WorldWideScience
1

Mechanisms and Methods in Glucose Metabolism and Cell Death  

OpenAIRE

Glucose metabolism represents a critical physiological program that not only provides energy to support cell proliferation, but also directly modulates signaling pathways of cell death. With the growing recognition of regulation of cell death by glucose metabolism, many techniques that can be applied in the study have been developed. This chapter discusses several protocols that aid in the analysis of glucose metabolism and cell death and the principles in practicing them under different cond...

Zhao, Yuxing; Wieman, Heather L.; Jacobs, Sarah R.; Rathmell, Jeffrey C.

2008-01-01

2

Tight Coupling between Glucose and Mitochondrial Metabolism in Clonal ?-Cells Is Required for Robust Insulin Secretion*  

OpenAIRE

The biochemical mechanisms underlying glucose-stimulated insulin secretion from pancreatic ?-cells are not completely understood. To identify metabolic disturbances in ?-cells that impair glucose-stimulated insulin secretion, we compared two INS-1-derived clonal ?-cell lines, which are glucose-responsive (832/13 cells) or glucose-unresponsive (832/2 cells). To this end, we analyzed a number of parameters in glycolytic and mitochondrial metabolism, including mRNA expression of genes involve...

Malmgren, Siri; Nicholls, David G.; Taneera, Jalal; Bacos, Karl; Koeck, Thomas; Tamaddon, Ashkan; Wibom, Rolf; Groop, Leif; Ling, Charlotte; Mulder, Hindrik; Sharoyko, Vladimir V.

2009-01-01

3

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

OpenAIRE

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...

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

2008-01-01

4

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

International Nuclear Information System (INIS)

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)

5

Glycated albumin suppresses glucose-induced insulin secretion by impairing glucose metabolism in rat pancreatic ?-cells  

Directory of Open Access Journals (Sweden)

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.

Muto Takashi

2011-04-01

6

Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R3.  

Science.gov (United States)

A homodimer of taste type 1 receptor 3 (T1R3) functions as a sweet taste-sensing receptor in pancreatic ?-cells. This receptor is activated by various sweet molecules including sugars such as glucose. To determine the role of this receptor in glucose-induced insulin secretion, we addressed whether or not this receptor modulates glucose metabolism in MIN6 cells. We measured changes in intracellular ATP ([ATP]i) in MIN6 cells expressing luciferase. Sucralose, an agonist of T1R3, induced immediate and sustained elevation of [ATP]i in the presence of 5.5 mM glucose. The effect of sucralose was dose-dependent and, at 5 mM, was greater than that induced by 25 mM glucose. In contrast, carbachol, GLP-1 or high concentration of potassium did not reproduce the sucralose action. Sucralose facilitated the increase in [ATP]i induced by a mitochondrial fuel methylsuccinate, and potentiated glucose-induced elevation of [ATP]i. Administration of a non-metabolizable glucose analogue, 3-O-methylglucose, which acts as an agonist of T1R3, induced a small and transient increase in [ATP]i. 3-O-Methylglucose augmented elevation of [ATP]i induced by methylsuccinate, and also enhanced glucose-induced increase in [ATP]i. Knock down of T1R3 by using shRNA attenuated [ATP]i-response to high concentration of glucose and also reduced the glucose-induced insulin secretion. These results indicate that activation of the homodimer of T1R3 facilitates the metabolic pathway in mitochondria and augments ATP production. The results obtained by using 3-O-methylglucose suggest that glucose, by acting on the homodimer of T1R3, promotes its own metabolism. PMID:24200979

Nakagawa, Yuko; Ohtsu, Yoshiaki; Nagasawa, Masahiro; Shibata, Hiroshi; Kojima, Itaru

2014-01-01

7

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

International Nuclear Information System (INIS)

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

8

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

OpenAIRE

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 ...

Tsacopoulos, M.; Eve?quoz-mercier, V.; Perrottet, P.; Buchner, E.

1988-01-01

9

Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides  

Science.gov (United States)

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.

Birsoy, K?vanç; 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

10

Quantitative aspects of glucose and glutamine metabolism by intestinal cells.  

OpenAIRE

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...

Newsholme, E. A.; Carrie?, A. L.

1994-01-01

11

Metformin, cancer and glucose metabolism.  

Science.gov (United States)

Metformin is the first-line treatment for type 2 diabetes. Results from several clinical studies have indicated that type 2 diabetic patients treated with metformin might have a lower cancer risk. One of the primary metabolic changes observed in malignant cell transformation is an increased catabolic glucose metabolism. In this context, once it has entered the cell through organic cation transporters, metformin decreases mitochondrial respiration chain activity and ATP production that, in turn, activates AMP-activated protein kinase, which regulates energy homeostasis. In addition, metformin reduces cellular energy availability and glucose entrapment by inhibiting hexokinase-II, which catalyses the glucose phosphorylation reaction. In this review, we discuss recent findings on molecular mechanisms that sustain the anticancer effect of metformin through regulation of glucose metabolism. In particular, we have focused on the emerging action of metformin on glycolysis in normal and cancer cells, with a drug discovery perspective. PMID:25273809

Salani, Barbara; Del Rio, Alberto; Marini, Cecilia; Sambuceti, Gianmario; Cordera, Renzo; Maggi, Davide

2014-12-01

12

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

OpenAIRE

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...

Lohmeier-vogel, E. M.; Hahn-ha?gerdal, B.; Vogel, H. J.

1995-01-01

13

Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification.  

Science.gov (United States)

The metabolic state of quiescent hematopoietic stem cells (HSCs) is an important regulator of self-renewal, but it is unclear whether or how metabolic parameters contribute to HSC lineage specification and commitment. Here, we show that the commitment of human and murine HSCs to the erythroid lineage is dependent upon glutamine metabolism. HSCs require the ASCT2 glutamine transporter and active glutamine metabolism for erythroid specification. Blocking this pathway diverts EPO-stimulated HSCs to differentiate into myelomonocytic fates, altering in vivo HSC responses and erythroid commitment under stress conditions such as hemolytic anemia. Mechanistically, erythroid specification of HSCs requires glutamine-dependent de novo nucleotide biosynthesis. Exogenous nucleosides rescue erythroid commitment of human HSCs under conditions of limited glutamine catabolism, and glucose-stimulated nucleotide biosynthesis further enhances erythroid specification. Thus, the availability of glutamine and glucose to provide fuel for nucleotide biosynthesis regulates HSC lineage commitment under conditions of metabolic stress. PMID:24953180

Oburoglu, Leal; Tardito, Saverio; Fritz, Vanessa; de Barros, Stéphanie C; Merida, Peggy; Craveiro, Marco; Mamede, João; Cretenet, Gaspard; Mongellaz, Cédric; An, Xiuli; Klysz, Dorota; Touhami, Jawida; Boyer-Clavel, Myriam; Battini, Jean-Luc; Dardalhon, Valérie; Zimmermann, Valérie S; Mohandas, Narla; Gottlieb, Eyal; Sitbon, Marc; Kinet, Sandrina; Taylor, Naomi

2014-08-01

14

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

Science.gov (United States)

In this work we evaluated several genes involved in gluconeogenesis, glycolysis and glycogen metabolism, the major pathways for carbohydrate catabolism and anabolism, in the BME26 Rhipicephalus microplus embryonic cell line. Genetic and catalytic control of the genes and enzymes associated with these pathways are modulated by alterations in energy resource availability (primarily glucose). BME26 cells in media were investigated using three different glucose concentrations, and changes in the transcription levels of target genes in response to carbohydrate utilization were assessed. The results indicate that several genes, such as glycogen synthase (GS), glycogen synthase kinase 3 (GSK3), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6 phosphatase (GP) displayed mutual regulation in response to glucose treatment. Surprisingly, the transcription of gluconeogenic enzymes was found to increase alongside that of glycolytic enzymes, especially pyruvate kinase, with high glucose treatment. In addition, RNAi data from this study revealed that the transcription of gluconeogenic genes in BME26 cells is controlled by GSK-3. Collectively, these results improve our understanding of how glucose metabolism is regulated at the genetic level in tick cells. PMID:25594873

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

2015-01-01

15

The influence of high glucose on the aerobic metabolism of endothelial EA.hy926 cells  

OpenAIRE

The endothelium is considered to be relatively independent of the mitochondrial energy supply. The goals of this study were to examine mitochondrial respiratory functions in endothelial cells and isolated mitochondria and to assess the influence of chronic high glucose exposure on the aerobic metabolism of these cells. A procedure to isolate of bioenergetically active endothelial mitochondria was elaborated. Human umbilical vein endothelial cells (EA.hy926 line) were grown in medium containin...

Koziel, Agnieszka; Woyda-ploszczyca, Andrzej; Kicinska, Anna; Jarmuszkiewicz, Wieslawa

2012-01-01

16

Metformin decreases glucose oxidation and increases the dependency of prostate cancer cells on reductive glutamine metabolism  

OpenAIRE

Metformin inhibits cancer cell proliferation and epidemiology studies suggest an association with increased survival in cancer patients taking metformin, however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabo...

Fendt, Sarah-maria; Bell, Eric L.; Keibler, Mark A.; Davidson, Shawn M.; Wirth, Gregory J.; Fiske, Brian; Mayers, Jared R.; Schwab, Matthias; Bellinger, Gary; Csibi, Alfredo; Patnaik, Akash; Jose Blouin, Marie; Cantley, Lewis C.; Guarente, Leonard; Blenis, John

2013-01-01

17

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

International Nuclear Information System (INIS)

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-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.)

18

Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism.  

Science.gov (United States)

Selectively eradicating cancer cells with minimum adverse effects on normal cells is a major challenge in the development of anticancer therapy. We hypothesize that nutrient-limiting conditions frequently encountered by cancer cells in poorly vascularized solid tumors might provide an opportunity for developing selective therapy. In this study, we investigated the function and molecular mechanisms of a natural compound, arctigenin, in regulating tumor cell growth. We demonstrated that arctigenin selectively promoted glucose-starved A549 tumor cells to undergo necrosis by inhibiting mitochondrial respiration. In doing so, arctigenin elevated cellular level of reactive oxygen species (ROS) and blocked cellular energy metabolism in the glucose-starved tumor cells. We also demonstrated that cellular ROS generation was caused by intracellular ATP depletion and played an essential role in the arctigenin-induced tumor cell death under the glucose-limiting condition. Furthermore, we combined arctigenin with the glucose analogue 2-deoxyglucose (2DG) and examined their effects on tumor cell growth. Interestingly, this combination displayed preferential cell-death inducing activity against tumor cells compared to normal cells. Hence, we propose that the combination of arctigenin and 2DG may represent a promising new cancer therapy with minimal normal tissue toxicity. PMID:22687625

Gu, Yuan; Qi, Chunting; Sun, Xiaoxiao; Ma, Xiuquan; Zhang, Haohao; Hu, Lihong; Yuan, Junying; Yu, Qiang

2012-08-15

19

Intestinal glucose metabolism revisited.  

Science.gov (United States)

It is long known that the gut can contribute to the control of glucose homeostasis via its high glucose utilization capacity. Recently, a novel function in intestinal glucose metabolism (gluconeogenesis) was described. The intestine notably contributes to about 20-25% of total endogenous glucose production during fasting. More importantly, intestinal gluconeogenesis is capable of regulating energy homeostasis through a communication with the brain. The periportal neural system senses glucose (produced by intestinal gluconeogenesis) in the portal vein walls, which sends a signal to the brain to modulate hunger sensations and whole body glucose homeostasis. Relating to the mechanism of glucose sensing, the role of the glucose receptor SGLT3 has been strongly suggested. Moreover, dietary proteins mobilize intestinal gluconeogenesis as a mandatory link between their detection in the portal vein and their effect of satiety. In the same manner, dietary soluble fibers exert their anti-obesity and anti-diabetic effects via the induction of intestinal gluconeogenesis. FFAR3 is a key neural receptor involved in the specific sensing of propionate to activate a gut-brain reflex arc triggering the induction of the gut gluconeogenic function. Lastly, intestinal gluconeogenesis might also be involved in the rapid metabolic improvements induced by gastric bypass surgeries of obesity. PMID:24969963

Mithieux, Gilles; Gautier-Stein, Amandine

2014-09-01

20

Glucagon-insulin interaction on fat cell metabolism using c14 glucose  

International Nuclear Information System (INIS)

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

21

Metformin decreases glucose oxidation and increases the dependency of prostate cancer cells on reductive glutamine metabolism  

Science.gov (United States)

Metformin inhibits cancer cell proliferation and epidemiology studies suggest an association with increased survival in cancer patients taking metformin, however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation while increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer. PMID:23687346

Fendt, Sarah-Maria; Bell, Eric L.; Keibler, Mark A.; Davidson, Shawn M.; Wirth, Gregory J.; Fiske, Brian; Mayers, Jared R.; Schwab, Matthias; Bellinger, Gary; Csibi, Alfredo; Patnaik, Akash; Jose Blouin, Marie; Cantley, Lewis C.; Guarente, Leonard; Blenis, John; Pollak, Michael N.; Olumi, Aria F.

2013-01-01

22

Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis  

OpenAIRE

The metabolic profiles of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. In particular, a wide range of both solid and liquid tumors use aerobic glycolysis to supply energy and support cell growth. This metabolic program leads to high rates of glucose consumption through glycolysis with secretion of lactate even in the presence of oxygen. Identifying the limiting events in aerobic glycolysis and the response of cancer cells to metabolic in...

Liu, T.; Kishton, R. J.; Macintyre, A. N.; Gerriets, V. A.; Xiang, H.; Liu, X.; Abel, E. D.; Rizzieri, D.; Locasale, J. W.; Rathmell, J. C.

2014-01-01

23

New Aspects of an Old Drug – Diclofenac Targets MYC and Glucose Metabolism in Tumor Cells  

OpenAIRE

Non-steroidal anti-inflammatory drugs such as diclofenac exhibit potent anticancer effects. Up to now these effects were mainly attributed to its classical role as COX-inhibitor. Here we show novel COX-independent effects of diclofenac. Diclofenac significantly diminished MYC expression and modulated glucose metabolism resulting in impaired melanoma, leukemia, and carcinoma cell line proliferation in vitro and reduced melanoma growth in vivo. In contrast, the non-selective COX inhibitor aspir...

Gottfried, Eva; Lang, Sven A.; Renner, Kathrin; Bosserhoff, Anja; Gronwald, Wolfram; Rehli, Michael; Einhell, Sabine; Gedig, Isabel; Singer, Katrin; Seilbeck, Anton; Mackensen, Andreas; Grauer, Oliver; Hau, Peter; Dettmer, Katja; Andreesen, Reinhard

2013-01-01

24

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

Energy Technology Data Exchange (ETDEWEB)

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 [{sup 3}H]thymidine (TdR) accumulation, and was compared with the uptake of two non-metabolized amino acids ([{sup 14}C]aminocyclopentane carboxylic acid (ACPC) and [{sup 14}C]aminoisobutyric acid (AIB)), and [{sup 18}F]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 (K{sub 1}) 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 (V{sub d}) 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 K{sub 1} and V{sub d} 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.)

Sasajima, Toshio [Department of Neurology, C799, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, NY 10021, New York (United States); Neurosurgical Service, Akita University Hospital, Akita (Japan); Miyagawa, Tadashi [Department of Neurology, C799, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, NY 10021, New York (United States); Department of Neurosurgery, Chiba University School of Medicine, Chuo-ku, Chiba (Japan); Oku, Takamitsu [Department of Neurology, C799, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, NY 10021, New York (United States); Department of Neurosurgery, Miyazaki Medical College, Miyazaki (Japan); Gelovani, Juri G. [Department of Neurology, C799, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, NY 10021, New York (United States); Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York (United States); Department of Experimental Diagnostic Imaging, The University of Texas, MD Anderson Cancer Center, TX 77030, Houston (United States); Finn, Ronald [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York (United States); Blasberg, Ronald [Department of Neurology, C799, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, NY 10021, New York (United States); Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York (United States)

2004-09-01

25

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

Science.gov (United States)

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. PMID:24632207

Bolado-Carrancio, A; Riancho, J A; Sainz, J; Rodríguez-Rey, J C

2014-04-01

26

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

OpenAIRE

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...

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

1998-01-01

27

Metabolic utilization of exogenous pyruvate by mutant p53 (R175H) human melanoma cells promotes survival under glucose depletion.  

Science.gov (United States)

Dominant-negative (DN) p53 mutations in the tumor suppressor p53 gene partly contribute to human cancer progression by inactivating the remaining wild type allele. Since tumor cells face glucose and growth factor shortage when growing distant from sites of vascularization, we used genetically-matched human C8161 melanoma harbouring wt p53 or a tumor-associated (DN) mutant p53 (R175H), to investigate whether this mutation influences survival under metabolic stress. Metabolic restriction (18 hours in glucose-free medium plus 2% serum) induced apoptosis-associated PARP cleavage in wt p53 melanoma, even when supplemented with 2.77 mM pyruvate or lactate. Mutant p53 melanoma were resistant to a comparable metabolic restriction, only showing PARP fragmentation when glucose depletion was accompanied by treatment with diphenylene iodonium (DPI), a NADPH oxidase inhibitor of superoxide (O2*-) generation. DPI-mediated apoptosis in mutant p53 cells was counteracted by 2.77 mM glucose or pyruvate, but not by lactate supplementation. Metabolic utilization and survival under glucose depletion was increased by pyruvate in mutant p53 (R175H) cells. Our results show for the first time that melanoma cells harbouring a p53 (R175H) mutation increase: a) survival under glucose depletion, counteracted by NADPH-oxidase modulators like DPI; b) resistance to DPI when supplemented with exogenous pyruvate. PMID:21832879

Chavez-Perez, Valery A; Strasberg-Rieber, Mary; Rieber, Manuel

2011-10-01

28

Placental-Fetal Glucose Exchange and Fetal Glucose Metabolism  

OpenAIRE

Fetal glucose metabolism depends on additive effects of fetal plasma glucose and insulin. Glucose-stimulated insulin secretion increases over gestation, is down-regulated by constant hyperglycemia, but enhanced by pulsatile hyperglycemia. Insulin production is diminished in fetuses with intrauterine growth restriction (IUGR) by inhibition of pancreatic ?-cell replication, but not by mechanisms that regulate insulin production or secretion, while the opposite occurs with hypoglycemia alone, d...

Hay, William W.

2006-01-01

29

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

International Nuclear Information System (INIS)

The influence of 0.5 mM ?-hexachlorocyclohexane (?-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 ?-, ?-HCH isomers and dieldrin reproduced the same inhibitory pattern, while ?-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

30

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

LENUS (Irish Health Repository)

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 ??(m) from -142 to -88 mV, with active caspase-3 potentiating this decrease. ATP synthase was reversed under such conditions, consuming ATP and stabilising ??(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.

Huber, Heinrich J

2011-03-01

31

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

International Nuclear Information System (INIS)

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

32

SH2B1 in ?-cells regulates glucose metabolism by promoting ?-cell survival and islet expansion.  

Science.gov (United States)

IGF-1 and insulin promote ?-cell expansion by inhibiting ?-cell death and stimulating ?-cell proliferation, and the phosphatidylinositol (PI) 3-kinase/Akt pathway mediates insulin and IGF-1 action. Impaired ?-cell expansion is a risk factor for type 2 diabetes. Here, we identified SH2B1, which is highly expressed in ?-cells, as a novel regulator of ?-cell expansion. Silencing of SH2B1 in INS-1 832/13 ?-cells attenuated insulin- and IGF-1-stimulated activation of the PI 3-kinase/Akt pathway and increased streptozotocin (STZ)-induced apoptosis; conversely, overexpression of SH2B1 had the opposite effects. Activation of the PI 3-kinase/Akt pathway in ?-cells was impaired in pancreas-specific SH2B1 knockout (PKO) mice fed a high-fat diet (HFD). HFD-fed PKO mice also had increased ?-cell apoptosis, decreased ?-cell proliferation, decreased ?-cell mass, decreased pancreatic insulin content, impaired insulin secretion, and exacerbated glucose intolerance. Furthermore, PKO mice were more susceptible to STZ-induced ?-cell destruction, insulin deficiency, and hyperglycemia. These data indicate that SH2B1 in ?-cells is an important prosurvival and proproliferative protein and promotes compensatory ?-cell expansion in the insulin-resistant state and in response to ?-cell stress. PMID:24150605

Chen, Zheng; Morris, David L; Jiang, Lin; Liu, Yong; Rui, Liangyou

2014-02-01

33

Upregulation of glucose metabolism by NF-?B2/p52 mediates enzalutamide resistance in castration-resistant prostate cancer cells.  

Science.gov (United States)

Cancer cells reprogram their metabolic pathways to facilitate fast proliferation. Previous studies have shown that overexpression of NF-?B2/p52 (p52) in prostate cancer cells promotes cell growth and leads to castration resistance through aberrant activation of androgen receptor (AR). In addition, these cells become resistant to enzalutamide. In this study, we investigated the effects of p52 activation on glucose metabolism and on response to enzalutamide therapy. Data analysis of gene expression arrays showed that genes including GLUT1 (SLC2A1), PKM2, G6PD, and ME1 involved in the regulation of glucose metabolism were altered in LNCaP cells overexpressing p52 compared with the parental LNCaP cells. We demonstrated an increased amount of glucose flux in the glycolysis pathway, as well as the pentose phosphate pathway (PPP) upon p52 activation. The p52-overexpressing cells increase glucose uptake and are capable of higher ATP and lactate production compared with the parental LNCaP cells. The growth of p52-overexpressing cells depends on glucose in the culture media and is sensitive to glucose deprivation compared with the parental LNCaP cells. Targeting glucose metabolism by the glucose analog 2-deoxy-d-glucose synergistically inhibits cell growth when combined with enzalutamide, and resensitizes p52-overexpressing cells to enzalutamide treatment. These results suggest that p52 modulates glucose metabolism, enhances glucose flux to glycolysis and PPPs, thus facilitating fast proliferation of the cells. Co-targeting glucose metabolism together with AR axis synergistically inhibits cell growth and restores enzalutamide-resistant cells to enzalutamide treatment. PMID:24659479

Cui, Yuanyuan; Nadiminty, Nagalakshmi; Liu, Chengfei; Lou, Wei; Schwartz, Chad T; Gao, Allen C

2014-06-01

34

Extracellular glucose can fuel metabolism in red blood cells from high glycemic Atlantic cod (Gadus morhua) but not low glycemic short-horned sculpin (Myoxocephalus scorpius).  

Science.gov (United States)

Energy metabolism was assessed in red blood cells (RBCs) from Atlantic cod and short-horned sculpin, two species that have markedly different levels of blood glucose. The objective was to determine whether the level of extracellular glucose has an impact on rates of glucose metabolism. The blood glucose level was 2.5 mmol l(-1) in Atlantic cod and 0.2 mmol l(-1) in short-horned sculpin, respectively. Oxygen consumption, lactate production and glucose utilization were measured in whole blood and related to grams of RBCs. Glucose utilization was assessed by measuring both glucose disappearance and the production of (3)H2O from [2-(3)H]-glucose. RBCs from both species have an aerobic-based metabolism. In Atlantic cod, extracellular glucose is sufficient to provide the sum of glucosyl equivalents to support both oxidative metabolism and lactate production. In contrast, extracellular glucose can account for only 10% of the metabolic rate in short-horned sculpin RBCs. In both species, about 70% of glucose enters the RBCs via facilitated transport. The difference in rates of extracellular glucose utilization is related to the extremely low levels of blood glucose in short-horned sculpin. In this species energy metabolism by RBCs must be supported by alternative fuels. PMID:25214484

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

2014-11-01

35

Phosphorus-31 and carbon-13 nuclear magnetic resonance studies of glucose and xylose metabolism in cell suspensions and agarose-immobilized cultures of Pichia stipitis and Saccharomyces cerevisiae.  

OpenAIRE

The metabolism of glucose and xylose as a function of oxygenation in Pichia stipitis and Saccharomyces cerevisiae cell suspensions was studied by 31P and 13C nuclear magnetic resonance spectroscopy. The rate of both glucose and xylose metabolism was slightly higher and the production of ethanol was slightly lower in aerobic than in anoxic cell suspensions of P. stipitis. As well, the cytoplasmic pH of oxygenated cells was more alkaline than that of nonoxygenated cells. In contrast, in S. cere...

Lohmeier-vogel, E. M.; Mcintyre, D. D.; Vogel, H. J.

1996-01-01

36

Glucose metabolism in ischemic myocardium  

International Nuclear Information System (INIS)

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 igion 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.)

37

Effects of increased transaldolase activity on D-xylulose and D-glucose metabolism in Saccharomyces cerevisiae cell extracts.  

OpenAIRE

In vitro metabolism of D-xylulose and D-glucose in extracts obtained from D-glucose- and D-xylulose-fermenting Saccharomyces cerevisiae cells was investigated with 10- and 100-fold-increased activity of the enzyme transaldolase (EC 2.2.1.2). The rate of sugar consumption was the same in most cases, whereas the rate of ethanol formation decreased with increased levels of transaldolase. The formation of glycerol, pentitols, and acetic acid was not dependent on added transaldolase but was depend...

Senac, T.; Hahn-ha?gerdal, B.

1991-01-01

38

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

International Nuclear Information System (INIS)

Objective: To study the insulin resistance and ?-cell function in individuals with normal glucose tolerance (NGT) and those with glucose metabolism dysfunction. Methods: Insulin resistance and ?-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, ?I30/?G30 and ISI decreased progressively with significant differences between those in successive groups (P30/?G30 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/?G30 were significantly correlated with ISI (F =96.3, 58.4 and 47.5 respectively). For principal component analysis display, the cumulative contriby, the cumulative contribution rate of four parameters (2hIns/2hPG, ISI, ?I30/?G30 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 ?-cell secretion followed. The parameters 2hIns/2hPG, ISI, 2h C-peptide ?I30/?G30 were especially useful for the investigation . (authors)

39

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

International Nuclear Information System (INIS)

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

40

Two p53-related metabolic regulators, TIGAR and SCO2, contribute to oroxylin A-mediated glucose metabolism in human hepatoma HepG2 cells.  

Science.gov (United States)

Metabolic alteration in cancer cells is one of the most conspicuous characteristics that distinguish cancer cells from normal cells. Many studies suggest that several underlying mechanisms lead to the Warburg effect (increased aerobic glycolysis) during cancer development. Here, we explored how oroxylin A affected the glycolytic metabolism in cancer cells and the underlying mechanism involved in this process. Our data revealed that both oroxylin A and adriamycin could inhibit lactate generation and glucose uptake in HepG2 cells at mild concentrations, without causing robust cell apoptosis. Oroxylin A has exerted little influence on the oxygen consumption, whereas adriamycin decreased oxygen consumption in a concentration-dependent manner. Moreover, oroxylin A could increase protein and mRNA expression of TP53-induced glycolysis and apoptosis regulator (TIGAR) and synthesis of cytochrome c oxidase 2 (SCO2), which are the key metabolic modulators regulated by p53. Meanwhile adriamycin could increase protein and mRNA expression of TIGAR and SCO2, but decrease that of phosphoglycerate mutase (PGM). Oroxylin A and adriamycin also modulated the stability and activity of p53 through inducing phosphorylation of p53 at Ser15 and suppressing the expression of MDM2. Furthermore, p53 siRNA and p53 inhibitor assay in wild-type p53 HepG2 cells both revealed the key role of p53 in oroxylin A and adriamycin-mediated glycolytic metabolism regulation. Transfecting wt p53 plasmid to p53-deficient H1299 cells could inverse some of the metabolic characteristics regulated by oroxylin A. This study revealed a new aspect of glucose metabolism regulation of oroxylin A, which may contribute to its new anticancer mechanism. PMID:23612020

Dai, Qinsheng; Yin, Yuehan; Liu, Wei; Wei, Libin; Zhou, Yuxin; Li, Zhiyu; You, Qidong; Lu, Na; Guo, Qinglong

2013-07-01

41

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

International Nuclear Information System (INIS)

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 evmatic analysis. These studies showed no evidence that sepsis disturbed RBC membrane function or metabolism

42

Intracellular Glucose Concentration in Derepressed Yeast Cells Consuming Glucose Is High Enough To Reduce the Glucose Transport Rate by 50%  

OpenAIRE

In Saccharomyces cerevisiae cells exhibiting high-affinity glucose transport, the glucose consumption rate at extracellular concentrations above 10 mM was only half of the zero trans-influx rate. To determine if this regulation of glucose transport might be a consequence of intracellular free glucose we developed a new method to measure intracellular glucose concentrations in cells metabolizing glucose, which compares glucose stereoisomers to correct for adhering glucose. The intracellular gl...

Teusink, Bas; Diderich, Jasper A.; Westerhoff, Hans V.; Dam, Karel; Walsh, Michael C.

1998-01-01

43

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

International Nuclear Information System (INIS)

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

44

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

International Nuclear Information System (INIS)

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)

45

SH2B1 in ?-cells promotes insulin expression and glucose metabolism in mice.  

Science.gov (United States)

Insulin deficiency drives the progression of both type 1 and type 2 diabetes. Pancreatic ?-cell insulin expression and secretion are tightly regulated by nutrients and hormones; however, intracellular signaling proteins that mediate nutrient and hormonal regulation of insulin synthesis and secretion are not fully understood. SH2B1 is an SH2 domain-containing adaptor protein. It enhances the activation of the Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription and the phosphatidylinositol 3-kinase pathways in response to a verity of hormones, growth factors, and cytokines. Here we identify SH2B1 as a new regulator of insulin expression. In rat INS-1 832/13 ?-cells, SH2B1 knockdown decreased, whereas SH2B1 overexpression increased, both insulin expression and glucose-stimulated insulin secretion. SH2B1-deficent islets also had reduced insulin expression, insulin content, and glucose-stimulated insulin secretion. Heterozygous deletion of SH2B1 decreased pancreatic insulin content and plasma insulin levels in leptin-deficient ob/ob mice, thus exacerbating hyperglycemia and glucose intolerance. In addition, overexpression of JAK2 increased insulin promoter activity, and SH2B1 enhanced the ability of JAK2 to activate the insulin promoter. Overexpression of SH2B1 also increased the expression of Pdx1 and the recruitment of Pdx1 to the insulin promoter in INS-1 832/13 cells, whereas silencing of SH2B1 had the opposite effects. Consistently, Pdx1 expression was lower in SH2B1-deficient islets. These data suggest that the SH2B1 in ?-cells promotes insulin synthesis and secretion at least in part by enhancing activation of JAK2 and/or Pdx1 pathways in response to hormonal and nutritional signals. PMID:24645678

Chen, Zheng; Morris, David L; Jiang, Lin; Liu, Yong; Rui, Liangyou

2014-05-01

46

Enzymes of glucose metabolism in Frankia sp.  

OpenAIRE

Enzymes of glucose metabolism were assayed in crude cell extracts of Frankia strains HFPArI3 and HFPCcI2 as well as in isolated vesicle clusters from Alnus rubra root nodules. Activities of the Embden-Meyerhof-Parnas pathway enzymes glucokinase, phosphofructokinase, and pyruvate kinase were found in Frankia strain HFPArI3 and glucokinase and pyruvate kinase were found in Frankia strain HFPCcI2 and in the vesicle clusters. An NADP+-linked glucose 6-phosphate dehydrogenase and an NAD-linked 6-p...

Lopez, M. F.; Torrey, J. G.

1985-01-01

47

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

DEFF Research Database (Denmark)

Type 2 diabetes is characterized by increased insulin resistance and impaired insulin secretion. Type 2 diabetes is also associated with low-grade inflammation and increased levels of proinflammatory cytokines such as TNF- ? . TNF- ? has been shown to impair peripheral insulin signaling in vitro and 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 plasma without impairing beta-cell function or hepatic insulin sensitivity

Ibfeldt, T; Fischer, Christian Philip

2014-01-01

48

The acute effects of low-dose TNF-? on glucose metabolism and ?-cell function in humans  

DEFF Research Database (Denmark)

Type 2 diabetes is characterized by increased insulin resistance and impaired insulin secretion. Type 2 diabetes is also associated with low-grade inflammation and increased levels of proinflammatory cytokines such as TNF-?. TNF-? has been shown to impair peripheral insulin signaling in vitro and 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-? acutelylowers 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 plasma without impairing beta-cell function or hepatic insulin sensitivity.

