid metabolism and glucose levels might be associated with the increased susceptibility to convulsions, which may contribute to further understanding of the toxic effects associated with these drugs. PMID:21633127

  14. 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.

  15. 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.

  16. 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.)

  17. 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.)

  18. Metabolic, enzymatic and gene involvement in cerebral glucose dysmetabolism after traumatic brain injury.

    Amorini, Angela Maria; Lazzarino, Giacomo; Di Pietro, Valentina; Signoretti, Stefano; Lazzarino, Giuseppe; Belli, Antonio; Tavazzi, Barbara

    2016-04-01

    In this study, the metabolic, enzymatic and gene changes causing cerebral glucose dysmetabolism following graded diffuse traumatic brain injury (TBI) were evaluated. TBI was induced in rats by dropping 450g from 1 (mild TBI; mTBI) or 2m height (severe TBI; sTBI). After 6, 12, 24, 48, and 120h gene expressions and enzymatic activities of glycolysis and pentose phosphate pathway (PPP) enzymes, and levels of lactate, ATP, ADP, ATP/ADP (indexing mitochondrial phosphorylating capacity), NADP(+), NADPH and GSH were determined in whole brain extracts (n=9 rats at each time for both TBI levels). Sham-operated animals (n=9) were used as controls. Results demonstrated that mTBI caused a late increase (48-120h post injury) of glycolytic gene expression and enzymatic activities, concomitantly with mitochondrial functional recovery (ATP and ATP/ADP normalization). No changes in lactate and PPP genes and enzymes, were accompanied by transient decrease in GSH, NADP(+), NADPH and NADPH/NADP(+). Animals following sTBI showed early increase (6-24h post injury) of glycolytic gene expression and enzymatic activities, occurring during mitochondrial malfunctioning (50% decrease in ATP and ATP/ADP). Higher lactate and lower GSH, NADP(+), NADPH, NADPH/NADP(+) than controls were recorded at anytime post injury (p<0.01). Both TBI levels caused metabolic and gene changes affecting glucose metabolism. Following mTBI, increased glucose flux through glycolysis is coupled to mitochondrial glucose oxidation. "True" hyperglycolysis occurs only after sTBI, where metabolic changes, caused by depressed mitochondrial phosphorylating capacity, act on genes causing net glycolytic flux increase uncoupled from mitochondrial glucose oxidation. PMID:26844378

  19. Metabolic engineering of CHO cells to alter lactate metabolism during fed-batch cultures.

    Toussaint, Cécile; Henry, Olivier; Durocher, Yves

    2016-01-10

    Recombinant yeast pyruvate carboxylase (PYC2) expression was previously shown to be an effective metabolic engineering strategy for reducing lactate formation in a number of relevant mammalian cell lines, but, in the case of CHO cells, did not consistently lead to significant improvement in terms of cell growth, product titer and energy metabolism efficiency. In the present study, we report on the establishment of a PYC2-expressing CHO cell line producing a monoclonal antibody and displaying a significantly altered lactate metabolism compared to its parental line. All clones exhibiting strong PYC2 expression were shown to experience a significant and systematic metabolic shift toward lactate consumption, as well as a prolonged exponential growth phase leading to an increased maximum cell concentration and volumetric product titer. Of salient interest, PYC2-expressing CHO cells were shown to maintain a highly efficient metabolism in fed-batch cultures, even when exposed to high glucose levels, thereby alleviating the need of controlling nutrient at low levels and the potential negative impact of such strategy on product glycosylation. In bioreactor operated in fed-batch mode, the higher maximum cell density achieved with the PYC2 clone led to a net gain (20%) in final volumetric productivity. PMID:26603123

  20. 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 who...... 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....

  1. 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

  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. Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism

    Molehin, Deborah

    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

  4. 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

  5. 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

  6. 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

  7. 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.; Gertjan J. M. den Hartog; 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...

  8. 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. Geriatr Gerontol Int 2016; 16 (Suppl. 1): 4-16. PMID:27018279

  9. Metabolic profiling of hematopoietic stem and progenitor cells during proliferation and differentiation into red blood cells.

    Daud, Hasbullah; Browne, Susan; Al-Majmaie, Rasoul; Murphy, William; Al-Rubeai, Mohamed

    2016-01-25

    An understanding of the metabolic profile of cell proliferation and differentiation should support the optimization of culture conditions for hematopoietic stem and progenitor cell (HSPC) proliferation, differentiation, and maturation into red blood cells. We have evaluated the key metabolic parameters during each phase of HSPC culture for red blood cell production in serum-supplemented (SS) and serum-free (SF) conditions. A simultaneous decrease in growth rate, total protein content, cell size, and the percentage of cells in the S/G2 phase of cell cycle, as well as an increase in the percentage of cells with a CD71(-)/GpA(+) surface marker profile, indicates HSPC differentiation into red blood cells. Compared with proliferating HSPCs, differentiating HSPCs showed significantly lower glucose and glutamine consumption rates, lactate and ammonia production rates, and amino acid consumption and production rates in both SS and SF conditions. Furthermore, extracellular acidification was associated with late proliferation phase, suggesting a reduced cellular metabolic rate during the transition from proliferation to differentiation. Under both SS and SF conditions, cells demonstrated a high metabolic rate with a mixed metabolism of both glycolysis and oxidative phosphorylation (OXPHOS) in early and late proliferation, an increased dependence on OXPHOS activity during differentiation, and a shift to glycolytic metabolism only during maturation phase. These changes indicate that cell metabolism may have an important impact on the ability of HSPCs to proliferate and differentiate into red blood cells. PMID:26013297

  10. Cardiac energy dependence on glucose increases metabolites related to glutathione and activates metabolic genes controlled by mechanistic target of rapamycin

    Schisler, Jonathan C; Grevengoed, Trisha J; Pascual, Florencia; Cooper, Daniel E; Ellis, Jessica M; Paul, David S; Willis, Monte S; Patterson, Cam; Jia, Wei; Coleman, Rosalind A

    2015-01-01

    glucose metabolism and 11 to cysteine and glutathione pathways. Concurrently, global cardiac transcriptional analysis revealed differential expression of 568 genes in Acsl1(H-/-) hearts, a subset of which we hypothesized were targets of mTOR; subsequently, we measured the transcriptional response of......-specific mTOR signaling. Increased glucose use also changed glutathione-related pathways and compensation by mTOR. The hypertrophy, oxidative stress, and metabolic changes that occur within the heart when glucose supplants FA as a major energy source suggest that substrate switching to glucose is not...

  11. Induction of a metabolic switch in insect cells by substrate-limited fed batch cultures.

    Ohman, L; Ljunggren, J; Hggstrm, L

    1995-11-01

    Insect cell metabolism was studied in substrate-limited fed batch cultures of Spodoptera frugiperda (Sf-9) cells. Results from a glucose-limited culture, a glutamine-limited culture, a culture limited in both glucose and glutamine, and a batch culture were compared. A stringent relation between glucose excess and alanine formation was found. In contrast, glucose limitation induced ammonium formation, while, at the same time, alanine formation was completely suppressed. Simultaneous glucose and glucosamine limitation suppressed both alanine and ammonium formation. Although the metabolism was influenced by substrate limitation, the specific growth rate was similar in all cultures. Alanine formation must involve incorporation of free ammonium, if ammonium formation is mediated by glutaminase and glutamate dehydrogenase, as our data suggest. On the basis of the results, two possible pathways for the formation of alanine in the intermediary metabolism are suggested. The cellular yield on glucose was increased 6.6 times during glucose limitation, independently of the cellular yield on glutamine, which was increased 50-100 times during glutamine limitation. The results indicate that alanine overflow metabolism is energetically wasteful and that glutamine is a dispensable amino acid for cultured Sf-9 cells. Preliminary data confirm that glutamine can be synthesized by the cells themselves in amounts sufficient to support growth. PMID:8590651

  12. 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

    2012-01-01

    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 disease course. Spinal blood flow was progressively decreased in the anterior gray matter (GM) from presymptomatic stage to 0.80-fold of wild-type (WT) mice, 0.61 at early-symptomatic, and 0.49 at end stage of the disease. Local spinal glucose utilization (LSGU) was transiently increased to 1.19-fold in anterior GM at presymptomatic stage, which in turn progressively decreased to 0.84 and 0.60 at early-symptomatic and end stage of the disease. The LSGU/SBF ratio representing flow–metabolism uncoupling (FMU) preceded the sequential pathological changes in the spinal cord of ALS mice and was preferentially found in the affected region of ALS. The present study suggests that this early and progressive FMU could profoundly involve in the whole disease process as a vascular factor of ALS pathology, and could also be a potential target for therapeutic intervention of ALS. PMID:22068226

  13. [Investigation of a compound, compatibility of Rhodiola crenulata, Cordyceps militaris, and Rheum palmatum, on metabolic syndrome treatment. V--Mechanisms on improving glucose metabolic disorders].

    Wang, Li; Zhang, Xiao-Lin; Li, Mo-Han; Tian, Jin-Ying; Zhang, Pei-Cheng; Ye, Fei

    2013-06-01

    To investigate the mechanisms of a compound (FF16), compatibility of Rhodiola crenulata, Cordyceps militaris, and Rheum palmatum, on glucose metabolic disorders, the IRF mice charactered with insulin resistance and glucose metabolic disorders induced by high-fat diet in C57BL/6J mice were randomly divided into 3 groups; IRF, rosiglitazone (Rosi) and FF16. The glucose metabolism was evaluated by fasting blood glucose (FBG) levels and intraperitoneal glucose tolerance test (IPGTT). The insulin sensitivity was estimated by insulin tolerance test (ITT), fasting serum insulin levels and the index of HOMA-IR. The expressions of Akt and its phosphorylation levels, GSK3beta and its phosphorylation levels in liver were detected by Western Blot. The results showed that FF16 significantly improved the glucose metabolic disorders through reducing FBG by 15.1%, decreasing AUC values in glucose tolerance tests by 22.3%. FF16 significantly improved the insulin sensitivity through decreasing AUC values in insulin tolerance tests by 22.1%, reducing the levels of serum insulin by 42.9% and of HOMA-IR by 49.5%, comparing with model control, respectively. After the treatment with FF16, the levels of p-Akt and p-GSK3beta were increased by 116.4% and 24.9%, respectively, in the liver of IRF mice. In conclusion, compound FF16 could improve glucose metabolic disorders in IRF mice through enhancing the glyconeogenesis. PMID:24066594

  14. Glucose allostasis

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert; Vozarova, Barbora; Bogardus, Clifton; de Courten, Barbora

    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...... concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus for...

  15. 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

  16. Analysis of the ammonia metabolism of rat primary hepatocytes and a human hepatocyte cell line Huh 7

    Takagi, Mutsumi; Kojima, Nobuhiko; Yoshida, Toshiomi

    2000-01-01

    Ammonia metabolism of ratprimary hepatocytes and a human hepatocyte cell line,Huh 7, at different concentrations of glutamine,glucose and ammonia was examined. During theincubation of the primary hepatocyte cells, glutamineand ammonia concentrations decreased, that of ureaincreased, and that of glucose remained the same. Inthe case of Huh 7 cells, glucose was consumed rapidly,the concentration of ammonia increased and that of urearemained the same. The major energy sources amongmedium compone...

  17. Single Glucose Biofuel Cells Implanted in Rats Power Electronic Devices

    Zebda, A.; Cosnier, S.; J.-P. Alcaraz; M. Holzinger; Le Goff, A.; C. Gondran; Boucher, F; Giroud, F.; Gorgy, K.; H. Lamraoui; 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...

  18. 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 (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...

  19. 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.

  20. Glucose Oxidation Is Critical for CD4+ T Cell Activation in a Mouse Model of Systemic Lupus Erythematosus.

    Yin, Yiming; Choi, Seung-Chul; Xu, Zhiwei; Zeumer, Leilani; Kanda, Nathalie; Croker, Byron P; Morel, Laurence

    2016-01-01

    We have previously shown that CD4(+) T cells from B6.Sle1Sle2.Sle3 lupus mice and patients present a high cellular metabolism, and a treatment combining 2-deoxy-d-glucose, which inhibits glucose metabolism, and metformin, which inhibits oxygen consumption, normalized lupus T cell functions in vitro and reverted disease in mice. We obtained similar results with B6.lpr mice, another model of lupus, and showed that a continuous treatment is required to maintain the beneficial effect of metabolic inhibitors. Further, we investigated the relative roles of glucose oxidation and pyruvate reduction into lactate in this process. Treatments of B6.Sle1Sle2.Sle3 mice with either 2-deoxy-d-glucose or metformin were sufficient to prevent autoimmune activation, whereas their combination was necessary to reverse the process. Treatment of B6.Sle1Sle2.Sle3 mice with dichloroacetate, an inhibitor of lactate production, failed to effectively prevent or reverse autoimmune pathology. In vitro, CD4(+) T cell activation upregulated the expression of genes that favor oxidative phosphorylation. Blocking glucose oxidation inhibited both IFN-? and IL-17 production, which could not be achieved by blocking pyruvate reduction. Overall, our data show that targeting glucose oxidation is required to prevent or reverse lupus development in mice, which cannot be achieved by simply targeting the pyruvate-lactate conversion. PMID:26608911

  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. Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella

    Kovatcheva-Datchary, Petia; Nilsson, Anne; Akrami, Rozita; Lee, Ying Shiuan; De Vadder, Filipe; Arora, Tulika; Hallen, Anna; Martens, Eric; Björck, Inger; Bäckhed, Gert Fredrik

    2015-01-01

    The gut microbiota plays an important role in human health by interacting with host diet, but there is substantial inter-individual variation in the response to diet. Here we compared the gut microbiota composition of healthy subjects who exhibited improved glucose metabolism following 3-day...... consumption of barley kernel-based bread (BKB) with those who responded least to this dietary intervention. The Prevotella/Bacteroides ratio was higher in responders than non-responders after BKB. Metagenomic analysis showed that the gut microbiota of responders was enriched in Prevotella copri and had...... increased potential to ferment complex polysaccharides after BKB. Finally, germ-free mice transplanted with microbiota from responder human donors exhibited improved glucose metabolism and increased abundance of Prevotella and liver glycogen content compared with germ-free mice that received non...

  3. 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.

  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. 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 response of the organism to stimulate gluconeogenesis. They showed for the first time that HCB causes impairment of the gluconeogenic pathway. Therefore, the reduced levels of glucose would thus be the consequence of decreased gluconeogenesis, enhanced glucose storage, and unaffected glycolysis. The impairment of gluconeogenesis (especially for PEPCK) and the related variation in glucose levels caused by HCB treatment could be a consequence of the oxidative stress produced by the fungicide. Tryptophan adds its effect to this decrease in the higher phases of HCB intoxication, where its levels overcome the control values possibly owing to the drastic decline of URO-D. This derangement of carbohydrates leads porphyric hepatocytes to have lower levels of free glucose. These results contribute to our understanding of the protective and modulatory effect that diets rich in carbohydrates have in hepatic porphyria disease. (orig.)

  6. 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

  7. 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...

  8. Morphological and Glucose Metabolism Abnormalities in Alcoholic Korsakoff's Syndrome: Group Comparisons and Individual Analyses

    Pitel, Anne-Lise; Aupée, Anne-Marie; Chételat, Gaël; Mézenge, Florence; Beaunieux, Hélène; de la Sayette, Vincent; Viader, Fausto; Baron, Jean-Claude; Eustache, Francis; Desgranges, Béatrice

    2009-01-01

    Background Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS). Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies. Methodology/Principal Findings Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission ...

  9. 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.

  10. Aerobic and anaerobic metabolism of Listeria monocytogenes in defined glucose medium.

    Romick, T L; Fleming, H P; McFeeters, R F

    1996-01-01

    A defined medium with glucose as the carbon source was used to quantitatively determine the metabolic end products produced by Listeria monocytogenes under aerobic and anaerobic conditions. Of 10 strains tested, all produced acetoin under aerobic conditions but not anaerobic conditions. Percent carbon recoveries of end products, typified by strain F5069, were as follows: lactate, 28%; acetate, 23%; and acetoin, 26% for aerobic growth and lactate, 79%; acetate, 2%; formate, 5.4%; ethanol, 7.8%...

  11. Changes in Cerebral Glucose Metabolism during Early Abstinence from Chronic Methamphetamine Abuse

    Berman, Steven M.; Voytek, Bradley; Mandelkern, Mark A.; Hassid, B. Daniel; Isaacson, Andrew; Monterosso, John; Miotto, Karen; Ling, Walter; London, Edythe D.

    2007-01-01

    Changes in brain function during the initial weeks of abstinence from chronic methamphetamine abuse may substantially affect clinical outcome, but are not well understood. We used positron emission tomography with [F-18]fluorodeoxyglucose (FDG) to quantify regional cerebral glucose metabolism, an index of brain function, during performance of a vigilance task. Ten methamphetamine-dependent subjects were tested after 5-9 days of abstinence, and after 4 additional weeks of supervised abstinence...

  12. 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

  13. 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) Dulbeccos Modified Eagles Medium (DMEM) with varying concentrations of the free fatty acid palmitate (01.0 mM). Then the cells were incubated with [18 F]-FDG (1 ?Ci/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

  14. 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.

  15. Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells

    Shen Junhui

    2012-07-01

    Full Text Available Abstract Background Diabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ?-3 and eicosapentaenoic acid (EPA, 20:5 ?-3. The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn2+ is essential for the activity of ?6 desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs ?-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood. Methods RF/6A cells were treated with different concentrations of high glucose, ?-linolenic acid and linoleic acid and Zn2+. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF secretion were evaluated. Results Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA and ?-linolenic acid (ALA, while the saturated fatty acid, palmitic acid was ineffective. A doseresponse study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn2+ and ALA. ALA was more potent that Zn2+. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed high-glucose-induced VEGF secretion by RF/6A cells. Conclusions These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.

  16. 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

  17. Changes in glucose metabolism and gene expression after transfer of anti-angiogenic genes in rat hepatoma

    Haberkorn, Uwe; Altmann, Annette [University of Heidelberg, INF 400, Department of Nuclear Medicine, Heidelberg (Germany); DKFZ and University of Heidelberg, INF 280, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Hoffend, Johannes [University of Heidelberg, INF 400, Department of Nuclear Medicine, Heidelberg (Germany); Schmidt, Kerstin [University of Heidelberg, INF 400, Department of Nuclear Medicine, Heidelberg (Germany); DKFZ and University of Heidelberg, INF 280, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Heidelberg, Anatomy and Developmental Biology, Medical Faculty Mannheim, Mannheim (Germany); Bonaterra, Gabriel A.; Kinscherf, Ralf [University of Heidelberg, Anatomy and Developmental Biology, Medical Faculty Mannheim, Mannheim (Germany); Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig G. [DKFZ and University of Heidelberg, INF 280, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Eisenhut, Michael [DKFZ, INF 280, Department of Radiopharmaceutical Chemistry, Heidelberg (Germany)

    2007-12-15

    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 {sup 18}F-fluorodeoxyglucose ({sup 18}FDG) 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. {sup 18}FDG 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 {sup 18}FDG, 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.)

  18. 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.)

  19. Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella.

    Kovatcheva-Datchary, Petia; Nilsson, Anne; Akrami, Rozita; Lee, Ying Shiuan; De Vadder, Filipe; Arora, Tulika; Hallen, Anna; Martens, Eric; Bjrck, Inger; Bckhed, Fredrik

    2015-12-01

    The gut microbiota plays an important role in human health by interacting with host diet, but there is substantial inter-individual variation in the response to diet. Here we compared the gut microbiota composition of healthy subjects who exhibited improved glucose metabolism following 3-day consumption ofbarley kernel-based bread (BKB) with those whoresponded least to this dietary intervention. The Prevotella/Bacteroides ratio was higher in responders than non-responders after BKB. Metagenomic analysis showed that the gut microbiota of responders was enriched in Prevotella copri and had increased potential to ferment complex polysaccharides after BKB. Finally, germ-free mice transplanted with microbiota from responder human donors exhibited improved glucose metabolism andincreased abundance of Prevotella and liver glycogen content compared with germ-free mice that received non-responder microbiota. Our findings indicate that Prevotella plays a role in the BKB-induced improvement in glucose metabolism observed in certain individuals, potentially by promoting increased glycogen storage. PMID:26552345

  20. 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

  1. The role of hepatic mitochondria in the regulation of glucose metabolism in BHE rats

    The interacting effects of dietary fat source and thyroxine treatment on the hepatic mitochondrial function and glucose metabolism were studied. In the first study, three different sources of dietary fatty acids and thyroxine treatment were used to investigate the hepatic mitochondrial thermotropic behavior in two strains of rat. The NIDDM BHE and Sprague-Dawley rats were used. Feeding coconut oil increased serum T4 levels and T4 treatment increased serum T3 levels in the BHE rats. In the mitochondria from BHE rats fed coconut oil and treated with T4, the transition temperature disappeared due to a decoupling of succinate supported respiration. This was not observed in the Sprague-Dawley rats. In the second study, two different sources of dietary fat and T4 treatment were used to investigate hepatic mitochondrial function. Coconut oil feeding increased Ca++Mg++ATPase and Mg++ATPase. T4 treatment had potentiated this effect. T4 increased the malate-aspartate shuttle and α-glycerophosphate shuttle activities. In the third study, the glucose turnover rate from D-[14C-U]/[6-3H]-glucose and gluconeogeneis from L-[14C-U]-alanine was examined. Dietary fat or T4 did not affect the glucose mass. T4 increased the irreversible fractional glucose turnover rate

  2. Metabolic measurements in cell culture and tissue constructs

    Rolfe, P.

    2008-10-01

    This paper concerns the study and use of biological cells in which there is a need for sensors and assemblies for the measurement of a diverse range of physical and chemical variables. In this field cell culture is used for basic research and for applications such as protein and drug synthesis, and in cell, tissue and organ engineering. Metabolic processes are fundamental to cell behaviour and must therefore be monitored reliably. Basic metabolic studies measure the transport of oxygen, glucose, carbon dioxide, lactic acid to, from, or within cells, whilst more advanced research requires examination of energy storage and utilisation. Assemblies are designed to incorporate bioreactor functions for cell culture together with appropriate sensing devices. Oxygen consumption by populations of cells is achieved in a flowthrough assembly that incorporates O2 micro-sensors based on either amperometry or fluorescence. Measurements in single cell are possible with intra-cellular fluorophores acting as biosensors together with optical stimulation and detection. Near infra-red spectroscopy (NIRS) is used for analysis within culture fluid, for example for estimation of glucose levels, as well as within cell populations, for example to study the respiratory enzymes.#

  3. 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; Jørgensen, Nils B; Clausen, Trine R; Wulff, Birgitte S; Kristiansen, Viggo B; Worm, Dorte; Hansen, Dorte L; Holst, Jens Juul; van Hall, Gerrit; Madsbad, Sten

    2013-01-01

    AIMS/HYPOTHESIS: Roux-en-Y gastric bypass surgery (RYGB) improves glucose tolerance in patients with type 2 diabetes, but also changes the glucose profile in response to a meal in glucose-tolerant individuals. We hypothesised that the driving force for the changed postprandial glucose profiles af...

  4. 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

  5. Delayed beta-cell response and glucose intolerance in young women with Turner syndrome

    Hjerrild, Britta E; Holst, Jens Juul; Juhl, Claus B; Christiansen, Jens S; Schmitz, Ole; Gravholt, Claus H

    2011-01-01

    by glucose tolerance (oral and intravenous glucose tolerance test (OGTT and IVGTT)), insulin sensitivity (hyperinsulinemic, euglycemic clamp), beta-cell function (hyperglycaemic clamp, arginine and GLP-1 stimulation) and insulin pulsatility. RESULTS: Fasting glucose and insulin levels were similar...

  6. 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 milk citrate during supplemental rbST in both non-cooled and cooled cows in early and mid lactation. Conclusion: The present study demonstrated that local changes for biosynthetic capacity within the mammary gland would be a factor in identification of the utilization of substrates in the rate of decline in milk yield. The proportion of glucose was metabolized less for lactose synthesis, but metabolized more via the Embden-Meyerhof pathway and the tricarboxylic acid cycle as lactation advanced to late lactation in both cooled and non-cooled cows whether supplemental rbST or not.

  7. 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.

  8. 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

  9. Calcium Co-regulates Oxidative Metabolism and ATP Synthase-dependent Respiration in Pancreatic Beta Cells

    De Marchi, Umberto; Thevenet, Jonathan; Hermant, Aurelie; Dioum, Elhadji; Wiederkehr, Andreas

    2014-01-01

    Mitochondrial energy metabolism is essential for glucose-induced calcium signaling and, therefore, insulin granule exocytosis in pancreatic beta cells. Calcium signals are sensed by mitochondria acting in concert with mitochondrial substrates for the full activation of the organelle. Here we have studied glucose-induced calcium signaling and energy metabolism in INS-1E insulinoma cells and human islet beta cells. In insulin secreting cells a surprisingly large fraction of total respiration under resting conditions is ATP synthase-independent. We observe that ATP synthase-dependent respiration is markedly increased after glucose stimulation. Glucose also causes a very rapid elevation of oxidative metabolism as was followed by NAD(P)H autofluorescence. However, neither the rate of the glucose-induced increase nor the new steady-state NAD(P)H levels are significantly affected by calcium. Our findings challenge the current view, which has focused mainly on calcium-sensitive dehydrogenases as the target for the activation of mitochondrial energy metabolism. We propose a model of tight calcium-dependent regulation of oxidative metabolism and ATP synthase-dependent respiration in beta cell mitochondria. Coordinated activation of matrix dehydrogenases and respiratory chain activity by calcium allows the respiratory rate to change severalfold with only small or no alterations of the NAD(P)H/NAD(P)+ ratio. PMID:24554722

  10. Characterization of acetate metabolism in tumor cells in relation to cell proliferation: Acetate metabolism in tumor cells

    To reveal the metabolic fate of acetate in neoplasms that may characterize the accumulation patterns of [1-11C]acetate in tumors depicted by positron emission tomography. Four tumor cell lines (LS174T, RPMI2650, A2780, and A375) and fibroblasts in growing and resting states were used. In uptake experiments, cells were incubated with[1-14C]acetate for 40 min. [14C]CO2 was measured in the tight-air chamber, and the metabolites in cells were identified by thin layer chromatography and paper chromatography. The glucose metabolic rate of each cell line was measured with [2,6-3H]2-deoxy-glucose (DG), and the growth activity of each cell line was estimated by measuring the incorporation of [3H]methyl thymidine into DNA. Compared with resting fibroblasts, all four tumor cell lines showed higher accumulation of 14C activity from [1-14C]acetate. These tumor-to-normal ratios of [1-14C]acetate were larger than those of DG. Tumor cells incorporated 14C activity into the lipid-soluble fraction, mostly of phosphatidylcholine and neutral lipids, more prominently than did fibroblasts. The lipid-soluble fraction of 14C accumulation in cells showed a positive correlation with growth activity, whereas the water-soluble and CO2 fractions did not. These findings suggest that the high tumor-to-normal ratio of [1-14C]acetate is mainly due to the enhanced lipid synthesis, which reflects the high growth activity of neoplasms. This in vitro study suggests that [1-11C]acetate is appropriate for estimating the growth activity of tumor cells

  11. Electrochemical performance of a glucose/oxygen microfluidic biofuel cell

    Zebda, A.; Cretin, M.; Innocent, C.; Tingry, S. [Institut Europeen des Membranes, UMR 5635, ENSCM-UMII-CNRS, place Eugene Bataillon, 34095 Montpellier (France); Renaud, L.; Ferrigno, R. [Institut des Nanotechnologies de Lyon, INL, CNRS UMR5270, Universite de Lyon, F-69003 Lyon (France); Universite Lyon 1, Villeurbanne F-69622 (France); Pichot, F. [Centrale de Technologies en Micro et Nanoelectronique, Universite Montpellier 2, place Eugene Bataillon, 34095 Montpellier (France)

    2009-09-05

    A microfluidic glucose/O{sub 2} biofuel cell, delivering electrical power, is developed based on both laminar flow and biological enzyme strategies. The device consists of a Y-shaped microfluidic channel in which fuel and oxidant streams flow laminarly in parallel at gold electrode surfaces without convective mixing. At the anode, the glucose is oxidized by the enzyme glucose oxidase whereas at the cathode, the oxygen is reduced by the enzyme laccase, in the presence of specific redox mediators. Such cell design protects the anode from interfering parasite reaction of O{sub 2} at the anode and works with different streams of oxidant and fuel for optimal operation of the enzymes. The dependence of the flow rate on the current is evaluated in order to determine the optimum flow that would provide little to no mixing while yielding high current densities. The maximum power density delivered by the assembled biofuel cell reaches 110 {mu}W cm{sup -2} at 0.3 V with 10 mM glucose at 23 C. This research demonstrates the feasibility of advanced microfabrication techniques to build an efficient microfluidic glucose/O{sub 2} biofuel cell device. (author)

  12. 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, Peoples 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. Inparticular, 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 over normal cells, different starvation periods were screened in order to achieve optimal treatment effects. Cancer cells were then fed using Glu-GNPs followed by X-ray irradiation treatment. For comparison, solid tumor MCF-7 cells (breast cancer cell line were studied as well. Our irradiation experimental results show that Glu-GNPs are better irradiation sensitizers to treat THP-1 cells than MCF-7 cells, or Glu-GNPs enhance the cancer killing of THP-1 cells 20% more than X-ray irradiation alone and GNP treatment alone. This finding can help oncologists to design therapeutic strategies to target cancer stem cells and cancer metastasis. Keywords: glucose capped gold nanoparticles, cancer metastasis, cancer stem cells, irradiation therapy, targeted treatment, suspension cancer cells

  13. 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

  14. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary glucose metabolism

    Galindo, C; Larsen, Mogens; Ouellet, D R; Maxin, G; Pellerin, D; Lapierre, H

    2015-01-01

    Nine Holstein cows fitted with rumen cannulas and indwelling catheters in splanchnic blood vessels were used to study the effects of supplementing AA on milk lactose secretion, whole-body rate of appearance (WB-Ra) of glucose, and tissue metabolism of glucose, lactate, glycerol, and β-OH-butyrate...