Ibfelt, Tobias; Fischer, Christian P

2014-01-01

49

Regulation of Glucose Transport and Metabolism in Thiobacillus novellus  

OpenAIRE

To investigate the physiological basis of decreased rate of glucose utilization by Thiobacillus novellus in a mixotrophic environment (R. C. Perez and A. Matin, J. Bacteriol. 142:633–638, 1980), its glucose transport system was characterized and the modulation of this system as well as enzymes of glucose metabolism by the growth environment was examined. Uptake of 2-deoxy-d-glucose by cell suspensions was almost abolished by respiratory chain inhibitors, and the sugar accumulated unchanged ...

Matin, A.; Schleiss, M.; Perez, R. C.

1980-01-01

50

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

DEFF Research Database (Denmark)

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 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 40%, P 50%, P 50%, P < 0.05). Furthermore, LIPO displayed reduced incremental glucose oxidation (P < 0.01), increased clamp free fatty acids (P < 0.05) and attenuated insulin-mediated suppression of lipid oxidation (P < 0.05) compared with NONLIPO. In combined study groups, RLF correlated with hepatic insulin sensitivity (r = 0.69), incremental glucose disposal (r = 0.71) and incremental exogenous glucose storage (r = 0.40), all P < 0.01. Disposition index (i.e. first-phase insulin response to intravenous glucose multiplied by incremental glucose disposal) was reduced by 46% (P = 0.05) in LIPO compared with the combined groups of NONLIPO and NAIVE, indicating an impaired adaptation of beta-cell function to insulin resistance in LIPO. CONCLUSION: Our data suggest that normoglycaemic lipodystrophic HIV-infected patients display impaired glucose and lipid metabolism in multiple pathways involving liver, muscle tissue and beta-cell function.

Haugaard, Steen B; Andersen, Ove

2005-01-01

51

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

DEFF Research Database (Denmark)

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 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 40%, P 50%, P 50%, P < 0.05). Furthermore, LIPO displayed reduced incremental glucose oxidation (P < 0.01), increased clamp free fatty acids (P < 0.05) and attenuated insulin-mediated suppression of lipid oxidation (P < 0.05) compared with NONLIPO. In combined study groups, RLF correlated with hepatic insulin sensitivity (r = 0.69), incremental glucose disposal (r = 0.71) and incremental exogenous glucose storage (r = 0.40), all P < 0.01. Disposition index (i.e. first-phase insulin response to intravenous glucose multiplied by incremental glucose disposal) was reduced by 46% (P = 0.05) in LIPO compared with the combined groups of NONLIPO and NAIVE, indicating an impaired adaptation of beta-cell function to insulin resistance in LIPO. CONCLUSION: Our data suggest that normoglycaemic lipodystrophic HIV-infected patients display impaired glucose and lipid metabolism in multiple pathways involving liver, muscle tissue and beta-cell function.

Haugaard, Steen B; Andersen, Ove

2005-01-01

52

Glycolysis inhibitor 2-deoxy-D-glucose suppresses carcinogen-induced rat hepatocarcinogenesis by restricting cancer cell metabolism.  

Science.gov (United States)

The abnormal metabolism of cancer cells is a crucial feature of tumors and provides promising therapeutic targets for cancer treatments. Aerobic glycolysis in cancer cells, termed the Warburg effect, is a highlighted characteristic of cancer?specific metabolism. However, the effect of glycolysis inhibition on hepatocarcinogenesis remains to be elucidated. In the present study, the effects of the glycolysis inhibitor 2?deoxy?D?glucose (2?DG) on the N?diethylnitrosamine (DEN)?induced rat hepatocarcinoma model and its underlying mechanisms were investigated. It was observed that 2?DG significantly delayed hepatocarcinogenesis and effectively prolonged survival time in the DEN?treated rats. The glycolysis inhibitor, 2?DG prominently decreased cell proliferation and increased cell apoptosis in the DEN?induced rat hepatoma and had no evident impact on the pericarcinomatous liver tissues. Further investigation revealed that 2?DG resulted in a reduction of glycolysis products, the compensatory increase of hexokinase 2 expression and a decrease in 6?phosphofructo?2?kinase, pyruvate kinase M2 and lactate dehydrogenase A expression in the hepatoma tissues. The inhibition of glycolysis further suppressed the tricarboxylic acid cycle, fatty acid and cholesterol biosynthesis and ATP production, while it promoted autophagic activation. In addition, the in vitro study demonstrated that hypoxia, an important factor in the tumor microenvironment, may assist in increasing 2?DG?induced inhibition of cell viability, cell cycle retardation and the decrease of colony formation ability in hepatoma cells. Taken together, the present results suggested that 2?DG may inhibit hepatocarcinogenesis in the DEN?treated rats via restricting cancer cell metabolism. This finding provides a promising measure in the prevention and treatment of hepatoma. PMID:25394852

Wang, Zhaofa; Zhang, Liming; Zhang, Dong; Sun, Rongsheng; Wang, Qingyan; Liu, Xinyi

2015-03-01

53

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

Science.gov (United States)

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 optimization, especially media optimization. Gaining knowledge on their interrelations could provide insight for obtaining higher immunoglobulin G (IgG) titer and better controlling glycosylation-related product quality. In this work, different fed-batch processes with two chemically defined proprietary media and feeds were studied using two IgG-producing cell lines. Our results indicate that the balance of glucose and amino acid concentration in the culture is important for cell growth, IgG titer and N-glycosylation. Accordingly, the ideal fate of glucose and amino acids in the culture could be mainly towards energy and recombinant product, respectively. Accumulation of by-products such as NH4(+) and lactate as a consequence of unbalanced nutrient supply to cell activities inhibits cell growth. The levels of Leu and Arg in the culture, which relate to cell growth and IgG productivity, need to be well controlled. Amino acids with the highest consumption rates correlate with the most abundant amino acids present in the produced IgG, and thus require sufficient availability during culture. Case-by-case analysis is necessary for understanding the effect of media and process optimization on glycosylation. We found that in certain cases the presence of Man5 glycan can be linked to limitation of UDP-GlcNAc biosynthesis as a result of insufficient extracellular Gln. However, under different culture conditions, high Man5 levels can also result from low ?-1,3-mannosyl-glycoprotein 2-?-N-acetylglucosaminyltransferase (GnTI) and UDP-GlcNAc transporter activities, which may be attributed to high level of NH4+ in the cell culture. Furthermore, galactosylation of the mAb Fc glycans was found to be limited by UDP-Gal biosynthesis, which was observed to be both cell line and cultivation condition-dependent. Extracellular glucose and glutamine concentrations and uptake rates were positively correlated with intracellular UDP-Gal availability. All these findings are important for optimization of fed-batch culture for improving IgG production and directing glycosylation quality. PMID:25220616

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

2015-03-01

54

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

DEFF Research Database (Denmark)

Glucagon like peptide-1 (GLP-1) stimulates insulin secretion from the pancreas but also has extra-pancreatic effects. GLP-1 may stimulate glucose uptake in cultured muscle cells but the mechanism is not clearly defined. Furthermore, while the pancreatic effects of GLP-1 are glucose-dependent, the glucose-dependency of its extra-pancreatic effects has not been examined.

Green, Charlotte J; Henriksen, Tora I

2012-01-01

55

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

OpenAIRE

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...

Mei Tian; Hong Zhang; Keigo Endo

2011-01-01

56

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

Science.gov (United States)

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. PMID:23114090

Zheng, Fang-Jing; Ye, Hao-Bin; Wu, Man-Si; Lian, Yi-Fan; Qian, Chao-Nan; Zeng, Yi-Xin

2012-11-01

57

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

Directory of Open Access Journals (Sweden)

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.

Chao-Nan Qian

2012-11-01

58

Altered glucose metabolism and proteolysis in pancreatic cancer cell conditioned myoblasts: searching for a gene expression pattern with a microarray analysis of 5000 skeletal muscle genes  

OpenAIRE

Background and aims: We verified whether conditioned media (CM) from pancreatic cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3) alter glucose metabolism and gene expression profiles (microarray experiment with a platform of 5000 skeletal muscle cDNA) in mice myoblasts.

Basso, D.; Millino, C.; Greco, E.; Romualdi, C.; Fogar, P.; Valerio, A.; Bellin, M.; Zambon, C-f; Navaglia, F.; Dussini, N.; Avogaro, A.; Pedrazzoli, S.; Lanfranchi, G.; Plebani, M.

2004-01-01

59

Glucose metabolism in injured tissue: A longitudinal study  

International Nuclear Information System (INIS)

Injured tissue is characterized by increased glucose uptake and increased lactate production as compared to normal tissue. These metabolic changes have been attributed to the presence of inflammatory cells in injured tissues. To correlate these metabolic changes with changes in the inflammatory cell population at various times after injury, we studied the lambda-carrageenan hindlimb wound model in anesthetized rats. Perfusion studies demonstrated that at 3 and 5 days after injury glucose uptake was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. At 3, 5, and 10 days after injury, lactate production from glucose was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. These metabolic changes were not related to differences in body weight or food intake. There was no difference in glucose oxidation or in oxygen consumption in injured hindlimbs, compared with hindlimbs from pair-fed control animals. The increased glucose uptake and increased lactate production from glucose was coincident with the presence of inflammatory cells--predominantly macrophages--at the site of injury. It is suggested that the glucose metabolism in injured tissue reflects the metabolism of the inflammatory cells at the site of injury

60

Glucose metabolism of malignant cells is not regulated by transketolase-like (TKTL)-1.  

Science.gov (United States)

An isoenzyme of transketolase, transketolase-like (TKTL)-1, has been hypothesized to play a pivotal role in the pathophysiology of malignant tumors. Available data are based on the detection of the putative TKTL-1 protein with one particular mouse monoclonal anti-TKTL-1 antibody, clone JFC12T10. In this study it was demonstrated that a) JFC12T10 detects multiple unspecific bands in Western blots, b) a 75-kDa band hitherto referred to as TKTL-1 corresponds to a nuclear protein and c) immunohistochemical detection of TKTL-1 in benign leiomyomas yields an expression pattern identical to that found in a variety of malignant tumors. In RT-PCR assays, using three different primer pairs for transketolase, TKTL-1 and yet another isogene of transketolase, TKTL-2, a relevant expression of TKTL-1 was not detectable in any of the 6 malignant tumor cell lines investigated (MCF-7, A549, HeLa, HT1080, M21 and TF-1). Expression levels of TKTL-1 were rather similar to those found for TKTL-2, although the latter has never been implicated in malignant disease. On the basis of these data, nutritional recommendations based on a hypothetically TKTL-1 controlled metabolism of tumor cells must be regarded as lacking scientific evidence. PMID:20596653

Mayer, Arnulf; Von Wallbrunn, Angelika; Vaupel, Peter

2010-08-01

61

Effects of fluctuating glucose concentrations on oxidative metabolism of glucose in cultured neurons and astroglia  

Directory of Open Access Journals (Sweden)

Full Text Available The objective of the present study was to evaluate the effects of hyperglycemia on glucose metabolism of brain cells. Not only a sustained hyperglycemic state, but also a fluctuating plasma glucose concentration has been implicated in the pathogenesis of diabetic angiopathy. Acutely increasing plasma glucose levels have not been reported to alter glucose utilization of the brain as a whole. In the present study, we examined the effects of chronic (3 weeks or short-term (24-hour exposure to a high glucose concentration on the oxidative metabolism of neurons and astroglia. Cells were prepared from Sprague-Dawley rats and cultured in the presence of a high (22 mM or low (5 mM concentration of glucose. The high or low glucose media did not alter either the rates of [14C]deoxyglucose phosphorylation (an indicator of total glucose utilization or [14C]lactate and [14C]pyruvate oxidation (indicators of oxidative glucose metabolism in neurons. In contrast, chronic or short-term exposure to a high glucose concentration resulted in significant decreases in oxidation of [14C]acetate, an astrocyte-specific reporter molecule, or [14C]lactate and [14C]pyruvate oxidation in the astroglia. Thus, either chronic or short-term increases in the glucose concentration suppressed oxidative metabolism only in astroglia, indicating neuro-protective roles against hyperglycemic brain cell injury in diabetes mellitus. These different responses of neurons and astroglia may also shed new light on brain energy metabolism in diabetic patients with either chronic high or fluctuating plasma glucose concentrations.

Takato Abe

2012-02-01

62

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

Directory of Open Access Journals (Sweden)

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.

Saddi-Rosa Pedro

2010-03-01

63

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

International Nuclear Information System (INIS)

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

64

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

65

A Quaternary Mechanism Enables the Complex Biological Functions of Octameric Human UDP-glucose Pyrophosphorylase, a Key Enzyme in Cell Metabolism.  

Science.gov (United States)

In mammals, UDP-glucose pyrophosphorylase (UGP) is the only enzyme capable of activating glucose-1-phosphate (Glc-1-P) to UDP-glucose (UDP-Glc), a metabolite located at the intersection of virtually all metabolic pathways in the mammalian cell. Despite the essential role of its product, the molecular basis of UGP function is poorly understood. Here we report the crystal structure of human UGP in complex with its product UDP-Glc. Beyond providing first insight into the active site architecture, we describe the substrate binding mode and intermolecular interactions in the octameric enzyme that are crucial to its activity. Importantly, the quaternary mechanism identified for human UGP in this study may be common for oligomeric sugar-activating nucleotidyltransferases. Elucidating such mechanisms is essential for understanding nucleotide sugar metabolism and opens the perspective for the development of drugs that specifically inhibit simpler organized nucleotidyltransferases in pathogens. PMID:25860585

Führing, Jana Indra; Cramer, Johannes Thomas; Schneider, Julia; Baruch, Petra; Gerardy-Schahn, Rita; Fedorov, Roman

2015-01-01

66

Glucose deprivation-induced metabolic oxidative stress and cancer therapy  

Directory of Open Access Journals (Sweden)

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.

Simons Andrean

2009-09-01

67

Evidence for Central Regulation of Glucose Metabolism*  

OpenAIRE

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...

Carey, Michelle; Kehlenbrink, Sylvia; Hawkins, Meredith

2013-01-01

68

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

OpenAIRE

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...

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

2001-01-01

69

Glucose Metabolism in Mentally Retarded Children  

International Nuclear Information System (INIS)

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)

70

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

International Nuclear Information System (INIS)

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

71

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

2013-11-15

72

Glucose metabolism of lactobacillus divergens  

International Nuclear Information System (INIS)

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

73

Heterogeneity in glucose sensitivity among pancreatic beta-cells is correlated to differences in glucose phosphorylation rather than glucose transport.  

Science.gov (United States)

Rat beta-cells differ in their individual rates of glucose-induced insulin biosynthesis and release. This functional heterogeneity has been correlated with intercellular differences in metabolic redox responsiveness to glucose. The present study compares glucose metabolism in two beta-cell subpopulations that have been separated on the basis of the presence (high responsive) or absence (low responsive) of a metabolic redox shift at 7.5 mM glucose. Mean rates of glucose utilization and glucose oxidation in high responsive beta-cells were 2- to 4-fold higher than in low responsive beta-cells, whereas their leucine and glutamine oxidation was only 10-50% higher. This heterogeneity in glucose metabolism cannot be attributed to differences in GLUT2 mRNA levels or in glucose transport. In both cell subpopulations, the rates of glucose transport (13-19 pmol/min/10(3) beta-cells) were at least 50-fold higher than corresponding rates of glucose utilization. On the other hand, rates of glucose phosphorylation (0.3-0.7 pmol/min/10(3) beta-cells) ranged within those of total glucose utilization (0.2-0.4 pmol/min/10(3) beta-cells). High responsive beta-cells exhibited a 60% higher glucokinase activity than low responsive beta-cells and their glucokinase mRNA level was 100% higher. Furthermore, glucose phosphorylation via low Km hexokinase was detected only in the high responsive beta-cell subpopulation. Heterogeneity in glucose sensitivity among pancreatic beta-cells can therefore be explained by intercellular differences in glucose phosphorylation rather than in glucose transport. PMID:8335003

Heimberg, H; De Vos, A; Vandercammen, A; Van Schaftingen, E; Pipeleers, D; Schuit, F

1993-01-01

74

The use of enzymopathic human red cells in the study of malarial parasite glucose metabolism.  

Science.gov (United States)

The in vitro growth of Plasmodium falciparum malaria parasites was assayed in mutant red cells deficient in either diphosphoglycerate mutase (DPGM) or phosphoglycerate kinase (PGK). In addition, cDNA probes developed for human DNA sequences coding for these enzymes were used to examine the parasite genome by means of restriction endonuclease digestion and Southern blot analysis of parasite DNA. In both types of enzymopathic red cells, parasite growth was normal. In infected DPGM deficient red cells, no DPGM activity could be detected, and in normal red cells, DPGM activity declined slightly in a manner suggestive of parasite catabolism of host protein. However, in infected PGK deficient red cells, there was a 100-fold increase in PGK activity, and in normal red cells, a threefold increase in PGK activity was observed. Parasite PGK could be recovered from isolated parasites, and a marked increase in heat instability of parasite PGK as compared with the host cell enzyme was noted. Neither cDNA probe was found to cross-react with DNA sequences in the parasite genome. It is concluded that the parasite has no requirement for DPGM, and probably has no gene for this enzyme. On the other hand, the parasite does require PGK, (an adenosine triphosphate [ATP] generating enzyme) and synthesizes its own enzyme, which must have been encoded in the parasite genome. The parasite PGK gene most likely lacks sufficient homology to be detected by a human cDNA probe. Enzymopathic red cells are useful tools for elucidating the glycolytic enzymology of parasites and their co-evolution with their human hosts. PMID:2833958

Roth, E; Joulin, V; Miwa, S; Yoshida, A; Akatsuka, J; Cohen-Solal, M; Rosa, R

1988-05-01

75

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

International Nuclear Information System (INIS)

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

76

Inhibitors of cannabinoid receptors and glucose metabolism.  

OpenAIRE

PURPOSE OF REVIEW: Abdominal obesity is closely related to type 2 diabetes and overactivity of the endocannabinoid system. The present review aims at evaluating the role of endocannabinoid system in glucose dysregulation and the effects of cannabinoid 1 receptor blockade on glucose metabolism in both animal models and overweight/obese humans, especially with type 2 diabetes. RECENT FINDINGS: Cannabinoid 1 receptors have been identified not only in the brain, but also in the adipose tissue, th...

Scheen, Andre?; Paquot, Nicolas

2008-01-01

77

Glucose metabolism in rat retinal pigment epithelium.  

Science.gov (United States)

The retinal pigment epithelium (RPE) is the major transport pathway for exchange of metabolites and ions between choroidal blood supply and the neural retina. To gain insight into the mechanisms controlling glucose metabolism in RPE and its possible relationship to retinopathy, we studied the influence of different glucose concentrations on glycogen and lactate levels and CO(2) production in RPE from normal and streptozotocin-treated diabetic rats. Incubation of normal RPE in the absence of glucose caused a decrease in lactate production and glycogen content. In normal RPE, increasing glucose concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose accumulation and CO(2) yield, as well as reduction in lactate and glycogen production. In RPE from diabetic rats glucose accumulation did not increase in the presence of high glucose substrate, but it showed a four- and a seven-fold increase in CO(2) production through the mitochondrial and pentose phosphate pathways, respectively. We found high glycogen levels in RPE which can be used as an energy reserve for RPE itself and/or neural retina. Findings further show that the RPE possesses a high oxidative capacity. The large increase in glucose shunting to the pentose phosphate pathway in diabetic retina exposed to high glucose suggests a need for reducing capacity, consistent with increased oxidative stress. PMID:16475003

Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

2006-01-01

78

Hepatocyte nuclear factor 4alpha regulates the expression of pancreatic beta -cell genes implicated in glucose metabolism and nutrient-induced insulin secretion  

OpenAIRE

Mutations in the HNF4alpha gene are associated with the subtype 1 of maturity-onset diabetes of the young (MODY1), which is characterized by impaired insulin secretory response to glucose in pancreatic beta-cells. Hepatocyte nuclear factor 4alpha (HNF4alpha) is a transcription factor critical for liver development and hepatocyte-specific gene expression. However, the role of HNF4alpha in the regulation of pancreatic beta-cell gene expression and its correlation with metabolism secretion coupl...

Wang, Haiyan; Maechler, Pierre; Antinozzi, Peter; Hagenfeldt-johansson, Kerstin Arlette; Wollheim, Claes

2000-01-01

79

CMPF Does Not Associate with Impaired Glucose Metabolism in Individuals with Features of Metabolic Syndrome  

Science.gov (United States)

Objective 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a metabolite produced endogenously from dietary sources of furan fatty acids. The richest source of furan fatty acids in human diet is fish. CMPF was recently shown to be elevated in fasting plasma in individuals with gestational diabetes and type 2 diabetes, and mechanistically high level of CMPF was linked to ? cell dysfunction. Here we aimed to study the association between plasma CMPF level and glucose metabolism in persons with impaired glucose metabolism. Methods Plasma CMPF concentration was measured from plasma samples of the study participants in an earlier controlled dietary intervention. All of them had impaired glucose metabolism and two other characteristics of the metabolic syndrome. Altogether 106 men and women were randomized into three groups for 12 weeks with different fish consumption (either three fatty fish meals per week, habitual fish consumption or maximum of one fish meal per week). Associations between concentration of CMPF and various glucose metabolism parameters at an oral glucose tolerance test at baseline and at the end of the study were studied. Results Fasting plasma CMPF concentration was significantly increased after a 12-week consumption of fatty fish three times per week, but the concentration remained much lower compared to concentrations reported in diabetic patients. Increases of plasma CMPF concentrations mostly due to increased fish consumption were not associated with impaired glucose metabolism in this study. Instead, elevated plasma CMPF concentration was associated with decreased 2-hour insulin concentration in OGTT. Conclusions Moderately elevated concentration of CMPF in plasma resulting from increased intake of fish is not harmful to glucose metabolism. Further studies are needed to fully explore the role of CMPF in the pathogenesis of impaired glucose metabolism. Trial Registration ClinicalTrials.gov NCT00573781 PMID:25874636

Lankinen, Maria A.; Hanhineva, Kati; Kolehmainen, Marjukka; Lehtonen, Marko; Auriola, Seppo; Mykkänen, Hannu; Poutanen, Kaisa; Schwab, Ursula; Uusitupa, Matti

2015-01-01

80

Cerebral glucose metabolism in childhood onset schizophrenia.  

Science.gov (United States)

Decreased frontal cortical glucose metabolism has been demonstrated in adult schizophrenics both at rest and while engaging in tasks that normally increase frontal metabolism, such as the Continuous Performance Test (CPT). The authors tested the hypothesis that adolescents with childhood onset schizophrenia would also demonstrate hypofrontality while performing the CPT. Cerebral glucose metabolism was examined in 16 adolescents (mean age 14.1 +/- 1.7) with onset of schizophrenia by age 12 (mean age at onset 9.9 +/- 1.8) and 26 healthy adolescents selected to be similar in age, sex and handedness using positron emission tomography and 18F-fluorodeoxyglucose. Patients with childhood onset schizophrenia made fewer correct and more incorrect identifications on the CPT. Region of interest analysis revealed no significant group differences in global cerebral glucose metabolism, but increased metabolic rate in supramarginal gyrus (F = 6.74, P < 0.05) and inferior frontal gyrus/insula (F = 7.09, P < 0.05) and decreased metabolic rate in middle frontal gyrus (F = 6.72, P < 0.05) and superior frontal gyrus (t = 2.04, P < 0.05) in schizophrenics. Comparison of effect sizes with an identically designed study of adult schizophrenics did not indicate more severe hypofrontality in childhood onset schizophrenia. Pixel-based analyses indicated a more complex pattern of group differences in cerebral metabolism with bilaterally increased cerebellar metabolic rate in childhood onset schizophrenics. These findings suggest that childhood onset schizophrenia may be associated with a similar, but not more severe, degree of hypofrontality relative to that seen in adult onset schizophrenia. PMID:9437771

Jacobsen, L K; Hamburger, S D; Van Horn, J D; Vaituzis, A C; McKenna, K; Frazier, J A; Gordon, C T; Lenane, M C; Rapoport, J L; Zametkin, A J

1997-10-31

81

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

DEFF Research Database (Denmark)

The growth and product formation of Saccharomyces kluyveri was characterized in aerobic batch cultivation on glucose. At these conditions it was found that ethyl acetate was a major overflow metabolite in S. kluyveri. During the exponential-growth phase on glucose ethyl acetate was produced at a 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 growth in aerobic glucose-limited continuous cultivation. It was found that in S. kluyveri the flux into the pentose phosphate pathway was 18.8 mmole per 100 mmole glucose consumed during respiratory growth in aerobic glucose-limited continuous cultivation. Such a low flux into the pentose phosphate pathway cannot provide the cell with enough NADPH for biomass formation which is why the remaining NADPH will have to be provided by another pathway. During batch cultivation of S. kluyveri the tricarboxylic acid cycle was working as a cycle with a considerable flux, that is in sharp contrast to what has 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.

MØller, Kasper; Christensen, B.

2002-01-01

82

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

International Nuclear Information System (INIS)

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 withithin 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

83

Adult glucose metabolism in extremely birthweight-discordant monozygotic twins  

DEFF Research Database (Denmark)

AIMS/HYPOTHESIS: 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. METHODS: Among 77,885 twins in the Danish Twin Registry, 155 of the most BW-discordant MZ twin pairs (median BW difference 0.5 kg) were assessed using a 2 h oral glucose tolerance test with sampling of plasma (p-)glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. HOMA for beta cell function (HOMA-?) and insulin resistance (HOMA-IR), and also insulin sensitivity index (BIGTT-SI) and acute insulin response (BIGTT-AIR), were calculated. Subgroup analyses were performed in those with: (1) double verification of BW difference; (2) difference in BW >0.5 kg; and (3) no overt metabolic disease (type 2 diabetes, hyperlipidaemia or thyroid disease). RESULTS: No intra-pair differences in p-glucose, insulin, C-peptide, incretin hormones, HOMA-?, HOMA-IR or BIGTT-SI were identified. p-Glucose at 120 min was higher in the twins with the highest BW without metabolic disease, and BIGTT-AIR was higher in those with the highest BW although not in pairs with a BW difference of >0.5 kg. CONCLUSIONS/INTERPRETATION: BW-discordant MZ twins provide no evidence for a detrimental effect of low BW on glucose metabolism in adulthood once genetic factors and rearing environment are controlled for.

Nielsen, Morten Frost Munk; Petersen, I

2012-01-01

84

Regulation of Blood Glucose by Hypothalamic Pyruvate Metabolism  

Science.gov (United States)

The brain keenly depends on glucose for energy, and mammalians have redundant systems to control glucose production. An increase in circulating glucose inhibits glucose production in the liver, but this negative feedback is impaired in type 2 diabetes. Here we report that a primary increase in hypothalamic glucose levels lowers blood glucose through inhibition of glucose production in rats. The effect of glucose requires its conversion to lactate followed by stimulation of pyruvate metabolism, which leads to activation of adenosine triphosphate (ATP)-sensitive potassium channels. Thus, interventions designed to enhance the hypothalamic sensing of glucose may improve glucose homeostasis in diabetes.

Lam, Tony K. T.; Gutierrez-Juarez, Roger; Pocai, Alessandro; Rossetti, Luciano

2005-08-01

85

D-Lactate production as a function of glucose metabolism in Saccharomyces cerevisiae.  

Science.gov (United States)

Methylglyoxal, a reactive, toxic dicarbonyl, is generated by the spontaneous degradation of glycolytic intermediates. Methylglyoxal can form covalent adducts with cellular macromolecules, potentially disrupting cellular function. We performed experiments using the model organism Saccharomyces cerevisiae, grown in media containing low, moderate and high glucose concentrations, to determine the relationship between glucose consumption and methylglyoxal metabolism. Normal growth experiments and glutathione depletion experiments showed that metabolism of methylglyoxal by log-phase yeast cultured aerobically occurred primarily through the glyoxalase pathway. Growth in high-glucose media resulted in increased generation of the methylglyoxal metabolite D-lactate and overall lower efficiency of glucose utilization as measured by growth rates. Cells grown in high-glucose media maintained higher glucose uptake flux than cells grown in moderate-glucose or low-glucose media. Computational modelling showed that increased glucose consumption may impair catabolism of triose phosphates as a result of an altered NAD?:NADH ratio. PMID:23361949

Stewart, Benjamin J; Navid, Ali; Kulp, Kristen S; Knaack, Jennifer L S; Bench, Graham

2013-02-01

86

Cerebral glucose metabolism in Parkinson's disease  

International Nuclear Information System (INIS)

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

87

Cardiovascular risk factors in adult patients with multisystem Langerhans-cell histiocytosis: evidence of glucose metabolism abnormalities.  

OpenAIRE

BACKGROUND: Langerhans-cell histiocytosis (LCH) is a rare disease with features of chronic inflammation and it may also induce hypopituitarism, conditions associated with an increased risk of cardiovascular diseases. AIM: Cardiovascular and metabolic risk profile investigation in multisystem LCH patients with and without anterior pituitary deficiency. DESIGN: Prospective, observational study. METHODS: Fourteen adult patients with LCH, 7 with and 7 without anterior pituitary deficiency, and 42...

Alexandraki, Ki; Makras, P.; Protogerou, Ad; Dimitriou, K.; Stathopoulou, A.; Papadogias, Ds; Voidonikola, P.; Piaditis, G.; Pittas, A.; Papamichael, Cm; Grossman, Ab; Kaltsas, G.

2008-01-01

88

Cancer metabolism: Is glutamine sweeter than glucose?  

OpenAIRE

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.

Lu, Weiqin; Pelicano, Helene; Huang, Peng

2010-01-01

89

Quantification of serial tumor glucose metabolism  

Energy Technology Data Exchange (ETDEWEB)

We developed a method to improve the quantitative precision of FDG-PET scans in cancer patients. The total-lesion evaluation method generates a correlation coefficient (r) constrained Patlak parametric image of the lesion together with three calculated glucose metabolic indices: (a) the total-lesion metabolic index ({open_quotes}K{sub T-tie}{close_quotes}, ml/min/lesion); (b) the total-lesion voxel index ({open_quotes}V{sub T-tie}{close_quotes}, voxels/lesion); and (c) the global average metabolic index ({open_quotes}K{sub V-tie}{close_quotes}, ml/min/voxel). The glucose metabolic indices obtained from conventional region of interest (ROI) and multiplane evaluation were used as standards to evaluate the accuracy of the total-lesion evaluation method. Computer simulations and four patients with metastatic melanoma before and after chemotherapy were studied. Computer simulations showed that the total-lesion evaluation method has improved precision (%s.d. <0.6%) and accuracy ({approximately}10% error) compared with the conventional ROI method (%S.d. {approximately}5%; {approximately}25% error). The K{sub T-tie} and V{sub T-tie} indices from human FDG-PET studies using the total-lesion evaluation method showed excellent correlations with the corresponding values obtained from the conventional ROI methods and multiplane evaluation (r{approximately}1.0) and CT lesion volume measurements. This method is a simple but reliable way to quantitatively monitor tumor FDG uptake. The method has several advantages over the conventional ROI method: (a) less sensitive to the ROI definition, (b) no need for image registration of serial scan data and (c) includes tumor volume changes in the global tumor metabolism. 18 refs., 8 figs., 4 tabs.

Wu, Hsiao-Ming; Hoh, C.K.; Huang, Sung-Cheng; Yao, Wei-Jen [UCLA School of Medicine, Los Angeles, CA (United States)] [and others

1996-03-01

90

Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production  

OpenAIRE

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

Lam, Tony K. T.

2007-01-01

91

Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin  

Science.gov (United States)

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

Wang, Zhi; Yang, Tieyi; Ying, Hui; Zhang, Yan; Liu, Shuyi

2015-01-01

92

Depressed cerebellar glucose metabolism in supratentorial tumors  

Energy Technology Data Exchange (ETDEWEB)

Fifty-four patients with supratentorial tumor and one with brainstem tumor were examined with positron emission tomography (PET) using (/sup 18/F)fluoro-deoxyglucose (FDG). Twenty-one of these cases had satisfactory studies of the cerebellum. Of these, 12 showed significant metabolic asymmetry between the two cerebellar hemispheres, with the rate of glucose utilization in the hemisphere contralateral to the cerebral tumor being 8-34% lower than on the ipsilateral side, as compared with a right-left asymmetry of only -1.6% +- 2.1% standard deviation for a group of 5 normal subjects. In these 12 cases the tumor involved the sensorimotor cortex and/or the thalamus with varying degrees of hemiparesis being present. For the remaining 9 patients with no significant cerebellar metabolic asymmetry, the tumor involved regions other than the sensorimotor cortex, and unilateral motor dysfunction was not a prominent clinical feature. The correlation between cerebellar metabolic suppression and unilateral motor dysfunction observed in these cases appears to be due to impairment or interruption of the cortico-thalamo-ponto-olivo-cerebellar circuitry by either the tumour itself or by edema. Thus FDG-PET scans are able to detect metabolic changes in areas of the brain remote from the primary lesion.