  15. Impaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1 (gys1 deletion in adult mice

    Chrysovalantou E. Xirouchaki

    2016-03-01

    In brief: This study demonstrates why the body prioritises muscle glycogen storage over liver glycogen storage despite the critical role of the liver in supplying glucose to the brain in the fasting state and shows that glycogen deficiency results in impaired glucose metabolism and reduced exercise capacity.

  16. Metabolic regulation of fatty acid esterification and effects of conjugated linoleic acid on glucose homeostasis in pig hepatocytes

    Conde Aguilera, Jose Alberto; Lachica, M.; Nieto, R; Fernández-Fígares, I.

    2012-01-01

    Conjugated linoleic acids (CLAs) are geometric and positional isomers of linoleic acid (LA) that promote growth, alter glucose metabolism and decrease body fat in growing animals, although the mechanisms are poorly understood. A study was conducted to elucidate the effects of CLA on glucose metabolism, triglyceride (TG) synthesis and IGF-1 synthesis in primary culture of porcine hepatocytes. In addition, hormonal regulation of TG and IGF-1 synthesis was addressed. Hepatocytes were isolated fr...

  17. 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...

  18. Effects of sleep disruption and high fat intake on glucose metabolism in mice.

    Ho, Jacqueline M; Barf, R Paulien; Opp, Mark R

    2016-06-01

    Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chronic conditions. Recovery sleep may offset adverse metabolic outcomes of accumulated sleep debt, but the extent to which this occurs is unclear. We examined whether recovery sleep improves glucose metabolism in mice subjected to prolonged sleep disruption, and whether high fat intake during sleep disruption exacerbates glycemic control. Adult male C57BL/6J mice were subjected to 18-h sleep fragmentation daily for 9 days, followed by 1 day of recovery. During sleep disruption, one group of mice was fed a high-fat diet (HFD) while another group was fed standard laboratory chow. Insulin sensitivity and glucose tolerance were assessed by insulin and glucose tolerance testing at baseline, after 3 and 7 days of sleep disruption, and at the end of the protocol after 24h of undisturbed sleep opportunity (recovery). To characterize changes in sleep architecture that are associated with sleep debt and recovery, we quantified electroencephalogram (EEG) recordings during sleep fragmentation and recovery periods from an additional group of mice. We now report that 9 days of 18-h daily sleep fragmentation significantly reduces rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Mice respond with increases in REMS, but not NREMS, during the daily 6-h undisturbed sleep opportunity. However, both REMS and NREMS increase significantly during the 24-h recovery period. Although sleep disruption alone has no effect in this protocol, high fat feeding in combination with sleep disruption impairs glucose tolerance, effects that are reversed by recovery sleep. Insulin sensitivity modestly improves after 3 days of sleep fragmentation and after 24h of recovery, with significantly greater improvements in mice exposed to HFD during sleep disruption. Improvements in both glucose tolerance and insulin sensitivity are associated with NREMS rebound, raising the possibility that this sleep phase contributes to restorative effects of recovery sleep on glycemic control. PMID:26943344

  19. 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

  20. 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

  1. Investigation of (/sup 18/F)2-fluoro-2-deoxyglucose for the measure of myocardial glucose metabolism

    Phelps, M.E.; Hoffman, E.J.; Selin, C.; Huang, S.C.; Robinson, G.; MacDonald, N.; Schelbert, H.; Kuhl, D.E.

    1978-12-01

    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.

  2. 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

  3. 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.

  4. 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.

  5. 2D-DIGE screening of high-productive CHO cells under glucose limitation--basic changes in the proteome equipment and hints for epigenetic effects.

    Wingens, Marc; Gätgens, Jochem; Schmidt, Anica; Albaum, Stefan P; Büntemeyer, Heino; Noll, Thomas; Hoffrogge, Raimund

    2015-05-10

    CHO derivates (Chinese hamster ovary) belong to the most important mammalian cells for industrial recombinant protein production. Many efforts have been made to improve productivity and stability of CHO cells in bioreactor processes. Here, we followed up one barely understood phenomenon observed with process optimizations: a significantly increased cell-specific productivity in late phases of glucose-limited perfusion cultivations, when glucose (and lactate) reserves are exhausted. Our aim was to elucidate the cellular activities connected to the metabolic shift from glucose surplus to glucose limitation phase. With 2D-DIGE, we compared three stages in a perfusion culture of CHO cells: the initial growth with high glucose concentration and low lactate production, the second phase with glucose going to limitation and high lactate level, and finally the state of glucose limitation and also low lactate concentration but increased cell-specific productivity. With our proteomic approach we were able to demonstrate consequences of glucose limitation for the protein expression machinery which also could play a role for a higher recombinant protein production. Most interestingly, we detected epigenetic effects on the level of proteins involved in histone modification (HDAC1/-2, SET, RBBP7, DDX5). Together with shifts in the protein inventory of energy metabolism, cytoskeleton and protein expression, a picture emerges of basic changes in the cellular equipment under long-term glucose limitation of CHO cells. PMID:25612871

  6. Effects of orexin A on glucose metabolism in human hepatocellular carcinoma invitro via PI3K/Akt/mTOR-dependent and -independent mechanism.

    Liu, Yuanyuan; Zhao, Yuyan; Guo, Lei

    2016-01-15

    Orexins are hypothalamic neuropeptides that regulate food intake, energy homeostasis, reward system and sleep/wakefulness states. The purpose of this study was to investigate the effects of orexin A on glucose metabolism in human hepatocellular carcinoma cell line, Hep3B, and determine the possible mechanisms. Hep3B cells were incubated with different concentrations of orexin A (10(-9)-10(-7)M) invitro in the presence or absence of the orexin receptor 1 (OX1R) inhibitor (SB334867), Akt inhibitor (PF-04691502) and mammalian target of rapamycin (mTOR) inhibitor (temsirolimus). Subsequently, OX1R protein expression, glucose transporter 1 (GLUT1) expression, glucose uptake, the mRNA expression of lactate dehydrogenase (LDHA), pyruvate dehydrogenase kinase 1 (PDK1) and pyruvate dehydrogenase B (PDHB), lactate generation and mitochondrial pyruvate dehydrogenase (PDH) enzyme activity were measured. The activity of phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling was also determined. OX1R was expressed in hepatoma tissues and Hep3B cells. Stimulation of the Hep3B cells with orexin A resulted in a dose-dependent increase of GLUT1 expression and glucose uptake, which was associated with the activation of PI3K/Akt/mTOR pathway. Further, orexin A increased PDHB expression and PDH enzyme activity, decreased LDHA, PDK1 mRNA levels and lactate generation independent of PI3K/Akt/mTOR pathway. Our results demonstrated that orexin A directed the cellular metabolism towards mitochondrial glucose oxidation rather than glycolysis. These findings provide functional evidence of the metabolic actions of orexin A in hepatocellular carcinoma cells. PMID:26549689

  7. 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 ...

  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. 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

  10. 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.

  11. Fad24 causes hyperplasia in adipose tissue and improves glucose metabolism.

    Johmura, Yoshikazu; Watanabe, Kayoko; Kishimoto, Keishi; Ueda, Takashi; Shimada, Shoichi; Osada, Shigehiro; Nishizuka, Makoto; Imagawa, Masayoshi

    2009-10-01

    We have previously reported that a novel gene, factor for adipocyte differentiation (fad) 24, promotes adipogenesis in vitro. To examine the role of fad24 in adipogenesis in vivo and the development of obesity, transgenic mice overexpressing fad24 were generated using mouse fad24 cDNA under the control of a chicken beta-actin promoter and cytomegalovirus enhancer. The comparison of the ability of fibroblasts from fad24 transgenic embryos to differentiate into adipocytes with that of fibroblasts from wild-type embryos revealed that fad24 overexpression promotes adipogenesis in embryonic fibroblasts. The weight and histology of white adipose tissues, and serum adipocytokine levels were compared between fad24 transgenic mice and wild-type mice, and we found that fad24 overexpression increased the number of smaller adipocytes, caused hyperplasia rather than hypertrophy in white adipose tissue and increased the serum adiponectin level in mice fed both normal chow and a high-fat diet. Glucose and insulin tolerance tests indicated that the activity for glucose metabolism is improved in fad24 transgenic mice fed normal chow in comparison with that in wild-type mice. Our findings suggest that fad24 is a positive regulator of adipogenesis in vivo. Moreover, the increase in the number of smaller adipocytes caused by the overexpression of fad24 appears to enhance glucose metabolic activity, perhaps by increasing the serum adiponectin level. PMID:19801824

  12. The Effects of Blood Sugar (Glucose Metabolism on the Sleep and Memory in Ahwaz Diabetic Patients

    Alireza Heideri

    2008-01-01

    Full Text Available This study was aimed to examine the effects of blood sugar (glucose metabolism on the sleep and memory in diabetic patients from Ahwaz metropolitan. The sample subsumed 90 diabetic patients from Ahwaz metropolitan whom were selected via two procedures: a systematic random sampling and incidental sampling procedure (within reach clients. The patients were allocated to three groups (two experimental and one control groups; the medical treatment or medicine therapy group (Hospitals clients, diet therapy group and the control group (from Diabetic Patients Association of Khouzastan Province registered patient members. The experimental groups` blood sugar (glucose metabolisms (the independent variable were manipulated by insulin treatment (insulin injection in medical therapy group and in diet therapy group through diet treatment training. Kimkarad Visual Memory Test, Immediate Auditory Memory Test and Groningen Sleep Quality Scale were implemented to collect data. Based on Multivariate Analysis of Variance (MANOVA as applied statistical method the outcome results revealed that: devious management of the blood glucose level through insulin injection and diet therapy improved sleep and audile and visual short term memory, mid term and long term memories in diabetic patients.

  13. 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

  14. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    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 /sup 82/Rb 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.

  15. 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

  16. Double-injection FDG method to measure cerebral glucose metabolism twice in a single procedure

    [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be used to examine changes in cerebral glucose metabolism in two physiological conditions. We proposed and evaluated a double injection-single session FDG method with biological constraints for this purpose. Simulated brain time-radioactivity curves (TACs) generated by using a plasma TAC from an actual study and physiological combinations of input values in a kinetic model were analyzed to evaluate the accuracy of the proposed method. The reproducibility of the estimated values obtained by this method was tested in five normal volunteers who were studied with a dynamic PET scan and two injections of FDG in a single session while fasting. The simulation study showed that the estimated values obtained by the proposed method agreed well with the input values. In the human study, plasma glucose levels were 5.3±0.2 and 5.0±0.2 mM in the first and second measurements, respectively. The difference between the plasma glucose measurements was small but statistically significant (p*1 or rCMRglc, there were small deviations in K* (less than 10%) and LC (less than 5%) with a statistical significance (p* and LC seemed to relate to the difference in the plasma glucose level. The double-injection FDG method with biological constrains can be used to estimate rCMRglc and LC sequentially in a single PET scanning session. (author)

  17. Evaluation of Chios mastic gum on lipid and glucose metabolism in diabetic mice.

    Georgiadis, Ioannis; Karatzas, Theodore; Korou, Laskarina-Maria; Agrogiannis, George; Vlachos, Ioannis S; Pantopoulou, Alkisti; Tzanetakou, Irene P; Katsilambros, Nikolaos; Perrea, Despina N

    2014-03-01

    Chios mastic gum (MG), a resin produced from Pistacia lentiscus var. Chia, is reported to possess beneficial cardiovascular and hepatoprotective properties. This study investigated the effect of crude Chios MG on metabolic parameters in diabetic mice. Streptozotocin-induced diabetic 12-week-old male C57bl/6 mice were assigned to three groups: NC (n=9) control; LdM (n=9) animals receiving low dose mastic for 8 weeks (20?mg/kg body weight [BW]); and HdM (n=9) animals receiving high dose mastic (500?mg/kg BW) for the same period. Serum lipid and glucose levels were determined at baseline, at 4 and 8 weeks. Serum total protein, adiponectin, and resistin levels were also measured at the end of the experiment. Histopathological examination for liver, kidney, aorta, and heart lesions was performed. After 4 weeks, MG administration resulted in decreased serum glucose and triglyceride levels in both LdM and HdM, whereas BW levels were reduced in LdM group compared with controls. At the end of the experiment, LdM presented significantly lower serum glucose, cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and improved high-density lipoprotein cholesterol levels compared with control group. HdM group had ameliorated serum triglyceride levels. Hepatic steatosis observed in control group was partially reversed in LdM and HdM groups. MG administered in low dosages improves glucose and lipid disturbances in diabetic mice while alleviating hepatic damage. PMID:24404977

  18. Effect of guar gum on glucose and lipid metabolism in white sea bream Diplodus sargus.

    Enes, P; Pouso-Ferreira, P; Salmern, C; Capilla, E; Navarro, I; Gutirrez, J; Oliva-Teles, A

    2013-04-01

    The aim of this study was to assess the role of soluble non-starch polysaccharide (guar gum) on white sea bream Diplodus sargus, glucose and lipid metabolism. A control diet was formulated to contain 40 % crude protein, 14 % crude lipids and 35 % pregelatinized maize starch, and three other diets were formulated similar to the control diet except for guar gum, which was included at 4 % (diet GG4), 8 % (diet GG8) or 12 % (diet GG12). Diets were fed to the fish for 9 weeks on a pair-feeding scheme. Guar gum had no effect on growth performance, feed efficiency, glycaemia, cholesterolaemia and plasma triacylglyceride levels. Hepatic glucokinase and pyruvate kinase activities, liver glycogen content and liver insulin-like growth factor-I gene expression were not affected by dietary guar gum, while fructose-1,6-bisphosphatase activity was lower in fish fed guar gum-supplemented diets. Hepatic glucose-6-phosphate dehydrogenase activity was higher in fish fed diets GG4 and GG8 than in the control group. Overall, data suggest that in contrast to mammals guar gum had no effect on white sea bream glucose utilization and in lowering plasma cholesterol and triacylglyceride levels. However, it seems to contribute to lower endogenous glucose production. PMID:22763699

  19. The Effect of Exercise on Glucose Metabolism in Patients with Type 2 Diabetes Mellitus

    Tuba Tulay Koca

    2015-09-01

    Full Text Available Diabetes mellitus is one of the major causes of disability and death due to the complications accompanying this disease. The incidence of type 2 diabetes mellitus and insulin resistance has increased worldwide during the last decades, despite the development of effective drug therapy and improved clinical diagnoses. Recent epidemiological studies indicate that individuals who maintain a physically active lifestyle are much less likely to develop impaired glucose tolerance and diabetes mellitus. Additional to protective effect of physical activity for individuals at highest risk of developing diabetes mellitus, physical activity has positive impacts on fasting glucose, insulin sensitivity and blood glucose level for patients with overt diabetes. The essential mechanism of exercises is enhancing sensitivity of insulin on pheripheral tissues (especially skeletal muscle. With exercise training significant improvements in glucose metabolism is observed in many of these studies. Especially, the improvements in insulin sensitivity with exercise training observed better in high magnitude of aerobic exercises. Also adaptation of patients is very high to combined type exercises. However worldwide standardization of these training programmes in many of the studies is lacking and current practice in daily life is unsatisfactory. [Archives Medical Review Journal 2015; 24(3.000: 306-316

  20. Glucose activates prenyltransferases in pancreatic islet {beta}-cells

    Goalstone, Marc [Department of Medicine, University of Colorado, VA Medical Center, Denver, CO 80220 (United States); Kamath, Vasudeva [Department of Pharmaceutical Sciences, Wayne State University, VA Medical Center, Detroit, MI 48201 (United States); Kowluru, Anjaneyulu, E-mail: akowluru@med.wayne.edu [Department of Pharmaceutical Sciences, Wayne State University, VA Medical Center, Detroit, MI 48201 (United States)

    2010-01-01

    A growing body of evidence implicates small G-proteins [e.g., Cdc42 and Rac1] in glucose-stimulated insulin secretion [GSIS] in the islet {beta}-cell. These signaling proteins undergo post-translational modifications [e.g., prenylation] at their C-terminal cysteine residue and appear to be essential for the transport and fusion of insulin-containing secretory granules with the plasma membrane and the exocytotic secretion of insulin. However, potential regulation of the prenylating enzymes by physiological insulin secretogues [e.g., glucose] has not been investigated thus far. Herein, we report immunological localization, sub-cellular distribution and regulation of farnesyltransferases [FTases] and geranylgeranyltransferase [GGTase] by glucose in insulin-secreting INS 832/13 {beta}-cells and normal rat islets. Our findings suggest that an insulinotropic concentration of glucose [20 mM] markedly stimulated the expression of the {alpha}-subunits of FTase/GGTase-1, but not the {beta}-subunits of FTase or GGTase-1 without significantly affecting the predominantly cytosolic distribution of these holoenzymes in INS 832/13 cells and rodent islets. Under these conditions, glucose significantly stimulated [2.5- to 4.0-fold over basal] the activities of both FTase and GGTase-1 in both cell types. Together, these findings provide the first evidence to suggest that GSIS involves activation of the endogenous islet prenyltransferases by glucose, culminating in the activation of their respective G-protein substrates, which is necessary for cytoskeletal rearrangement, vesicular transport, fusion and secretion of insulin.

  1. Isotope inequilibrium of glucose metabolites in intact cells and particlefree supernatants of Ehrlich ascites tumor

    With an enzyme degradative technique, isotope inequilibrium of glucose metabolites was demonstrated in intact cells and particle-free supernatants of Ehrlich ascites tumor using I-14C-glucose as tracer. Inequilibrium was found between glucose and glucose-6-phosphate, glucose and fructose-6-phosphate, glucose and 6-phosphogluconate, while glucose-6-phosphate and fructose-6-phosphate were found to be in near equilibrium within the incubation time investigated. Glucose and lactate were found to be in near equilibrium after 8 min in intact cells. Calculations based on the equilibrium levels found, showed that these inequilibria could not be explained by the effects of the pentose cycle. (U.S.)

  2. 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

  3. Study on the effect of valproate (VPA) on glucose metabolism in pediatric patients with epilepsy

    Objective: To study the effect on glucose metabolism in pediatric patients with epilepsy under valproate treatment. Methods: Fasting serum glucose (with oxidase method) and insulin (with RIA) levels, insulin resistance index, body weight, BMI were examined in (1) 65 pediatric patients with epilepsy before valproate treatment (2) 65 patients after 3 months' valproate treatment (3) 65 patients after 6 months' treatment and (4) 65 controls. Results: In the patients after 3 months' treatment, the body weight, BMI, fasting insulin levels were significantly higher than those in patients before treatment (P 0.05). The calculated HOMA did not change much throughout the whole study. The proportion of patients with increased appetite after 6 months' treatment was 47 /65 (vs 20 /65 before treatment, P < 0.05). Conclusion: The increase of body weight and BMI asually observed during valproate treatment is mainly due to increased appetite with limited increase of fasting insulin level. Insulin resistance was not found in present study. (authors)

  4. Metabolism of 14C-1 labelled glucose in the rat. A radiation protection approach

    The metabolism of 14C-1 labelled glucose was studied in the rat during 620 d. The results concerning (1) elimination by the exhalated air, urine and feces, (2) activity uptakes in 25 tissues or organes, (3) cumulated activity from the 4th to the 627 d are presented and discussed. About 50% of the activity is eliminated as CO2 in the 24 first hours, the remaining is eliminated more slowly. Some tissues such as bone and spinal cord have especially long retention half-lives. Consequently the dose delivered to these tissues is higher by a factor 10. In man, the dose should be generally around 10-4 rem per μCi of C-1 glucose administered

  5. Regulation effects of Crataegus pinnatifida leaf on glucose and lipids metabolism.

    Wang, Tao; An, Yating; Zhao, Chunfeng; Han, Lifeng; Boakye-Yiadom, Mavis; Wang, Wei; Zhang, Yi

    2011-05-11

    The leaf of Crataegus pinnatifida (Rosaceae) is commonly consumed either raw or cooked to improve digestion and promote blood circulation in China. To investigate the regulation effects of it on glucose and lipid metabolism, the flavonoids fraction was prepared and analyzed by HPLC and LC-MS. In vivo, at doses of 250 and 500 mg/kg, the flavonoids fraction showed inhibitory effects on TG and glucose absorption, accelerating effects on gastrointestinal transit but no effect on gastric emptying. In vitro, treatment of 3T3-L1 preadipocytes with 30 μg/mL flavonoids fraction significantly suppressed the accumulation of TG and free fatty acid. It also suppressed the gene expressions of C/EBPα, PPARγ, SREBP 1c, aP2 and adiponectin but did not affect that of leptin. C. pinnatifida leaf may be useful for type 2 diabetics and hyperlipidemics as a foodstuff. PMID:21425878

  6. Sucrose, glucose and fructose have similar genotoxicity in the rat colon and affect the metabolism

    Hansen, Max; Baunsgaard, D.; Autrup, H.; Vogel, Ulla Birgitte; Møller, P.; Lindecrona, R.; Wallin, H.; Poulsen, H. E.; Loft, S.; Dragsted, L. O.

    2008-01-01

    We have shown previously that a high sucrose intake increases the background level of somatic mutations and the level of bulky DNA adducts in the colon epithelium of rats. The mechanism may involve either glucose or fructose formed by hydrolysis of sucrose. Male Big Blue (R) rats were fed 30......% sucrose, glucose, fructose or potato starch as part of the diet. Mutation rates and bulky DNA adduct levels were determined in colon and liver. The concentration of short-chain fatty acids and pH were deter-mined in caecum, C-peptide was determined in plasma, biomarkers for oxidative damage and...... metabonomic studies indicated disturbed amino acid metabolism and decrease in plasma and urinary acetate as a common feature for all sugars and confirmed triglyceridemic effects of fructose. In conclusion, the genotoxicity may be related to the altered chemical environment in the caecum and thereby also in...

  7. Bifurcate effects of glucose on caspase-independent cell death during hypoxia

    We investigated the effect of glucose on hypoxic death of rat cardiomyocyte-derived H9c2 cells and found that there is an optimal glucose concentration for protection against hypoxic cell death. Hypoxic cell death in the absence of glucose is accompanied by rapid ATP depletion, release of apoptosis-inducing factor from mitochondria, and nuclear chromatin condensation, all of which are inhibited by glucose in a dose-dependent manner. In contrast, excessive glucose also induces hypoxic cell death that is not accompanied by these events, suggesting a change in the mode of cell death between hypoxic cells with and without glucose supplementation.

  8. Study of regional cerebral metabolic rate of glucose with positron emission computed tomography in Alzheimer's disease

    Using positron emission computed tomography with F-18 fluoro-D-deoxyglucose, regional cerebral metabolic rate of glucose (rCMRglc) was measured in 8 patients with Alzheimer's disease and 3 healthy volunteers. A decreased rCMRglc was observed in the widespread cortex and basal ganglia of the cerebrum, but not observed in white matter, thalamus, and cerebellum. There was no bilateral difference. rCMRglc was the lowest in the parietal lobe, followed by the temporal lobe and the curvature of the frontal lobe. A decrease in rCMRglu was relatively mild in the inner part of the frontal lobe, primary sensory and motor area of the cerebral cortex, and cerebral basilar ganglia. Alzheimer's disease proved to be characterized by severe glucose metabolic disorder in the association area of the bilateral cerebral cortices. The degree of metabolic disorder was correlated with the degree of dementia in the outer part of the left frontal lobe and the curvature of the cerebral cortex. (Namekawa, K.)

  9. Effect of triiodothyronine and insulin on glucose metabolism in tissue explants and isolated adipocytes from lean and obese Zucker rats

    Glucose metabolism in adipocytes from 6 week old lean and obese Zucker rats were sensitive to direct and chronic treatment with insulin and triidothyronine (T3). Insulin had a large stimulatory effect on glucose metabolism in acutely isolated adipocytes. This effect was greater in the lean than in the obese. Fatty acid, CO2, and glycerol-glyceride formation from radiolabeled glucose was elevated in the obese over the leans. Pretreatment of isolated adipocytes with pharmacological concentrations of T3 for 30 minutes prior to the measurement of glucose metabolism had a greater effect on lean than obese adipocytes. The presence of insulin was required to observe the acute effects of T3. A 2-hour exposure to physiological levels of T3 in the presence of insulin in both lean and obese adipocytes decreased lipogenesis. In the absence of insulin, a 2 hour pretreatment with physiological levels of T3 in tissue from a euthyroid animal produced increased lipogenesis

  10. Dyrk1A induces pancreatic ? cell mass expansion and improves glucose tolerance

    Rachdi, Latif; Kariyawasam, Dulanjalee; Aello, Virginie; Herault, Yann; Janel, Nathalie; Delabar, Jean-Maurice; Polak, Michel; Scharfmann, Raphal

    2014-01-01

    Type 2 diabetes is caused by a limited capacity of insulin-producing pancreatic ? cells to increase their mass and function in response to insulin resistance. The signaling pathways that positively regulate functional ? cell mass have not been fully elucidated. DYRK1A (also called minibrain/MNB) is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. A significant amount of data implicates DYRK1A in brain growth and Down syndrome, and recent data indicate that Dyrk1A haploinsufficient mice have a low functional ? cell mass. Here we ask whether Dyrk1A upregulation could be a way to increase functional ? cell mass. We used mice overexpressing Dyrk1A under the control of its own regulatory sequences (mBACTgDyrk1A). These mice exhibit decreased glucose levels and hyperinsulinemia in the fasting state. Improved glucose tolerance is observed in these mice as early as 4 weeks of age. Upregulation of Dyrk1A in ? cells induces expansion of ? cell mass through increased proliferation and cell size. Importantly, mBACTgDyrk1A mice are protected against high-fat-diet-induced ? cell failure through increase in ? cell mass and insulin sensitivity. These studies show the crucial role of the DYRK1A pathway in the regulation of ? cell mass and carbohydrate metabolism in vivo. Activating the DYRK1A pathway could thus represent an innovative way to increase functional ? cell mass. PMID:24870561

  11. The effect of microbial glucose metabolism on bytownite feldspar dissolution rates between 5 and 35C

    Welch, S. A.; Ullman, W. J.

    1999-10-01

    The rate of Si release from dissolving bytownite feldspar in abiotic batch reactors increased as temperatures increased from 5 to 35C. Metabolically inert subsurface bacteria (bacteria in solution with no organic substrate) had no apparent effect on dissolution rates over this temperature range. When glucose was added to the microbial cultures, the bacteria responded by producing gluconic acid, which catalyzed the dissolution reaction by both proton- and ligand-promoted mechanisms. The metabolic production, excretion, and consumption of gluconic acid in the course of glucose oxidation, and therefore, the degree of microbial enhancement of mineral dissolution, depend on temperature. There was little accumulation of gluconic acid and therefore, no significant enhancement of mineral dissolution rates at 35C compared to the abiotic controls. At 20C, gluconate accumulated in the experimental solutions only at the beginning of the experiment and led to a twofold increase in dissolved Si release compared to the controls, primarily by the ligand-promoted dissolution mechanism. There was significant accumulation of gluconic acid in the 5C experiment, which is reflected in a significant reduction in pH, leading to 20-fold increase in Si release, primarily attributable to the proton-promoted dissolution mechanism. These results indicate that bacteria and microbial metabolism can affect mineral dissolution rates in organic-rich, nutrient-poor environments; the impact of microbial metabolism on aluminum silicate dissolution rates may be greater at lower rather than at higher temperatures due to the metabolic accumulation of dissolution-enhancing protons and ligands in solution.