Patronas, N.J.; Di Chiro, G.; Smith, B.H.; Paz, R. de la; Brooks, R.A.; Milam, H.L.; Kornblith, P.L.; Bairamian, D.; Mansi, L. (National Inst. of Neurological Diseases and Stroke, Bethesda, MD (USA))

1984-01-16

93

Depressed cerebellar glucose metabolism in supratentorial tumors  

International Nuclear Information System (INIS)

Fifty-four patients with supratentorial tumor and one with brainstem tumor were examined with positron emission tomography (PET) using [18F]fluoro-deoxyglucose (FDG). Twenty-one of these cases had satisfactory studies of the cerebellum. Of these, 12 showed significant metabolic asymmetry between the two cerebellar hemispheres, with the rate of glucose utilization in the hemisphere contralateral to the cerebral tumor being 8-34% lower than on the ipsilateral side, as compared with a right-left asymmetry of only -1.6% +- 2.1% standard deviation for a group of 5 normal subjects. In these 12 cases the tumor involved the sensorimotor cortex and/or the thalamus with varying degrees of hemiparesis being present. For the remaining 9 patients with no significant cerebellar metabolic asymmetry, the tumor involved regions other than the sensorimotor cortex, and unilateral motor dysfunction was not a prominent clinical feature. The correlation between cerebellar metabolic suppression and unilateral motor dysfunction observed in these cases appears to be due to impairment or interruption of the cortico-thalamo-ponto-olivo-cerebellar circuitry by either the tumour itself or by edema. Thus FDG-PET scans are able to detect metabolic changes in areas of the brain remote from the primary lesion. (Auth.)

94

[Val12] HRAS downregulates GLUT2 in beta cells of transgenic mice without affecting glucose homeostasis.  

OpenAIRE

Glucose-induced insulin release from pancreatic beta cells depends on the beta-cell metabolism of glucose, which generates intracellular signals for secretion. The beta-cell glucose transporter isotype GLUT2 and the glucose phosphorylating enzyme glucokinase have both been implicated in coupling insulin secretion to extracellular glucose levels. Here we present evidence that a pronounced decrease in beta-cell GLUT2 has no immediate effect on glucose homeostasis. Analysis of transgenic mice ov...

Tal, M.; Wu, Y. J.; Leiser, M.; Surana, M.; Lodish, H.; Fleischer, N.; Weir, G.; Efrat, S.

1992-01-01

95

Pentose pathway of glucose metabolism in isolated granular pneumocytes. Metabolic regulation and stimulation by paraquat.  

Science.gov (United States)

Activity of the pentose phosphate pathway of glucose metabolism was measured in isolated granular pneumocytes under a variety of metabolic conditions known to alter this pathway in intact lungs. Granular pneumocytes were isolated by trypsinization of rat lungs and maintained in primary culture for 24 hr before use. Cells were incubated for 1 hr at 37 degrees with 5.5 mM glucose specifically labeled as 1-14C, 6-14C, U-14C, or 5-3H for determination of glucose utilization, pentose cycle activity, and partition of CO2 production between mitochondrial and pentose pathways. With control cells, total glucose utilization was 111 +/- 4.8 nmoles X hr-1 X (10(6) cells)-1 (mean +/- S.E., N = 19), and 2.2% was metabolized by the pentose cycle. Pentose cycle CO2 production was 7.3 nmoles X hr-1 X (10(6) cells)-1 representing 34% of total CO2 production. Dinitrophenol (50 microM) stimulated mitochondrial CO2 production 5-fold but had no effect on the pentose cycle activity. Phenazine methosulfate (5 microM) had no effect on mitochondrial activity but stimulated pentose cycle activity 15-fold. Antimycin A (0.4 micrograms/ml) markedly inhibited both pathways. After a 30-min preincubation with paraquat (3 mM), the pentose cycle CO2 production increased to 107 nmoles X hr-1 X (10(6) cells)-1 accounting for 39.6% of glucose utilization and 88.4% of CO2 production. Mitochondrial CO2 production was unchanged with paraquat. These studies demonstrate that the pentose cycle in resting granular pneumocytes accounts for a major fraction of the CO2 production from glucose and that activity of this pathway is regulated by the utilization of cytoplasmic reducing equivalents. Paraquat produces marked stimulation of pentose cycle activity in granular pneumocytes, resulting in maximal utilization of cytoplasmic NADPH. PMID:6424685

Fisher, A B; Reicherter, J

1984-04-15

96

Effects of Glucose on Differentiation and Fat Metabolism of Chicken Preadipocytes  

Directory of Open Access Journals (Sweden)

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.

Zhao Taotao

2012-01-01

97

Metabolically engineered glucose-utilizing Shewanella strains under anaerobic conditions.  

Science.gov (United States)

Comparative genome analysis of Shewanella strains predicted that the strains metabolize preferably two- and three-carbon carbohydrates as carbon/electron source because many Shewanella genomes are deficient of the key enzymes in glycolysis (e.g., glucokinase). In addition, all Shewanella genomes are known to have only one set of genes associated with the phosphotransferase system required to uptake sugars. To engineer Shewanella strains that can utilize five- and six-carbon carbohydrates, we constructed glucose-utilizing Shewanella oneidensis MR-1 by introducing the glucose facilitator (glf; ZMO0366) and glucokinase (glk; ZMO0369) genes of Zymomonas mobilis. The engineered MR-1 strain was able to grow on glucose as a sole carbon/electron source under anaerobic conditions. The glucose affinity (Ks) and glucokinase activity in the engineered MR-1 strain were 299.46 mM and 0.259 ± 0.034 U/g proteins. The engineered strain was successfully applied to a microbial fuel cell system and exhibited current generation using glucose as the electron source. PMID:24384311

Choi, Donggeon; Lee, Sae Bom; Kim, Sohyun; Min, Byoungnam; Choi, In-Geol; Chang, In Seop

2014-02-01

98

Microcalorimetric Measurements of Glucose Metabolism by Marine Bacterium Vibrio alginolyticus  

Science.gov (United States)

Microcalorimetric measurements of heat production from glucose by Vibrio alginolyticus were made to assess the viability of calorimetry as a technique for studying the metabolism of marine bacteria at organic nutrient concentrations found in marine waters. The results show that the metabolism of glucose by this bacterium can be measured by calorimetry at submicromolar concentrations. A linear correlation between glucose concentration and total heat production was observed over a concentration range of 8 mM to 0.35 ?M. It is suggested that these data indicate a constant efficiency of metabolism for this bacterium over the wide range of glucose concentrations studied. PMID:16346131

Gordon, Andrew S.; Millero, Frank J.; Gerchakov, Sol M.

1982-01-01

99

Glucose Metabolism in Breast Cancer and its Implication in Cancer Therapy  

Directory of Open Access Journals (Sweden)

Full Text Available It is well known that malignant cells have accelerated glucose uptake and metabolism in order to maintain their fast proliferation rates. With the increased influx of glucose into cancer cells, glycolysis is facilitated through a coordinated regulation of metabolic enzymes and pyruvate consumption. Shiftting from mitochondrial oxidative phosphorylation to glycolysis and other pathways such as pentose phosphate pathway (PPP and de novo fatty acid synthesis in the breast tumor provides not only energy but also the materials needed for cell proliferation. Glucose augmentation in tumor cells can be due to the elevated level of glucose transporter (GLUT proteins, such as the over-expression of GLUT1 and expression of GLUT5 in breast cancers. Moreover, other factors such as hypoxia-inducible factor-1 (HIF-1, estrogen and growth factors are important modulators of glucose metabolism in the progression of breast carcinomas. Therapies targeting at the glycolytic pathway, fatty acid synthesis and GLUTs expression are currently being investigated. Restoring tumor cells to its normal glucose metabolic state would endow tumor specific and accessible treatment that targets glucose metabolism.

Yuewen Gong

2011-05-01

100

Microcalorimetric Measurements of Glucose Metabolism by Marine Bacterium Vibrio alginolyticus  

OpenAIRE

Microcalorimetric measurements of heat production from glucose by Vibrio alginolyticus were made to assess the viability of calorimetry as a technique for studying the metabolism of marine bacteria at organic nutrient concentrations found in marine waters. The results show that the metabolism of glucose by this bacterium can be measured by calorimetry at submicromolar concentrations. A linear correlation between glucose concentration and total heat production was observed over a concentration...

Gordon, Andrew S.; Millero, Frank J.; Gerchakov, Sol M.

1982-01-01

101

Utilization of dietary glucose in the metabolic syndrome  

OpenAIRE

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 ex...

Alemany Marià

2011-01-01

102

Glucose metabolic gene expression in growth hormone transgenic coho salmon.  

Science.gov (United States)

Salmonids are generally known to be glucose intolerant. However, previous studies have shown that growth hormone (GH) transgenic coho salmon display modified nutritional regulation of glycolysis and lipogenesis compared to non-transgenic fish, suggesting the potential for better use of glucose in GH transgenic fish. To examine this in detail, GH transgenic and non-transgenic coho salmon were subjected to glucose tolerance test and subsequent metabolic assessments. After intra-peritoneal injection of 250mg/kg glucose, we analysed post-injection kinetics of glycaemia and expression of several key target genes highly involved in glucose homeostasis in muscle and liver tissues. Our data show no significant differences in plasma glucose levels during peak hyperglycaemia (3-6h after injection), demonstrating a similar glucose tolerance between transgenic and non transgenic. However, and unrelated to the hyperglycaemic episode, GH transgenic fish return to a slightly lower basal glycaemia values 24h after injection. Correspondingly, GH transgenic fish exhibited higher mRNA levels of glucokinase (GK) and glucose-6-phosphate dehydrogenase (G6PDH) in liver, and glucose transporter (GLUT4) in muscle. These data suggest that these metabolic actors may be involved in different glucose use in GH transgenic fish, which would be expected to influence the glucose challenge response. Overall, our data demonstrate that GH transgenic coho salmon may be a pertinent animal model for further study of glucose metabolism in carnivorous fish. PMID:24486143

Panserat, Stéphane; Kamalam, Biju Sam; Fournier, Jeanne; Plagnes-Juan, Elisabeth; Woodward, Krista; Devlin, Robert H

2014-04-01

103

Flow-Regulated Glucose and Lipid Metabolism in Adipose Tissue, Endothelial Cell and Hepatocyte Cultures in a Modular Bioreactor  

OpenAIRE

Abstract Static cell culture has serious limitations in its ability to represent cellular behaviour within a live organism. In vivo, cells are constantly exposed to the flow of bodily fluids and contact with other cell types. Bioreactors provide the opportunity to study cells in an environment that more closely resembles the in vivo setting because cell cultures can be exposed to dynamic flow in contact with or in proximity to other cell types. In this study we compare the me...

Vinci, Bruna; Murphy, Ellen; Iori, Elisabeta; Marescotti, Maria Cristina; Avogaro, Angelo; Ahluwalia, Arti

2010-01-01

104

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

Science.gov (United States)

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 IL4R?, 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 IL4R? expression increases proliferation thus enhancing primary mammary tumor growth. In vitro, IL4-enhanced glucose consumption and lactate production in 4T1 cells was mediated by IL4R?. Expression of the glucose transporter GLUT1 increased in response to IL4 in vitro, and enhanced GLUT1 expression was associated with the presence of IL4R? 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/IL4R?-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 IL4R? as a possible target for effective breast cancer therapy. PMID:25746764

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

2015-05-01

105

Regulation of exogenous and endogenous glucose metabolism by insulin and acetoacetate in the isolated working rat heart. A three tracer study of glycolysis, glycogen metabolism, and glucose oxidation.  

OpenAIRE

Myocardial glucose use is regulated by competing substrates and hormonal influences. However, the interactions of these effectors on the metabolism of exogenous glucose and glucose derived from endogenous glycogen are not completely understood. In order to determine changes in exogenous glucose uptake, glucose oxidation, and glycogen enrichment, hearts were perfused with glucose (5 mM) either alone, or glucose plus insulin (40 microU/ml), glucose plus acetoacetate (5 mM), or glucose plus insu...

Russell, R. R.; Cline, G. W.; Guthrie, P. H.; Goodwin, G. W.; Shulman, G. I.; Taegtmeyer, H.

1997-01-01

106

Regional glucose metabolism using PETT in normal and psychiatric populations  

International Nuclear Information System (INIS)

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

107

Glucose metabolism in pregnant sheep when placental growth is restricted  

Energy Technology Data Exchange (ETDEWEB)

The effect of restricting placental growth on glucose metabolism in pregnant sheep in late gestation was determined by primed constant infusions of D-(U-{sup 14}C)- and D-(2-{sup 3}H)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.

Owens, J.A.; Falconer, J.; Robinson, J.S. (Univ. of Adelaide Medical School (Australia))

1989-08-01

108

Glucose metabolism in pregnant sheep when placental growth is restricted  

International Nuclear Information System (INIS)

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

109

Abnormal glucose metabolism in patients treated with antipsychotics.  

OpenAIRE

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...

Scheen, Andre?; Hert, M. A.

2007-01-01

110

Skeleton and Glucose Metabolism: A Bone-Pancreas Loop  

Science.gov (United States)

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

Luce, Vincenza; Ventura, Annamaria; Colucci, Silvia; Cavallo, Luciano; Grano, Maria

2015-01-01

111

Endocytosis and vacuolar degradation of the yeast cell surface glucose sensors Rgt2 and Snf3.  

Science.gov (United States)

Sensing and signaling the presence of extracellular glucose is crucial for the yeast Saccharomyces cerevisiae because of its fermentative metabolism, characterized by high glucose flux through glycolysis. The yeast senses glucose through the cell surface glucose sensors Rgt2 and Snf3, which serve as glucose receptors that generate the signal for induction of genes involved in glucose uptake and metabolism. Rgt2 and Snf3 detect high and low glucose concentrations, respectively, perhaps because of their different affinities for glucose. Here, we provide evidence that cell surface levels of glucose sensors are regulated by ubiquitination and degradation. The glucose sensors are removed from the plasma membrane through endocytosis and targeted to the vacuole for degradation upon glucose depletion. The turnover of the glucose sensors is inhibited in endocytosis defective mutants, and the sensor proteins with a mutation at their putative ubiquitin-acceptor lysine residues are resistant to degradation. Of note, the low affinity glucose sensor Rgt2 remains stable only in high glucose grown cells, and the high affinity glucose sensor Snf3 is stable only in cells grown in low glucose. In addition, constitutively active, signaling forms of glucose sensors do not undergo endocytosis, whereas signaling defective sensors are constitutively targeted for degradation, suggesting that the stability of the glucose sensors may be associated with their ability to sense glucose. Therefore, our findings demonstrate that the amount of glucose available dictates the cell surface levels of the glucose sensors and that the regulation of glucose sensors by glucose concentration may enable yeast cells to maintain glucose sensing activity at the cell surface over a wide range of glucose concentrations. PMID:24451370

Roy, Adhiraj; Kim, Jeong-Ho

2014-03-01

112

Utilization of dietary glucose in the metabolic syndrome  

Directory of Open Access Journals (Sweden)

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

Alemany Marià

2011-10-01

113

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

International Nuclear Information System (INIS)

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

114

Cerebral glucose transport and metabolism with dynamic PET  

International Nuclear Information System (INIS)

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

115

Transcriptional Regulation of Glucose Sensors in Pancreatic ?-Cells and Liver: An Update  

OpenAIRE

Pancreatic ?-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 ?-cells or hepatocytes where it is metabolized. In the ?-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 rol...

Jin-Sik Bae; Tae-Hyun Kim; Mi-Young Kim; Joo-Man Park; Yong-Ho Ahn

2010-01-01

116

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

DEFF Research Database (Denmark)

Accumulating evidence suggest that the pyridine nucleotide NAD has far wider biological functions than its classical role in energy metabolism. NAD is used by hundreds of enzymes that catalyse substrate oxidation and as such it plays a key role in various biological processes such as aging, cell 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+]/[NADH] ratio determined in prostate cancer cells was 4 times higher than in breast cancer cells. This higher ratio reflects adistinct 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+]/[NADH] ratio, the bioprobe will enable better understanding of the origin of diverse pathological states of the cell as well as monitor cellular consequences of diseases and/or treatments.

Christensen, Caspar Elo; Karlsson, Magnus

2014-01-01

117

Glucose and glutamine metabolism control by APC and SCF during the G1-to-S phase transition of the cell cycle.  

Science.gov (United States)

Recent studies have given us a clue as to how modulations of both metabolic pathways and cyclins by the ubiquitin system influence cell cycle progression. Among these metabolic modulations, an aerobic glycolysis and glutaminolysis represent an initial step for metabolic machinery adaptation. The enzymes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and glutaminase-1 (GLS1) maintain a high abundance in glycolytic intermediates (for synthesis of non-essential amino acids, the use of ribose for the synthesis of nucleotides and hexosamine biosynthesis), as well as tricarboxylic acid cycle intermediates (replenishing the loss of mitochondrial citrate), respectively. On the one hand, regulation of these key metabolic enzymes by ubiquitin ligases anaphase-promoting complex/cyclosome (APC/C) and Skp1/cullin/F-box (SCF) has revealed the importance of anaplerosis by both glycolysis and glutaminolysis to overcome the restriction point of the G1 phase by maintaining high levels of glycolytic and glutaminolytic intermediates. On the other hand, only glutaminolytic intermediates are necessary to drive cell growth through the S and G2 phases of the cell cycle. It is interesting to appreciate how this reorganization of the metabolic machinery, which has been observed beyond cellular proliferation, is a crucial determinant of a cell's decision to proliferate. Here, we explore a unifying view of interactions between the ubiquitin system, metabolic activity, and cyclin-dependent kinase complexes activity during the cell cycle. PMID:24604252

Estévez-García, Irving Omar; Cordoba-Gonzalez, Verónica; Lara-Padilla, Eleazar; Fuentes-Toledo, Abel; Falfán-Valencia, Ramcés; Campos-Rodríguez, Rafael; Abarca-Rojano, Edgar

2014-06-01

118

A link between sleep loss, glucose metabolism and adipokines  

Scientific Electronic Library Online (English)

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.

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

2011-10-01

119

Metabolism of tritiated D-glucose in rat erythrocytes.  

Science.gov (United States)

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. PMID:1895964

Manuel y Keenoy, B; Malaisse-Lagae, F; Malaisse, W J

1991-09-01

120

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

OpenAIRE

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...

Abseyi, Nilay; S??klar, Zeynep; Berberog?lu, Merih; Hac?hamdiog?lu, Bu?lent; Savas? Erdeve, S?enay; O?c?al, Go?nu?l

2012-01-01

121

Multi-institute study finds protein controlling glucose metabolism also a tumor suppressor  

Science.gov (United States)

A protein known to regulate how cells process glucose also appears to be a tumor suppressor, adding to the potential that therapies directed at cellular metabolism may help suppress tumor growth. In their report in the Dec. 7 issue of Cell, a multi-institutional research team describes finding that cells lacking the enzyme SIRT6, which controls how cells process glucose, quickly become cancerous. They also found evidence that uncontrolled glycolysis, a stage in normal glucose metabolism, may drive tumor formation in the absence of SIRT6 and that suppressing glycolysis can halt tumor formation. The research team included scientists from the Massachusetts General Hospital (a component of the Dana-Farber Cancer Institute) and the University of Michigan, which is home to the University of Michigan Comprehensive Cancer Center.

122

Higher transport and metabolism of glucose in astrocytes compared with neurons: a multiphoton study of hippocampal and cerebellar tissue slices.  

Science.gov (United States)

Glucose is the most important energy substrate for the brain, and its cellular distribution is a subject of great current interest. We have employed fluorescent glucose probes, the 2-deoxy-D-glucose derivates 6- and 2-([N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose) (2-NBDG), to measure transport and metabolism of glucose in acute slices of mouse hippocampus and cerebellum. In the hippocampus, 6-NBDG, which is not metabolized and hence indicates glucose transport, was taken up faster in astrocyte-rich layers (Stratum radiatum [S.r.], Stratum oriens [S.o.]) than in pyramidal cells. Metabolizable 2-NBDG showed larger signals in S.r. and S.o. than in Stratum pyramidale, suggesting faster glucose utilization rate in the astrocyte versus the neuronal compartment. Similarly, we found higher uptake and temperature-sensitive metabolism of 2-NBDG in Bergmann glia when compared with adjacent Purkinje neurons of cerebellar slices. A comparison between 6-NBDG transport and glucose transport in cultured cells using a fluorescence resonance energy transfer nanosensor showed that relative to glucose, 6-NBDG is transported better by neurons than by astrocytes. These results indicate that the preferential transport and metabolism of glucose by glial cells versus neurons proposed for the hippocampus and cerebellum by ourselves (in vitro) and for the barrel cortex by Chuquet et al. (in vivo) is more pronounced than anticipated. PMID:23042735

Jakoby, Patrick; Schmidt, Elke; Ruminot, Iván; Gutiérrez, Robin; Barros, L Felipe; Deitmer, Joachim W

2014-01-01

123

Effects of Increasing Intravenous Glucose Infusions on Lactation Performance, Metabolic Profiles, and Metabolic Gene Expression in Dairy Cows  

OpenAIRE

Knowledge on the precise effects of surplus glucose supply in dairy cows is limited by the lack of information on how intermediary metabolism adapts at different levels of glucose availability. Therefore, a gradual increase of glucose supply via intravenous glucose infusion was used in the present study to test the dose effect of surplus provision of glucose on the metabolic status and milk production of dairy cows. Furthermore, the effects of increasing levels of surplus glucose on mRNA expr...

Bahaaaldeen, Al-trad

2010-01-01

124

Cholinergic denervation of the hippocampal formation does not produce long-term changes in glucose metabolism  

International Nuclear Information System (INIS)

Decreased glucose metabolism is found in Alzheimer's disease associated with a loss of cholinergic neurons. The relationship between the chronic cholinergic denervation produced by medial septal lesions and glucose metabolism was studied using 2-deoxy-D-[3H]glucose in the rat hippocampal formation. Hippocampal glucose metabolism was increased 1 week after medial septal lesions. Three weeks after lesions, glucose metabolism was profoundly suppressed in all regions. By 3 months, intraregional hippocampal glucose metabolism had returned to control values. Our results demonstrate that chronic cholinergic denervation of the hippocampal formation does not result in permanent alterations of metabolic activity

125

Dementia with impaired glucose metabolism in late onset metachromatic leukodystrophy  

DEFF Research Database (Denmark)

An unusual case of very-late-onset metachromatic leukodystrophy (MLD) with dementia was studied. The patient was a 41-year-old male who presented with mild dementia and a single generalized tonic clonic seizure. Neuropsychological assessment demonstrated mild amnesia, visuospatial dysfunction and attention deficits with a slow psychomotor speed. MR brain imaging displayed confluent hyperintensities of periventricular and subcortical white matter. Low levels of arylsulfatase A confirmed the diagnosis. Impaired cortical glucose metabolism especially of the medial temporal and frontal cortices was observed using positron emission tomography and fluor-18-labeled fluorodesoxyglucose. The neuropsychological deficits are related to the location of deficits in glucose metabolism.

Johannsen, P.; Ehlers, L.

2001-01-01

126

Tff3, as a Novel Peptide, Regulates Hepatic Glucose Metabolism  

OpenAIRE

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder strongly associated with hepatic glucose intolerance and insulin resistance. The trefoil peptides are a family of small regulatory proteins and Tff3 is widely expressed in multiple tissues including liver. But the roles of Tff3 in regulation of glucose metabolism and insulin sensitivity in liver remain unclear. Here we show that the hepatic Tff3 expression levels were decreased in ob/ob and high-fat diet-induced obese mice. Overe...

Xue, Yuan; Shen, Lian; Cui, Ying; Zhang, Huabing; Chen, Qi; Cui, Anfang; Fang, Fude; Chang, Yongsheng

2013-01-01

127

Snail modulates cell metabolism in MDCK cells  

Energy Technology Data Exchange (ETDEWEB)

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.

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

128

Snail modulates cell metabolism in MDCK cells  

International Nuclear Information System (INIS)

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

129

Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony  

OpenAIRE

Recent data underscore the importance of intertissue communication in the maintenance of normal glucose homeostasis. Important signals are conveyed by hormones, cytokines, and fuel substrates and are sensed through a variety of cellular mechanisms. The ability of tissues to sense and adapt to changes in metabolic status and fuel availability is altered in insulin-resistant states including type 2 diabetes. Here we review the roles of glucose and its metabolites as signaling molecules and the ...

Herman, Mark A.; Kahn, Barbara B.

2006-01-01

130

Chemosensitizing and cytotoxic effects of 2-deoxy-D-glucose on breast cancer cells  

OpenAIRE

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 cellula...

Zhang Fanjie; Aft Rebecca

2009-01-01

131

Cerebral glucose metabolic abnormality in patients with congenital scoliosis  

OpenAIRE

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 ...

Park, Weon Wook; Suh, Kuen Tak; Kim, Jeung Il; Ku, Ja Gyung; Lee, Hong Seok; Kim, Seong-jang; Kim, In-ju; Kim, Yong-ki; Lee, Jung Sub

2008-01-01

132

A distinct metabolic signature predicts development of fasting plasma glucose  

Directory of Open Access Journals (Sweden)

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.

Hische Manuela

2012-02-01

133

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

OpenAIRE

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 acti...

Chao-Nan Qian; Yi-Fan Lian; Man-Si Wu; Hao-Bin Ye; Fang-Jing Zheng; Yi-Xin Zeng

2012-01-01

134

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

International Nuclear Information System (INIS)

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

135

Radiorespirometric study of glucose metabolism in liver-damaged rats  

International Nuclear Information System (INIS)

Changes in glucose metabolism in rats during feeding with 3'-methyl-4-(dimethylamino)azobenzene(3'-Me-DAB) were investigated by radiorespirometry with 14C-labelled carbohydrates as substrates, in relation to the levels of liver glycolytic enzyme activities. Rats were fed on 0.06% 3'-Me-DAB for 7 weeks. Radiorespirometry was carried out by the IP administration of [U-14C]glucose 2.5 ?Ci or [1-14C]acetate 2.0 ?Ci weekly during the experimental period. In the analysis of the radiorespirometric pattern obtained with [U-14C]glucose, the peak time (PT) was markedly shortened at week 4. At week 6 of 3'-Me-DAB feeding, the peak height (PH) and yield value (YV) both increased significantly with concomitant shortening of PT. The duration of the activation in radiorespirometric parameters was paralleled reasonably well by that of glycolytic enzyme activity; the activation of liver glucose-6-phosphate dehydrogenase (G-6-PDH) shortens PT, while the activation of the tricarboxylic acid (TCA) cycle increases YV. This study showed that the radiorespirometric pattern reflected glucose metabolism in the liver well. In conclusion, radiorespirometric analysis with 14C-labelled glucose as a substrate may be useful for the clinical diagnosis of liver diseases. (orig.)

136

Effect of metformin on glucose metabolism in the splanchnic bed.  

Science.gov (United States)

1. Use of the antihyperglycaemic agent, metformin, is often associated with a small rise in circulating lactate. This study investigates the source of the lactate and examines the effect of metformin on glucose metabolism by the intestine and liver of rats. 2. Changes in plasma glucose and lactate were measured in the inferior vena cava (IVC), hepatic portal vein (HPV), hepatic vein (HV) and aorta (A) after intrajejunal administration of metformin (50 and 250 mg kg-1) without and with glucose (2 g kg-1). 3. Metformin 250 mg kg-1 reduced the hyperglycaemic response to a glucose challenge, associated with a greater reduction of glucose concentrations in the HPV (average decrease of 33% at 60 and 120 min) than at other sites. 4. Both doses of metformin increased lactate concentrations in the glucose-loaded state: the highest concentration (2.5 fold increase) was recorded in the HPV 60 min after administration of 250 mg kg-1 metformin, with a high lactate concentration persisting in the HV at 120 min. Metformin 250 mg kg-1 also increased lactate concentrations in the basal state, with highest concentrations (2 fold increase) in the HPV. 5. Two hours after intrajejunal administration of metformin, 50 mg kg-1, rings of tissue from the small intestine showed an average 22% decrease in glucose oxidation ([14C]-glucose conversion to 14CO2) and a 10% increase in lactate production. Since glucose metabolism in the gut is predominantly anaerobic, metformin caused an overall 9.5% increase of intestinal glucose utilization.6. Metformin, 10-6 and I0- mol 1', did not significantly alter glucose oxidation or lactate production by isolated hepatocytes, but a very high concentration of metformin (102 mol 1') increased lactate production by 60%.7. The results support the view that metformin increased intestinal glucose utilization and lactate production by the intestine. Under basal conditions there was net extraction of lactate by the liver but not after an enteral glucose load. PMID:1504710

Bailey, C J; Wilcock, C; Day, C

1992-04-01

137

?-Glutamyl carboxylase in osteoblasts regulates glucose metabolism in mice.  

Science.gov (United States)

Vitamin K-dependent ?-glutamyl carboxylase (GGCX) is an enzyme that catalyzes the conversion of glutamic acid to gamma-carboxyglutamic acid in substrate proteins. Among GGCX target proteins, recent evidence indicates that osteocalcin regulates insulin sensitivity and secretion. However, the precise contribution of GGCX to glucose metabolism remains to be clarified. To address this question, we generated osteoblast-specific Ggcx-deficient (i.e., conditional knockout [cKO]) mice using collagen type 1 ?1 (Col1)-Cre mice. Ggcx cKO mice exhibited altered metabolism compared with their controls; serum glucose levels could be maintained with low amounts of insulin, and the weight of white adipose tissue (WAT) significantly decreased in Ggcx cKO mice. Our findings suggest that GGCX expressed in osteoblasts is critical for the maintenance of blood glucose and WAT. PMID:25264202

Shiba, Sachiko; Ikeda, Kazuhiro; Azuma, Kotaro; Hasegawa, Tomoka; Amizuka, Norio; Horie-Inoue, Kuniko; Inoue, Satoshi

2014-10-24

138

Transcriptional Regulation of Glucose Sensors in Pancreatic ?-Cells and Liver: An Update  

Directory of Open Access Journals (Sweden)

Full Text Available Pancreatic ?-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 ?-cells or hepatocytes where it is metabolized. In the ?-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 ?-cells.

Jin-Sik Bae

2010-05-01

139

UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets  

DEFF Research Database (Denmark)

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.

Dalgaard, Louise Torp

2012-01-01

140

Pancreatic resection: effects on glucose metabolism.  

Science.gov (United States)

Pancreatic resection results in hormonal abnormalities that are dependent on the extent and location (proximal versus distal) of the resected portion of the gland. The form of glucose intolerance which results from pancreatic resection is termed pancreatogenic diabetes. It is associated with features distinct from both type I (insulin-dependent) and type II (insulin-independent, or adult-onset) diabetes. Hepatic insulin resistance with persistent endogenous glucose production and enhanced peripheral insulin sensitivity result in a brittle form of diabetes which can be difficult to manage. In addition to insulin deficiency, the endocrine abnormalities that accompany pancreatic resection can include glucagon deficiency or pancreatic polypeptide (PP) deficiency if the resection is distal or proximal, respectively. Glucagon deficiency can contribute to iatrogenic hypoglycemia, and PP deficiency can contribute to persistent hyperglycemia due to impaired hepatic insulin action. Pancreatic resections that spare the duodenum, such as distal pancreatectomy, duodenum-preserving pancreatic head resection (Beger procedure), or extended lateral pancreaticojejunostomy with excavation of the pancreatic head (Frey procedure), are associated with a lower incidence of new or worsened diabetes than the standard or pylorus-preserving pancreaticoduodenectomy (Whipple procedure) or total pancreatectomy. Operative considerations for the treatment of pancreatic disease should include strategies to minimize the hormonal impairment of pancreatic resection. PMID:11344398

Slezak, L A; Andersen, D K

2001-04-01

141

HRG-1 enhances cancer cell invasive potential and couples glucose metabolism to cytosolic/extracellular pH gradient regulation by the vacuolar-H(+) ATPase.  