  12. Thermodynamics of Microbial Growth Coupled to Metabolism of Glucose, Ethanol, Short-Chain Organic Acids, and Hydrogen ▿ †

    Roden, Eric E.; Jin, Qusheng

    2011-01-01

    A literature compilation demonstrated a linear relationship between microbial growth yield and the free energy of aerobic and anaerobic (respiratory and/or fermentative) metabolism of glucose, ethanol, formate, acetate, lactate, propionate, butyrate, and H2. This relationship provides a means to estimate growth yields for modeling microbial redox metabolism in soil and sedimentary environments.

  13. GLUCOSE METABOLISM AND INSULIN SENSITIVITY WERE UNAFFECTED BY DIETARY FRUCTOSE INTAKE (AND GLYCEMIC INDEX) IN OBESE AND LEAN ADOLESCENTS

    There is growing concern that the increased consumption of fructose has detrimental effects on carbohydrate metabolism in adolescents. This study was designed to determine whether a high dietary fructose intake consumed over the short term adversely affects glucose metabolism, insulin secretion or ...

  14. OXIDATION OF GLUCOSE, GLUTAMATE, AND GLUTAMINE BY ISOLATED OVINE ENTEROCYTES IN VITRO IS DECREASED BY PRESENCE OF OTHER METABOLIC FUELS

    The objective of this study was to evaluate oxidative metabolism of glucose, glutamate, and glutamine by isolated ovine enterocytes in presence of other metabolic fuels in vitro. Mucosal enterocytes were isolated from crossbred wether sheep (n=6) fed a mixed forage-concentrate diet, and incubated f...

  15. Analysis of metabolism of 6FDG: a PET glucose transport tracer

    Introduction: We are developing 18F-labeled 6-fluoro-6-deoxy-D-glucose ([18F]6FDG) as a tracer of glucose transport. As part of this process it is important to characterize and quantify putative metabolites. In contrast to the ubiquitous positron emission tomography (PET) tracer 18F-labeled 2-fluoro-2-deoxy-D-glucose ([18F]2FDG) which is phosphorylated and trapped intracellularly, the substitution of fluorine for a hydroxyl group at carbon-6 in [18F]6FDG should prevent its phosphorylation. Consequently, [18F]6FDG has the potential to trace the transport step of glucose metabolism without the confounding effects of phosphorylation and subsequent steps of metabolism. Herein the focus is to determine whether, and the degree to which, [18F]6FDG remains unchanged following intravenous injection. Methods: Biodistribution studies were performed using 6FDG labeled with 18F or with the longer-lived radionuclides 3H and 14C. Tissues were harvested at 1, 6, and 24 h following intravenous administration and radioactivity was extracted from the tissues and analyzed using a combination of ion exchange columns, high-performance liquid chromatography, and chemical reactivity. Results: At the 1 h time-point, the vast majority of radioactivity in the liver, brain, heart, skeletal muscle, and blood was identified as 6FDG. At the 6-h and 24-h time points, there was evidence of a minor amount of radioactive material that appeared to be 6-fluoro-6-deoxy-D-sorbitol and possibly 6-fluoro-6-deoxy-D-gluconic acid. Conclusion: On the time scale typical of PET imaging studies radioactive metabolites of [18F]6FDG are negligible.

  16. Analysis of metabolism of 6FDG: a PET glucose transport tracer

    Muzic, Raymond F., E-mail: raymond.muzic@case.edu [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106 (United States); Chandramouli, Visvanathan [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Huang, Hsuan-Ming [Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106 (United States); Wu Chunying; Wang Yanming [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Ismail-Beigi, Faramarz [Department of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

    2011-07-15

    Introduction: We are developing {sup 18}F-labeled 6-fluoro-6-deoxy-D-glucose ([{sup 18}F]6FDG) as a tracer of glucose transport. As part of this process it is important to characterize and quantify putative metabolites. In contrast to the ubiquitous positron emission tomography (PET) tracer {sup 18}F-labeled 2-fluoro-2-deoxy-D-glucose ([{sup 18}F]2FDG) which is phosphorylated and trapped intracellularly, the substitution of fluorine for a hydroxyl group at carbon-6 in [{sup 18}F]6FDG should prevent its phosphorylation. Consequently, [{sup 18}F]6FDG has the potential to trace the transport step of glucose metabolism without the confounding effects of phosphorylation and subsequent steps of metabolism. Herein the focus is to determine whether, and the degree to which, [{sup 18}F]6FDG remains unchanged following intravenous injection. Methods: Biodistribution studies were performed using 6FDG labeled with {sup 18}F or with the longer-lived radionuclides {sup 3}H and {sup 14}C. Tissues were harvested at 1, 6, and 24 h following intravenous administration and radioactivity was extracted from the tissues and analyzed using a combination of ion exchange columns, high-performance liquid chromatography, and chemical reactivity. Results: At the 1 h time-point, the vast majority of radioactivity in the liver, brain, heart, skeletal muscle, and blood was identified as 6FDG. At the 6-h and 24-h time points, there was evidence of a minor amount of radioactive material that appeared to be 6-fluoro-6-deoxy-D-sorbitol and possibly 6-fluoro-6-deoxy-D-gluconic acid. Conclusion: On the time scale typical of PET imaging studies radioactive metabolites of [{sup 18}F]6FDG are negligible.

  17. Simultaneous measurement of blood flow and glucose metabolism by autoradiographic techniques

    A double tracer autoradiographic technique using 131I-iodo-antipyrine and 14C-deoxyglucose is presented for the simultaneous measurement of blood flow and cerebral glucose utilization in the same animal. 131I is a gamma emitting isotope with a half life of 8.06 days and can be detected with adequate resolution on standard autoradiographic films. Autoradiograms are made before and after decay of 131I; the time interval between the 2 exposures and the concentration of the 2 tracers is adjusted to avoid significant cross-contamination. In this way, 2 film exposures are obtained which can be processed quantitatively like single tracer autoradiograms. The validity of the method for the investigation of local coupling of flow and metabolism was tested under various physiological and pathophysiological conditions. Coupling was tight in barbiturate-anesthetized healthy animals, but not under halothane anesthesia where uncoupling occurred in various subcortical structures. Focal seizures induced by topical application of penicillin on the cortical surface led to a coupled increase of metabolism and flow in thalamic relay nuclei but not at the site of penicillin administration where increased glucose utilization was not accompanied by similar increase in blood flow. Both coupled and uncoupled increases in local glucose utilization were observed in spreading depression and in circumscribed areas of experimental brain tumors. The results obtained demonstrate that double tracer autoradiography allows allows the very precise local assessment of cerebral blood flow and glucose utilization, and, therefore, is particularly suited to the study of regional coupling processes under various experimental conditions

  18. D-(U-11C)glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects

    Gutniak, M.; Blomqvist, G.; Widen, L.; Stone-Elander, S.; Hamberger, B.; Grill, V. (Karolinska Hospital and Institute, Stockholm (Sweden))

    1990-05-01

    We used D-(U-11C)glucose to evaluate transport and metabolism of glucose in the brain in eight nondiabetic and six insulin-dependent diabetes mellitus (IDDM) subjects. IDDM subjects were treated by continuous subcutaneous insulin infusion. Blood glucose was regulated by a Biostator-controlled glucose infusion during a constant insulin infusion. D-(U-11C)-glucose was injected for positron emission tomography studies during normoglycemia as well as during moderate hypoglycemia (arterial plasma glucose 2.74 +/- 0.14 in nondiabetic and 2.80 +/- 0.26 mmol/l (means +/- SE) in IDDM subjects). Levels of free insulin were constant and similar in both groups. The tracer data were analyzed using a three-compartment model with a fixed correction for 11CO2 egression. During normoglycemia the influx rate constant (k1) and blood-brain glucose flux did not differ between the two groups. During hypoglycemia k1 increased significantly and similarly in both groups (from 0.061 +/- 0.007 to 0.090 +/- 0.006 in nondiabetic and from 0.061 +/- 0.006 to 0.093 +/- 0.013 ml.g-1.min-1 in IDDM subjects). During normoglycemia the tracer-calculated metabolism of glucose was higher in the whole brain in the nondiabetic than in the diabetic subjects (22.0 +/- 1.9 vs. 15.6 +/- 1.1 mumol.100 g-1.min-1, P less than 0.01). During hypoglycemia tracer-calculated metabolism was decreased by 40% in nondiabetic subjects and by 28% in diabetic subjects. The results indicate that uptake of glucose is normal, but some aspect of glucose metabolism is abnormal in a group of well-controlled IDDM subjects.

  19. Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals.

    Kumar Jha, Pawan; Challet, Etienne; Kalsbeek, Andries

    2015-12-15

    Most aspects of energy metabolism display clear variations during day and night. This daily rhythmicity of metabolic functions, including hormone release, is governed by a circadian system that consists of the master clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and many secondary clocks in the brain and peripheral organs. The SCN control peripheral timing via the autonomic and neuroendocrine system, as well as via behavioral outputs. The sleep-wake cycle, the feeding/fasting rhythm and most hormonal rhythms, including that of leptin, ghrelin and glucocorticoids, usually show an opposite phase (relative to the light-dark cycle) in diurnal and nocturnal species. By contrast, the SCN clock is most active at the same astronomical times in these two categories of mammals. Moreover, in both species, pineal melatonin is secreted only at night. In this review we describe the current knowledge on the regulation of glucose and lipid metabolism by central and peripheral clock mechanisms. Most experimental knowledge comes from studies in nocturnal laboratory rodents. Nevertheless, we will also mention some relevant findings in diurnal mammals, including humans. It will become clear that as a consequence of the tight connections between the circadian clock system and energy metabolism, circadian clock impairments (e.g., mutations or knock-out of clock genes) and circadian clock misalignments (such as during shift work and chronic jet-lag) have an adverse effect on energy metabolism, that may trigger or enhancing obese and diabetic symptoms. PMID:25662277

  20. Glucose Metabolism in the Insula and Cingulate is affected by Systemic Inflammation in Humans

    Hannestad, Jonas; Subramanyam, Kalyani; DellaGioia, Nicole; Planeta-Wilson, Beata; Weinzimmer, David; Pittman, Brian; Carson, Richard E.

    2013-01-01

    Depression is associated with systemic inflammation, and endotoxin administration, which causes systemic inflammation, elicits mild depressive symptoms, such as fatigue and reduced interest. The neural correlates of depressive symptoms that result from systemic inflammation are poorly defined. The aim of this study was to use FDG-PET to identify brain regions involved in the response to endotoxin administration in humans. Methods Nine healthy subjects received double-blind endotoxin (0.8 ng/kg) and placebo on different days. FDG-PET was used to measure differences in the cerebral metabolic rate of glucose in regions of interest: insula, cingulate, and amygdala. Serum levels of tumor necrosis factor-alpha and interleukin-6 were used to gauge the systemic inflammatory response, and depressive symptoms were measured with the Montgomery-sberg Depression Rating Scale (MADRS) and other scales. Results Endotoxin administration was associated with an increase in MADRS score, increased fatigue, reduced social interest, increased levels of inflammatory cytokines, higher normalized glucose metabolism (NGM) in the insula and, at a trend level, lower NGM in the cingulate. Secondary analyses of insula and cingulate subregions indicated that these changes were driven by the right anterior insula and the right anterior cingulate. There was a negative correlation between peak cytokine levels and change in social interest, and between peak cytokine levels and change in insula NGM. There was a positive correlation between the change in NGM in the insula and change in social interest. Conclusion Systemic inflammation in humans causes an increase in depressive symptoms and concurrent changes in glucose metabolism in the insula and cingulate, brain regions that are involved in interoception, positive emotionality, and motivation. PMID:22414635

  1. Glucose and Glycogen Metabolism in Brugia malayi Is Associated with Wolbachia Symbiont Fitness.

    Voronin, Denis; Bachu, Saheed; Shlossman, Michael; Unnasch, Thomas R; Ghedin, Elodie; Lustigman, Sara

    2016-01-01

    Wolbachia are endosymbiotic bacteria found in the majority of arthropods and filarial nematodes of medical and veterinary importance. They have evolved a wide range of symbiotic associations. In filarial nematodes that cause human lymphatic filariasis (Wuchereria bancrofti, Brugia malayi) or onchocerciasis (Onchocerca volvulus), Wolbachia are important for parasite development, reproduction and survival. The symbiotic bacteria rely in part on nutrients and energy sources provided by the host. Genomic analyses suggest that the strain of Wolbachia found in B. malayi (wBm) lacks the genes for two glycolytic enzymes-6-phosphofructokinase and pyruvate kinase-and is thus potentially unable to convert glucose into pyruvate, an important substrate for energy generation. The Wolbachia surface protein, wBm00432, is complexed to six B. malayi glycolytic enzymes, including aldolase. In this study we characterized two B. malayi aldolase isozymes and found that their expression is dependent on Wolbachia fitness and number. We confirmed by immuno-transmission electron microscopy that aldolase is associated with the Wolbachia surface. RNAi experiments suggested that aldolase-2 plays a significant role in both Wolbachia survival and embryogenesis in B. malayi. Treatment with doxycycline reduced Wolbachia fitness and increased the amount of both glucose and glycogen detected in the filarial parasite, indicating that glucose metabolism and glycogen storage in B. malayi are associated with Wolbachia fitness. This metabolic co-dependency between Wolbachia and its filarial nematode indicates that glycolysis could be a shared metabolic pathway between the bacteria and B. malayi, and thus a potential new target for anti-filarial therapy. PMID:27078260

  2. Comparison of Cerebral Glucose Metabolism between Possible and Probable Multiple System Atrophy

    Kyum-Yil Kwon

    2009-05-01

    Full Text Available Background: To investigate the relationship between presenting clinical manifestations and imaging features of multisystem neuronal dysfunction in MSA patients, using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET. Methods: We studied 50 consecutive MSA patients with characteristic brain MRI findings of MSA, including 34 patients with early MSA-parkinsonian (MSA-P and 16 with early MSA-cerebellar (MSA-C. The cerebral glucose metabolism of all MSA patients was evaluated in comparison with 25 age-matched controls. 18F-FDG PET results were assessed by the Statistic Parametric Mapping (SPM analysis and the regions of interest (ROI method. Results: The mean time from disease onset to 18F-FDG PET was 25.9±13.0 months in 34 MSA-P patients and 20.1±11.1 months in 16 MSA-C patients. Glucose metabolism of the putamen showed a greater decrease in possible MSA-P than in probable MSA-P (p=0.031. Although the Unified Multiple System Atrophy Rating Scale (UMSARS score did not differ between possible MSA-P and probable MSA-P, the subscores of rigidity (p=0.04 and bradykinesia (p= 0.008 were significantly higher in possible MSA-P than in probable MSA-P. Possible MSA-C showed a greater decrease in glucose metabolism of the cerebellum than probable MSA-C (p=0.016. Conclusions: Our results may suggest that the early neuropathological pattern of possible MSA with a predilection for the striatonigral or olivopontocerebellar system differs from that of probable MSA, which has prominent involvement of the autonomic nervous system in addition to the striatonigral or olivopontocerebellar system.

  3. Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy. Assessment by F-18-FDG PET study

    In an investigation of myocardial metabolic abnormalities in hypertrophic myocardium, the myocardial glucose metabolism was evaluated with F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in 32 patients with hypertrophic cardiomyopathy, and the results were compared with those in 9 patients with hypertensive heart disease. F-18-FDG PET study was performed in the fasting and glucose-loading states. The myocardial regional %dose uptake was calculated quantitatively. The average regional %dose uptake in the fasting state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was significantly higher than that in the patients with hypertensive heart disease (0.75±0.34%, 0.65±0.25%, and 0.43±0.22%/100 g myocardium, respectively). In contrast, the average %dose uptake in the glucose-loading state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was not significantly different from that in patients with hypertensive heart disease (1.17±0.49%, 0.80±0.44% and 0.99±0.45%, respectively). The patients with apical hypertrophy had also low %dose uptake in the fasting state (0.38±0.21%) as in the hypertensive heart disease patients, so that the characteristics of asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy are considered to be high FDG uptake throughout the myocardium in the fasting state. Patients with apical hypertrophy are considered to belong to other disease categories metabolically. F-18-FDG PET study is useful in the evaluation of the pathophysiologic diagnosis of patients with hypertrophic cardiomyopathy. (author)

  4. Effect of x irradiation on the biochemical maturation of rat cerebellum: Metabolism of [14C]glucose and [14C]acetate

    The effect was studied of selective x-irradiation of the cerebellum (100 R daily in the first 10 days after birth) on the maturation of glucose metabolism and the development of metabolic compartmentation, in 10-, 16-, and 23-day-old rats by using, respectively, [2-14C]glucose and [1-14C] acetate (40 ? Ci/100 g body weight each) as precursors. At day 10 significant changes, in comparison with the unirradiated controls, were observed: aspartate and ?-aminobutyrate, respectively, contained 36 percent and 64 percent more and glutamine 42 percent less glucose-carbon combined in amino acids; the glutamine/glutamate specific radioactivity ratio (RSA) was 25 percent less, and the conversion of both glucose and acetate carbons into acid-insoluble constituents was markedly reduced. However, in the postirradiation period both the conversion of glucose carbon into amino acids, and the RSA of glutamine after the administration of [14C]acetate increased in a more or less normal fashion, although certain quantitative differences were noted. It seems, therefore, that the normal progress of biochemical differentiation was only affected to a small degree by the irradiation of the cerebellum, although the treatment interfered severely with cell proliferation. (U.S.)

  5. GLUCOSE METABOLITE PATTERNS AS MARKERS OF FUNCTIONAL DIFFERENTIATION IN FRESHLY ISOLATED AND CULTURED MOUSE MAMMARY EPITHELIAL CELLS

    Emerman, J.T.; Bartley, J.C.; Bissell, M.J.

    1980-06-01

    In the mammary gland of nonruminant animals, glucose is utilized in a characteristic and unique way during lactation. We have measured the incorporation of glucose carbon from [U-{sup 14}C] glucose into intermediary metabolites and metabolic products in mammary epithelial cells from virgin, pregnant, and lactating mice and demonstrate that glucose metabolite patterns can be used to recognize stages of differentiated function. For these cells, the rates of synthesis of glycogen and lactose, the ratio of lactate to alanine, and the ratio of citrate to malate were important parameters in identifying the degree of expression of differentiation. We further show that these patterns can be used as markers to determine the differentiated state of cultured mammary epithelial cells. Cells maintained on plastic substrates lose their distinctive glucose metabolite patterns while those on floating collagen gels do not. Cells from pregnant mice have a pattern similar to freshly isolated cells from pregnant mice. The pattern of cells from lactating mice is different from that of the cells of origin, and resembles that of the cells from pregnant mice. Our findings suggest that the floating collagen gels under the culture conditions used in these experiments provide an environment for the functional expression of the pregnant state, while additional factors are needed for the expression of the lactating state.

  6. Interactions of glucagon and free fatty acids with insulin in control of glucose metabolism

    To study the interactions of physiological glucagon and free fatty acids (FFA) concentrations with insulin in the control of glucose metabolism, we determined in normal subjects the response of endogenous glucose production (EGP) and glucose utilization (Rd) to a progressive and moderate increase of insulinemia in the presence of glucagon and FFA levels either decreased (somatostatin [SRIF] and insulin infusion, C test) or maintained to normal postabsorptive values isolated (SRIF + insulin + glucagon infusion, G test; SRIF + insulin + Intralipid infusion, IL test) or in association (SRIF + insulin + glucagon + Intralipid infusion, IL + G test). Compared with the C test, maintenance of glucagon level had only small and inconsistent effects on glucose Rd, but induced a shift to the right of the dose-response curve to insulin of EGP (apparent ED50: C test, 10.9 mU.L-1; G test, 15.2 mU.L-1). Intralipid infusion resulted, whether glucagon was substituted or not, in a near total suppression of the insulin-induced increase of glucose Rd (Rd at the end of the tests: C test, 6.13 +/- 0.85 mg.kg-1.min-1; G test, 7.29 +/- 0.87 mg.kg-1.min-1; IL test, 3.30 +/- 0.65 mg.kg-1.min-1; IL + G test, 3.57 +/- 0.42 mg.kg-1.min-1). In the absence of glucagon, substitution Intralipid infusion also antagonized the action of insulin on EGP. However, this effect was no longer apparent when glucagon was replaced (dose-response curve to insulin of EGP during the G and the IL + G test were comparable)

  7. Area-Level Socioeconomic Status and Incidence of Abnormal Glucose Metabolism

    Williams, Emily D; Magliano, Dianna J.; Zimmet, Paul Z; Kavanagh, Anne M.; Stevenson, Christopher E; Oldenburg, Brian F.; Shaw, Jonathan E.

    2012-01-01

    OBJECTIVE To examine the role of area-level socioeconomic status (SES) on the development of abnormal glucose metabolism (AGM) using national, population-based data. RESEARCH DESIGN AND METHODS The Australian Diabetes, Obesity and Lifestyle (AusDiab) study is a national, population-based, longitudinal study of adults aged ≥25 years. A sample of 4,572 people provided complete baseline (1999 to 2000) and 5-year follow-up (2004 to 2005) data relevant for these analyses. Incident AGM was assessed...

  8. Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

    Jocken, Johan W. E.; Goossens, Gijs H.; Blaak, Ellen E

    2014-01-01

    With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocy...

  9. Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

    Johan W.E. Jocken

    2014-10-01

    Full Text Available With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocytes. Recent evidence suggests involvement of several hormones, membrane receptors, and intracellular signalling cascades, which has added complexity to the regulation of cytosolic lipolysis. Interestingly, a specific form of autophagy, called lipophagy, has been implicated as alternative lipolytic pathway. Defective regulation of cytosolic lipolysis and lipophagy might have substantial effects on lipid metabolism, thereby contributing to adipose tissue dysfunction, insulin resistance, and related cardiometabolic (cMet diseases. This review will discuss recent advances in our understanding of classical lipolysis and lipophagy in adipocyte lipid metabolism under normal and pathological conditions. Furthermore, the question of whether modulation of adipocyte lipolysis and lipophagy might be a potential therapeutic target to combat cMet disorders will be addressed.

  10. Regulation of intracellular calcium is closely linked to glucose metabolism in J774 macrophages.

    Darbha, S; Marchase, R B

    1996-10-01

    The effects of 2-deoxy-D-glucose (2dGlc) and glucose deprivation were investigated in the J774 murine macrophage-like cell line. 2dGlc addition or glucose deprivation for 4 min led to an inhibition in the transient increase in cytoplasmic free Ca2+ ([Ca2+]i) that otherwise occurs in response to three different agonists: IgG, ATP and platelet activating factor. This inhibition was preceded by a partial release of Ca2+ from intracellular, thapsigargin-sensitive stores. In contrast, the transition from 5 to 30 mM glucose caused a decrease in [Ca2+]i and a corresponding increase in thapsigargin-sensitive sequestered Ca2+. The effects of an alternate glycolytic inhibitor, NaF, and a mitochondrial inhibitor, rotenone, were also tested. These inhibitors caused neither a release of Ca2+ from intracellular stores nor an inhibition in any of the agonist responses. The capacitative influx of extracellular Ca2+ following depletion of intracellular stores was also found to be selectively inhibited by the prior addition of 2dGlc or with glucose deprivation. In addition, when an elevated plateau of [Ca2+]i was established by the irreversible depletion of intracellular Ca2+ stores, the addition of 2dGlc caused a decrease in the on-going capacitative entry of Ca2+. PMID:8939356

  11. A radical explanation for glucose-induced ? cell dysfunction

    Brownlee, Michael

    2003-01-01

    The development of type 2 diabetes requires impaired ? cell function. Hyperglycemia itself causes further decreases in glucose-stimulated insulin secretion. A new study demonstrates that hyperglycemia-induced mitochondrial superoxide production activates uncoupling protein 2, which decreases the ATP/ADP ratio and thus reduces the insulin-secretory response. These data suggest that pharmacologic inhibition of mitochondrial superoxide overproduction in ? cells exposed to hyperglycemia could pre...

  12. Real-time monitoring of lactate extrusion and glucose consumption of cultured cells using a lab-on-valve system.

    Schulz, Craig M; Scampavia, Louis; Ruzicka, Jaromir

    2002-12-01

    Microsequential injection (microST) provides microfluidic operations that are ideally suited for cellular function studies and as a means of validating targets for drug discovery. MicroSI carried out within the lab-on-valve (LOV) manifold, is an ideal platform for spectroscopic studies on living cells that are grown on microcarrier beads and kept thermostated while their metabolism is probed in real-time. In this paper a microbioreactor is integrated into the LOV manifold allowing measurement of cellular lactate extrusion and glucose consumption rates of a cell culture that is automatically renewed prior to each measurement. Glucose consumption and lactate extrusion are monitored using NAD-linked enzymatic assays. The microSI-LOV setup has demonstrated a linear analysis range of 0.05-1.00 mM for lactate and 0.1-5.6 mM for glucose. These assays were conducted in a serial fashion requiring 3 microL of cellular perfusate and 10 s for glucose determination and 30 s for the lactate assay. Overall waste generated per lactate/glucose assay is < 200 microL. This work was performed using two different transfected hepatocyte cell lines, which adhere to Cytopore microcarrier beads. This novel approach to metabolic screening allows for the rapid evaluation of the effects of dosing cells with chemical agents. PMID:12537364

  13. Glucose sensing in the pancreatic beta cell: a computational systems analysis

    Philipson Louis H

    2010-05-01

    Full Text Available Abstract Background Pancreatic beta-cells respond to rising blood glucose by increasing oxidative metabolism, leading to an increased ATP/ADP ratio in the cytoplasm. This leads to a closure of KATP channels, depolarization of the plasma membrane, influx of calcium and the eventual secretion of insulin. Such mechanism suggests that beta-cell metabolism should have a functional regulation specific to secretion, as opposed to coupling to contraction. The goal of this work is to uncover contributions of the cytoplasmic and mitochondrial processes in this secretory coupling mechanism using mathematical modeling in a systems biology approach. Methods We describe a mathematical model of beta-cell sensitivity to glucose. The cytoplasmic part of the model includes equations describing glucokinase, glycolysis, pyruvate reduction, NADH and ATP production and consumption. The mitochondrial part begins with production of NADH, which is regulated by pyruvate dehydrogenase. NADH is used in the electron transport chain to establish a proton motive force, driving the F1F0 ATPase. Redox shuttles and mitochondrial Ca2+ handling were also modeled. Results The model correctly predicts changes in the ATP/ADP ratio, Ca2+ and other metabolic parameters in response to changes in substrate delivery at steady-state and during cytoplasmic Ca2+ oscillations. Our analysis of the model simulations suggests that the mitochondrial membrane potential should be relatively lower in beta cells compared with other cell types to permit precise mitochondrial regulation of the cytoplasmic ATP/ADP ratio. This key difference may follow from a relative reduction in respiratory activity. The model demonstrates how activity of lactate dehydrogenase, uncoupling proteins and the redox shuttles can regulate beta-cell function in concert; that independent oscillations of cytoplasmic Ca2+ can lead to slow coupled metabolic oscillations; and that the relatively low production rate of reactive oxygen species in beta-cells under physiological conditions is a consequence of the relatively decreased mitochondrial membrane potential. Conclusion This comprehensive model predicts a special role for mitochondrial control mechanisms in insulin secretion and ROS generation in the beta cell. The model can be used for testing and generating control hypotheses and will help to provide a more complete understanding of beta-cell glucose-sensing central to the physiology and pathology of pancreatic ?-cells.

  14. Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles.