Science.gov (United States)

Haeme-responsive gene (HRG)-1 encodes a 16-kDa transmembrane protein that is induced by insulin-like growth factor-1 (IGF-1) and associates with the vacuolar-(H(+)) ATPase (V-ATPase). We previously reported that HRG-1 is essential for V-ATPase activity in endosomal acidification and receptor trafficking. Here, we show that in highly invasive and migratory cancer cell lines, HRG-1 and the V-ATPase are co-expressed at the plasma membrane, whereas in less invasive cell lines and non-transformed cells HRG-1 over-expression remains confined to intracellular compartments. Stable suppression of HRG-1 in invasive breast cancer MDA-MB-231 cells decreases extracellular pH, cell growth, migration and invasion. Ectopic expression of HRG-1 in non-invasive MCF-7 cells enhances V-ATPase activity, lowers the extracellular pH and increases the pH-dependent activity of MMP2 and MMP9 matrix metalloproteinases. HRG-1 enhances trafficking of the glucose transporter-1 (GLUT-1) with a concomitant increase in glucose uptake and lactate production. HRG-1 also promotes trafficking of the insulin-like growth factor I receptor (IGF-1R), ?1-integrin and IGF-1 signalling. Taken together, our findings indicate that HRG-1 expression at the plasma membrane enhances V-ATPase activity, drives glycolytic flux and facilitates cancer cell growth, migration and invasion. Thus, HRG-1 may represent a novel target for selectively disrupting V-ATPase activity and the metastatic potential of cancer cells. PMID:24141772

Fogarty, F M; O'Keeffe, J; Zhadanov, A; Papkovsky, D; Ayllon, V; O'Connor, R

2014-09-18

142

Metabolic engineering of Acinetobacter baylyi ADP1 for improved growth on gluconate and glucose.  

Science.gov (United States)

A high growth rate in bacterial cultures is usually achieved by optimizing growth conditions, but metabolism of the bacterium limits the maximal growth rate attainable on the carbon source used. This limitation can be circumvented by engineering the metabolism of the bacterium. Acinetobacter baylyi has become a model organism for studies of bacterial metabolism and metabolic engineering due to its wide substrate spectrum and easy-to-engineer genome. It produces naturally storage lipids, such as wax esters, and has a unique gluconate catabolism as it lacks a gene for pyruvate kinase. We engineered the central metabolism of A. baylyi ADP1 more favorable for gluconate catabolism by expressing the pyruvate kinase gene (pykF) of Escherichia coli. This modification increased growth rate when cultivated on gluconate or glucose as a sole carbon source in a batch cultivation. The engineered cells reached stationary phase on these carbon sources approximately twice as fast as control cells carrying an empty plasmid and produced similar amount of biomass. Furthermore, when grown on either gluconate or glucose, pykF expression did not lead to significant accumulation of overflow metabolites and consumption of the substrate remained unaltered. Increased growth rate on glucose was not accompanied with decreased wax ester production, and the pykF-expressing cells accumulated significantly more of these storage lipids with respect to cultivation time. PMID:25192990

Kannisto, Matti; Aho, Tommi; Karp, Matti; Santala, Ville

2014-11-01

143

Mutual adjustment of glucose uptake and metabolism in Trypanosoma brucei grown in a chemostat.  

OpenAIRE

The mutual adjustment of glucose uptake and metabolism in the insect stage of the protozoan parasite Trypanosoma brucei was studied. T. brucei was preadapted in the chemostat to conditions in which either glucose or proline served as the major carbon and energy source. Cells were grown and adapted to either energy or non-energy limitation at a low dilution rate (0.5 day-1) or a high dilution rate (1 day-1). The cells were then used in short- to medium-term uptake experiments with D-[14C]gluco...

Ter Kuile, B. H.; Opperdoes, F. R.

1992-01-01

144

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

OpenAIRE

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...

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

1995-01-01

145

MAPK14/p38?-dependent modulation of glucose metabolism affects ROS levels and autophagy during starvation.  

Science.gov (United States)

Increased glycolytic flux is a common feature of many cancer cells, which have adapted their metabolism to maximize glucose incorporation and catabolism to generate ATP and substrates for biosynthetic reactions. Indeed, glycolysis allows a rapid production of ATP and provides metabolic intermediates required for cancer cells growth. Moreover, it makes cancer cells less sensitive to fluctuations of oxygen tension, a condition usually occurring in a newly established tumor environment. Here, we provide evidence for a dual role of MAPK14 in driving a rearrangement of glucose metabolism that contributes to limiting reactive oxygen species (ROS) production and autophagy activation in condition of nutrient deprivation. We demonstrate that MAPK14 is phosphoactivated during nutrient deprivation and affects glucose metabolism at 2 different levels: on the one hand, it increases SLC2A3 mRNA and protein levels, resulting in a higher incorporation of glucose within the cell. This event involves the MAPK14-mediated enhancement of HIF1A protein stability. On the other hand, MAPK14 mediates a metabolic shift from glycolysis to the pentose phosphate pathway (PPP) through the modulation of PFKFB3 (6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase 3) degradation by the proteasome. This event requires the presence of 2 distinct degradation sequences, KEN box and DSG motif Ser273, which are recognized by 2 different E3 ligase complexes. The mutation of either motif increases PFKFB3 resistance to starvation-induced degradation. The MAPK14-driven metabolic reprogramming sustains the production of NADPH, an important cofactor for many reduction reactions and for the maintenance of the proper intracellular redox environment, resulting in reduced levels of ROS. The final effect is a reduced activation of autophagy and an increased resistance to nutrient deprivation. PMID:25046111

Desideri, Enrico; Vegliante, Rolando; Cardaci, Simone; Nepravishta, Ridvan; Paci, Maurizio; Ciriolo, Maria Rosa

2014-09-01

146

T-cell metabolism in autoimmune disease.  

Science.gov (United States)

Cancer cells have long been known to fuel their pathogenic growth habits by sustaining a high glycolytic flux, first described almost 90 years ago as the so-called Warburg effect. Immune cells utilize a similar strategy to generate the energy carriers and metabolic intermediates they need to produce biomass and inflammatory mediators. Resting lymphocytes generate energy through oxidative phosphorylation and breakdown of fatty acids, and upon activation rapidly switch to aerobic glycolysis and low tricarboxylic acid flux. T cells in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have a disease-specific metabolic signature that may explain, at least in part, why they are dysfunctional. RA T cells are characterized by low adenosine triphosphate and lactate levels and increased availability of the cellular reductant NADPH. This anti-Warburg effect results from insufficient activity of the glycolytic enzyme phosphofructokinase and differentiates the metabolic status in RA T cells from those in cancer cells. Excess production of reactive oxygen species and a defect in lipid metabolism characterizes metabolic conditions in SLE T cells. Owing to increased production of the glycosphingolipids lactosylceramide, globotriaosylceramide and monosialotetrahexosylganglioside, SLE T cells change membrane raft formation and fail to phosphorylate pERK, yet hyperproliferate. Borrowing from cancer metabolomics, the metabolic modifications occurring in autoimmune disease are probably heterogeneous and context dependent. Variations of glucose, amino acid and lipid metabolism in different disease states may provide opportunities to develop biomarkers and exploit metabolic pathways as therapeutic targets. PMID:25776624

Yang, Zhen; Matteson, Eric L; Goronzy, Jörg J; Weyand, Cornelia M

2015-12-01

147

Cerebral glucose metabolic differences in patients with panic disorder  

Energy Technology Data Exchange (ETDEWEB)

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.

Nordahl, T.E.; Semple, W.E.; Gross, M.; Mellman, T.A.; Stein, M.B.; Goyer, P.; King, A.C.; Uhde, T.W.; Cohen, R.M. (NIMH, Bethesda, MD (USA))

1990-08-01

148

Cerebral glucose metabolic differences in patients with panic disorder  

International Nuclear Information System (INIS)

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

149

Gut microbiota may have influence on glucose and lipid metabolism.  

DEFF Research Database (Denmark)

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.

Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost

2013-01-01

150

Cerebral metabolism of glucose in benign hereditary chorea  

Energy Technology Data Exchange (ETDEWEB)

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 YF-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.

Suchowersky, O.; Hayden, M.R.; Martin, W.R.; Stoessl, A.J.; Hildebrand, A.M.; Pate, B.D.

1986-01-01

151

Cerebral metabolism of glucose in benign hereditary chorea  

International Nuclear Information System (INIS)

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

152

Glucose metabolism in rats submitted to skeletal muscle denervation  

Scientific Electronic Library Online (English)

Full Text Available O estudo analisou os efeitos locais e sistêmicos da imobilização por desnervação do músculo esquelético sobre o metabolismo glicidico. Ratos foram submetidos à secção do nervo ciático da pata direita. Observou-se redução da captação de glicose pelo músculo sóleo isolado da pata desnervada após 3 e 7 [...] mas não após 28 dias em relação a animais controle. Não houve diferença após 3 e 7 dias na captação de glicose pelo músculo sóleo da pata contralateral intacta em relação ao controle. Houve aumento da captação de glicose nesta mesma pata 28 dias após a desnervação. A taxa de remoção da glicose em resposta à insulina exógena após 28 dias de desnervação foi significantemente superior à do controle e àquelas observadas após 3 e 7 dias da desnervação. Esses resultados sugerem que a imobilização por desnervação interfere não só no metabolismo da glicose no músculo esquelético envolvido como também em outros tecidos. Abstract in english 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.

Wilton Marlindo Santana, Nunes; Maria Alice Rostom de, Mello.

2005-07-01

153

GSM mobile phone radiation suppresses brain glucose metabolism  

OpenAIRE

We investigated the effects of mobile phone radiation on cerebral glucose metabolism using high-resolution positron emission tomography (PET) with the 18F-deoxyglucose (FDG) tracer. A long half-life (109?minutes) of the 18F isotope allowed a long, natural exposure condition outside the PET scanner. Thirteen young right-handed male subjects were exposed to a pulse-modulated 902.4?MHz Global System for Mobile Communications signal for 33?minutes, while performing a simple visual vigilance...

Kwon, Myoung Soo; Vorobyev, Victor; Ka?nna?la?, Sami; Laine, Matti; Rinne, Juha O.; Toivonen, Tommi; Johansson, Jarkko; Tera?s, Mika; Lindholm, Harri; Alanko, Tommi; Ha?ma?la?inen, Heikki

2011-01-01

154

Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism  

OpenAIRE

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...

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

2011-01-01

155

The Lin28/let-7 axis regulates glucose metabolism  

Science.gov (United States)

SUMMARY The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by blocking let-7 biogenesis. In studies of the Lin28/let-7 pathway, we discovered unexpected roles in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promoted an insulin-sensitized state that resisted high fat diet-induced diabetes, whereas muscle-specific loss of Lin28a and overexpression of let-7 resulted in insulin resistance and impaired glucose tolerance. These phenomena occurred in part through let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. The mTOR inhibitor rapamycin abrogated the enhanced glucose uptake and insulin-sensitivity conferred by Lin28a in vitro and in vivo. In addition, we found that let-7 targets were enriched for genes that contain SNPs associated with type 2 diabetes and fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. PMID:21962509

Zhu, Hao; Shyh-Chang, Ng; Segrè, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.

2012-01-01

156

Glucose Metabolism during the Early “Flow Phase” After Burn Injury  

Science.gov (United States)

Background Burn injury (BI) is associated with insulin resistance and hyperglycemia which complicate clinical management. We investigated the impact of BI on glucose metabolism in a rabbit model of burn injury using a combination of PET and stable isotope studies under Euglycemic Insulin Clamp (EIC) conditions. Materials/Methods Twelve male rabbits were subjected to either full thickness burn injury (B) or sham burn (SB). Three days after treatment, an EIC condition was established by constant infusion of insulin, concomitantly with a variable rate of dextrose infusion. PET imaging of the hind limbs was conducted to determine the rates of peripheral O2 and glucose utilization. Each animal also received a primed constant infusion of [6,6,2H2] glucose to determine endogenous glucose production. Results The fasting blood glucose in the burned rabbits was higher than in the sham group. Under EIC conditions, the SB group required more exogenous dextrose than the B group in order to maintain blood glucose at physiological levels (22.2 ± 2.6 vs 13.3 ± 2.9 mg/min, P < 0.05), indicating a state of insulin resistance. PET imaging demonstrated that the rates of O2 consumption and FDG utilization by skeletal muscle remained at similar levels in both groups. Hepatic gluconeogenesis determined by the stable isotope tracer study was found significantly increased in the BI group. Conclusions These findings demonstrated that hyperglycemia and insulin resistance develop during the early “flow phase” after BI. Unsuppressed hepatic gluconeogenesis, but not peripheral skeletal muscular utilization of glucose contributes to hyperglycemia at this stage. PMID:22459295

Xu, Hongzhi; Yu, Yong-Ming; Ma, Harry; Carter, Edward A; Fagan, Shawn; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

157

Altered glucose metabolism in mouse and humans conceived by IVF.  

Science.gov (United States)

In vitro fertilization (IVF) may influence the metabolic health of children. However, in humans, it is difficult to separate out the relative contributions of genetics, environment, or the process of IVF, which includes ovarian stimulation (OS) and embryo culture. Therefore, we examined glucose metabolism in young adult humans and in adult male C57BL/6J mice conceived by IVF versus natural birth under energy-balanced and high-fat-overfeeding conditions. In humans, peripheral insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamp (80 mU/m(2)/min), was lower in IVF patients (n = 14) versus control subjects (n = 20) after 3 days of an energy-balanced diet (30% fat). In response to 3 days of overfeeding (+1,250 kcal/day, 45% fat), there was a greater increase in systolic blood pressure in IVF versus controls (P = 0.02). Mice conceived after either OS alone or IVF weighed significantly less at birth versus controls (P diet (60% fat). Thus, OS impaired fetal growth in the mouse, but only embryo culture resulted in changes in glucose metabolism that may increase the risk of the development of metabolic diseases later in life, in both mice and humans. PMID:24760136

Chen, Miaoxin; Wu, Linda; Zhao, Junli; Wu, Fang; Davies, Michael J; Wittert, Gary A; Norman, Robert J; Robker, Rebecca L; Heilbronn, Leonie K

2014-10-01

158

Glucose desensitization in INS-1 cells : evidence of impaired function caused by glucose metabolite(s) rather than by the glucose molecule per se  

DEFF Research Database (Denmark)

Type 2 diabetes characteristically involves disturbances of the beta-cell function including reduced insulin secretion in response to elevated glucose. In experimental diabetes, beta cells are often "blind" to glucose, and clonal beta-cell lines chronically exposed to glucose show impaired glucose sensing. The present study focuses on the effect of long-term exposure to high-glucose concentrations on insulin secretion, insulin store, and insulin mRNA content in the beta-cell line INS-1. The cellular insulin mRNA content has been shown to be reduced by approximately 90% on such exposure for 4 days. This decrement could be partly counteracted by subsequent culture for 4 days at low glucose, while daily alternate culture in high and low glucose did not prevent the insulin mRNA content from being reduced. The insulin release from cells cultured at high glucose was simultaneously reduced by 50%. This change was, however, not reversed by subsequent culture at low glucose, a pattern also found for the intracellular insulin stores. The suppression of insulin mRNA, insulin release, and intracellular insulin stores induced by high glucose was completely neutralized by the metabolic glucokinase blocker, mannoheptulose, while 2-deoxyglucose, a phosphoglucose isomerase blocker, had no impact. This suggests that glucokinase activity may have a negative regulatory effect. Addition of D-glyceraldehyde (DG) induced an increase in insulin release, while insulin mRNA remained unaltered. It would therefore seem that at least one glucose metabolite is involved in the glucose desensitization in INS-1 cells, which opens the prospect of regulatory factor(s), which possess(es) negative, as well as positive, actions.

Brock, Birgitte; Mogensen, Jane H

2002-01-01

159

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

International Nuclear Information System (INIS)

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)

160

UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets  

Energy Technology Data Exchange (ETDEWEB)

Highlights: Black-Right-Pointing-Pointer UCP2 mRNA levels are decreased in islets of Langerhans from glucokinase deficient mice. Black-Right-Pointing-Pointer UCP2 mRNA up-regulation by glucose is dependent on glucokinase. Black-Right-Pointing-Pointer Absence of UCP2 increases GSIS of glucokinase heterozygous pancreatic islets. Black-Right-Pointing-Pointer This may protect glucokinase deficient mice from hyperglycemic damages. -- Abstract: Uncoupling Protein 2 (UCP2) is expressed in the pancreatic {beta}-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.

Dalgaard, Louise T., E-mail: ltd@ruc.dk [Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (United States); Department of Science, Systems and Models, Roskilde University (Denmark)

2012-01-06

161

UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets  

International Nuclear Information System (INIS)

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 ?-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.

162

Metabolic regulation of lateral hypothalamic glucose-inhibited orexin neurons may influence midbrain reward neurocircuitry.  

Science.gov (United States)

Lateral hypothalamic area (LHA) orexin neurons modulate reward-based feeding by activating ventral tegmental area (VTA) dopamine (DA) neurons. We hypothesize that signals of peripheral energy status influence reward-based feeding by modulating the glucose sensitivity of LHA orexin glucose-inhibited (GI) neurons. This hypothesis was tested using electrophysiological recordings of LHA orexin-GI neurons in brain slices from 4 to 6week old male mice whose orexin neurons express green fluorescent protein (GFP) or putative VTA-DA neurons from C57Bl/6 mice. Low glucose directly activated ~60% of LHA orexin-GFP neurons in both whole cell and cell attached recordings. Leptin indirectly reduced and ghrelin directly enhanced the activation of LHA orexin-GI neurons by glucose decreases from 2.5 to 0.1mM by 53±12% (n=16, Pneurons by decreased glucose, as would be predicted by these hormonal effects. We also evaluated putative VTA-DA neurons in a novel horizontal slice preparation containing the LHA and VTA. Decreased glucose increased the frequency of spontaneous excitatory post-synaptic currents (sEPSCs; 125 ± 40%, n=9, Pneurons. sEPSCs were completely blocked by AMPA and NMDA glutamate receptor antagonists (CNQX 20 ?M, n=4; APV 20?M, n=4; respectively), demonstrating that these sEPSCs were mediated by glutamatergic transmission onto VTA DA neurons. Orexin-1 but not 2 receptor antagonism with SB334867 (10?M; n=9) and TCS-OX2-29 (2?M; n=5), respectively, blocks the effects of decreased glucose on VTA DA neurons. Thus, decreased glucose increases orexin-dependent excitatory glutamate neurotransmission onto VTA DA neurons. These data suggest that the glucose sensitivity of LHA orexin-GI neurons links metabolic state and reward-based feeding. PMID:25107627

Sheng, Zhenyu; Santiago, Ammy M; Thomas, Mark P; Routh, Vanessa H

2014-09-01

163

Estradiol stimulates glucose metabolism via 6-phosphofructo-2-kinase (PFKFB3).  

Science.gov (United States)

Estradiol (E2) administered to estrogen receptor-positive (ER(+)) breast cancer patients stimulates glucose uptake by tumors. Importantly, this E2-induced metabolic flare is predictive of the clinical effectiveness of anti-estrogens and, as a result, downstream metabolic regulators of E2 are expected to have utility as targets for the development of anti-breast cancer agents. The family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) control glycolytic flux via their product, fructose-2,6-bisphosphate (F26BP), which activates 6-phosphofructo-1-kinase (PFK-1). We postulated that E2 might promote PFKFB3 expression, resulting in increased F26BP and glucose uptake. We demonstrate that PFKFB3 expression is highest in stage III lymph node metastases relative to normal breast tissues and that exposure of human MCF-7 breast cancer cells to E2 causes a rapid increase in [(14)C]glucose uptake and glycolysis that is coincident with an induction of PFKFB3 mRNA (via ER binding to its promoter), protein expression and the intracellular concentration of its product, F26BP. Importantly, selective inhibition of PFKFB3 expression and activity using siRNA or a PFKFB3 inhibitor markedly reduces the E2-mediated increase in F26BP, [(14)C]glucose uptake, and glycolysis. Furthermore, co-treatment of MCF-7 cells with the PFKFB3 inhibitor and the anti-estrogen ICI 182,780 synergistically induces apoptotic cell death. These findings demonstrate for the first time that the estrogen receptor directly promotes PFKFB3 mRNA transcription which, in turn, is required for the glucose metabolism and survival of breast cancer cells. Importantly, these results provide essential preclinical information that may allow for the ultimate design of combinatorial trials of PFKFB3 antagonists with anti-estrogen therapies in ER(+) stage IV breast cancer patients. PMID:24515104

Imbert-Fernandez, Yoannis; Clem, Brian F; O'Neal, Julie; Kerr, Daniel A; Spaulding, Robert; Lanceta, Lilibeth; Clem, Amy L; Telang, Sucheta; Chesney, Jason

2014-03-28

164

Estradiol Stimulates Glucose Metabolism via 6-Phosphofructo-2-kinase (PFKFB3)*  

Science.gov (United States)

Estradiol (E2) administered to estrogen receptor-positive (ER+) breast cancer patients stimulates glucose uptake by tumors. Importantly, this E2-induced metabolic flare is predictive of the clinical effectiveness of anti-estrogens and, as a result, downstream metabolic regulators of E2 are expected to have utility as targets for the development of anti-breast cancer agents. The family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1–4) control glycolytic flux via their product, fructose-2,6-bisphosphate (F26BP), which activates 6-phosphofructo-1-kinase (PFK-1). We postulated that E2 might promote PFKFB3 expression, resulting in increased F26BP and glucose uptake. We demonstrate that PFKFB3 expression is highest in stage III lymph node metastases relative to normal breast tissues and that exposure of human MCF-7 breast cancer cells to E2 causes a rapid increase in [14C]glucose uptake and glycolysis that is coincident with an induction of PFKFB3 mRNA (via ER binding to its promoter), protein expression and the intracellular concentration of its product, F26BP. Importantly, selective inhibition of PFKFB3 expression and activity using siRNA or a PFKFB3 inhibitor markedly reduces the E2-mediated increase in F26BP, [14C]glucose uptake, and glycolysis. Furthermore, co-treatment of MCF-7 cells with the PFKFB3 inhibitor and the anti-estrogen ICI 182,780 synergistically induces apoptotic cell death. These findings demonstrate for the first time that the estrogen receptor directly promotes PFKFB3 mRNA transcription which, in turn, is required for the glucose metabolism and survival of breast cancer cells. Importantly, these results provide essential preclinical information that may allow for the ultimate design of combinatorial trials of PFKFB3 antagonists with anti-estrogen therapies in ER+ stage IV breast cancer patients. PMID:24515104

Imbert-Fernandez, Yoannis; Clem, Brian F.; O'Neal, Julie; Kerr, Daniel A.; Spaulding, Robert; Lanceta, Lilibeth; Clem, Amy L.; Telang, Sucheta; Chesney, Jason

2014-01-01

165

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

International Nuclear Information System (INIS)

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

166

Abnormal Glucose Metabolism and Metabolic Syndrome in Non-Diabetic Kidney Transplant Recipients Early After Transplantation  

Science.gov (United States)

Background Abnormal glucose metabolism (AGM) and metabolic syndrome (MS) are individually associated with a poor cardiovascular outcome in kidney transplant recipients. We prospectively studied the relationship between AGM and MS in non-diabetic kidney transplant recipients early after transplantation. Methods A total of 203 de novo kidney transplant recipients underwent standard 2-hr glucose tolerance test 10 weeks after transplantation. Demographic and clinical characteristics were collected. AGM was defined as impaired fasting glucose, impaired glucose tolerance, and new onset diabetes after transplant according to the WHO criteria, and MS was defined according to the National Cholesterol Education Expert Panel criteria. Results Overall, 97 patients (47.8%) met the diagnosis of AGM and 98 patients (48.3%) met the criteria of MS. AGM and MS are highly associated (?2, Ptransplant are independent predictors common for AGM and MS. Age predicts AGM with and without MS, whereas body mass index before transplant predicts MS. Patients with impaired glucose tolerance and new-onset diabetes after transplant displayed significant worsening of their fasting plasma glucose levels during the 10-week observational period. MS and the components of MS, but not AGM, were associated with reduced transplant renal function (P=0.002). Conclusion The early screening of AGM and MS should be emphasized, and the role of early therapeutic interventions aimed at both conditions explored. The long-term follow-up of these patients will yield more insight on the significance of such findings. PMID:20130496

Luan, Fu L.; Stuckey, Linda J.; Ojo, Akinlolu O.

2015-01-01

167

GSM mobile phone radiation suppresses brain glucose metabolism  

Science.gov (United States)

We investigated the effects of mobile phone radiation on cerebral glucose metabolism using high-resolution positron emission tomography (PET) with the 18F-deoxyglucose (FDG) tracer. A long half-life (109?minutes) of the 18F isotope allowed a long, natural exposure condition outside the PET scanner. Thirteen young right-handed male subjects were exposed to a pulse-modulated 902.4?MHz Global System for Mobile Communications signal for 33?minutes, while performing a simple visual vigilance task. Temperature was also measured in the head region (forehead, eyes, cheeks, ear canals) during exposure. 18F-deoxyglucose PET images acquired after the exposure showed that relative cerebral metabolic rate of glucose was significantly reduced in the temporoparietal junction and anterior temporal lobe of the right hemisphere ipsilateral to the exposure. Temperature rise was also observed on the exposed side of the head, but the magnitude was very small. The exposure did not affect task performance (reaction time, error rate). Our results show that short-term mobile phone exposure can locally suppress brain energy metabolism in humans. PMID:21915135

Kwon, Myoung Soo; Vorobyev, Victor; Kännälä, Sami; Laine, Matti; Rinne, Juha O; Toivonen, Tommi; Johansson, Jarkko; Teräs, Mika; Lindholm, Harri; Alanko, Tommi; Hämäläinen, Heikki

2011-01-01

168

Regional cerebral glucose metabolism in frontotemporal lobar degeneration  

International Nuclear Information System (INIS)

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 FTLDFTLD

169

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

International Nuclear Information System (INIS)

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

170

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

Science.gov (United States)

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

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

2015-05-01

171

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

Directory of Open Access Journals (Sweden)

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.

AliMobasheri

2012-12-01

172

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

DEFF Research Database (Denmark)

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 after RYGB is rapid entry of glucose into the systemic circulation due to modified gastrointestinal anatomy, causing hypersecretion of insulin and other hormones influencing glucose disappearance and endogenous glucose production. METHODS: We determined glucose absorption and metabolism and the rate of lipolysis before and 3 months after RYGB in obese glucose-tolerant individuals using the double-tracer technique during a mixed meal. RESULTS: After RYGB, the postprandial plasma glucose profile changed, with a higher peak glucose concentration followed by a faster return to lower than basal levels. These changes were brought about by changes in glucose kinetics: (1) a more rapid appearance of ingested glucose in the systemic circulation, and a concomitant increase in insulin and glucagon-like peptide-1 secretion; (2) postprandial glucose disappearance was maintained at a high rate for a longer time after RYGB. Endogenous glucose production was similar before and after surgery. Postoperative glucagon secretion increased and showed a biphasic response after RYGB. Adipose tissue basal rate of lipolysis was higher after RYGB. CONCLUSIONS/INTERPRETATION: A rapid rate of absorption of ingested glucose into the systemic circulation, followed by increased insulin secretion and glucose disappearance appears to drive the changes in the glucose profile observed after RYGB, while endogenous glucose production remains unchanged. TRIAL REGISTRATION: ClinicalTrials.gov NCT01559792. FUNDING: The study was part of the UNIK program: Food, Fitness & Pharma for Health and Disease (see www.foodfitnesspharma.ku.dk ). Funding was received from the Novo Nordisk foundation and the Strategic Research Counsel for the Capital Area and Danish Research Agency. The primary investigator received a PhD scholarship from the University of Copenhagen, which was one-third funded by Novo Nordisk.

Jacobsen, Siv H; Bojsen-MØller, Kirstine N

2013-01-01

173

Glucose Metabolism as a Target of Histone Deacetylase Inhibitors  

OpenAIRE

The therapeutic efficacy of histone deacetylase inhibitors (HDACI) is generally attributed to their ability to alter gene expression secondary to their effects on the acetylation status of transcription factors and histones. However, because HDACIs exhibit similar transcriptional effects in most cells, the molecular basis for their therapeutic selectivity toward malignant cells is largely unknown. In this study, we report that HDACI, of distinct chemotypes, quantitatively inhibit glucose tran...

Wardell, Suzanne E.; Ilkayeva, Olga R.; Wieman, Heather L.; Frigo, Daniel E.; Rathmell, Jeffrey C.; Newgard, Christopher B.; Mcdonnell, Donald P.

2008-01-01

174

Regulation of ?-cell glucose transporter gene expression  

International Nuclear Information System (INIS)

It has been postulated that a glucose transporter of ? 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 ?-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 ? 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 ? cells, but not liver, is subject to regulation by certain perturbations in blood glucose homeostasis

175

Metabolic Stress in Autophagy and Cell Death Pathways  

OpenAIRE

Growth factors and oncogenic kinases play important roles in stimulating cell growth during development and transformation. These processes have significant energetic and synthetic requirements and it is apparent that a central function of growth signals is to promote glucose metabolism to support these demands. Because metabolic pathways represent a fundamental aspect of cell proliferation and survival, there is considerable interest in targeting metabolism as a means to eliminate cancer. A ...

Altman, Brian J.; Rathmell, Jeffrey C.

2012-01-01

176

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

Directory of Open Access Journals (Sweden)

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/?-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.

PaulaMAlves

2011-09-01

177

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

International Nuclear Information System (INIS)

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.)

178

Overexpression of the Pdx-1 Homeodomain Transcription Factor Impairs Glucose Metabolism in Cultured Rat Hepatocytes  

Directory of Open Access Journals (Sweden)

Full Text Available The Pdx-1 transcription factor plays crucial functions both during pancreas development and in the adult β cells. Previous studies have indicated that ectopic Pdx-1 expression in liver or intestinal primary and immortalized cells is sufficient to promote activation of insulin gene expression. This work is focused on the molecular and physiological consequences of Pdx-1 overexpression in liver cells. We present evidence that Pdx-1 affects the level of expression of one of the four mammalian hexokinase isozymes. These are glucose phosphorylating enzymes involved in essential cellular functions such as glucose sensing, metabolic energy production and apoptosis. Specifically, our data show that over-expression of Pdx-1 in cultured hepatocytes is able to repress the expression of hexokinase 2 (Hxk 2 and the phenomenon is mediated via binding of Pdx-1 to a specific sequence on the Hxk 2 gene promoter. As a consequence, liver cells over-expressing Pdx-1 present interesting alterations concerning glucose metabolism.

Gianfranco Risuleo

2008-10-01

179

Patient-specific Glucose Metabolism Models for Model Predictive Control of T1DM Glycemia  

OpenAIRE

The development of a predictive control algorithm for glycaemia regulation in diabetic subjects requires patient-specific models of the glucose metabolism which are physiologically relevant, parsimonious, yet able to accurately forecast blood glucose. Given the measured data: total plasma insulin mIU/L; plasma glucose mg/dL; plasma glucose rate of appearance after intestinal absorption mg/kg/min, the objective was to find individualized, simple and plausible glucose-insulin interaction...

Cescon, Marzia; Johansson, Rolf

2012-01-01

180

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

OpenAIRE

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...

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

1981-01-01

181

Starch digestion and glucose metabolism in the ruminant: a review  

Scientific Electronic Library Online (English)

Full Text Available SciELO Venezuela | Language: English Abstract in portuguese Neste trabalho se revisa a digestão do amido em ruminantes por ação de diferentes enzimas produzidas pelas glândulas salivares, microorganismos ruminais, pâncreas e intestino delgado. Também se discute o metabolismo de glicose em rúmen, sua absorção pos rumina e os requerimentos de glicose no rumina [...] nte. Abstract in spanish En este trabajo se revisa la digestión del almidón en rumiantes por acción de diferentes enzimas producidas por las glándulas salivales, microorganismos ruminales, páncreas e intestino delgado. También se discute el metabolismo de glucosa en rumen, su absorción postruminal y los requerimientos de gl [...] ucosa en el rumiante. Abstract in english The objective of this manuscript is to review starch digestion to glucose in ruminants by the action of several enzymes produced by the salivary glands, rumen microorganisms, the pancreas and small intestine. Glucose metabolism in the rumen and its post-ruminal absorption and glucose requirements of [...] the ruminant are also discussed.

M. Esther, Ortega Cerrilla; Germán, Mendoza Martínez.

2003-07-01

182

Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis.  