    Hu, Chenxia; Niestroj, Martin; Yuan, Daniel; Chang, Steven; Chen, Jie

    2015-01-01

    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 over normal cells, different starvation periods were screened in order to achieve optimal treatment effects. Cancer cells were then fed using Glu-GNPs followed by X-ray irradiation treatment. For comparison, solid tumor MCF-7 cells (breast cancer cell line) were studied as well. Our irradiation experimental results show that Glu-GNPs are better irradiation sensitizers to treat THP-1 cells than MCF-7 cells, or Glu-GNPs enhance the cancer killing of THP-1 cells 20% more than X-ray irradiation alone and GNP treatment alone. This finding can help oncologists to design therapeutic strategies to target cancer stem cells and cancer metastasis. PMID:25844037

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

    Dyar, Kenneth A.; 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; Rizzuto, Rosario; Bicciato, Silvio; Pilegaard, Henriette; Blaauw, Bert; Schiaffino, Stefano

    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-s...... is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle. © 2013 The Authors.......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...

  16. Glucose metabolism of fetal rat brain in utero, measured with labeled deoxyglucose

    Mammals have low cerebral metabolic rates immediately after birth and, by inference, also before birth. In this study, we extended the deoxyglucose method to the fetal rat brain in utero. Rate constants for deoxyglucose transfer across the maternal placental and fetal blood-brain barriers, and lumped constant, have not been reported. Therefore, we applied a new method of determining the lumped constant regionally to the fetal rat brain in utero. The lumped constant averaged 0.55 0.15 relative to the maternal circulation. On this basis, we determined the glucose metabolic rate of the fetal rat brain to be one third of the corresponding maternal value, or 19 2 ?mol hg-1 min-1. (author)

  17. Study of cerebral metabolism of glucose in normal human brain correlated with age

    Full text: The objective was to determine whether cerebral metabolism in various regions of the brain differs with advancing age by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They (with the age ranging from 21 to 88; mean age+/-SD: 49.77+/-13.51) were selected with: (i)absence of clear focal brain lesions (epilepsy.cerebrovascular diseases etc);(ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes;(iii) absence of psychiatric disorders and abuse of drugs and alcohol. They were sub grouped into six groups with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose were matched. All subgroups were compared to the control group of 31-40 years old (84 samples; mean age+/-SD: 37.15+/-2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later, their brains were scanned for 10min. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2) .The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three-dimensional localized by MNI Space utility (MSU) software. Results:Relative hypometabolic brain areas detected are mainly in the cortical structures such as bilateral prefrontal cortex, superior temporal gyrus(BA22), parietal cortex (inferior parietal lobule and precuneus(BA40, insula(BA13)), parahippocampal gyrus and amygdala (p<0.01).It is especially apparent in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7) (p<0.001), while basal ganglia and cerebellum remained metabolically unchanged with advancing age. Conclusions Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7).In spite of the cerebral atrophy of aging, these relative hypometabolic brain areas are considered to be correlated with structural and functional cerebral changes and cognitive dysfunction such as verbal and spatial working memory deficit in the process of normal brain aging. The study of cerebral metabolism of glucose in normal human brains can be used for reference and instruction in future clinical studies and in normal brain aging. (author)

  18. Uptake and metabolism of sugars by suspension-cultured catharanthus roseus cells

    The Uptake and metabolism of sugars by suspension-cultured Catharanthus roseus cells were investigated. Substantially all the sucrose in the culture medium was hydrolyzed to glucose and fructose before being taken up by the cells. The activity of invertase bound to cell walls, determined in situ, was high at the early stage of culture. Glucose was more easily taken up by the cells than was fructose. Tracer experiments using [U-14C]glucose and [U-14C]fructose indicated that glucose is a better precursor for respiration than fructose, while fructose is preferentially utilized for the synthesis of sucrose, especially in the early phase of cell growth. These results suggest that fructose is utilized for the synthesis of sucrose via the reaction catalyzed by sucrose synthase, prior to the phosphorylation by hexokinase or fructokinase

  19. Uptake and metabolism of sugars by suspension-cultured catharanthus roseus cells

    Ashihara, Hiroshi; Sagishima, Kyoko; Kubota, Kaoru (Ochanomizu Univ., Tokyo (Japan))

    1989-04-01

    The Uptake and metabolism of sugars by suspension-cultured Catharanthus roseus cells were investigated. Substantially all the sucrose in the culture medium was hydrolyzed to glucose and fructose before being taken up by the cells. The activity of invertase bound to cell walls, determined in situ, was high at the early stage of culture. Glucose was more easily taken up by the cells than was fructose. Tracer experiments using (U-{sup 14}C)glucose and (U-{sup 14}C)fructose indicated that glucose is a better precursor for respiration than fructose, while fructose is preferentially utilized for the synthesis of sucrose, especially in the early phase of cell growth. These results suggest that fructose is utilized for the synthesis of sucrose via the reaction catalyzed by sucrose synthase, prior to the phosphorylation by hexokinase or fructokinase.

  20. Relationship between salivary cortisol levels and regional cerebral glucose metabolism in nondemented elderly subjects

    Cortisol is a primary stress hormone for flight-or-fight response in human. Increased levels of cortisol have been associated with memory and learning impairments. However, little is known about the role of cortisol on brain/cognitive functions in older adults. We compared regional cerebral glucose metabolism between elderly subjects with high and low cortisol levels using FDG PET. Salivary cortisol levels were measured four times during a day, and an average of the four measurements was used as the standard cortisol level for the analyses. From a population of 120 nondemented elderly subjects, 19 (mean age, 70.14.9 y: 2 males and 17 females) were identified as the high (> mean + 1 SD of the total population) cortisol subjects (mean cortisol, 0.690.09 ? g/dL), while 14 (mean age, 67.24.5 y: all females) as the low (< mean 1 SD) cortisol (mean cortisol, 0.270.03 ? g/dL). A voxel-wise comparison of FDG PET images from the high and low cortisol subjects was performed using SPM99. When compared with the low cortisol group, the high cortisol group had significant hypometabolism in the right middle temporal gyrus, left precuneus, right parahippocampal gyrus, right inferior temporal and superior temporal gyri (P < 0.01 uncorrected, k = 100). There was no significant increase of glucose metabolism in the high cortisol group compared with the low cortisol group (P < 0.01 uncorrected, k = 100). The high cortisol elderly subjects had hypometabolism in the parahippocampal and temporal gyri and precuneus, regions involved in memory and other cognitive functions. This may represent the preclinical metabolic correlates of forthcoming cognitive dysfunction associated with stress in the elderly. Longitudinal studies of brain metabolism and cognitive function are warranted

  1. Role of the fission yeast cell integrity MAPK pathway in response to glucose limitation

    Madrid Marisa

    2013-02-01

    Full Text Available Abstract Background Glucose is a signaling molecule which regulates multiple events in eukaryotic organisms and the most preferred carbon source in the fission yeast Schizosaccharomyces pombe. The ability of this yeast to grow in the absence of glucose becomes strongly limited due to lack of enzymes of the glyoxylate cycle that support diauxic growth. The stress-activated protein kinase (SAPK pathway and its effectors, Sty1 MAPK and transcription factor Atf1, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bisphosphatase. The cell integrity Pmk1 pathway is another MAPK cascade that regulates various processes in fission yeast, including cell wall construction, cytokinesis, and ionic homeostasis. Pmk1 pathway also becomes strongly activated in response to glucose deprivation but its role during glucose exhaustion and ensuing adaptation to respiratory metabolism is currently unknown. Results We found that Pmk1 activation in the absence of glucose takes place only after complete depletion of this carbon source and that such activation is not related to an endogenous oxidative stress. Notably, Pmk1 MAPK activation relies on de novo protein synthesis, is independent on known upstream activators of the pathway like Rho2 GTPase, and involves PKC ortholog Pck2. Also, the Glucose/cAMP pathway is required operative for full activation of the Pmk1 signaling cascade. Mutants lacking Pmk1 displayed a partial growth defect in respiratory media which was not observed in the presence of glucose. This phenotype was accompanied by a decreased and delayed expression of transcription factor Atf1 and target genes fbp1+ and pyp2+. Intriguingly, the kinetics of Sty1 activation in Pmk1-less cells was clearly altered during growth adaptation to non-fermentable carbon sources. Conclusions Unknown upstream elements mediate Pck2-dependent signal transduction of glucose withdrawal to the cell integrity MAPK pathway. This signaling cascade reinforces the adaptive response of fission yeast to such nutritional stress by enhancing the activity of the SAPK pathway.

  2. Adenylosuccinate Is an Insulin Secretagogue Derived from Glucose-Induced Purine Metabolism

    Jessica R. Gooding

    2015-10-01

    Full Text Available Pancreatic islet failure, involving loss of glucose-stimulated insulin secretion (GSIS from islet β cells, heralds the onset of type 2 diabetes (T2D. To search for mediators of GSIS, we performed metabolomics profiling of the insulinoma cell line 832/13 and uncovered significant glucose-induced changes in purine pathway intermediates, including a decrease in inosine monophosphate (IMP and an increase in adenylosuccinate (S-AMP, suggesting a regulatory role for the enzyme that links the two metabolites, adenylosuccinate synthase (ADSS. Inhibition of ADSS or a more proximal enzyme in the S-AMP biosynthesis pathway, adenylosuccinate lyase, lowers S-AMP levels and impairs GSIS. Addition of S-AMP to the interior of patch-clamped human β cells amplifies exocytosis, an effect dependent upon expression of sentrin/SUMO-specific protease 1 (SENP1. S-AMP also overcomes the defect in glucose-induced exocytosis in β cells from a human donor with T2D. S-AMP is, thus, an insulin secretagogue capable of reversing β cell dysfunction in T2D.

  3. Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

    Zhai Hua-Ling

    2012-01-01

    Full Text Available Abstract Background There is a high prevalence of diabetes mellitus (DM and dyslipidemia in women with polycystic ovary syndrome (PCOS. The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet. Methods Female Sprague-Dawley rats were divided into 3 groups: the control group(C, n = 10; the andronate-treated group (Andronate, n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks; and the andronate-treated and high-fat diet group (Andronate+HFD, n = 10. The rate of glucose appearance (Ra of glucose, gluconeogenesis (GNG, and the rate of glycerol appearance (Ra of glycerol were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured. Results Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P P Conclusions Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS.

  4. Effect of aspirin and prostaglandins on the carbohydrate metabolism in albino rats.: glucose oxidation through different pathways and glycolytic enzymes

    The effect of chronic and acute doses of aspirin and prostaglandins F2? and E2 individually on the oxidation of glucose through Embden Meyerhof-TCA cycle and pentose phosphate pathways and some key glycolytic enzymes of liver were studied in male albino rats. Studies were extended to find the combined effect of PGF2? and E2 with an acute dose of aspirin. There was increased utilisation of both 1-14C glucose and 6-14C glucose on aspirin treatment. However, the metabolism through the EM-TCA pathway was more pronounced as shown by a reduced ratio of 14CO2 from 1-14C and 6-14C glucose. Two hepatic key glycolytic enzymes viz. hexokinase and pyruvate kinase were increased due to aspirin treatment. Withdrawal of aspirin corrected the above impaired carbohydrate metabolism in liver. Prostaglandin F2? also caused a reduction in the utilisation of 1-14C glucose, while PGE2 recorded an increase in the utilisation of both 1-14C and 6-14C glucose when compared to controls, indicating that different members of prostaglandins could affect metabolisms and differently. Administration of the PGs and aspirin together showed an increase in the utilisation of 6-14C glucose. (auth.)

  5. Quantitative autoradiography of 14C-D-glucose metabolism of normal and traumatized rat brain using micro-absorption photometry

    It could be shown using 14C-glucose as energy-providing substrate for brain tissue metabolism that for bolus type application a retarded and even channelling of the substrate into the metabolic process takes place. The presence of tracer in the tissue was established using autoradiography. A linear correlation between the amount of tissue-incorporated 14C section thickness and exposure time could be established by means of densitometric measurement of brain sections of various thicknesses, by applying various 14C-activities and by different exposure times. From these correlations direct conclusions may be made regarding the specific activity of the tissue provided that exposure time and section thickness of the sample are known. Comparative studies between cortex and narrow and between traumatized and non-traumatized brain tissue show that the rate of metabolism in brain cortex is markedly higher than in the marrow and that 14C-incorporation is higher in traumatized tissue than in non-traumatized tissue. Whilst the difference in rate of metabolism between brain cortex and marrow can be clearly related to the differing cell count/unit surface area for cortex and marrow, the different energy conversion rates for functionally damaged and normal brain tissue is a specific characteristic of injury. Apart from the fact that an increased 14C-deposition is in no way indicative of an increased metabolic activity, the possibility of quantifying 14C-tissue content provides a basis for estimating therapeutic effects e.g. in the treatment of trauma-caused brain edema. (orig.)

  6. Loss of function of PTEN alters the relationship between glucose concentration and cell proliferation, increases glycolysis, and sensitizes cells to 2-deoxyglucose.

    Blouin, Marie-Jos; Zhao, Yunhua; Zakikhani, Mahvash; Algire, Carolyn; Piura, Esther; Pollak, Michael

    2010-03-28

    PTEN loss of function enhances proliferation, but effects on cellular energy metabolism are less well characterized. We used an inducible PTEN expression vector in a PTEN-null glioma cell line to examine this issue. While proliferation of PTEN-positive cells was insensitive to increases in glucose concentration beyond 2.5mM, PTEN-null cells significantly increased proliferation with increasing glucose concentration across the normal physiologic range to approximately 10mM, coinciding with a shift to glycolysis and "glucose addiction". This demonstrates that the impact of loss of function of PTEN is modified by glucose concentration, and may be relevant to epidemiologic results linking hyperglycemia to cancer risk and cancer mortality. PMID:19744772

  7. Laccase/AuAg Hybrid Glucose Microfludic Fuel Cell

    López-González, B.; Cuevas-Muñiz, F. M.; Guerra-Balcázar, M.; Déctor, A.; Arjona, N.; Ledesma-García, J.; Arriaga, L. G.

    2013-12-01

    In this work a hybrid microfluidic fuel cell was fabricated and evaluated with a AuAg/C bimetallic material for the anode and an enzymatic cathode. The cathodic catalyst was prepared adsorbing laccase and ABTS on Vulcan carbon (Lac-ABTS/C). This material was characterized by FTIR-ATR, the results shows the presence of absorption bands corresponding to the amide bounds. The electrochemical evaluation for the materials consisted in cyclic voltammetry (CV). The glucose electrooxidation reaction in AuAg/C occurs around - 0.3 V vs. NHE. Both electrocatalytic materials were placed in a microfluidic fuel cell. The fuel cell was fed with PBS pH 5 oxygen saturated solution in the cathodic compartment and 5 mM glucose + 0.3 M KOH in the anodic side. Several polarization curves were performed and the maximum power density obtained was 0.3 mWcm-2 .