Science.gov (United States)

Reprogrammed glucose metabolism as a result of increased glycolysis and glucose uptake is a hallmark of cancer. Here we show that cancer cells can suppress glucose uptake by non-tumour cells in the premetastatic niche, by secreting vesicles that carry high levels of the miR-122 microRNA. High miR-122 levels in the circulation have been associated with metastasis in breast cancer patients, and we show that cancer-cell-secreted miR-122 facilitates metastasis by increasing nutrient availability in the premetastatic niche. Mechanistically, cancer-cell-derived miR-122 suppresses glucose uptake by niche cells in vitro and in vivo by downregulating the glycolytic enzyme pyruvate kinase. In vivo inhibition of miR-122 restores glucose uptake in distant organs, including brain and lungs, and decreases the incidence of metastasis. These results demonstrate that, by modifying glucose utilization by recipient premetastatic niche cells, cancer-derived extracellular miR-122 is able to reprogram systemic energy metabolism to facilitate disease progression. PMID:25621950

Fong, Miranda Y; Zhou, Weiying; Liu, Liang; Alontaga, Aileen Y; Chandra, Manasa; Ashby, Jonathan; Chow, Amy; O'Connor, Sean Timothy Francis; Li, Shasha; Chin, Andrew R; Somlo, George; Palomares, Melanie; Li, Zhuo; Tremblay, Jacob R; Tsuyada, Akihiro; Sun, Guoqiang; Reid, Michael A; Wu, Xiwei; Swiderski, Piotr; Ren, Xiubao; Shi, Yanhong; Kong, Mei; Zhong, Wenwan; Chen, Yuan; Wang, Shizhen Emily

2015-02-01

183

Glucose-6-phosphate dehydrogenase in rat lung alveolar epithelial cells. An ultrastructural enzyme-cytochemical study  

OpenAIRE

Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme of the pentose phosphate pathway in carbohydrate metabolism, and it plays an important role in cell proliferation and antioxidant regulation within cells in various organs. Although marked cell proliferation and oxidant/antioxidant metabolism occur in lung alveolar epithelial cells, definite data has been lacking as to whether cytochemically detectable G6PD is present in alveolar epithelial cells. The distribution pattern of G6PD with...

Sato, I.; Izumi, A.; Watanabe, T.; Koike, T.; Takayama, T.; Yamada, T.; Oshikawa, K.; Matsubara, S.; Kato, T.

2010-01-01

184

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

International Nuclear Information System (INIS)

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 demonstratet 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)

185

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

Directory of Open Access Journals (Sweden)

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.

Jordà Joel

2012-05-01

186

Glucose activates prenyltransferases in pancreatic islet ?-cells  

International Nuclear Information System (INIS)

A growing body of evidence implicates small G-proteins [e.g., Cdc42 and Rac1] in glucose-stimulated insulin secretion [GSIS] in the islet ?-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 ?-cells and normal rat islets. Our findings suggest that an insulinotropic concentration of glucose [20 mM] markedly stimulated the expression of the ?-subunits of FTase/GGTase-1, but not the ?-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.

187

Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy  

International Nuclear Information System (INIS)

To find a clue to elucidate pathophysiology of hypertrophic cardiomyopathy (HCM), myocardial glucose metabolism was investigated by using positron computed tomography (PET) with F-18-fluorodeoxyglucose (F-18 FDG) in 28 HCM patients and 9 hypetensive (H) patients. The degree of F-18 FDG uptake in the myocardium was quantitatively determined by %dose uptake per myocardium of 30 g. A group of H patients had almost normal pattern; i.e., fasting F-18 FDG uptake was low (0.13±0.07%/myocardium of 30 g) and was remarkably increased on glucose loading (0.30±0.14%). In all HCM patients but 4 of apical type (AT), however, fasting F-18 FDG uptake was remarkably high (0.20±0.08% for 12 patients with asymmetrical septal hypertrophy (ASH), 0.17±0.07% for 6 of diffuse type (DT) and 0.20±0.07% for 6 of dilated phase (DP)). Decreased uptake of F-18 FDG was seen on glucose loading for DP (0.19±0.08%) and AT (0.17±0.11%), although it was almost normal for ASH (0.33±0.15%). According to regional myocardium, fasting F-18 FDG uptake was decreased in the entire myocardium in all HCM patients but those of AT. F-18 FDG was decreased on glucose loading in bokth DT and DP patients, suggesting the presence of myocardial disturbance. In conclusion, HCM patients were characterized by having increased uptake of F-18 FDG on fasting. This has an important implication for the understanding of its pathophysiology and diagnosis of hyertrophic myocardium. (N.K.)

188

Shilianhua extract inhibits GSK-3? and promotes glucose metabolism  

OpenAIRE

The extract of plant Shilianhua (SLH; Sinocrassula indica Berge) is a component in a commercial product for control of blood glucose. However, it remains to be investigated whether the SLH extract enhances insulin sensitivity in a model of type 2 diabetes. To address this question, the SLH crude extract was fractionated into four parts on the basis of polarity, and bioactivities of each part were tested in cells. One of the fractions, F100, exhibited a strong activity in the stimulation of gl...

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

2009-01-01

189

A glucose biofuel cell implanted in rats.  

OpenAIRE

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

Cinquin, Philippe; Gondran, Chantal; Giroud, Fabien; Mazabrard, Simon; Pellissier, Aymeric; Boucher, Franc?ois; Alcaraz, Jean-pierre; Gorgy, Karine; Lenouvel, Franc?ois; Mathe?, Ste?phane; Porcu, Paolo; Cosnier, Serge

2010-01-01

190

Sex-specific differences in lipid and glucose metabolism.  

Science.gov (United States)

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-utilization patterns; i.e., females store more lipids and have higher whole-body insulin sensitivity than males, while males tend to oxidize more lipids than females. These patterns are influenced by the menstrual phase in females, and by nutritional status and exercise intensity in both sexes. This minireview focuses on sex-specific mechanisms in lipid and glucose metabolism and their regulation by sex hormones, with a primary emphasis on studies in humans and the most relevant pre-clinical model of human physiology, non-human primates. PMID:25646091

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

2014-01-01

191

Influence of Egr-1 in Cardiac Tissue-Derived Mesenchymal Stem Cells in Response to Glucose Variations  

OpenAIRE

Mesenchymal stem cells (MSCs) represent a promising cell population for cell therapy and regenerative medicine applications. However, how variations in glucose are perceived by MSC pool is still unclear. Since, glucose metabolism is cell type and tissue dependent, this must be considered when MSCs are derived from alternative sources such as the heart. The zinc finger transcription factor Egr-1 is an important early response gene, likely to play a key role in the glucose-induced response. Our...

Daniela Bastianelli; Camilla Siciliano; Rosa Puca; Andrea Coccia; Colin Murdoch; Antonella Bordin; Giorgio Mangino; Giulio Pompilio; Antonella Calogero; Elena De Falco

2014-01-01

192

Inhibition of Autophagic Turnover in ?-Cells by Fatty Acids and Glucose Leads to Apoptotic Cell Death.  

Science.gov (United States)

Autophagy, a cellular recycling process responsible for turnover of cytoplasmic contents, is critical for maintenance of health. Defects in this process have been linked to diabetes. Diabetes-associated glucotoxicity/lipotoxicity contribute to impaired ?-cell function and have been implicated as contributing factors to this disease. We tested the hypothesis that these two conditions affect ?-cell function by modulating autophagy. We report that exposure of ?-cell lines and human pancreatic islets to high levels of glucose and lipids blocks autophagic flux and leads to apoptotic cell death. EM analysis showed accumulation of autophagy intermediates (autophagosomes), with abundant engulfed cargo in palmitic acid (PA)- or glucose-treated cells, indicating suppressed autophagic turnover. EM studies also showed accumulation of damaged mitochondria, endoplasmic reticulum distention, and vacuolar changes in PA-treated cells. Pulse-chase experiments indicated decreased protein turnover in ?-cells treated with PA/glucose. Expression of mTORC1, an inhibitor of autophagy, was elevated in ?-cells treated with PA/glucose. mTORC1 inhibition, by treatment with rapamycin, reversed changes in autophagic flux, and cell death induced by glucose/PA. Our results indicate that nutrient toxicity-induced cell death occurs via impaired autophagy and is mediated by activation of mTORC1 in ?-cells, contributing to ?-cell failure in the presence of metabolic stress. PMID:25548282

Mir, Shakeel U R; George, Nicholas M; Zahoor, Lubna; Harms, Robert; Guinn, Zachary; Sarvetnick, Nora E

2015-03-01

193

Mechanisms of glucose sensing in the pancreatic ?-cell: A computational systems-based analysis  

OpenAIRE

Pancreatic ?-cells respond to rising blood glucose by increasing oxidative metabolism, leading to an increased ATP/ADP ratio in the cytoplasm with a subsequent influx of calcium and the eventual secretion of insulin. The mechanisms of glucose sensing in the pancreatic ?-cell involve the coupling of cytoplasmic and mitochondrial processes. Our analysis, based on mathematical models of data from multiple sources has implications for ?-cell function and the treatment of type 2 diabetes (Fridl...

Fridlyand, Leonid E.; Philipson, Louis H.

2011-01-01

194

Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage  

International Nuclear Information System (INIS)

Tumour hypoxia and elevated glycolysis (Warburg effect) predict poor prognosis. Each parameter is assessable separately with positron emission tomography, but they are linked through anaerobic glycolysis (Pasteur effect). Here, we compare the oxygenation-dependent retention of fluoroazomycin arabinoside ([18F]FAZA), a promising but not well-characterised hypoxia-specific tracer, and fluorodeoxyglucose ([18F]FDG) in four carcinoma cell lines. Cells seeded on coverslips were positioned in modified Petri dishes that allow physically separated cells to share the same tracer-containing medium pool. Following oxic, hypoxic or anoxic tracer incubation, coverslips were analysed for radioactivity ([18F]FDG+[18F]FAZA) or re-incubated in tracer-free oxygenated medium and then measured ([18F]FAZA). Next, we tested the reliability of [18F]FDG as a relative measure of glucose metabolic rate. Finally, from two cell lines, xenografts were established in mice, and the tracer distribution between hypoxic and well-oxygenated areas were deduced from tissue sections. Three hours of anoxia strongly stimulated [18F]FAZA retention with anoxic-to-oxic uptake ratios typically above 30. Three out of four cell lines displayed similar selectivity of [18F]FDG versus glucose, but oxic uptake and anoxic-to-oxic uptake ratio of [18F]FDG varied considerably. Although less pronounced, [18F]FAZAough less pronounced, [18F]FAZA also showed superior in vivo hypoxia specificity compared with [18F]FDG. [18F]FAZA displays excellent in vitro characteristics for hypoxia imaging including modest cell-to-cell line variability and no binding in oxic cells. In contrast, the usability of [18F]FDG as a surrogate marker for hypoxia is questionable due to large variations in baseline (oxic) glucose metabolism and magnitudes of the Pasteur effects. (orig.)

195

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

International Nuclear Information System (INIS)

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 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

196

Novel method to differentiate 3T3 L1 cells in vitro to produce highly sensitive adipocytes for a GLUT4 mediated glucose uptake using fluorescent glucose analog  

OpenAIRE

Adipocytes play a vital role in glucose metabolism. 3T3 L1 pre adipocytes after differentiation to adipocytes serve as excellent in vitro models and are useful tools in understanding the glucose metabolism. The traditional approaches adopted in pre adipocyte differentiation are lengthy exercises involving the usage of IBMX and Dexamethasone. Any effort to shorten the time of differentiation and quality expression of functional differentiation in 3T3 L1 cells in terms of enhanced Insulin sensi...

Vishwanath, Divya; Srinivasan, Harini; Patil, Manjunath S.; Seetarama, Sowmya; Agrawal, Sachin Kumar; Dixit, M. N.; Dhar, Kakali

2013-01-01

197

Enhanced Neuronal Glucose Transporter Expression Reveals Metabolic Choice in a HD Drosophila Model  

Science.gov (United States)

Huntington’s disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93). We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP) impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK) which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the PPP, extended significantly the lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to synthesize NADPH involved in cell survival by maintenance of the redox state, we showed that tolerance to experimental oxidative stress was enhanced in flies co-expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK were able to circumvent mitochondrial deficits induced by specific silencing of genes necessary for mitochondrial homeostasis. Our study confirms the involvement of bioenergetic deficits in HD course; they can be rescued by specific expression of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent, the glycolysis seem to mediate the hGluT3 protective effects, whereas, in addition, the PPP provides increased protection to oxidative stress. PMID:25761110

Besson, Marie Thérèse; Alegría, Karin; Garrido-Gerter, Pamela; Barros, Luis Felipe; Liévens, Jean-Charles

2015-01-01

198

Enhanced Neuronal Glucose Transporter Expression Reveals Metabolic Choice in a HD Drosophila Model.  

Science.gov (United States)

Huntington's disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93). We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP) impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK) which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the PPP, extended significantly the lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to synthesize NADPH involved in cell survival by maintenance of the redox state, we showed that tolerance to experimental oxidative stress was enhanced in flies co-expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK were able to circumvent mitochondrial deficits induced by specific silencing of genes necessary for mitochondrial homeostasis. Our study confirms the involvement of bioenergetic deficits in HD course; they can be rescued by specific expression of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent, the glycolysis seem to mediate the hGluT3 protective effects, whereas, in addition, the PPP provides increased protection to oxidative stress. PMID:25761110

Besson, Marie Thérèse; Alegría, Karin; Garrido-Gerter, Pamela; Barros, Luis Felipe; Liévens, Jean-Charles

2015-01-01

199

Endothelial cell metabolism: parallels and divergences with cancer cell metabolism  

OpenAIRE

The stromal vasculature in tumors is a vital conduit of nutrients and oxygen for cancer cells. To date, the vast majority of studies have focused on unraveling the genetic basis of vessel sprouting (also termed angiogenesis). In contrast to the widely studied changes in cancer cell metabolism, insight in the metabolic regulation of angiogenesis is only just emerging. These studies show that metabolic pathways in endothelial cells (ECs) importantly regulate angiogenesis in conjunction with gen...

Verdegem, Dries; Moens, Stijn; Stapor, Peter; Carmeliet, Peter

2014-01-01

200

The glucose sensor protein glucokinase is expressed in glucagon-producing alpha-cells.  

Science.gov (United States)

Expression of glucokinase in hepatocytes and pancreatic 6-cells is of major physiologic importance to mammalian glucose homeostasis. Liver glucokinase catalyzes the first committed step in the disposal of glucose, and beta-cell glucokinase catalyzes a rate-limiting step required for glucose-regulated insulin release. The present study reports the expression of glucokinase in rat glucagon-producing alpha-cells, which are negatively regulated by glucose. Purified rat alpha-cells express glucokinase mRNA and protein with the same transcript length, nucleotide sequence, and immunoreactivity as the beta-cell isoform. Glucokinase activity accounts for more than 50% of glucose phosphorylation in extracts of alpha-cells and for more than 90% of glucose utilization in intact cells. The glucagon-producing tumor MSL-G-AN also contained glucokinase mRNA, protein, and enzymatic activity. These data indicate that glucokinase may serve as a metabolic glucose sensor in pancreatic alpha-cells and, hence, mediate a mechanism for direct regulation of glucagon release by extracellular glucose. Since these cells do not express Glut2, we suggest that glucose sensing does not necessarily require the coexpression of Glut2 and glucokinase. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8692940

Heimberg, H; De Vos, A; Moens, K; Quartier, E; Bouwens, L; Pipeleers, D; Van Schaftingen, E; Madsen, O; Schuit, F

1996-01-01

201

Insulin effect on glucose transport in thymocytes and splenocytes from rats with metabolic syndrome  

OpenAIRE

Abstract Metabolic syndrome (MS) may comprise several clinical conditions such as obesity, diabetes and inflammatory disorders, which are characterized by metabolic imbalances. The study of glucose transport and regulation by insulin in lymphocytes is important, since the way they increase inflammation and susceptibility to infections are common in MS. We studied glucose internalization in isolated thymocytes and splenocytes, its regulation by insulin, and the role of three glucose transporte...

Carbó Roxana; Guarner Verónica

2010-01-01

202

Multiple metabolic alterations exist in mutant PI3K cancers, but only glucose is essential as a nutrient source.  

Science.gov (United States)

Targeting tumour metabolism is becoming a major new area of pharmaceutical endeavour. Consequently, a systematic search to define whether there are specific energy source dependencies in tumours, and how these might be dictated by upstream driving genetic mutations, is required. The PI3K-AKT-mTOR signalling pathway has a seminal role in regulating diverse cellular processes including cell proliferation and survival, but has also been associated with metabolic dysregulation. In this study, we sought to define how mutations within PI3KCA may affect the metabolic dependency of a cancer cell, using precisely engineered isogenic cell lines. Studies revealed gene expression signatures in PIK3CA mutant cells indicative of a consistent up-regulation of glycolysis. Interestingly, the genes up- and down-regulated varied between isogenic models suggesting that the primary node of regulation is not the same between models. Additional gene expression changes were also observed, suggesting that metabolic pathways other than glycolysis, such as glutaminolysis, were also affected. Nutrient dependency studies revealed that growth of PIK3CA mutant cells is highly dependent on glucose, whereas glutamine dependency is independent of PIK3CA status. In addition, the glucose dependency exhibited by PIK3CA mutant cells could not be overridden by supplementation with other nutrients. This specific dependence on glucose for growth was further illustrated by studies evaluating the effects of targeted disruption of the glycolytic pathway using siRNA and was also found to be present across a wider panel of cancer cell lines harbouring endogenous PIK3CA mutations. In conclusion, we have found that PIK3CA mutations lead to a shift towards a highly glycolytic phenotype, and that despite suggestions that cancer cells are adept at utilising alternative nutrient sources, PIK3CA mutant cells are not able to compensate for glucose withdrawal. Understanding the metabolic dependencies of PIK3CA mutant cancers will provide critical information for the design of effective therapies and tumour visualisation strategies. PMID:23028762

Foster, Rebecca; Griffin, Sue; Grooby, Suzanne; Feltell, Ruth; Christopherson, Cindy; Chang, Monica; Sninsky, John; Kwok, Shirley; Torrance, Chris

2012-01-01

203

Statins Impair Glucose Uptake in Tumor Cells  

Directory of Open Access Journals (Sweden)

Full Text Available Statins, HMG-CoA reductase inhibitors, are used in the prevention and treatment of cardiovascular diseases owing to their lipid-lowering effects. Previous studies revealed that, by modulating membrane cholesterol content, statins could induce conformational changes in cluster of differentiation 20 (CD20 tetraspanin. The aim of the presented study was to investigate the influence of statins on glucose transporter 1 (GLUT1-mediated glucose uptake in tumor cells. We observed a significant concentration- and time-dependent decrease in glucose analogs' uptake in several tumor cell lines incubated with statins. This effect was reversible with restitution of cholesterol synthesis pathway with mevalonic acid as well as with supplementation of plasma membrane with exogenous cholesterol. Statins did not change overall GLUT1 expression at neither transcriptional nor protein levels. An exploratory clinical trial revealed that statin treatment decreased glucose uptake in peripheral blood leukocytes and lowered 18F-fluorodeoxyglucose (18F-FDG uptake by tumor masses in a mantle cell lymphoma patient. A bioinformatics analysis was used to predict the structure of human GLUT1 and to identify putative cholesterol-binding motifs in its juxtamembrane fragment. Altogether, the influence of statins on glucose uptake seems to be of clinical significance. By inhibiting 18F-FDG uptake, statins can negatively affect the sensitivity of positron emission tomography, a diagnostic procedure frequently used in oncology.

Agata Malenda

2012-04-01

204

Statins impair glucose uptake in tumor cells.  

Science.gov (United States)

Statins, HMG-CoA reductase inhibitors, are used in the prevention and treatment of cardiovascular diseases owing to their lipid-lowering effects. Previous studies revealed that, by modulating membrane cholesterol content, statins could induce conformational changes in cluster of differentiation 20 (CD20) tetraspanin. The aim of the presented study was to investigate the influence of statins on glucose transporter 1 (GLUT1)-mediated glucose uptake in tumor cells. We observed a significant concentration- and time-dependent decrease in glucose analogs' uptake in several tumor cell lines incubated with statins. This effect was reversible with restitution of cholesterol synthesis pathway with mevalonic acid as well as with supplementation of plasma membrane with exogenous cholesterol. Statins did not change overall GLUT1 expression at neither transcriptional nor protein levels. An exploratory clinical trial revealed that statin treatment decreased glucose uptake in peripheral blood leukocytes and lowered (18)F-fluorodeoxyglucose ((18)F-FDG) uptake by tumor masses in a mantle cell lymphoma patient. A bioinformatics analysis was used to predict the structure of human GLUT1 and to identify putative cholesterol-binding motifs in its juxtamembrane fragment. Altogether, the influence of statins on glucose uptake seems to be of clinical significance. By inhibiting (18)F-FDG uptake, statins can negatively affect the sensitivity of positron emission tomography, a diagnostic procedure frequently used in oncology. PMID:22577346

Malenda, Agata; Skrobanska, Anna; Issat, Tadeusz; Winiarska, Magdalena; Bil, Jacek; Oleszczak, Bozenna; Sinski, Maciej; Firczuk, Ma?gorzata; Bujnicki, Janusz M; Chlebowska, Justyna; Staruch, Adam D; Glodkowska-Mrowka, Eliza; Kunikowska, Jolanta; Krolicki, Leszek; Szablewski, Leszek; Gaciong, Zbigniew; Koziak, Katarzyna; Jakobisiak, Marek; Golab, Jakub; Nowis, Dominika A

2012-04-01

205

Reprogramming of Intestinal Glucose Metabolism and Glycemic Control in Rats After Gastric Bypass  

OpenAIRE

The resolution of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) attests to the important role of the gastrointestinal tract in glucose homeostasis. Previous studies in RYGB-treated rats have shown that the Roux limb displays hyperplasia and hypertrophy. Here, we report that the Roux limb of RYGB-treated rats exhibits reprogramming of intestinal glucose metabolism to meet its increased bioenergetic demands; glucose transporter-1 is up-regulated, basolateral glucose uptake is enhanced, ...

Saeidi, Nima; Meoli, Luca; Nestoridi, Eirini; Gupta, Nitin K.; Kvas, Stephanie; Kucharczyk, John; Bonab, Ali A.; Fischman, Alan J.; Yarmush, Martin L.; Stylopoulos, Nicholas

2013-01-01

206

Metabolic engineering of Corynebacterium glutamicum to produce GDP-L-fucose from glucose and mannose.  

Science.gov (United States)

Wild-type Corynebacterium glutamicum was metabolically engineered to convert glucose and mannose into guanosine 5'-diphosphate (GDP)-L-fucose, a precursor of fucosyl-oligosaccharides, which are involved in various biological and pathological functions. This was done by introducing the gmd and wcaG genes of Escherichia coli encoding GDP-D-mannose-4,6-dehydratase and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase, respectively, which are known as key enzymes in the production of GDP-L-fucose from GDP-D-mannose. Coexpression of the genes allowed the recombinant C. glutamicum cells to produce GDP-L-fucose in a minimal medium containing glucose and mannose as carbon sources. The specific product formation rate was much higher during growth on mannose than on glucose. In addition, the specific product formation rate was further increased by coexpressing the endogenous phosphomanno-mutase gene (manB) and GTP-mannose-1-phosphate guanylyl-transferase gene (manC), which are involved in the conversion of mannose-6-phosphate into GDP-D-mannose. However, the overexpression of manA encoding mannose-6-phosphate isomerase, catalyzing interconversion of mannose-6-phosphate and fructose-6-phosphate showed a negative effect on formation of the target product. Overall, coexpression of gmd, wcaG, manB and manC in C. glutamicum enabled production of GDP-L-fucose at the specific rate of 0.11 mg g cell(-1) h(-1). The specific GDP-L-fucose content reached 5.5 mg g cell(-1), which is a 2.4-fold higher than that of the recombinant E. coli overexpressing gmd, wcaG, manB and manC under comparable conditions. Well-established metabolic engineering tools may permit optimization of the carbon and cofactor metabolisms of C. glutamicum to further improve their production capacity. PMID:23404100

Chin, Young-Wook; Park, Jin-Byung; Park, Yong-Cheol; Kim, Kyoung Heon; Seo, Jin-Ho

2013-06-01

207

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

DEFF Research Database (Denmark)

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. Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia. The aim of this study was to characterize the ammonia-detoxifying mechanisms as well as the effects of ammonia on energy-generating metabolic pathways in a 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 enhanced the synthesis and release of alanine. Collectively, our results demonstrate that (1) formation of glutamine is seminal for detoxification of ammonia; (2) neuronal oxidative metabolism is increased in the presence of ammonia; and (3) synthesis and release of alanine is likely to be important for ammonia detoxification as a supplement to formation of glutamine.

Leke, Renata; Bak, Lasse Kristoffer

2011-01-01

208

Detoxification of Ammonia in Mouse Cortical GABAergic Cell Cultures Increases Neuronal Oxidative Metabolism and Reveals an Emerging Role for Release of Glucose-Derived Alanine  

DEFF Research Database (Denmark)

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. Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia. The aim of this study was to characterize the ammonia-detoxifying mechanisms as well as the effects of ammonia on energy-generating metabolic pathways in a 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 enhanced the synthesis and release of alanine. Collectively, our results demonstrate that (1) formation of glutamine is seminal for detoxification of ammonia; (2) neuronal oxidative metabolism is increased in the presence of ammonia; and (3) synthesis and release of alanine is likely to be important for ammonia detoxification as a supplement to formation of glutamine.

Leke, Renata; Bak, Lasse K

2011-01-01

209

Relationship between glucose metabolism and hepatic encephalopathy in patients with liver cirrhosis  

Directory of Open Access Journals (Sweden)

Full Text Available ObjectiveTo observe the changes in blood glucose in patients with liver cirrhosis and investigate the relationship between glucose metabolism and hepatic encephalopathy (HE. MethodsSixty patients with liver cirrhosis (cirrhosis group and 30 patients without liver cirrhosis (control group, who were hospitalized in Department of Gastroenterology, Jiading District Central Hospital from August 2008 to August 2010, were included in the study. The general data were collected; the consciousness of patients was observed; the physical examination was performed for detecting flapping tremors; blood samples were collected for measuring blood glucose. The cirrhosis group was further divided into flapping tremor subgroup and non-flapping tremor subgroup. The cirrhosis group and control group were compared in terms of the incidence rate of abnormal glucose metabolism. The patients were divided into normal glucose metabolism group and abnormal glucose metabolism group, and the two groups were compared in terms of the incidence rates of flapping tremors and HE. ResultsOf the 60 patients in cirrhosis group, 28 had no flapping tremors, and 32 had flapping tremors. The incidence rate of abnormal glucose metabolism was significantly lower in the control group than in the cirrhosis group (13.33% vs 26.67%; ?2=2?058, P?0.05. The incidence rates of flapping tremors and HE were 50.00% and 34.09% in the normal glucose metabolism group, versus 62.50% and 37.50% in the abnormal glucose metabolism group (P?0.05. ConclusionThe patients with liver cirrhosis have abnormal glucose metabolism, but which is not necessarily associated with HE. It suggests that the patients with HE may have impaired glucose utilization in the brain.

ZHANG Lihang

2013-07-01

210

Inhibitory effects of 2-deoxy-D-glucose on methanol metabolism in Torulopsis sp  

International Nuclear Information System (INIS)

Inhibitory effects of 2-deoxy-D-glucose (2dG) on methanol metabolism in Torulopsis A-12 were investigated. The remarkable inhibition was observed on growth in the presence of 50 ?g/ml of 2dG when methanol was used as a carbon source. At the earlier time of incubation with 2dG, the incorporation of 14C-methanol into hexose-phosphate by intact cells was inhibited by 2dG, and this led to the reduction of the intracellular concentration of hexosephosphates. In the later period of incubation the specific activity of alcohol oxidase reduced, and formate accumulated extracellularly. (auth.)

211

Polychlorinated biphenyl exposure and glucose metabolism in 9-year-old Danish children  

DEFF Research Database (Denmark)

CONTEXT: Human exposure to polychlorinated biphenyls (PCBs) has been associated to type 2 diabetes in adults. OBJECTIVE: We aimed to determine whether concurrent plasma PCB concentration was associated with markers of glucose metabolism in healthy children. SETTING AND DESIGN: Cross-sectional study of 771 healthy Danish third grade school children ages 8-10 years in the municipality of Odense were recruited in 1997 through a two-stage cluster sampling from 25 schools stratified according to location and socioeconomic character; 509 (9.7 ± 0.8 y, 53% girls) had adequate amounts available for PCB analyses. OUTCOME MEASURES: Fasting serum glucose and insulin were measured and a homeostasis assessment model of insulin resistance (HOMA-IR) and ?-cell function (HOMA-B) calculated. Plasma PCB congeners and other persistent compounds were measured and ?PCB calculated. RESULTS: PCBs were present in plasma at low concentrations, median, 0.19 ?g/g lipid (interquartile range, 0.12-0.31). After adjustment for putativeconfounding factors, the second, third, fourth, and fifth quintiles of total PCB were significantly inversely associated with serum insulin (-14.6%, -21.7%, -18.9%, -23.1%, P trend < .01), compared with the first quintile, but not with serum glucose (P = .45). HOMA-IR and HOMA-B were affected in the same direction due to the declining insulin levels with increasing PCB exposure. Similar results were found for individual PCB congeners, for ?HCB (hexachlorobenzen) and pp-DDE (dichlorodiphenyldichloroethylene). CONCLUSIONS: A strong inverse association between serum insulin and PCB exposure was found while fasting glucose remained within the expected narrow range. Our findings suggest that PCB may not exert effect through decreased peripheral insulin sensitivity, as seen in obese and low-fit children, but rather through a toxicity to ?-cells. It remains to be demonstrated whether lower HOMA-B is caused by destruction of ?-cell-reducing peripheral insulin resistance and thereby increase fasting glucose as previously found.

Jensen, Tina K; Timmermann, Amalie G

2014-01-01

212

? Cells in Pancreatic Islets and Glucose Regulation  

Science.gov (United States)

We present a model for oscillatory behaviors of ? cells in pancreatic islets and glucose regulation. With attention to the noise induced by channel-gating stochasticity and coupling via gap junctions, we obtain via extensive numerical simulations complex oscillations including clusters of bursting action potentials, slow and fast oscillations of calcium and insulin secretion, and so on.

Jo, J.; Kang, H.; Choi, M. Y.; Koh, D.-S.

213

Effects of glucose on sorbitol pathway activation, cellular redox, and metabolism of myo-inositol, phosphoinositide, and diacylglycerol in cultured human retinal pigment epithelial cells.  

OpenAIRE

Sorbitol (aldose reductase) pathway flux in diabetes perturbs intracellular metabolism by two putative mechanisms: reciprocal osmoregulatory depletion of other organic osmolytes e.g., myo-inositol, and alterations in NADPH/NADP+ and/or NADH/NAD+. The "osmolyte" and "redox" hypotheses predict secondary elevations in CDP-diglyceride, the rate-limiting precursor for phosphatidylinositol synthesis, but through different mechanisms: the "osmolyte" hypothesis via depletion of intracellular myo-inos...

Thomas, T. P.; Porcellati, F.; Kato, K.; Stevens, M. J.; Sherman, W. R.; Greene, D. A.

1994-01-01

214

Glucose metabolism in mice during and after whole-body hyperthermia  

International Nuclear Information System (INIS)

Researchers studied glucose turnover in male inbred mice during and after whole-body hyperthermia for 1 hour at 40 degrees or 41 degrees C by giving them injections of [14C]glucose with and without a glucose load and measuring the expired 14Co2. Expiration of 14CO2 was increased during hyperthermia but decreased considerably afterward. The latter effect was enhanced by a glucose load. This inhibition depended on the glucose concentration. Metabolic studies showed a depletion of several glycolytic metabolites, especially glycogen and lactate, after whole-body hyperthermia. Combined treatment of hyperthermia and a glucose injection 1 hour later led to an increased level of glucose 6-phosphate, which indicated a block in glycolysis between glucose 6-phosphate and fructose 1,6-diphosphate. This inhibition did not occur when glucose was given before the hyperthermia treatment. Lactate accumulation was not observed under any conditions

215

Regional brain glucose metabolism and blood flow in streptozocin-induced diabetic rats  

International Nuclear Information System (INIS)

Brain regional glucose metabolism and regional blood flow were measured from autoradiographs by the uptake of [3H]-2-deoxy-D-glucose and [14C]iodoantipyrine in streptozocin-induced diabetic (STZ-D) rats. After 2 days of diabetes, glucose metabolism in the neocortex, basal ganglia, and white matter increased by 34, 37, and 8%, respectively, whereas blood flow was unchanged. After 4 mo, glucose metabolism in the same three regions was decreased by 32, 43, and 60%. This reduction was paralleled by a statistically nonsignificant reduction in blood flow in neocortex and basal ganglia. It is suggested that the decrease of brain glucose metabolism in STZ-D reflects increased ketone body oxidation and reduction of electrochemical work

216

Insulin regulation of renal glucose metabolism in conscious dogs.  

OpenAIRE

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...

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

1994-01-01

217

Relationship between regional brain glucose metabolism and temperament factor of personality  

International Nuclear Information System (INIS)

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 ntal 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

218

Relationship between regional brain glucose metabolism and temperament factor of personality  

Energy Technology Data Exchange (ETDEWEB)

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.

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

2005-07-01

219

The relationship between fasting serum glucose and cerebral glucose metabolism in late-life depression and normal aging  

Science.gov (United States)

Evidence exists for late-life depression (LLD) as both a prodrome of and risk factor for Alzheimer’s disease (AD). The underlying neurobiological mechanisms are poorly understood. Impaired peripheral glucose metabolism may explain the association between depression and AD given the connection between type 2 diabetes mellitus with both depression and AD. Positron emission tomography (PET) measures of cerebral glucose metabolism are sensitive to detecting changes in neural circuitry in LLD and AD. Fasting serum glucose (FSG) in non-diabetic young (YC; n=20) and elderly controls (EC; n=12) and LLD patients (n=16) was correlated with PET scans of cerebral glucose metabolism on a voxel-wise basis. The negative correlations were more extensive in EC versus YC and in LLD patients versus EC. Increased FSG correlated with decreased cerebral glucose metabolism in LLD patients to a greater extent than in EC in heteromodal association cortices involved in mood symptoms and cognitive deficits observed in LLD and dementia. Negative correlations in YC were observed in sensory and motor regions. Understanding the neurobiological consequences of diabetes and associated conditions will have substantial public health significance given that this is a modifiable risk factor for which prevention strategies could have an important impact on lowering dementia risk. PMID:24650451

Marano, Christopher M.; Workman, Clifford I.; Lyman, Christopher H.; Kramer, Elisse; Hermann, Carol R.; Ma, Yilong; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David; Smith, Gwenn S.

2015-01-01

220

Ciglitazone enhances ovarian cancer cell death via inhibition of glucose transporter-1.  

Science.gov (United States)

Ciglitazone is a peroxisome proliferator-activated receptor ? (PPAR?) agonist and improves insulin sensitivity. Apart from antidiabetic activity, ciglitazone elicits inhibitory effects on cancer cell growth. Recent studies indicate that glucose metabolism plays a key role in malignant diseases. Significant increase in glucose consumption is found under malignant conditions. The role of ciglitazone in cancer cell death in relation to glucose metabolism is unclear. Thus we designed this study to determine the effect of ciglitazone on glucose metabolism. First, we found ciglitazone inhibited glucose uptake in ovarian cancer cells but did not affect hexokinase activity. Ciglitazone decreased expression levels of glucose transporter-1 (GLUT-1). We also found that ciglitazone and siGLUT-1 treatments induced cell death in ovarian cancer cells. We identified that ciglitazone decreased expressions of specific protein 1 (Sp-1) and ?-catenin while increased phosphorylation levels of AMP-activated protein kinase. In vivo study using NOD-scid IL2Rgamma(null) mice confirmed that ciglitazone significantly decreased ovarian cancer mass transplanted onto the back of the mice. Finally, we determined GLUT-1 expressions in patients with serous type ovarian cancer and found that GLUT-1 expression was markedly increased in cancer patients and expression level was proportional to the degree of cancer stages. These results suggest that ciglitazone induces apoptosis in ovarian cancer cells by the inhibition of GLUT-1 and provides a possible therapeutic effect of ciglitazone as an adjuvant drug in the treatment of ovarian cancer. PMID:25240713

Shin, So Jin; Kim, Jin Young; Kwon, Sun Young; Mun, Kyo-Cheol; Cho, Chi Heum; Ha, Eunyoung

2014-11-15

221

Bile acids as regulators of hepatic lipid and glucose metabolism.  

Science.gov (United States)

Besides their well-established roles in dietary lipid absorption and cholesterol homeostasis, bile acids (BA) also act as metabolically active signaling molecules. The flux of reabsorbed BA undergoing enterohepatic circulation, arriving in the liver with the co-absorbed nutrients (e.g. glucose, lipids), provides a signal that coordinates hepatic triglyceride (TG), glucose and energy homeostasis. As signaling molecules with systemic endocrine functions, BA can activate protein kinases A and C as well as mitogen-activated protein kinase pathways. Additionally, they are ligands for a G-protein-coupled BA receptor (TGR5/Gpbar-1) and activate nuclear receptors such as farnesoid X receptor (FXR; NR1H4). FXR and its downstream targets play a key role in the control of hepatic de novo lipogenesis, very-low-density lipoprotein-TG export and plasma TG turnover. BA-activated FXR and signal transduction pathways are also involved in the regulation of hepatic gluconeogenesis, glycogen synthesis and insulin sensitivity. Via TGR5, BA are able to stimulate glucagon-like peptide-1 secretion in the small intestine and energy expenditure in brown adipose tissue and skeletal muscle. Dysregulation of BA transport and impaired BA receptor signaling may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Thus, BA transport and BA-controlled nuclear receptors and signaling pathways are promising drug targets for treatment of NAFLD. As such, FXR and/or TGR5 ligands have shown promising results in animal models of NAFLD and clinical pilot studies. Despite being a poor FXR and TGR5 ligand, ursodeoxycholic acid (UDCA) improves hepatic ER stress and insulin sensitivity. Notably, norUDCA, a side chain-shortened homologue of UDCA, improves fatty liver and atherosclerosis in Western diet-fed ApoE(-/-) mice. Collectively, these findings suggest that BA and targeting their receptor/signaling pathways may represent a promising approach to treat NAFLD and closely linked disorders such as obesity, diabetes, dyslipidemia and arteriosclerosis. PMID:20460915

Trauner, Michael; Claudel, Thierry; Fickert, Peter; Moustafa, Tarek; Wagner, Martin

2010-01-01

222

Liver Med23 ablation improves glucose and lipid metabolism through modulating FOXO1 activity.  

Science.gov (United States)

Mediator complex is a molecular hub integrating signaling, transcription factors, and RNA polymerase II (RNAPII) machinery. Mediator MED23 is involved in adipogenesis and smooth muscle cell differentiation, suggesting its role in energy homeostasis. Here, through the generation and analysis of a liver-specific Med23-knockout mouse, we found that liver Med23 deletion improved glucose and lipid metabolism, as well as insulin responsiveness, and prevented diet-induced obesity. Remarkably, acute hepatic Med23 knockdown in db/db mice significantly improved the lipid profile and glucose tolerance. Mechanistically, MED23 participates in gluconeogenesis and cholesterol synthesis through modulating the transcriptional activity of FOXO1, a key metabolic transcription factor. Indeed, hepatic Med23 deletion impaired the Mediator and RNAPII recruitment and attenuated the expression of FOXO1 target genes. Moreover, this functional interaction between FOXO1 and MED23 is evolutionarily conserved, as the in vivo activities of dFOXO in larval fat body and in adult wing can be partially blocked by Med23 knockdown in Drosophila. Collectively, our data revealed Mediator MED23 as a novel regulator for energy homeostasis, suggesting potential therapeutic strategies against metabolic diseases. PMID:25223702

Chu, Yajing; Gómez Rosso, Leonardo; Huang, Ping; Wang, Zhichao; Xu, Yichi; Yao, Xiao; Bao, Menghan; Yan, Jun; Song, Haiyun; Wang, Gang

2014-10-01

223

Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.  

Science.gov (United States)

Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of ?-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited ?-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma. PMID:23029529

Tirado-Vélez, José Manuel; Joumady, Insaf; Sáez-Benito, Ana; Cózar-Castellano, Irene; Perdomo, Germán

2012-01-01

224

Direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics.  

Science.gov (United States)

The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under euglycemic and hyperglycemic conditions. Young, healthy men (n = 10) underwent three trials in a randomized, controlled, crossover study. Each trial consisted of a two-stage (euglycemia and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism was measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial, and common carotid artery blood flow and flow-mediated dilation of the brachial artery) were also measured. The three trials differed as follows: 1) saline [control (CON)], 2) glucagon-like peptide (GLP-1, 0.5 pmol·kg(-1)·min(-1)), and 3) glucose-dependent insulinotropic polypeptide (GIP, 1.5 pmol·kg(-1)·min(-1)). No between-trial differences in glucose infusion rates (GIR) or glucose or glycerol kinetics were seen during euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of disappearance during GLP-1 compared with CON and GIP (P blood flow during hyperglycemia with GIP (vs. CON and GLP-1, P metabolism or hemodynamics during euglycemia. On the contrary, during hyperglycemia, GIP increases femoral artery blood flow with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal, potentially due to increased insulin levels. PMID:25564476

Karstoft, Kristian; Mortensen, Stefan P; Knudsen, Sine H; Solomon, Thomas P J

2015-03-01

225

Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass.  

Science.gov (United States)

The resolution of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) attests to the important role of the gastrointestinal tract in glucose homeostasis. Previous studies in RYGB-treated rats have shown that the Roux limb displays hyperplasia and hypertrophy. Here, we report that the Roux limb of RYGB-treated rats exhibits reprogramming of intestinal glucose metabolism to meet its increased bioenergetic demands; glucose transporter-1 is up-regulated, basolateral glucose uptake is enhanced, aerobic glycolysis is augmented, and glucose is directed toward metabolic pathways that support tissue growth. We show that reprogramming of intestinal glucose metabolism is triggered by the exposure of the Roux limb to undigested nutrients. We demonstrate by positron emission tomography-computed tomography scanning and biodistribution analysis using 2-deoxy-2-[18F]fluoro-D-glucose that reprogramming of intestinal glucose metabolism renders the intestine a major tissue for glucose disposal, contributing to the improvement in glycemic control after RYGB. PMID:23888041

Saeidi, Nima; Meoli, Luca; Nestoridi, Eirini; Gupta, Nitin K; Kvas, Stephanie; Kucharczyk, John; Bonab, Ali A; Fischman, Alan J; Yarmush, Martin L; Stylopoulos, Nicholas

2013-07-26

226

Roles of microRNA on cancer cell metabolism  

Directory of Open Access Journals (Sweden)

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.

Chen Bing

2012-11-01

227

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

International Nuclear Information System (INIS)

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

228

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

International Nuclear Information System (INIS)

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

229

Glucose concentration and streptomycin alter in vitro muscle function and metabolism.  

Science.gov (United States)

Cell culture conditions can vary between laboratories and have been optimised for 2D cell culture. In this study, engineered muscle was cultured in 5.5?mM low glucose (LG) or 25?mM high glucose (HG) and in the absence or presence (+S) of streptomycin and the effect on C2C12 tissue-engineered muscle function and metabolism was determined. Following 2 weeks differentiation, streptomycin (3-fold) and LG (0.5-fold) significantly decreased force generation. LG and/or streptomycin resulted in upward and leftward shifts in the force-frequency curve and slowed time-to-peak tension and half-relaxation time. Despite changes in contractile dynamics, no change in myosin isoform was detected. Instead, changes in troponin isoform, calcium sequestering proteins (CSQ and parvalbumin) and the calcium uptake protein SERCA predicted the changes in contractile dynamics. Culturing in LG and/or streptomycin resulted in increased fatigue resistance despite no change in the mitochondrial enzymes SDH, ATPsynthase and cytochrome C. However, LG resulted in increases in the ?-oxidation enzymes LCAD and VLCAD and the fatty acid transporter CPT-1, indicative of a greater capacity for fat oxidation. In contrast, HG resulted in increased GLUT4 content and the glycolytic enzyme PFK, indicative of a more glycolytic phenotype. These data suggest that streptomycin has negative effects on force generation and that glucose can be used to shift engineered muscle phenotype via changes in calcium-handling and metabolic proteins. J. Cell. Physiol. 230: 1226-1234, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company. PMID:25358470

Khodabukus, Alastair; Baar, Keith

2015-06-01

230

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

International Nuclear Information System (INIS)

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 alkalosisetabolic alkalosis

231

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

Science.gov (United States)

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

de Graaf-Roelfsema, Ellen

2014-01-01

232

The effect of long-term exercise on glucose metabolism and peripheral insulin sensitivity in Standardbred horses  

OpenAIRE

Reasons for performing study: To study the long term effect of improved glucose tolerance in horses after long-term training, as the impact of exercise training on glucose metabolism is still unclear in the equine species. It is not known whether there is a direct long-term effect of training or if the measurable effect on glucose metabolism is the residual effect of the last exercise session. Objectives: To determine the chronic effect on glucose metabolism and periph...

Graaf-roelfsema, E.; Ginneken, M. M. E.; Breda, E.; Wijnberg, I. D.; Keizer, H. A.; Kolk, J. H.

2006-01-01

233

AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells?  

OpenAIRE

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that appears to have arisen during early eukaryotic evolution. In the unicellular eukaryote Saccharomyces cerevisiae, the AMPK orthologue is activated by glucose starvation and is required for the switch from glycolysis (fermentation) to oxidative metabolism when glucose runs low. In mammals, rapidly proliferating cells (including tumour cells) and immune cells involved in inflammation, both tend to utilize rapid gl...

Dandapani, Madhumita; Hardie, D. Grahame

2013-01-01

234

Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice  

OpenAIRE

The Mouse Metabolic Phenotyping Center (MMPC) Consortium was established to address the need to characterize the growing number of mouse models of metabolic diseases, particularly diabetes and obesity. A goal of the MMPC Consortium is to propose standard methods for assessing metabolic phenotypes in mice. In this article, we discuss issues pertaining to the design and performance of various tests of glucose metabolism. We also propose guidelines for the description of methods, presentation of...

Ayala, Julio E.; Samuel, Varman T.; Morton, Gregory J.; Obici, Silvana; Croniger, Colleen M.; Shulman, Gerald I.; Wasserman, David H.; Mcguinness, Owen P.

2010-01-01

235

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

Energy Technology Data Exchange (ETDEWEB)

Highlights: •HIF-1?-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.

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

236

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

International Nuclear Information System (INIS)

Highlights: •HIF-1?-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

237

Computational model of cellular metabolic dynamics : effect of insulin on glucose disposal in human skeletal muscle  

DEFF Research Database (Denmark)

Identifying the mechanisms by which insulin regulates glucose metabolism in skeletal muscle is critical to understanding the etiology of insulin resistance and type 2 diabetes. Our knowledge of these mechanisms is limited by the difficulty of obtaining in vivo intracellular data. To quantitatively distinguish significant transport and metabolic mechanisms from limited experimental data, we developed a physiologically based, multiscale mathematical model of cellular metabolic dynamics in skeletal muscle. The model describes mass transport and metabolic processes including distinctive processes of the cytosol and mitochondria. The model simulated skeletal muscle metabolic responses to insulin corresponding to human hyperinsulinemic-euglycemic clamp studies. Insulin-mediated rate of glucose disposal was the primary model input. For model validation, simulations were compared with experimental data: intracellular metabolite concentrations and patterns of glucose disposal. Model variations were simulated to investigate three alternative mechanisms to explain insulin enhancements: Model 1 (M.1), simple mass action; M.2, insulin-mediated activation of key metabolic enzymes (i.e., hexokinase, glycogen synthase, pyruvate dehydrogenase); or M.3, parallel activation by a phenomenological insulin-mediated intracellular signal that modifies reaction rate coefficients. These simulations indicated that models M.1 and M.2 were not sufficient to explain the experimentally measured metabolic responses. However, by application of mechanism M.3, the model predicts metabolite concentration changes and glucose partitioning patterns consistent with experimental data. The reaction rate fluxes quantified by this detailed model of insulin/glucose metabolism provide information that can be used to evaluate the development of type 2 diabetes.

Li, Yanjun; Solomon, Thomas

2010-01-01

238

Cross-regulation of hepatic glucose metabolism via ChREBP and Nuclear Receptors  

OpenAIRE

Abstract There is a worldwide epidemic of obesity and type 2 diabetes, two major public health concerns associated with alterations in both insulin and glucose signaling pathways. Glucose is not only an energy source but also controls the expression of key genes involved in energetic metabolism, through the glucose-signaling transcription factor, Carbohydrate Responsive Element Binding Protein (ChREBP). ChREBP has emerged as a central regulator of de novo fatty acid synthesis (lipo...

2011-01-01

239

Glucose metabolism and gene expression in juvenile zebrafish (Danio rerio) challenged with a high carbohydrate diet: effects of an acute glucose stimulus during late embryonic life.  

Science.gov (United States)

Knowledge on the role of early nutritional stimuli as triggers of metabolic pathways in fish is extremely scarce. The objective of the present study was to assess the long-term effects of glucose injection in the yolk (early stimulus) on carbohydrate metabolism and gene regulation in zebrafish juveniles challenged with a high-carbohydrate low-protein (HC) diet. Eggs were microinjected at 1 d post-fertilisation (dpf) with either glucose (2 m) or saline solutions. Up to 25 dpf, fish were fed a low-carbohydrate high-protein (LC) control diet, which was followed by a challenge with the HC diet. Survival and growth of 35 dpf juveniles were not affected by injection or the HC diet. Glucose stimulus induced some long-term metabolic changes in the juveniles, as shown by the altered expression of genes involved in glucose metabolism. On glycolysis, the expression levels of hexokinase 1 (HK1) and phosphofructokinase-6 (6PFK) were up-regulated in the visceral and muscle tissues, respectively, of juveniles exposed to the glucose stimulus, indicating a possible improvement in glucose oxidation. On gluconeogenesis, the inhibition of the expression levels of PEPCK in fish injected with glucose suggested lower production of hepatic glucose. Unexpectedly, fructose-1,6-bisphosphatase (FBP) expression was induced and 6PFK expression reduced by glucose stimulus, leaving the possibility of a specific regulation of the FBP-6PFK metabolic cycle. Glucose metabolism in juveniles was estimated using a [14C]glucose tracer; fish previously exposed to the stimulus showed lower retention of [14C]glucose in visceral tissue (but not in muscle tissue) and, accordingly, higher glucose catabolism, in comparison with the saline group. Globally, our data suggest that glucose stimulus at embryo stage has the potential to alter particular steps of glucose metabolism in zebrafish juveniles. PMID:25609020

Rocha, Filipa; Dias, Jorge; Engrola, Sofia; Gavaia, Paulo; Geurden, Inge; Dinis, Maria Teresa; Panserat, Stephane

2015-02-01

240

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

Energy Technology Data Exchange (ETDEWEB)

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).

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

241

Association of glucose metabolism with diastolic function along the diabetic continuum  

OpenAIRE

Hyperglycaemia and insulin resistance have been linked to diastolic dysfunction experimentally. We investigated the association between glucose metabolism and diastolic function along the whole spectrum of glucose metabolism states.In the observational Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Diastolic Heart Failure (DIAST-CHF) study, patients with risk factors for heart failure were included. We analysed data including comprehensive echocardiography fro...

Stahrenberg, R.; Edelmann, F.; Mende, M.; Kockska?mper, A.; Du?ngen, H.; Scherer, M.; Kochen, Michael M.; Binder, L.; Herrmann-lingen, C.; Gelbrich, G.; Hasenfuß, G.; Pieske, B.; Wachter, R.

2010-01-01

242

Altered glucose metabolism of tumors: an attractive target for improving radiation and chemotherapy of tumors  

International Nuclear Information System (INIS)

Poorly differentiated and rapidly growing malignant tumors are generally characterized by higher rates of glucose usage and glycolysis as compared to corresponding normal tissues. Therefore, modulating the glucose metabolism using 2-DG provides a unique opportunity to selectively destroy tumors and significantly enhance the efficacy of radio and chemotherapy

243

Upregulation of glucose metabolism by granulocyte-monocyte colony-stimulating factor  

Energy Technology Data Exchange (ETDEWEB)

Alterations of glucose metabolism were investigated for 6 hours following an intraarterial injection of murine recombinant granulocyte-monocyte colony-stimulating factor (GM-CSF). GM-CSF resulted in a transient elevation of plasma glucose. The rate of whole body glucose appearance, as measured by infusion of (6-{sup 3}H)glucose, was increased by about 10% between 0.5 and 3 hours following GM-CSF injection. In vivo glucose utilization of individual tissues was investigated by the tracer 2-deoxyglucose technique. At 30 min, GM-CSF increased glucose utilization by 80-90% in liver and lung, and 50-60% in skin and spleen. At 3 and 6 hours, glucose utilization by these tissues returned toward control levels except for lung. There was a 40-50% increase in glucose utilization by skeletal muscle 30 min after GM-CSF which was sustained for 6 hours. Glucose utilization of testis, ileum and kidney did not change significantly. Plasma concentrations of insulin, glucagon and tumor necrosis factor were not altered in response to GM-CSF. These findings indicate that some of the acute metabolic effects of a short-term administration of GM-CSF are observed in macrophage-rich tissues, and suggest that GM-CSF may be involved in the metabolic upregulation of immunologically active tissues.

Schuler, A.; Spolarics, Z.; Lang, C.H.; Bagby, G.J.; Nelson, S.; Spitzer, J.J. (Louisiana State Univ., New Orleans (United States))

1991-01-01

244

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

Science.gov (United States)

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

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

2014-09-01

245

The impact of sleep disorders on glucose metabolism: endocrine and molecular mechanisms.  

Science.gov (United States)

Modern lifestyle has profoundly modified human sleep habits. Sleep duration has shortened over recent decades from 8 to 6.5 hours resulting in chronic sleep deprivation. Additionally, irregular sleep, shift work and travelling across time zones lead to disruption of circadian rhythms and asynchrony between the master hypothalamic clock and pacemakers in peripheral tissues. Furthermore, obstructive sleep apnea syndrome (OSA), which affects 4 - 15% of the population, is not only characterized by impaired sleep architecture but also by repetitive hemoglobin desaturations during sleep. Epidemiological studies have identified impaired sleep as an independent risk factor for all cause of-, as well as for cardiovascular, mortality/morbidity. More recently, sleep abnormalities were causally linked to impairments in glucose homeostasis, metabolic syndrome and Type 2 Diabetes Mellitus (T2DM). This review summarized current knowledge on the metabolic alterations associated with the most prevalent sleep disturbances, i.e. short sleep duration, shift work and OSA. We have focused on various endocrine and molecular mechanisms underlying the associations between inadequate sleep quality, quantity and timing with impaired glucose tolerance, insulin resistance and pancreatic ?-cell dysfunction. Of these mechanisms, the role of the hypothalamic-pituitary-adrenal axis, circadian pacemakers in peripheral tissues, adipose tissue metabolism, sympathetic nervous system activation, oxidative stress and whole-body inflammation are discussed. Additionally, the impact of intermittent hypoxia and sleep fragmentation (key components of OSA) on intracellular signaling and metabolism in muscle, liver, fat and pancreas are also examined. In summary, this review provides endocrine and molecular explanations for the associations between common sleep disturbances and the pathogenesis of T2DM. PMID:25834642

Briançon-Marjollet, Anne; Weiszenstein, Martin; Henri, Marion; Thomas, Amandine; Godin-Ribuot, Diane; Polak, Jan

2015-01-01

246

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder  

International Nuclear Information System (INIS)

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

247

Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis.  

Science.gov (United States)

We performed silencing and overexpression studies of flavin containing monooxygenase (FMO) 3 in hyperlipidemic mouse models to examine its effects on trimethylamine N-oxide (TMAO) levels and atherosclerosis. Knockdown of hepatic FMO3 in LDL receptor knockout mice using an antisense oligonucleotide resulted in decreased circulating TMAO levels and atherosclerosis. Surprisingly, we also observed significant decreases in hepatic lipids and in levels of plasma lipids, ketone bodies, glucose, and insulin. FMO3 overexpression in transgenic mice, on the other hand, increased hepatic and plasma lipids. Global gene expression analyses suggested that these effects of FMO3 on lipogenesis and gluconeogenesis may be mediated through the PPAR? and Kruppel-like factor 15 pathways. In vivo and in vitro results were consistent with the concept that the effects were mediated directly by FMO3 rather than trimethylamine/TMAO; in particular, overexpression of FMO3 in the human hepatoma cell line, Hep3B, resulted in significantly increased glucose secretion and lipogenesis. Our results indicate a major role for FMO3 in modulating glucose and lipid homeostasis in vivo, and they suggest that pharmacologic inhibition of FMO3 to reduce TMAO levels would be confounded by metabolic interactions. PMID:25378658

Shih, Diana M; Wang, Zeneng; Lee, Richard; Meng, Yonghong; Che, Nam; Charugundla, Sarada; Qi, Hannah; Wu, Judy; Pan, Calvin; Brown, J Mark; Vallim, Thomas; Bennett, Brian J; Graham, Mark; Hazen, Stanley L; Lusis, Aldons J

2015-01-01

248

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

International Nuclear Information System (INIS)

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 foof the individual rate constants in the four-parameter fitting of brief dynamic scan sequences in studies of metabolic rate using 2-deoxy-2-fluoroglucose

249

PKA phosphorylation couples hepatic inositol-requiring enzyme 1alpha to glucagon signaling in glucose metabolism.  

Science.gov (United States)

The endoplasmic reticulum (ER)-resident protein kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1) is activated through transautophosphorylation in response to protein folding overload in the ER lumen and maintains ER homeostasis by triggering a key branch of the unfolded protein response. Here we show that mammalian IRE1? in liver cells is also phosphorylated by a kinase other than itself in response to metabolic stimuli. Glucagon-stimulated protein kinase PKA, which in turn phosphorylated IRE1? at Ser(724), a highly conserved site within the kinase activation domain. Blocking Ser(724) phosphorylation impaired the ability of IRE1? to augment the up-regulation by glucagon signaling of the expression of gluconeogenic genes. Moreover, hepatic IRE1? was highly phosphorylated at Ser(724) by PKA in mice with obesity, and silencing hepatic IRE1? markedly reduced hyperglycemia and glucose intolerance. Hence, these results suggest that IRE1? integrates signals from both the ER lumen and the cytoplasm in the liver and is coupled to the glucagon signaling in the regulation of glucose metabolism. PMID:21911379

Mao, Ting; Shao, Mengle; Qiu, Yifu; Huang, Jialiang; Zhang, Yongliang; Song, Bo; Wang, Qiong; Jiang, Lei; Liu, Yi; Han, Jing-Dong J; Cao, Pengrong; Li, Jia; Gao, Xiang; Rui, Liangyou; Qi, Ling; Li, Wenjun; Liu, Yong

2011-09-20

250

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

International Nuclear Information System (INIS)

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)generalized epilepsy in El mice. (author)

251

Cerebral glucose metabolism is decreased in white matter changes in patients with phenylketonuria.  

Science.gov (United States)

Cerebral magnetic resonance imaging (MRI) has revealed white matter changes in patients with phenylketonuria (PKU), an inborn error of metabolism with increased plasma phenylalanine level. Because the significance of these lesions is unknown, this study was undertaken to determine whether glucose metabolism was depressed in cerebral white matter MRI changes in patients with PKU. Four patients with PKU and nine healthy volunteers with an average age of 23 y (range 19-26 y) and 23 y (range 20-27 y), respectively, were studied. The IQ of patients with PKU was between 58 and 97. Cerebral MRI and positron emission tomography images with 18F-deoxyglucose were obtained, and arteriovenous differences for oxygen and glucose as well as cerebral blood flow was measured simultaneously to determine global cerebral oxygen and glucose metabolism. Cerebral MRI revealed that all patients with PKU had white matter changes with characteristic localization. In patients with PKU, regional glucose metabolism was 36% lower in the anterior periventricular areas, 0.14 +/- 0.06 compared with 0.22 +/- 0.04 mumol.g-1.min-1 in controls (mean +/- SD, p < 0.05, Mann-Whitney). Further, the ratio between glucose metabolism in the affected white matter and the cortex was 14% lower in the patients, decreasing from 0.57 +/- 0.05 to 0.48 +/- 0.06 (p < 0.05). Global cerebral blood flow, oxygen and glucose consumption were similar in the two groups. In conclusion, regional glucose metabolism is lower in MRI-demonstrated white matter changes. In mildly intellectually impaired patients with PKU, global cerebral glucose and oxygen metabolism remain intact. PMID:8798240

Hasselbalch, S; Knudsen, G M; Toft, P B; Høgh, P; Tedeschi, E; Holm, S; Videbaek, C; Henriksen, O; Lou, H C; Paulson, O B

1996-07-01

252

Glucose challenge increases circulating progenitor cells in Asian Indian male subjects with normal glucose tolerance which is compromised in subjects with pre-diabetes: A pilot study  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Haematopoietic stem cells undergo mobilization from bone marrow to blood in response to physiological stimuli such as ischemia and tissue injury. The aim of study was to determine the kinetics of circulating CD34+ and CD133+CD34+ progenitor cells in response to 75 g glucose load in subjects with normal and impaired glucose metabolism. Methods Asian Indian male subjects (n = 50 with no prior history of glucose imbalance were subjected to 2 hour oral glucose tolerance test (OGTT. 24 subjects had normal glucose tolerance (NGT, 17 subjects had impaired glucose tolerance (IGT and 9 had impaired fasting glucose (IFG. The IGT and IFG subjects were grouped together as pre-diabetes group (n = 26. Progenitor cell counts in peripheral circulation at fasting and 2 hour post glucose challenge were measured using direct two-color flow cytometry. Results The pre-diabetes group was more insulin resistant (p + cells (p = 0.003 and CD133+CD34+ (p = 0.019 cells was seen 2 hours post glucose challenge in the NGT group. This increase for both the cell types was attenuated in subjects with IGT. CD34+ cell counts in response to glucose challenge inversely correlated with neutrophil counts (? = -0.330, p = 0.019, while post load counts of CD133+CD34+ cells inversely correlated with serum creatinine (? = -0.312, p = 0.023. Conclusion There is a 2.5-fold increase in the circulating levels of haematopoietic stem cells in response to glucose challenge in healthy Asian Indian male subjects which is attenuated in subjects with pre-diabetes.

Bairagi Soumi

2011-01-01

253

A glucose biofuel cell implanted in rats.  

Science.gov (United States)

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

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

2010-01-01

254

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

OpenAIRE

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

Acosta, Mari?a Lourdes; Sa?nchez, Asterio; Garci?a, Francisco; Contreras, Antonio; Molina, Emilio

2007-01-01

255

High glucose inhibits gene expression of tyrosyl-tRNA synthetase in osteoblast cells.  

Science.gov (United States)

It has been suggested that bone metabolism disorders are one of the major complications of diabetes mellitus. However, the exact mechanisms as to how diabetes affects bone metabolism are yet to be determined. In the present study, we have searched for high glucose regulated genes in osteoblast-like UMR-106 cells. UMR-106 cells were treated with normal glucose (5.5 mM), high glucose (16.5 mM or 30.5 mM) and mannitol (16.5 mM) as a hyperosmotic control. Following the isolation of total RNA, GeneFishing differential display-PCR (DDPCR) was carried out and followed by cloning, sequencing and searching in a gene bank data base to identify the high glucose induced gene(s). Through the DD-PCR technique which employs Annealing Control Primer, or ACP, it has been found that expression of a PCR product was significantly decreased by high glucose treatment: it was identified as tyrosyl-tRNA synthetase. Furthermore, reverse transcriptase PCR analysis confirmed that high glucose significantly decreases mRNA expression of tyrosyl-tRNA synthetase, whereas mannitol treatment does not cause any change in such expression. These results suggest that high glucose may play a significant role in the protein synthesis process of osteoblast cells by decreasing expression of tyrosyl-tRNA synthetase. In a Western blot analysis, the protein expression of tyrosyl-tRNA synthetase was also decreased by high glucose treatment. Taken together, these results suggest that high glucose could affect bone metabolism by regulating the expression of tyrosyl-tRNA synthetase genes. PMID:20140272

Kim, Jun Hoe; Kim, Yun-Young; Kim, Sung-Jin

2009-12-01

256

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

DEFF Research Database (Denmark)

OBJECTIVE: We have recently shown that the level of soluble urokinase plasminogen activator receptor (suPAR), which is associated with the immune status of HIV-infected patients undergoing highly active antiretroviral therapy (HAART), correlates with the insulin action of such patients. Here we 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(composite)), prehepatic insulin secretion, proinsulin level and suppression of free fatty acids (FFA) were determined during an OGTT. Stability of suPAR was tested in 6 HIV-infected patients during a 3h OGTT. RESULTS: Lipodystrophy was associated with a 70% increase in plasma suPAR (P<0.05). During the OGTT, plasma suPAR 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: suPAR associated to important glucose metabolic aberrations in HIV-infected patients on HAART. Moreover, suPAR was stable after a glucose challenge. Future research is required to confirm these findings and explore the potential of suPAR as marker of dysmetabolism in HIV-infected patients Udgivelsesdato: 2008/7

Andersen, Ove; Eugen-Olsen, Jesper

2008-01-01

257

Influence of acetate on glucose metabolism in the perfused hind-quarter of the rat.  