  8. Laccase/AuAg Hybrid Glucose Microfludic Fuel Cell

    In this work a hybrid microfluidic fuel cell was fabricated and evaluated with a AuAg/C bimetallic material for the anode and an enzymatic cathode. The cathodic catalyst was prepared adsorbing laccase and ABTS on Vulcan carbon (Lac-ABTS/C). This material was characterized by FTIR-ATR, the results shows the presence of absorption bands corresponding to the amide bounds. The electrochemical evaluation for the materials consisted in cyclic voltammetry (CV). The glucose electrooxidation reaction in AuAg/C occurs around − 0.3 V vs. NHE. Both electrocatalytic materials were placed in a microfluidic fuel cell. The fuel cell was fed with PBS pH 5 oxygen saturated solution in the cathodic compartment and 5 mM glucose + 0.3 M KOH in the anodic side. Several polarization curves were performed and the maximum power density obtained was 0.3 mWcm−2

  9. Advances in the Relationship Between Tumor Cell Metabolism and Tumor Metastasis

    Yalong ZHANG

    2014-11-01

    Full Text Available Intracellular nutrients and the rate of energy flowing in tumor cells are often higher than that in normal cells due to the prolonged stress of tumor-specific microenvironment. In this context, the metabolism of tumor cells provides the fuel of bio-synthesis and energy required for tumor metastasis. Consistent with this, the abnormal metabolism such as extremely active glucose metabolism and excessive accumulating of fatty acid is also discovered in metastatic tumors. Previous Studies have confirmed that the regulation of tumor metabolism can affect the tumor metastasis, and some of these have been successfully applied in clinical effective, positive way. Thus, targeting metabolism of tumor cells might be an effectively positive way to prevent the metastasis of tumor. So, our review is focused on the research development of the relationship between tumor metabolism and metastasis as well as the underlying mechanism.

  10. [Advances in the relationship between tumor cell metabolism and tumor metastasis].

    Zhang, Yalong; Fang, Nianzhen; You, Jiacong; Zhou, Qinghua

    2014-11-01

    Intracellular nutrients and the rate of energy flowing in tumor cells are often higher than that in normal cells due to the prolonged stress of tumor-specific microenvironment. In this context, the metabolism of tumor cells provides the fuel of bio-synthesis and energy required for tumor metastasis. Consistent with this, the abnormal metabolism such as extremely active glucose metabolism and excessive accumulating of fatty acid is also discovered in metastatic tumors. Previous Studies have confirmed that the regulation of tumor metabolism can affect the tumor metastasis, and some of these have been successfully applied in clinical effective, positive way. Thus, targeting metabolism of tumor cells might be an effectively positive way to prevent the metastasis of tumor. So, our review is focused on the research development of the relationship between tumor metabolism and metastasis as well as the underlying mechanism. PMID:25404272

  11. Comparison of different methods for attenuation correction in brain PET: Influence on the calculation of the metabolic glucose rate

    Aim: There are several approaches for correcting the effects of photon scatter or absorption by body tissues on positron emission tomography (PET). We examined the influence of cold, hot and segmented transmission as well as of a mathematical procedure on attenuation correction using regional cerebral glucose metabolism (rMRGlu). Methods: 6 patients with different cerebral diseases were examined under resting conditions using an ECAT Exact 922/47. The attenuation-corrected data (corrected by means of cold, hot and segmented transmission as well as a mathematical procedure) were then quantified absolutely for assessment of regional glucose metabolism in 16 regions of interest (ROIs). Results: Using absolutely quantified glucose metabolism in 16 ROIs, no significant differences were found between cold transmission and the mathematical procedure except for three regions (left and right temporal occipital and right parietal occipital). Unlike the mathematical procedure, both hot and segmented transmission showed a significantly lower value for regional glucose utilisation in all 16 ROIs than did cold transmission. The left and the right hemisphere both showed metabolic values (rMRGlu) in the same decreasing order: Cold transmission, the mathematical procedure, hot or segemented transmission. There was no significant difference between global cerebral glucose metabolism values for cold transmission and the mathematical procedure (p=0.25) while those for hot (p=0.03) and segmented transmission (p=0.03) did show a significant difference. (orig.)

  12. Alterations in glucose and protein metabolism in animals subjected to simulated microgravity

    Mondon, C. E.; Rodnick, K. J.; Azhar, S.; Reaven, G. M.; Dolkas, C. B.

    1992-01-01

    Reduction of physical activity due to disease or environmental restraints, such as total bed rest or exposure to spaceflight, leads to atrophy of skeletal muscle and is frequently accompanied by alterations in food intake and the concentration of metabolic regulatory hormones such as insulin. Hindlimb suspension of laboratory rats, as a model for microgravity, also shows marked atrophy of gravity-dependent muscles along with a reduced gain in body weight. Suspended rats exhibit enhanced sensitivity to insulin-induced glucose uptake when compared with normal control rats and resistance to insulin action when compared with control rats matched similarly for reduced body weight gain. These changes are accompanied by decreased insulin binding and tyrosine kinase activity in soleus but not plantaris muscle, unchanged glucose uptake by perfused hindlimb and decreased sensitivity but not responsiveness to insulin-induced suppression of net proteolysis in hindlimb skeletal muscle. These findings suggest that loss of insulin sensitivity during muscle atrophy is associated with decreased insulin binding and tyrosine kinase activity in atrophied soleus muscle along with decreased sensitivity to the effects of insulin on suppressing net protein breakdown but not on enhancing glucose uptake by perfused hindlimb.

  13. Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset

    No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect

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

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

    2003-01-01

    Intralipid infusion. At LI, glucose oxidation decreased by 10%, whereas glucose disposal, glycolytic flux, glucose storage, and glucose production were not significantly altered. At HI, glucose disposal, and glucose oxidation decreased by 12% and 24%, respectively, during Intralipid infusion. Glycolytic flux...

  15. Gender differences in age-related decline in regional cerebral glucose metabolism

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Park, Hyun Soo; Lee, Eun Ju; Kim, Yu Kyeong; Kim, Sang Sun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In this study, we investigated gender differences in age-related declines in regional cerebral glucose metabolism using FDG-PET in a large population sample with a broad age range. 230 healthy subjects (90 male; age: 34-80 y, 140 females; age: 33-82 y) participated. Correlation maps showing age related declines in glucose uptake were created separately for each gender in SPM2. Using population-based probabilistic volume of interests (VOIs), VOIs were defined for the regions showing significant decline with aging. Age related declines were separately assessed within each age range using analysis of covariate in SPSS 13.0. In the total population without gender effect, age-related negative correlation of glucose metabolism was found in the bilateral inferior frontal gyri, bilateral caudate, bilateral thalamus, left insula, left superior frontal gyrus, left uncus, right superior temporal gyrus, right medial frontal gyrus, right parahippocampal gyrus, right anterior cingulate gyrus (P < 0.001 corrected, extent threshold k = 100). 14 VOIs values of brain regions were calculated based on this negative correlation results. The rate of decline across all defined VOIs assessed in the age category of 'more than 70' referenced to the category of '30- 39years' were 7.85% in the entire sample; 7.62% in male and 8.09% in female. Detailed analyses of declines in each age range showed separable patterns of declines across gender. In males, greater decline was observed after the age 60 (20.45%) than the ages of 30 and 50(7.98%). Whereas in females, greater declines were found in age 60s (20.15%) compared to 50s, and in 40(14.84%) compared to 30s. Age-related decline in cerebral glucose metabolism was found in both genders. We further observed that males show a relatively constant pattern of decline across a life span; whereas, females show a pattern of steep changes aging to 60s and to 40s, which may be related to changes in sex hormone levels after menopause.

  16. Gender differences in age-related decline in regional cerebral glucose metabolism

    In this study, we investigated gender differences in age-related declines in regional cerebral glucose metabolism using FDG-PET in a large population sample with a broad age range. 230 healthy subjects (90 male; age: 34-80 y, 140 females; age: 33-82 y) participated. Correlation maps showing age related declines in glucose uptake were created separately for each gender in SPM2. Using population-based probabilistic volume of interests (VOIs), VOIs were defined for the regions showing significant decline with aging. Age related declines were separately assessed within each age range using analysis of covariate in SPSS 13.0. In the total population without gender effect, age-related negative correlation of glucose metabolism was found in the bilateral inferior frontal gyri, bilateral caudate, bilateral thalamus, left insula, left superior frontal gyrus, left uncus, right superior temporal gyrus, right medial frontal gyrus, right parahippocampal gyrus, right anterior cingulate gyrus (P < 0.001 corrected, extent threshold k = 100). 14 VOIs values of brain regions were calculated based on this negative correlation results. The rate of decline across all defined VOIs assessed in the age category of 'more than 70' referenced to the category of '30- 39years' were 7.85% in the entire sample; 7.62% in male and 8.09% in female. Detailed analyses of declines in each age range showed separable patterns of declines across gender. In males, greater decline was observed after the age 60 (20.45%) than the ages of 30 and 50(7.98%). Whereas in females, greater declines were found in age 60s (20.15%) compared to 50s, and in 40(14.84%) compared to 30s. Age-related decline in cerebral glucose metabolism was found in both genders. We further observed that males show a relatively constant pattern of decline across a life span; whereas, females show a pattern of steep changes aging to 60s and to 40s, which may be related to changes in sex hormone levels after menopause

  17. Cerebral glucose metabolism 2 weeks following an 8000 m high altitude excursion

    Introduction: Little is known of regional cerebral glucose metabolism (LCMRglu) following high altitude excursions. The purpose of this study was to evaluate LCMRglu following an 40 day high altitude excursion. Methods: The study was performed on 11 male mountaineers, mean age 31.36 y, range 27-36. The subjects climbed Mount Shisha Pangma in the Himalaya (8048 m), an excursion which lasted 43 days. The total duration above 6000 m was 18 days. 18F-FDG PET was performed before and 2 weeks after the excursion on a GE Advance scanner. A single 10 minute image was acquired 40 minutes following the injection of 70 MBq 18F-FDG. The scans were first transformed into stereotactic space and normalized to mean whole brain activity, then statistical parametric mapping (SPM) was performed to assess the change of LCMRglu. In addition a region of interest analysis was performed on the interesting structures identified by SPM. Results: Significant increases (corrected for multiple comparisons) of relative FDG uptake were found in cerebellum (Z=5.36, 7.67.0, means.d. of percent increase) and the left thalamus (Z= 4.91, 8.23.2%). The right thalamus demonstrated a trend towards increased LCMRglu. Conclusion: There are circumscribed areas with an increase in glucose metabolism following exposure to high altitude. The physiological meaning of this finding is at present not clear. One could speculate that it represents a compensatory reaction to excessive hypoxic stress

  18. Regional difference of glucose metabolism reduction in equivocal Alzheimer's disease and elderly depressed patients

    The aim of this study was to investigate the difference in cerebral glucose metabolism between patients with equivocal Alzheimer's disease (eAD) and those with elderly major depression (DEP). 31 patients with eAD, 7 patients with DEP, and 15 age matched normal controls were scanned with FDG-PET. Each FDG-PET images was normalized to the cerebellar activity before voxel-voxel analysis using SPM99. In comparison with normal controls, the eAD patents showed the most significant reduction of glucose metabolism (hypometabolism) in anterior inferior temporal gyrus in left, followed by bilateral posterior cingulate, left thalamus, and inferior parietal lobe. Patients with DEP showed hypometabolism in precuneus, inferior and middle frontal gyri in left, and right angular gyrus. Significantly lower activity was found in left inferior temporal gyrus in DEP in comparison to the eAD. Patients with eAD and DEP showed different pattern of hypometabolism, especially in inferior temporal gyrus. FDG brain PET may be useful in differential diagnosis between equivocal Alzheimer's disease and elderly depression

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

    Høfsten, Dan E; Løgstrup, Brian B; Møller, Jacob E; Pellikka, Patricia A; Egstrup, Kenneth

    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...... atrial volume index (p = 0.10). During a median follow-up of 21 months, 32 patients died, and 39 patients met the secondary end point of death or hospitalization for heart failure. After adjustment for differences in LV function, as well as other relevant characteristics, newly detected, as well as known...... diabetes were independent predictors of both all-cause mortality (hazard ratios [HR]: 4.2 [95% confidence interval (CI): 1.1 to 17.1] and HR: 5.7 [95% CI: 1.3 to 25.2], respectively), and the composite of death or hospitalization for heart failure (HR: 4.3 [95% CI: 1.2 to 15.6] and HR: 5.8 [95% CI: 1.5 to...

  20. Studies on glucose metabolism and blood perfusion in childhood partial seizure by positron emission CT

    To investigate the glucose metabolism and blood perfusion of the interictal epileptic focus, 15 positron emission tomography (PET) measurements were performed in 14 children with partial seizures (2 with simple partial seizures, 2 with complex partial seizures, and 10 with partial seizures evolving to secondary generalized seizures), comprising 7 males and 7 females aged 1 to 12 years old at the onset of the epileptic seizures. The intervals between the seizure onset and PET examinations were 1 month to 7 years (mean 3 1/4 years). Radiopharmaceuticals such as 11C-glucose, 11CO2 and 11CO were used as indicators of local cerebral glucose metabolism, blood perfusion and blood flow, respectively. Apart from 2 cases, none of the patients showed abnormal x-ray computed tomographic scans (X-CT). The abnormal X-CT findings included cortical atrophy of the cerebrum apart from the epiletic focus in one case and cavum vergae in the other. Hypometabolism and hypoperfusion at the epileptic focus were observed in 10 patients undergoing single examinations who had suffered from epileptic seizures for more than 1 year. Out of 4 patients who had suffered from epileptic seizures for 1 year or less, one revealed a zone of hypometabolism and hypoperfusion in the epileptic focus and expanded region larger than that of the epileptic focus on the electroencephalogram. Two other patients revealed a zone of hypometabolism and hypoperfusion in an area contralateral to the epileptic focus. In the remaining one patient, PET examinations were performed twice. The initial PET pictures one year after seizure onset revealed a zone of hypermetabolism and hyperperfusion in the cerebellum ipsilateral to the epileptic focus, and the second PET at 6 months after the initial examination revealed hypometabolism and hypoperfusion in the focus, similarly to the 10 cases mentioned above. (J.P.N.)