Science.gov (United States)

The metabolism of U-14C-glucose and U-14C-acetate and the interaction between the two substrates in the perfused hind-quarter of the rat was studied. 5% of glucose taken up was oxidized to CO2, accounting for 15% of total oxygen consumption. Glucose was mainly incorporated into glycogen, while incorporation into lipids was negligible. Acetate did not significantly alter glucose uptake, 14C-glucose oxidation or the incorporation of 14C-glucose into glycogen and lipids. 45% of acetate taken up was oxidized to CO2, accounting for 20-25% of total oxygen consumption. Insulin did not affect acetate uptake but increased 14C-acetate oxidation. Oxygen consumption was slightly increased by simultaneous oxidation of glucose and acetate and in this situation the tissue content.of high-energy phosphate compounds was slightly elevated. It is concluded that only minor effects by acetate on glucose metabolism in the perfused skeletal muscle were found. The insignificant effects compared to previously reported studies on heart tissue (Neely and Morgan 1974) can be explained by differences in acetate metabolism between the two tissues. PMID:998283

Karlsson, N; Fellenius, E; Kiessling, K H

1976-11-01

258

Acute effect of glucose on cerebral blood flow, blood oxygenation, and oxidative metabolism.  

Science.gov (United States)

While it is known that specific nuclei of the brain, for example hypothalamus, contain glucose-sensing neurons thus their activity is affected by blood glucose level, the effect of glucose modulation on whole-brain metabolism is not completely understood. Several recent reports have elucidated the long-term impact of caloric restriction on the brain, showing that animals under caloric restriction had enhanced rate of tricarboxylic acid cycle (TCA) cycle flux accompanied by extended life span. However, acute effect of postprandial blood glucose increase has not been addressed in detail, partly due to a scarcity and complexity of measurement techniques. In this study, using a recently developed noninvasive MR technique, we measured dynamic changes in global cerebral metabolic rate of O2 (CMRO2 ) following a 50 g glucose ingestion (N?=?10). A time dependent decrease in CMRO2 was observed, which was accompanied by a reduction in oxygen extraction fraction (OEF) with unaltered cerebral blood flow (CBF). At 40 min post-ingestion, the amount of CMRO2 reduction was 7.8?±?1.6%. A control study without glucose ingestion was performed (N?=?10), which revealed no changes in CMRO2 , CBF, or OEF, suggesting that the observations in the glucose study was not due to subject drowsiness or fatigue after staying inside the scanner. These findings suggest that ingestion of glucose may alter the rate of cerebral metabolism of oxygen in an acute setting. PMID:25324201

Xu, Feng; Liu, Peiying; Pascual, Juan M; Xiao, Guanghua; Huang, Hao; Lu, Hanzhang

2015-02-01

259

[The mineral dietary composition affects glucose metabolism and modulates insulin effect in intact rats].  

Science.gov (United States)

The experiments on intact rats showed that an excess sodium chloride consumption and the use of giposol (NaCl substitute) produce a hypoglycemic effect. Giposol increases, whereas NaCl decreases, the glucose tolerance. Giposol activates hexokinase and glucose-6-phosphate dehydrogenase (the key enzymes of the glucose metabolism in tissues) and reduces the effect of insulin. Both giposol and NaCl increase the level of glucose absorption in small intestine. The gastric motility is activated by NaCl and not affected by giposol. PMID:11022306

Ratyni, O A; Shtrygol', S Iu; Slobodin, V B; Sadin, A V; Nazarenko, M E

2000-01-01

260

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

Directory of Open Access Journals (Sweden)

Full Text Available Incretins, hormones released by the gut after meal ingestion, are essential for maintaining systemic glucose homeostasis by stimulating insulin secretion. The effect of incretins on insulin secretion occurs only at elevated glucose concentrations and is mediated by cAMP signaling, but the mechanism linking glucose metabolism and cAMP action in insulin secretion is unknown. We show here, using a metabolomics-based approach, that cytosolic glutamate derived from the malate-aspartate shuttle upon glucose stimulation underlies the stimulatory effect of incretins and that glutamate uptake into insulin granules mediated by cAMP/PKA signaling amplifies insulin release. Glutamate production is diminished in an incretin-unresponsive, insulin-secreting ? 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.

Ghupurjan Gheni

2014-10-01

261

Steviol Glycosides Modulate Glucose Transport in Different Cell Types  

Science.gov (United States)

Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway. PMID:24327825

Rizzo, Benedetta; Zambonin, Laura; Leoncini, Emanuela; Vieceli Dalla Sega, Francesco; Prata, Cecilia; Fiorentini, Diana; Hrelia, Silvana

2013-01-01

262

Yeast cells with impaired drug resistance accumulate glycerol and glucose.  

Science.gov (United States)

Multiple drug resistance (MDR) in yeast is effected by two major superfamilies of membrane transporters: the major facilitator superfamily (MFS) and the ATP-binding cassette (ABC) superfamily. In the present work, we investigated the cellular responses to disruptions in both MFS (by deleting the transporter gene, QDR3) and ABC (by deleting the gene for the Pdr3 transcription factor) transporter systems by growing diploid homozygous deletion yeast strains in glucose- or ammonium-limited continuous cultures. The transcriptome and the metabolome profiles of these strains, as well as the flux distributions in the optimal solution space, reveal novel insights into the underlying mechanisms of action of QDR3 and PDR3. Our results show how cells rearrange their metabolism to cope with the problems that arise from the loss of these drug-resistance genes, which likely evolved to combat chemical attack from bacterial or fungal competitors. This is achieved through the accumulation of intracellular glucose, glycerol, and inorganic phosphate, as well as by repurposing genes that are known to function in other parts of metabolism in order to minimise the effects of toxic compounds. PMID:24157722

Dikicioglu, Duygu; Oc, Sebnem; Rash, Bharat M; Dunn, Warwick B; Pir, P?nar; Kell, Douglas B; Kirdar, Betul; Oliver, Stephen G

2014-01-01

263

The direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics  

DEFF Research Database (Denmark)

The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under eu- and hyperglycemic conditions. Young, healthy males (n=10) underwent three trials in a randomized, controlled, cross-over study. Each trial consisted of a 2-stage (eu- and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism were measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial and common carotid artery blood flow; and flow-mediated dilation [FMD] of brachial artery) were also measured. The three trials differed by the following additional infusions: (I) Saline (control; CON); (II) GLP-1 (0.5 pmol/kg/min); and (III) GIP (1.5 pmol/kg/min). No between-trial differences in glucose infusion rates (GIR), glucose or glycerol kinetics were seen during euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of disappearance (Rd) during GLP-1 compared to CON and GIP (P<0.01 for all). However, when normalized to insulin levels, no differences between trials were seen for GIR or glucose Rd. Besides a higher femoral blood flow during hyperglycemia in GIP (vs. CON and GLP-1, P<0.001), no between-trial differences were seen for the hemodynamic variables. In conclusion, GLP-1 and GIP have no direct effect on whole body glucose metabolism or hemodynamics during euglycemia. On contrary, during hyperglycemia, GIP increases femoral artery blood flow with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal, potentially, however, due to increased insulin levels.

Karstoft, Kristian; Mortensen, Stefan

2015-01-01

264

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

Energy Technology Data Exchange (ETDEWEB)

Cerebral glucose metabolism was evaluated in patients with either Wernicke's (N = 7), Broca's (N = 11), or conduction (N = 10) aphasia using /sup 18/F-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.

Metter, E.J.; Kempler, D.; Jackson, C.; Hanson, W.R.; Mazziotta, J.C.; Phelps, M.E.

1989-01-01

265

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

1985-05-01

266

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

International Nuclear Information System (INIS)

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

267

Re-thinking cell cycle regulators: the cross-talk with metabolism  

OpenAIRE

Analysis of genetically engineered mice deficient in cell cycle regulators, including E2F1, cdk4, and pRB, showed that the major phenotypes are metabolic perturbations. These key cell cycle regulators contribute to lipid synthesis, glucose production, insulin secretion, and glycolytic metabolism. It has been shown that deregulation of these pathways can lead to metabolic perturbations and related metabolic diseases, such as obesity and type II diabetes. The cyclin–cdk–Rb–E2F1 pathway re...

Fajas, Lluis

2013-01-01

268

Loss of HIF-1? impairs GLUT4 translocation and glucose uptake by the skeletal muscle cells.  

Science.gov (United States)

Defects in glucose uptake by the skeletal muscle cause diseases linked to metabolic disturbance such as type 2 diabetes. The molecular mechanism determining glucose disposal in the skeletal muscle in response to cellular stimuli including insulin, however, remains largely unknown. The hypoxia-inducible factor-1? (HIF-1?) is a transcription factor operating in the cellular adaptive response to hypoxic conditions. Recent studies have uncovered pleiotropic actions of HIF-1? in the homeostatic response to various cellular stimuli, including insulin under normoxic conditions. Thus we hypothesized HIF-1? is involved in the regulation of glucose metabolism stimulated by insulin in the skeletal muscle. To this end, we generated C2C12 myocytes in which HIF-1? is knocked down by short-hairpin RNA and examined the intracellular signaling cascade and glucose uptake subsequent to insulin stimulation. Knockdown of HIF-1? expression in the skeletal muscle cells resulted in abrogation of insulin-stimulated glucose uptake associated with impaired mobilization of glucose transporter 4 (GLUT4) to the plasma membrane. Such defect seemed to be caused by reduced phosphorylation of the protein kinase B substrate of 160 kDa (AS160). AS160 phosphorylation and GLUT4 translocation by AMP-activated protein kinase activation were abrogated as well. In addition, expression of the constitutively active mutant of HIF-1? (CA-HIF-1?) or upregulation of endogenous HIF-1? in C2C12 cells shows AS160 phosphorylation comparable to the insulin-stimulated level even in the absence of insulin. Accordingly GLUT4 translocation was increased in the cells expressing CA-HIF1?. Taken together, HIF-1? is a determinant for GLUT4-mediated glucose uptake in the skeletal muscle cells thus as a possible target to alleviate impaired glucose metabolism in, e.g., type 2 diabetes. PMID:24619881

Sakagami, Hidemitsu; Makino, Yuichi; Mizumoto, Katsutoshi; Isoe, Tsubasa; Takeda, Yasutaka; Watanabe, Jun; Fujita, Yukihiro; Takiyama, Yumi; Abiko, Atsuko; Haneda, Masakazu

2014-05-01

269

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

DEFF Research Database (Denmark)

Context: Human exposure to polychlorinated biphenyls (PCBs) has been associated to type 2 diabetes in adults. Objectives: To determine whether concurrent serum PCB concentration was associated with markers of glucose metabolism in healthy children. Design: Cross-sectional study. Settings and participants: A total of 771 healthy Danish third grade school children aged 8-10 years in the municipality of Odense were recruited in 1997 through a two-stage cluster sampling from 25 different schools stratified according to location and socioeconomic character; 509 (9.7±0.8 years, 53% girls) had adequate amounts available for PCB and analyses. Main outcome measures: Fasting plasma glucose and serum insulin were measured and a homeostasis assessment model of insulin resistance (HOMA-IR) and ?-cell function (HOMA-B) calculated. Serum PCB congeners and other persistent compounds were measured and ?PCB calculated. Results: PCBs were present in serum at low concentrations, median 0.19? g/g lipid (interquartile range, IQR: 0.12-0.31). After adjustment for putative confounding factors, the second, third, fourth and fifth quintiles of total PCB were significantly inversely associated with serum insulin (-14.6%, -21.7%, -18.9%, -23.1%, p-trend<0.01), compared to the first quintile, but not with plasma glucose (p=0.45). HOMA-IR and HOMA-B were affected in the same direction due to the declining insulin levels with increasing PCB exposure. Similar results were found for individual PCB congeners, for ?HCB and pp-DDE. Conclusion: A strong inverse association between serum insulin and PCB exposure was found while fasting plasma glucose remained within the expected narrow range. Our findings suggest that PCB may not exert effect through decreased peripheral insulin sensitivity, as seen in obese and low fit children, but rather through a toxicity to ?-cells. It remains to be shown if lower HOMA-B is caused by destruction of ?-cell reducing peripheral insulin resistance and thereby increase fasting plasma glucose as previously found.

Jensen, Tina K; Timmermann, Amalie G

2014-01-01

270

Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides  

OpenAIRE

Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 we...

Mcdonald, Tanya S.; Tan, Kah Ni; Hodson, Mark P.; Borges, Karin

2013-01-01

271

The Entner-Doudoroff pathway in Escherichia coli is induced for oxidative glucose metabolism via pyrroloquinoline quinone-dependent glucose dehydrogenase.  

OpenAIRE

The Entner-Doudoroff pathway was shown to be induced for oxidative glucose metabolism when Escherichia coli was provided with the periplasmic glucose dehydrogenase cofactor pyrroloquinoline quinone (PQQ). Induction of the Entner-Doudoroff pathway by glucose plus PQQ was established both genetically and biochemically and was shown to occur in glucose transport mutants, as well as in wild-type E. coli. These data complete the body of evidence that proves the existence of a pathway for oxidative...

Fliege, R.; Tong, S.; Shibata, A.; Nickerson, K. W.; Conway, T.

1992-01-01

272

Cell biology. Metabolic control of cell death.  

Science.gov (United States)

Beyond their contribution to basic metabolism, the major cellular organelles, in particular mitochondria, can determine whether cells respond to stress in an adaptive or suicidal manner. Thus, mitochondria can continuously adapt their shape to changing bioenergetic demands as they are subjected to quality control by autophagy, or they can undergo a lethal permeabilization process that initiates apoptosis. Along similar lines, multiple proteins involved in metabolic circuitries, including oxidative phosphorylation and transport of metabolites across membranes, may participate in the regulated or catastrophic dismantling of organelles. Many factors that were initially characterized as cell death regulators are now known to physically or functionally interact with metabolic enzymes. Thus, several metabolic cues regulate the propensity of cells to activate self-destructive programs, in part by acting on nutrient sensors. This suggests the existence of "metabolic checkpoints" that dictate cell fate in response to metabolic fluctuations. Here, we discuss recent insights into the intersection between metabolism and cell death regulation that have major implications for the comprehension and manipulation of unwarranted cell loss. PMID:25237106

Green, Douglas R; Galluzzi, Lorenzo; Kroemer, Guido

2014-09-19

273

[Glucose induced transport of H+, K+ and lactate in the cells of Acholeplasma laidlawii].  

Science.gov (United States)

Currents of H+ and K+ ions initiated under the effect of facultative anaerobe of A. laidlawii, valinomycin, nigericin and carbonyl cyanide chloride phenylhydrasone on the membrane are recorded by means of the system of cation sensitive electrodes. It is stated that during glucose transport a redistribution of H+ and K+ and lactate between the cellular content and the medium takes place. Preincubation of cells with 3-o-methyl-D-glucose essentially decreases the effect of induced ion transport. It is concluded that ion transport observed in the experiments with glucose is related not to glucose transport through the cell membrane but to the release of its metabolic products from the cells. PMID:35239

Kapitanov, A B; Ivanov, A S; Tarshis, M A; Antonov, V F

1979-01-01

274

Metabolism of [1-13C]-glucose in spheroids from rat prostate tumors  

International Nuclear Information System (INIS)

As the U.S. population ages, the number of prostatic cancers, which currently account for 20% of all male cancers, will substantially increase. Prostatic adenocarcinomas vary markedly in their growth characteristics for individual patients. Improvement of the diagnosis and therapy of these tumors requires an enhanced understanding of their biology. In order to evaluate metabolic subclasses of these tumors, the authors have developed a spheroid model from two Dunning rat prostatic tumor cell line (R 3327 H) that differ in their degree of differentiation. The spheroid diameter of the well-differentiated line (HI) increases 100 microns/24 hrs, while that of the poorly-differentiated line (AT1) increases 228 microns/24 hrs. Analysis of perfused tumor spheroids by 13CNMR spectroscopy, utilizing [1-13C]-glucose, has revealed metabolic differences between these two lines, most notably in the rates of glutamate, alanine, and citrate synthesis. The growth characteristics, as well as the metabolic patterns detectable by NMR, discriminating between the well- and poorly-differentiated spheroids will be presented in detail

275

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

International Nuclear Information System (INIS)

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

276

A 2-Pyridone-Amide Inhibitor Targets the Glucose Metabolism Pathway of Chlamydia trachomatis  

Science.gov (United States)

ABSTRACT In a screen for compounds that inhibit infectivity of the obligate intracellular pathogen Chlamydia trachomatis, we identified the 2-pyridone amide KSK120. A fluorescent KSK120 analogue was synthesized and observed to be associated with the C. trachomatis surface, suggesting that its target is bacterial. We isolated KSK120-resistant strains and determined that several resistance mutations are in genes that affect the uptake and use of glucose-6-phosphate (G-6P). Consistent with an effect on G-6P metabolism, treatment with KSK120 blocked glycogen accumulation. Interestingly, KSK120 did not affect Escherichia coli or the host cell. Thus, 2-pyridone amides may represent a class of drugs that can specifically inhibit C. trachomatis infection. PMID:25550323

Engström, Patrik; Krishnan, K. Syam; Ngyuen, Bidong D.; Chorell, Erik; Normark, Johan; Silver, Jim; Bastidas, Robert J.; Welch, Matthew D.; Hultgren, Scott J.; Wolf-Watz, Hans; Valdivia, Raphael H.

2014-01-01

277

A dual role of lipasin (betatrophin) in lipid metabolism and glucose homeostasis: consensus and controversy.  

Science.gov (United States)

Metabolic syndrome includes glucose intolerance and dyslipidemia, both of which are strong risk factors for developing diabetes and atherosclerotic cardiovascular diseases. Recently, multiple groups independently studied a previously uncharacterized gene, officially named C19orf80 (human) and Gm6484 (mouse), but more commonly known as RIFL, Angptl8, betatrophin and lipasin. Both exciting and conflicting results have been obtained, and significant controversy is ongoing. Accumulating evidence from genome wide association studies and mouse genetic studies convincingly shows that lipasin is involved in lipid regulation. However, the mechanism of action, the identity of transcription factors mediating its nutritional regulation, circulating levels, and relationship among lipasin, Angptl3 and Angptl4, remain elusive. Betatrophin represents a promising drug target for replenishing ?-cell mass, but current results have not been conclusive regarding its potency and specificity. Here, we summarize the consensus and controversy regarding functions of lipasin/betatrophin based on currently available evidence. PMID:25212743

Zhang, Ren; Abou-Samra, Abdul B

2014-01-01

278

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

Science.gov (United States)

Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-? (A?) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of A? in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor ? in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. PMID:25855193

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

2015-04-01

279

Demographic and metabolic characteristics of individuals with progressive glucose tolerance  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english We evaluated changes in glucose tolerance of 17 progressors and 62 non-progressors for 9 years to improve our understanding of the pathogenesis of type 2 diabetes mellitus. Changes in anthropometric measurements and responses to an oral glucose tolerance test (OGTT) were analyzed. We identified 14 p [...] airs of individuals, one from each group, who were initially normal glucose tolerant and were matched for gender, age, weight, and girth. We compared initial plasma glucose and insulin curves (from OGTT), insulin secretion (first and second phases) and insulin sensitivity indices (from hyperglycemic clamp assay) for both groups. In the normal glucose tolerant phase, progressors presented: 1) a higher OGTT blood glucose response with hyperglycemia in the second hour and a similar insulin response vs non-progressors; 2) a reduced first-phase insulin secretion (2.0 ± 0.3 vs 2.3 ± 0.3 pmol/L; P

A.L., Mendes; M.L., Santos; C.R., Padovani; W.P., Pimenta.

2009-03-01

280

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

International Nuclear Information System (INIS)

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)

281

Insulin effect on glucose transport in thymocytes and splenocytes from rats with metabolic syndrome  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Metabolic syndrome (MS may comprise several clinical conditions such as obesity, diabetes and inflammatory disorders, which are characterized by metabolic imbalances. The study of glucose transport and regulation by insulin in lymphocytes is important, since the way they increase inflammation and susceptibility to infections are common in MS. We studied glucose internalization in isolated thymocytes and splenocytes, its regulation by insulin, and the role of three glucose transporters (Gluts in control and in MS rats. Control glucose internalization and insulin responses were lower in splenocytes than in thymocytes. Control and insulin-induced glucose internalization in thymocytes declined with age, while transport by splenocyte continued to respond to insulin. Control thymocyte glucose internalization was blocked by antibodies against Glut 1 and 4, while the insulin response also was blocked by an anti-Glut 3 antibody. On four month old control and insulin-induced response, splenocyte transport was only blocked by Glut 1 and 4 antibodies. At six months splenocyte glucose internalization depended on Glut 1 and was less sensitive to the effects of an anti-Glut 4 antibody. In MS splenocytes the capacity of anti-Glut 1 antibodies to inhibit control and insulin-dependent glucose transport was less significant, and we found that in MS rats, glucose internalization was dependent on Glut 3 and Glut 4. In summary, the altered metabolic state present in MS rats shows signs of modulation of glucose internalization by the Glut1, Glut 3 and Glut 4 transporters, compared with its own age control.

Carbó Roxana

2010-11-01

282

Ambient glucose and aldose reductase-induced myo-inositol depletion modulate basal and carbachol-stimulated inositol phospholipid metabolism and diacylglycerol accumulation in human retinal pigment epithelial cells in culture.  

OpenAIRE

Physiological hyperglycemia has been speculated to alter phosphoinositide (PPI; inositol phospholipid) signal transduction in cells prone to diabetic complications by two separate mass-action mechanisms with antiparallel putative effects on diacylglycerol (DAG): (i) sorbitol-induced depletion of myo-inositol leads to diminished PPI synthesis and turnover and DAG release, and (ii) elevated glucose-derived DAG precursors enhance de novo DAG synthesis. Because the first mechanism is mediated by ...

Thomas, T. P.; Feldman, E. L.; Nakamura, J.; Kato, K.; Lien, M.; Stevens, M. J.; Greene, D. A.

1993-01-01

283

Role of oxygen vs. glucose in energy metabolism in a mammary carcinoma perfused ex vivo: direct measurement by 31P NMR.  

OpenAIRE

The role of glycolysis vs. respiration in tumor energy metabolism has been studied, to date, primarily in vitro by using single cells, multicellular spheroids, or tissue slices. With the advent of in vivo NMR spectroscopy, several investigators have shown that tumor energy status depends on its blood flow. Since manipulation of blood flow alters both oxygen and glucose delivery to a solid tumor, these studies have not been able to separate the relative contribution of oxygen vs. glucose in en...

Eskey, C. J.; Koretsky, A. P.; Domach, M. M.; Jain, R. K.

1993-01-01

284

Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats  

Energy Technology Data Exchange (ETDEWEB)

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 ?{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.

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

285

Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats  

International Nuclear Information System (INIS)

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 ?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

286

Loss of GLUT4 induces metabolic reprogramming and impairs viability of breast cancer cells.  

Science.gov (United States)

Metabolic reprogramming strategies focus on the normalization of metabolism of cancer cells and constitute promising targets for cancer treatment. Here, we demonstrate that the glucose transporter 4 (GLUT4) has a prominent role in basal glucose uptake in MCF7 and MDA-MB-231 breast cancer cells. We show that shRNA-mediated down-regulation of GLUT4 diminishes glucose uptake and induces metabolic reprogramming by reallocating metabolic flux to oxidative phosphorylation. This reallocation is reflected on an increased activity of the mitochondrial oxidation of pyruvate and lower lactate release. Altogether, GLUT4 inhibition compromises cell proliferation and critically affects cell viability under hypoxic conditions, providing proof-of-principle for the feasibility of using pharmacological approaches to inhibit GLUT4 in order to induce metabolic reprogramming in vivo in breast cancer models. PMID:24931902

Garrido, Pablo; Osorio, Fernando G; Morán, Javier; Cabello, Estefanía; Alonso, Ana; Freije, José M P; González, Celestino

2015-01-01

287

Pentose synthesis in glucose-grown cells of Lactobacillus casei.  

Science.gov (United States)

The pathway of pentose synthesis in glucose-grown cells of Lactobacillus casei was ascertained. Glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were present in glucose-grown cells, while transaldolase and transketolase were present only in traces. This suggested that only the oxidative arm of this pathway was operative in glucose-grown cells. On the other hand, in ribose-grown cells, transaldolase was induced with a concomitant suppression of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. These results were confirmed by the detection of labelled CO2 produced by L. casei grown on [1-14C]glucose. The activities of the enzymes of the oxidative pentose phosphate pathway as also the rate of CO2 formation were higher in the exponential phase of growth as compared to the stationary phase, when the requirement of the cells for pentoses for the formation of DNA and RNA was higher. PMID:2111278

Menezes, L; Kelkar, S M; Kaklij, G S

1990-02-01

288

Experimental identification and quantification of glucose metabolism in seven bacterial species.  

Science.gov (United States)

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 investigated Agrobacterium tumefaciens, two pseudomonads, Sinorhizobium meliloti, Rhodobacter sphaeroides, Zymomonas mobilis, and Paracoccus versutus, which grow on glucose as the sole carbon source, represent fundamentally different metabolic lifestyles (aerobic, anaerobic, photoheterotrophic, and chemoheterotrophic), and are phylogenetically distinct (firmicutes, gamma-proteobacteria, and alpha-proteobacteria). Compared to those of the model bacteria Escherichia coli and Bacillus subtilis, metabolisms of the investigated species differed significantly in several respects: (i) the Entner-Doudoroff pathway was the almost exclusive catabolic route; (ii) the pentose phosphate pathway exhibited exclusively biosynthetic functions, in many cases also requiring flux through the nonoxidative branch; (iii) all aerobes exhibited fully respiratory metabolism without significant overflow metabolism; and (iv) all aerobes used the pyruvate bypass of the malate dehydrogenase reaction to a significant extent. Exclusively, Pseudomonas fluorescens converted most glucose extracellularly to gluconate and 2-ketogluconate. Overall, the results suggest that metabolic data from model species with extensive industrial and laboratory history are not representative of microbial metabolism, at least not quantitatively. PMID:15716428

Fuhrer, Tobias; Fischer, Eliane; Sauer, Uwe

2005-03-01

289

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

International Nuclear Information System (INIS)

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)thor)

290

Dibenzoylmethane Exerts Metabolic Activity through Regulation of AMP-Activated Protein Kinase (AMPK)-Mediated Glucose Uptake and Adipogenesis Pathways  

Science.gov (United States)

Dibenzoylmethane (DBM) has been shown to exert a variety of beneficial effects on human health. However, the mechanism of action is poorly understood. In this study, DBM increased phosphorylation of AMP-activated protein kinase (AMPK) and stimulated glucose uptake in a skeletal muscle cell line. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor blocked DBM-induced glucose uptake. DBM increased the concentration of intracellular calcium and glucose uptake due to DBM was abolished by STO-609 (a calcium/calmodulin-dependent protein kinase inhibitor). DBM stimulated phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which was blocked by pretreatment with compound C, an AMPK inhibitor. The expression of glucose transporter type 4 (GLUT4) was increased by DBM. The translocation of GLUT4 to the plasma membrane was also increased by DBM in AMPK dependently. In addition, DBM suppressed weight gain and prevented fat accumulation in the liver and abdomen in mice fed a high-fat diet. In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis. Expression of the adipogenic gene, fatty acid synthase (FAS), was suppressed by DBM in an AMPK-dependent manner. These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes. PMID:25756788

Kim, Nami; Kim, Hong Min; Lee, Eun Soo; Lee, Jung Ok; Lee, Hye Jeong; Lee, Soo Kyung; Moon, Ji Wook; Kim, Ji Hae; Kim, Joong Kwan; Kim, Su Jin; Park, Sun Hwa; Chung, Choon Hee; Kim, Hyeon Soo

2015-01-01

291

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english 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.

A.S., Moura.

1089-10-01

292

Network identification and flux quantification of glucose metabolism in Rhodobacter sphaeroides under photoheterotrophic H(2)-producing conditions.  

Science.gov (United States)

The nonsulfur purple bacteria that exhibit unusual metabolic versatility can produce hydrogen gas (H(2)) using the electrons derived from metabolism of organic compounds during photoheterotrophic growth. Here, based on (13)C tracer experiments, we identified the network of glucose metabolism and quantified intracellular carbon fluxes in Rhodobacter sphaeroides KD131 grown under H(2)-producing conditions. Moreover, we investigated how the intracellular fluxes in R. sphaeroides responded to knockout mutations in hydrogenase and poly-?-hydroxybutyrate synthase genes, which led to increased H(2) yield. The relative contribution of the Entner-Doudoroff pathway and Calvin-Benson-Bassham cycle to glucose metabolism differed significantly in hydrogenase-deficient mutants, and this flux change contributed to the increased formation of the redox equivalent NADH. Disruption of hydrogenase and poly-?-hydroxybutyrate synthase resulted in a significantly increased flux through the phosphoenolpyruvate carboxykinase and a reduced flux through the malic enzyme. A remarkable increase in the flux through the tricarboxylic acid cycle, a major NADH producer, was observed for the mutant strains. The in vivo regulation of the tricarboxylic acid cycle flux in photoheterotrophic R. sphaeroides was discussed based on the measurements of in vitro enzyme activities and intracellular concentrations of NADH and NAD(+). Overall, our results provide quantitative insights into how photoheterotrophic cells manipulate the metabolic network and redistribute intracellular fluxes to generate more electrons for increased H(2) production. PMID:22056932

Tao, Yongzhen; Liu, Deng; Yan, Xing; Zhou, Zhihua; Lee, Jeong K; Yang, Chen

2012-01-01

293

Imatinib Mesylate Inhibits Glucose Uptake in Gastrointestinal Stromal Tumor Cells by Downregulation of the Glucose Transporters Recruitment to the Plasma Membrane  

Directory of Open Access Journals (Sweden)

Full Text Available Imatinib mesylate, the inhibitor of the KIT protein tyrosine kinase that is constitutively activated in Gastrointestinal Stromal Tumors (GISTs, has been established as the first highly effective drug in the treatment of patients with advanced GISTs. Recent studies suggest that changes in the glucose metabolism could be an additional mechanism of the anti-proliferative action of imatinib. The aim of this study was to investigate the effect on glucose flux and metabolism in a human GIST882 cell line after exposure to imatinib. Imatinib induced a concentration-dependent inhibition of cell proliferation in GIST882 cells (IC50, 0.030 ± 0.006 µM. By 18F-FDG uptake measurements, after 24 h exposure to the drug at concentrations of 0.03 µM and 0.3 µM, the glucose uptake decreased by ~25% and ~95%, respectively. Moreover, after a 3-h treatment at the concentration of 0.3 µM of imatinib the decrease in glucose-uptake was already more than 50%. After 24-h of treatment with 0.3 µM imatinib, the measurements of the hexokinase and glucose-6-phosphate dehydrogenase activity revealed a 30% and 37% decrease, respectively. Western blotting disclosed mainly expression of glucose transporter GLUT-2 in GIST cells. Exposure of GIST cells to imatinib resulted in the decline of the GLUT-2 receptor recruitment to cell membrane, which paralleled with the elevated amount of the total KIT protein. These findings suggest that a rapid decline in glucose uptake following imatinib treatment in GIST cells is dependent on glucose transporter impaired anchorage to the plasma membrane, with the subsequent recruitment of KIT protein.

Hans Prenen

2005-01-01

294

Kinetics and Metabolism of Bifidobacterium adolescentis MB 239 Growing on Glucose, Galactose, Lactose, and Galactooligosaccharides?  

OpenAIRE

The kinetics and the metabolism of Bifidobacterium adolescentis MB 239 growing on galactooligosaccharides (GOS), lactose, galactose, and glucose were investigated. An unstructured unsegregated model for growth in batch cultures was developed, and kinetic parameters were calculated with a recursive algorithm. The growth rate and cellular yield were highest on galactose, followed by lactose and GOS, and were lowest on glucose. Lactate, acetate, and ethanol yields allowed the calculation of carb...

Amaretti, Alberto; Bernardi, Tatiana; Tamburini, Elena; Zanoni, Simona; Lomma, Mariella; Matteuzzi, Diego; Rossi, Maddalena

2007-01-01

295

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

International Nuclear Information System (INIS)

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 depresally 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

296

Non-Invasive Glucose Measurement by Use of Metabolic Heat Conformation Method  

OpenAIRE

A non-invasive glucose measurement system based on the method of metabolic heat conformation (MHC) is presented in this paper. This system consists of three temperature sensors, two humidity sensors, an infrared sensor and an optical measurement device. The glucose level can be deduced from the quantity of heat dissipation, blood flow rate of local tissue and degree of blood oxygen saturation. The methodology of the data process and the measurement error are also analyzed. The system is appli...

Junfeng Li; Dongsheng Wang; Xiaohao Wang; Fei Tang

2008-01-01

297

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

International Nuclear Information System (INIS)

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 (P/sub i/), phosphodiesters, and diphosphates including sugar diphosphates and polyphosphate. Addition of glucose resulted in a decrease in cytoplasmic P/sub i/ 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) ll extracts. Addition of insulin (100 nM) with the glucose had the following effects relative to glucose alone: (i) a 24% increase in the rate of ethanol production; (ii) a 38% increase in the rate of alanine production; (iii) a 27% increase 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

298

Adverse Effect of High Glucose Concentration on Stem Cell Therapy  

Directory of Open Access Journals (Sweden)

Full Text Available Stem cell therapy could have great potential for the treatment of a wide variety of diseases. Stem cells might have the ability to differentiate into a widespread cell types, and to repopulate and revitalize the damaged cells with healthy tissue, and improve its performance. We provide here the evidence supporting the critical use of stem cell as a treatment in disease conditions existing with high glucose complaint such as diabetes. The reduction of glucose stimulated cell proliferation and high glucose enhanced apoptosis in rat model, which may be a problem in therapeutic strategies based on ex vivo expansion of stem cell, and may also propagate the development of osteoporosis in high glucose complaint such as diabetes. This leads to the hypothesis that, high glucose could be more deleterious to stem cell therapy that may be due to the aggravation of oxidative stress triggered by high glucose. These findings may help to understand the possible reasons associated with high glucose induced detrimental effects on stem cells as well as provide novel therapeutic strategies for preventing the adverse effects of glucose on the development and progression of stem cells in patients with diabetes.

Najmaldin Saki

2013-07-01

299

Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism.  

Science.gov (United States)

Genetic variation can modulate gene expression, and thereby phenotypic variation and susceptibility to complex diseases such as type 2 diabetes (T2D). Here we harnessed the potential of DNA and RNA sequencing in human pancreatic islets from 89 deceased donors to identify genes of potential importance in the pathogenesis of T2D. We present a catalog of genetic variants regulating gene expression (eQTL) and exon use (sQTL), including many long noncoding RNAs, which are enriched in known T2D-associated loci. Of 35 eQTL genes, whose expression differed between normoglycemic and hyperglycemic individuals, siRNA of tetraspanin 33 (TSPAN33), 5'-nucleotidase, ecto (NT5E), transmembrane emp24 protein transport domain containing 6 (TMED6), and p21 protein activated kinase 7 (PAK7) in INS1 cells resulted in reduced glucose-stimulated insulin secretion. In addition, we provide a genome-wide catalog of allelic expression imbalance, which is also enriched in known T2D-associated loci. Notably, allelic imbalance in paternally expressed gene 3 (PEG3) was associated with its promoter methylation and T2D status. Finally, RNA editing events were less common in islets than previously suggested in other tissues. Taken together, this study provides new insights into the complexity of gene regulation in human pancreatic islets and better understanding of how genetic variation can influence glucose metabolism. PMID:25201977

Fadista, João; Vikman, Petter; Laakso, Emilia Ottosson; Mollet, Inês Guerra; Esguerra, Jonathan Lou; Taneera, Jalal; Storm, Petter; Osmark, Peter; Ladenvall, Claes; Prasad, Rashmi B; Hansson, Karin B; Finotello, Francesca; Uvebrant, Kristina; Ofori, Jones K; Di Camillo, Barbara; Krus, Ulrika; Cilio, Corrado M; Hansson, Ola; Eliasson, Lena; Rosengren, Anders H; Renström, Erik; Wollheim, Claes B; Groop, Leif

2014-09-23

300

Glucose metabolism in gamma-irradiated rice seeds  

International Nuclear Information System (INIS)

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

301

The metabolic cooperation between cells in solid cancer tumors.  

Science.gov (United States)

Cancer cells cooperate with stromal cells and use their environment to promote tumor growth. Energy production depends on nutrient availability and O? concentration. Well-oxygenated cells are highly proliferative and reorient the glucose metabolism towards biosynthesis, whereas glutamine oxidation replenishes the TCA cycle coupled with OXPHOS-ATP production. Glucose, glutamine and alanine transformations sustain nucleotide and fatty acid synthesis. In contrast, hypoxic cells slow down their proliferation, enhance glycolysis to produce ATP and reject lactate which is recycled as fuel by normoxic cells. Thus, glucose is spared for biosynthesis and/or for hypoxic cell function. Environmental cells, such as fibroblasts and adipocytes, serve as food donors for cancer cells, which reject waste products (CO? , H?, ammoniac, polyamines…) promoting EMT, invasion, angiogenesis and proliferation. This metabolic-coupling can be considered as a form of commensalism whereby non-malignant cells support the growth of cancer cells. Understanding these cellular cooperations within tumors may be a source of inspiration to develop new anti-cancer agents. PMID:24983675

Icard, Philippe; Kafara, Perrine; Steyaert, Jean-Marc; Schwartz, Laurent; Lincet, Hubert

2014-08-01

302

Glucose-lactate metabolic cooperation in cancer: insights from a spatial mathematical model and implications for targeted therapy.  

Science.gov (United States)

A recent study has hypothesised a glucose-lactate metabolic symbiosis between adjacent hypoxic and oxygenated regions of a developing tumour, and proposed a treatment strategy to target this symbiosis. However, in vivo experimental support remains inconclusive. Here we develop a minimal spatial mathematical model of glucose-lactate metabolism to examine, in principle, whether metabolic symbiosis is plausible in human tumours, and to assess the potential impact of inhibiting it. We find that symbiosis is a robust feature of our model system-although on the length scale at which oxygen supply is diffusion-limited, its occurrence requires very high cellular metabolic activity-and that necrosis in the tumour core is reduced in the presence of symbiosis. Upon simulating therapeutic inhibition of lactate uptake, we predict that targeted treatment increases the extent of tissue oxygenation without increasing core necrosis. The oxygenation effect is correlated strongly with the extent of wild-type hypoxia and only weakly with wild-type symbiotic behaviour, and therefore may be promising for radiosensitisation of hypoxic, lactate-consuming tumours even if they do not exhibit a spatially well-defined symbiosis. Finally, we conduct in vitro experiments on the U87 glioblastoma cell line to facilitate preliminary speculation as to where highly malignant tumours might fall in our parameter space, and find that these experiments suggest a weakly symbiotic regime for U87 cells, thus raising the new question of what relationship might exist between symbiosis and tumour malignancy. PMID:25264268

McGillen, Jessica B; Kelly, Catherine J; Martínez-González, Alicia; Martin, Natasha K; Gaffney, Eamonn A; Maini, Philip K; Pérez-García, Víctor M

2014-11-21

303

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

Energy Technology Data Exchange (ETDEWEB)

Research highlights: {yields} A new mutant of PQQ-GDH designed for glucose biosensors application. {yields} First mutant of PQQ-GDH with higher activity for D-glucose than the Wild type. {yields} Position N428 is a key point to increase the enzyme activity. {yields} 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.

Durand, Fabien [Universite de Bordeaux, Centre de Recherche Paul Pascal (CRPP), UPR 8641, Avenue Albert Schweitzer, 33600 Pessac (France); Stines-Chaumeil, Claire [Universite de Bordeaux, CNRS, Institut de Biochimie et de Genetique Cellulaires, 1 rue Camille Saint Saens, 33077 Bordeaux Cedex (France); Flexer, Victoria [Universite de Bordeaux, Centre de Recherche Paul Pascal (CRPP), UPR 8641, Avenue Albert Schweitzer, 33600 Pessac (France); Andre, Isabelle [Universite de Toulouse, INSA, UPS, INP, LISBP, 135 Avenue de Rangueil, F-31077 Toulouse (France); CNRS, UMR5504, F-31400 Toulouse (France); INRA, UMR 792 Ingenierie des Systemes Biologiques et des Procedes, F-31400 Toulouse (France); Mano, Nicolas, E-mail: mano@crpp-bordeaux.cnrs.fr [Universite de Bordeaux, Centre de Recherche Paul Pascal (CRPP), UPR 8641, Avenue Albert Schweitzer, 33600 Pessac (France)

2010-11-26

304

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

International Nuclear Information System (INIS)

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.

305

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

International Nuclear Information System (INIS)

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

306

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

Directory of Open Access Journals (Sweden)

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.

Logullo Carlos

2010-02-01

307

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

International Nuclear Information System (INIS)

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

308

Lysozyme enhances the inhibitory effects of the peroxidase system on glucose metabolism of Streptococcus mutans.  

Science.gov (United States)

The combined effect of the salivary peroxidase system and lysozyme on the glucose uptake of Streptococcus mutans NCTC 10449 was investigated. The bacteria were grown to late-exponential phase, washed, re-suspended in buffer at pH6, and incubated with (1) 50 micrograms/mL lysozyme from human milk for 60 min; (2) 7-15 mumol/L hypothiocyanous acid/hypothiocyanite for 10 min; and (3) lysozyme for 60 min prior to addition of and incubation with hypothiocyanous acid/hypothiocyanite for 10 min. Glucose uptake was initiated by adding the bacterial suspensions to 10 mL of pre-warmed 50 mumol/L glucose containing 0.98 mumol/L D-(U-14C-)-glucose, and the mixture was incubated in a shaking water-bath at 37 degrees C. Samples were withdrawn at various time intervals, rapidly filtered through 0.45-microns membranes, washed with ice-chilled buffer, and the incorporated radioactivity determined. Lysozyme stimulated S. mutans glucose uptake slightly, but significantly inhibited S. rattus glucose metabolism. A 20-30% inhibition of radiolabeled glucose incorporation was observed with hypothiocyanous acid/hypothiocyanite alone. Incubation of the bacteria with lysozyme prior to addition of hypothiocyanous acid/hypothiocyanite containing peroxidase resulted in a total inhibition of the glucose uptake. In contrast, lysozyme in combination with hypothiocyanous acid/hypothiocyanite without peroxidase gave only a 30-50% inhibition. The addition of 5 mmol/L dithiothreitol after incubation with lysozyme and hypothiocyanous acid/hypothiocyanite eliminated the inhibition of the bacterial glucose uptake. The viability of S. mutans was not affected by treatment with any of the components used. Our results indicate that physiological concentrations of lysozyme and the salivary peroxidase system components have a synergistic effect which results in a significant inhibition of glucose metabolism by S. mutans. PMID:1573081

Lenander-Lumikari, M; Månsson-Rahemtulla, B; Rahemtulla, F

1992-03-01

309

Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides.  

Science.gov (United States)

Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of ?-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6?Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain. PMID:24169853

McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin

2014-01-01

310

Impact of the reg1 mutation glycocen accumulation and glucose consumption rates in Saccharomyces cerevisiae cells based on a macrokinetic model  

OpenAIRE

In S. cerevisiae, catabolite repression controls glycogen accumulation and glucose consumption. Glycogen is responsible for stress resistance, and its accumulation in derepression conditions results in a yeast with good quality. In yeast cells, catabolite repression also named glucose effect takes place at the transcriptional levels, decreasing enzyme respiration and causing the cells to enter a fermentative metabolism, low cell mass yield and yeast with poor quality. Since glucose is always ...

Rocha-Leão M.H.M.; Coelho M. A. Z.; Araújo O. Q. F.

2003-01-01

311

Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography  

International Nuclear Information System (INIS)

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

312

Glucose and Fatty Acid Metabolism in Placental Explants From Pregnancies Complicated With Gestational Diabetes Mellitus.  

Science.gov (United States)

Placental metabolism is an important mechanism for the regulation of fetal growth and long-term health of the newborns. In this study, we investigated the effects of maternal metabolic environment on human placental fatty acid and glucose metabolism. We used placental explants from uncomplicated pregnancies or pregnancies complicated with gestational diabetes mellitus (GDM), undergoing vaginal delivery (VD) or cesarean section (CS). Fatty acid oxidation (FAO) and glucose uptake (2-DOG) were similar in both modes of delivery in normal and GDM pregnancies. However, placental explants from GDM exhibited 40% to 50% reduced FAO capacity compared to control placentas in women undergoing VD or CS. In contrast, 2-DOG uptake was 2- to 3-fold higher in placental explants from GDM compared to control placentas in women undergoing VD or CS, respectively. In conclusion, ex vivo placental fuel selection is influenced by maternal GDM, but placental metabolic characteristics are not altered by the mode of delivery. PMID:25491487

Visiedo, Francisco; Bugatto, Fernando; Quintero-Prado, Rocío; Cózar-Castellano, Irene; Bartha, Jose L; Perdomo, Germán

2014-12-01

313

Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer  

International Nuclear Information System (INIS)

Purpose: To determine the dose-response relationship between the probability of tumor control on the basis of pathologic tumor response (pTCP) and the residual metabolic rate of glucose (MRglc) in response to preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer and to define the level of residual MRglc that corresponds to pTCP 50% and pTCP ?95%. Methods and Materials: Quantitative dynamic 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography was performed to measure regional MRglc at the primary lesion before and 2 weeks after preoperative chemoradiotherapy in an initial group of 13 patients with locally advanced NSCLC. A simplified kinetic method was developed subsequently from the initial dynamic study and used in the subsequent 16 patients. The preoperative radiotherapy programs consisted of (1) a split course of 42 Gy in 28 fractions within a period of 28 days using a twice-daily treatment schedule for Stage IIIA(N2) NSCLC (n=18) and (2) standard once-daily radiation schedule of 45-63 Gy in 25-35 fractions during a 5-7-week period (n=11). The preoperative chemotherapy regimens included two cycles of cisplatin, vinblastine, and 5-fluorouracil (n=24), cisplatin and etoposide (n=2), and cisplatin, Taxol, and 5-fluorouracil (n=3). Patients free of tumor progression after preoperative chemoradiotherapy underwent surgery. The degree of residual MRglc measured 2 weeks after preoperative chemoradiotherapy and 2 weeks before surgeemoradiotherapy and 2 weeks before surgery was correlated with the pathologic tumor response. The relationship between MRglc and pTCP was modeled using logistic regression. Results: Of 32 patients entered into the study, 29 (16 men and 13 women; 30 lesions) were evaluated for the correlation between residual MRglc and pathologic tumor response. Three patients did not participate in the second study because of a steady decline in general condition. The median age was 60 years (range 42-78). One of the 29 patients had two separate lesions, and MRglc was measured in each separately. The tumor histologic types included squamous cell carcinoma (n=9), adenocarcinoma (n=13), large cell carcinoma (n=6), and poorly differentiated carcinoma (n=2). The extent of the primary and nodal disease was as follows: Stage IIB (T3N0M0), Pancoast tumor (n=2); Stage IIIA, T2-T3N2M0 (n=18); Stage IIIB: T1-T3N3M0 (n=5) and T4N0M0 (n=2); a second lesion, T1 (n=1); and localized stump recurrence (n=2). A pathologically complete response was obtained in 14 (47%) of the 30 lesions. The remaining 16 lesions had residual cancer. The mean baseline value of the maximal MRglc was 0.333 ± 0.087 ?mol/min/g (n=16), and it was reduced to 0.0957 ± 0.059 ?mol/min/g 2 weeks after chemoradiotherapy (p=0.011). The correlation between residual MRglc and pTCP was made using an increment value of 0.02 ?mol/min/g between the maximal and minimal values of MRglc. A pathologically complete response was obtained in 6 of 6 patients with residual MRglc of ?0.050 ?mol/min/g, 3 of 4 with ?0.070, 4 of 7 with ?0.090, 0 of 4 with ?0.110, 1 of 3 with ?0.130, and 0 of 6 with ?0.130 ?mol/min/g. The fitted logistic model showed that residual MRglc corresponding to pTCP 50% and pTCP ?95% was 0.076 and ?0.040 ?mol/min/g, respectively. Conclusion: The correlation between the gradient of residual MRglc after chemoradiotherapy and pTCP is an inverse dose-response relationship. Residual MRglc of 0.076 and ?0.040 ?mol/min/g, representing pTCP 50% and pTCP ?95%, respectively, may be useful surrogate markers for the tumor response to radiotherapy or chemoradiotherapy in lung cancer

314

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

OpenAIRE

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...

Fuhrer, Tobias; Fischer, Eliane; Sauer, Uwe

2005-01-01

315

Elevated glucose metabolism in the amygdala during an inhibitory avoidance task  

OpenAIRE

There is a long-standing debate as to whether the memory process of consolidation is neurochemically similar to or the same as the set of processes involved in retrieval and reconsolidation of that memory. In addition, although we have previously shown that initial memory processing in the hippocampus causes a drainage of hippocampal glucose because of increased local metabolic demand, it is unknown what metabolic changes occur elsewhere in the brain or during subsequent processing of a previ...

Sandusky, Leslie A.; Flint, Robert W.; Mcnay, Ewan C.

2013-01-01

316

Noninvasive measurement of regional myocardial glucose metabolism by positron emission computed tomography  

International Nuclear Information System (INIS)

While the results of regional myocardial glucose metabolism measurements using positron emission computed tomography (13N-ammonia) are promising, their utility and value remains to be determined in man. If this technique can be applied to patients with acute myocardial ischemia or infarction it may permit delineation of regional myocardial segments with altered, yet still active metabolism. Further, it may become possible to evaluate the effects of interventions designed to salvage reversibly injured myocardium by this technique

317

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

International Nuclear Information System (INIS)

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)

318

Activation-specific metabolic requirements for NK Cell IFN-? production.  

Science.gov (United States)

There has been increasing recognition of the importance of cellular metabolism and metabolic substrates for the function and differentiation of immune cells. In this study, for the first time to our knowledge, we investigate the metabolic requirements for production of IFN-? by freshly isolated NK cells. Primary murine NK cells mainly use mitochondrial oxidative phosphorylation at rest and with short-term activation. Remarkably, we discovered significant differences in the metabolic requirements of murine NK cell IFN-? production depending upon the activation signal. Stimulation of NK cell IFN-? production was independent of glycolysis or mitochondrial oxidative phosphorylation when cells were activated with IL-12 plus IL-18. By contrast, stimulation via activating NK receptors required glucose-driven oxidative phosphorylation. Prolonged treatment with high-dose, but not low-dose, IL-15 eliminated the metabolic requirement for receptor stimulation. In summary, this study demonstrates that metabolism provides an essential second signal for induction of IFN-? production by activating NK cell receptors that can be reversed with prolonged high-dose IL-15 treatment. PMID:25595780

Keppel, Molly P; Saucier, Nermina; Mah, Annelise Y; Vogel, Tiphanie P; Cooper, Megan A

2015-02-15

319

Effects of 5-thio-d-glucose on hexose transport and metabolism  

International Nuclear Information System (INIS)

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) a/sup>C] 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

320

Chemosensitizing and cytotoxic effects of 2-deoxy-D-glucose on breast cancer cells  

Directory of Open Access Journals (Sweden)

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.

Zhang Fanjie

2009-09-01

321

Q's next: The diverse functions of glutamine in metabolism, cell biology and cancer  

OpenAIRE

Several decades of research have sought to characterize tumor cell metabolism in the hopes that tumor-specific activities can be exploited to treat cancer. Having originated from Warburg's seminal observation of aerobic glycolysis in tumor cells, most of this attention has focused on glucose metabolism. However, since the 1950s cancer biologists have also recognized the importance of glutamine (Q) as a tumor nutrient. Glutamine contributes to essentially every core metabolic task of prolifera...

Deberardinis, Ralph J.; Cheng, Tzuling

2009-01-01

322

Fulfilling the metabolic requirements for cell proliferation.  

Science.gov (United States)

The activity of key metabolic enzymes is regulated by the ubiquitin ligases that control the function of the cyclins; therefore the activity of these ubiquitin ligases explains the coordination of cell-cycle progression with the supply of substrates necessary for cell duplication. APC/C (anaphase-promoting complex/cyclosome)-Cdh1, the ubiquitin ligase that controls G(1)- to S-phase transition by targeting specific degradation motifs in cell-cycle proteins, also regulates the glycolysis-promoting enzyme PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3) and GLS1 (glutaminase 1), a critical enzyme in glutaminolysis. A decrease in the activity of APC/C-Cdh1 in mid-to-late G(1) releases both proteins, thus explaining the simultaneous increase in the utilization of glucose and glutamine during cell proliferation. This occurs at a time consistent with the point in G(1) that has been described as the nutrient-sensitive restriction point and is responsible for the transition from G(1) to S. PFKFB3 is also a substrate at the onset of S-phase for the ubiquitin ligase SCF (Skp1/cullin/F-box)-?-TrCP (?-transducin repeat-containing protein), so that the activity of PFKFB3 is short-lasting, coinciding with a peak in glycolysis in mid-to-late G(1), whereas the activity of GLS1 remains high throughout S-phase. The differential regulation of the activity of these proteins indicates that a finely-tuned set of mechanisms is activated to fulfil specific metabolic demands at different stages of the cell cycle. These findings have implications for the understanding of cell proliferation in general and, in particular, of cancer, its prevention and treatment. PMID:22835215

Moncada, Salvador; Higgs, E Annie; Colombo, Sergio L

2012-08-15

323

The regulation of cerebral glucose uptake and metabolism in normal and diabetic man  

International Nuclear Information System (INIS)

The effects of changes in serum insulin and glucose on brain glucose metabolism using PET technology were investigated. Eight normal, right-handed, male subjects were studied on three separate occasions at least one week apart. In each subject a PET scan was performed under three different metabolic circumstances: basal conditions after an overnight fast, euglycemic clamp, and hypoglycemic clamp in which the plasma glucose was maintained at 55 mg/dl. Exogenous insulin was infused at the same rate in the euglycemic and hypoglycemic clamp studies. In the latter study, the concomitant glucose infusion rate was reduced to allow the plasma glucose concentration to fall to the desired level of mild hypoglycemia. During each study, dynamic positron emission tomography was used to characterize cerebral uptake and distribution of the Fluorine-18 2-deoxyglucose radiotracer as a function of time. Analysis of the brain uptake curve and tracer input function provided rate constants for transport and phosphorylation in accord with a 3 compartmental model (Sokoloff, 1979). Dynamic scans were performed on each study occasion allowing individual rate constants to be studied. In addition to the brain uptake curves, plasma glucose, F-18 2DG levels and counterregulatory hormone values were determined from frequent arterialized venous blood samples

324

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

DEFF Research Database (Denmark)

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.

Hao, Qin; Yadav, Rachita

2015-01-01

325

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

Science.gov (United States)

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

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

326

Chromium supplementation alters both glucose and lipid metabolism in feedlot cattle during the receiving period  

Science.gov (United States)

Crossbred steers (n = 20; 235 +/- 4 kg) were fed 53 days during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brandChromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0...

327

Chromium supplementation alters the glucose and lipid metabolism of feedlot cattle during the receiving period  

Science.gov (United States)

Crossbreed steers (n = 20; 235 ± 4 kg) were fed 53 d during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brand Chromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0 (C...

328

In study by the Broad Institute and Massachusetts General, new clues about cancer cell metabolism emerge  

Science.gov (United States)

For almost a century, researchers have known that cancer cells have peculiar appetites, devouring glucose in ways that normal cells do not. But glucose uptake may tell only part of cancer’s metabolic story. Researchers from the Broad Institute and Massachusetts General Hospital looked across 60 well-studied cancer cell lines, analyzing which of more than 200 metabolites were consumed or released by the fastest dividing cells. Their research yields the first large-scale atlas of cancer metabolism and points to a key role for the smallest amino acid, glycine, in cancer cell proliferation. Their results appear in the May 25 issue of the journal Science.

329

Clinical significance of determination of serum leptin, insulin levels and blood sugar in pregnant women with glucose metabolism disturbances  

International Nuclear Information System (INIS)

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 ?g/L (vs controls 9.8 ± 1.7 ?g/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)

330

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

DEFF Research Database (Denmark)

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-constitutive transformants grew even faster (0.27-0.30 h(-1)) in pure glucose medium than the wild type strain (0.24 h(-1)).

Klein, Christopher; Olsson, Lisbeth

1997-01-01

331

Glucose and glutamine provide similar proportions of energy to mucosal cells of rat small intestine.  

Science.gov (United States)

The objectives of this study were to establish a reliable method for quantifying glycolytic flux in intestinal epithelial cells, to determine the proportion of energy provided to small intestine epithelial cells by glucose vs. glutamine, and to determine whether there was an energetic advantage to having both substrates present simultaneously. There was substantial retention of 3H in alanine and lactate when [2-(3)H]glucose was used as tracer for quantifying glycolysis, and the magnitude of the 3H retention was influenced by the presence of other substrates and metabolites. Detritiation was at least 99% complete, however, when [3-(3)H]glucose was used as tracer in this system and the tritium was recovered as 3H2O. Glycolytic flux was six- to sevenfold higher in cells of the proximal than distal small intestine but was not significantly different for young adult (4 mo) vs. aged adult (24 mo) rats. Net ATP production from exogenous substrates was higher when both glucose and glutamine were present simultaneously than when either substrate was present alone, and glucose was calculated to provide 50-60% of the net ATP produced from these two substrates. Most of the energy produced from glucose was produced via the anaerobic metabolic pathways (78% for glucose alone, 95% with glucose and glutamine). Net energy production was calculated to be 10% lower in cells from aged animals than in those from young animals, since CO2 production from these major substrates was lower in cells from aged animals. PMID:9357843

Fleming, S E; Zambell, K L; Fitch, M D

1997-10-01

332

Control of hepatic glucose metabolism by islet and brain.  

Science.gov (United States)

Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP) contribute to hyperglycaemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver but also through a mechanism involving the brain. Yet, the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice, investigating whether the direct hepatic action of insulin is necessary for normal HGP: when the hepatic insulin signalling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here, we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients. PMID:25200294

Rojas, J M; Schwartz, M W

2014-09-01

333

Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients  

DEFF Research Database (Denmark)

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.Journal of Cerebral Blood Flow & Metabolism advance online publication, 8 October 2014; doi:10.1038/jcbfm.2014.169.

Stender, Johan; Kupers, Ron

2014-01-01

334

Determination of patterns of regional cerebral glucose metabolism in normal aging and dementia  

International Nuclear Information System (INIS)

Regional cerebral metabolic rates for glucose (rCMRGlc) were measured using 18F-FDG and positron emission tomography (PET) in 14 patients with probable Alzheimer's disease (AD) (age=64), 9 elderly controls (age=61), and 9 young controls (age=28). PET studies were performed without sensory stimulation or deprivation. Metabolic rates in individual brain regions were determined using an atlas overlay. Relative metabolic rates (rCMRGl c/global CMRGlc) were determined for all subjects. Comparison of young and elderly controls demonstrated significant decreases in frontal metabolism (rho<0.005) and right inferior parietal (IP) metabolism (rho<0.02) with normal aging. Patients with mild-moderate AD (NMAD) (n=8) when compared to age-matched controls, showed further reduction in right IP metabolism (rho<0.02). SAD patients also demonstrated metabolic decrements in left hemisphere language areas (rho<0.01). This latter finding is consistent with language disturbance observed late in the course of the disease. Out data reveal progressive changes in patterns of cerebral glucose utilization with aging and demential with reflect salient clinical features of these processes

335

Deoxyglucose method for the estimation of local myocardial glucose metabolism with positron computed tomography  

International Nuclear Information System (INIS)

The deoxyglucose method originally developed for measurements of the local cerebral metabolic rate for glucose has been investigated in terms of its application to studies of the heart with positron computed tomography (PCT) and FDG. Studies were performed in dogs to measure the tissue kinetics of FDG with PCT and by direct arterial-venous sampling. The operational equation developed in our laboratory as an extension of the Sokoloff model was used to analyze the data. The FDG method accurately predicted the true MMRGlc even when the glucose metabolic rate was normal but myocardial blood flow (MBF) was elevated 5 times the control value or when metabolism was reduced to 10% of normal and MBF increased 5 times normal. Improvements in PCT resolution are required to improve the accuracy of the estimates of the rate constants and the MMRGlc

336

Cerebral oxygen and glucose metabolism and blood flow in mitochondrial encephalomyopathy: a PET study  

International Nuclear Information System (INIS)

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

337

Effect of breakfast skipping on diurnal variation of energy metabolism and blood glucose.  

Science.gov (United States)

Epidemiological studies suggest an association between breakfast skipping and body weight gain, insulin resistance or type 2 diabetes. Time when meal is consumed affects postprandial increase in energy expenditure and blood glucose, and breakfast skipping may reduce 24 h energy expenditure and elevate blood glucose level. The present study evaluated the effect of breakfast skipping on diurnal variation of energy metabolism and blood glucose. The skipped breakfast was compensated by following big meals at lunch and supper. In a randomized repeated-measure design with or without breakfast, eight males stayed twice in a room-size respiratory chamber. Blood glucose was recorded with a continuous glucose monitoring system. Breakfast skipping did not affect 24 h energy expenditure, fat oxidation and thermic effect of food, but increased overall 24 h average of blood glucose (83 ± 3 vs 89 ± 2 mg/dl, P breakfast skipping. These observations suggest that changes in glucose homeostasis precede that of energy balance, in the potential sequence caused by breakfast skipping, if this dietary habit has any effect on energy balance.: PMID:24847666

Kobayashi, Fumi; Ogata, Hitomi; Omi, Naomi; Nagasaka, Shoichiro; Yamaguchi, Sachiko; Hibi, Masanobu; Tokuyama, Kumpei

2014-01-01

338

The prevalence of glucose metabolism abnormalities in Greek women with polycystic ovary syndrome.  

Science.gov (United States)

The prevalence of glucose metabolism abnormalities in PCOS women worldwide varies between 10 and 40% but there are no data in Greek PCOS women. In this retrospective study the prevalence of glucose abnormalities and the indices of insulin resistance (IR) and whole-body insulin sensitivity were estimated in a Greek population with PCOS. Impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and type 2 diabetes mellitus (t2DM) were calculated. The prevalence of IGT, IFG and t2DM in our PCOS population was 7.6, 5.1 and 1.7%, respectively. The total prevalence of glucose abnormalities was estimated as 14.1%. The prevalence of t2DM was three- to four-fold higher than in the general Greek female population of the same age as this was estimated by 2, recently published studies. PCOS women with increased BMI and waist circumference and age greater than 30 years, present more severe IR and decreased whole-body insulin sensitivity. Our data indicates a relatively high prevalence of glucose intolerance and t2DM in a Greek population with PCOS. Obese women with PCOS are in higher risk to develop glucose abnormalities and probably t2DM later in life and therefore every woman diagnosed with PCOS should undergo a 2-h post load OGTT. PMID:22571176

Trakakis, Eftihios; Basios, George; Peppa, Melpomeni; Simeonidis, George; Labos, George; Creatsa, Maria; Misailidou, Maria; Boutati, Eleni; Vaggopoulos, Vassilios; Panagopoulos, Perikles; Dimitriades, George; Kassanos, Dimitrios

2012-11-01

339

A study on glucose metabolism in a small cohort of children and adolescents with kidney transplant.  

Science.gov (United States)

Post-transplant diabetes mellitus (PTDM) and impaired glucose tolerance are now considered among the major adverse events following organ transplantation. The present study was aimed at investigating the regulation of glucose metabolism in pediatric recipients of a kidney transplant (KT), receiving tacrolimus or cyclosporine A-based immunosuppression. Twelve subjects, eight males and four females, aged 12.1+/-3.8 yr, and with a mean time from KT of 45.6 months were enrolled in the study. All patients had a basal evaluation of fasting glucose (GF), fasting insulin (IF), C-peptide and glycated hemoglobin (HbA1c) levels. They then underwent oral glucose tolerance test (OGTT), with measurement of blood glucose and insulin concentration. Two children had impaired GF, associated with supernormal HbA1c levels, one patient showed impaired glucose tolerance, none had PTDM. Peripheral insulin resistance, as measured by quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment estimate of insulin sensitivity (HOMA-IR) index, was enhanced in 3 patients. Subsequently, GF significantly increased with time from transplant (p=0.01), while fasting C-peptide and the area under the curve of insulin correlated with creatinine clearance. In conclusion, our results, although generated in a small sample size, would suggest that long-term follow-up of children receiving a KT should extend to explore the response to oral glucose load and at least the basal measure of insulin response. PMID:16699299

Giordano, M; Colella, V; Dammacco, A; Torelli, C; Grandaliano, G; Teutonico, A; Depalo, T; Caringella, D A; Di Paolo, S

2006-04-01

340

Effect of ?-radiation on the ratio of [18F]2-fluoro-2-deoxy- D-glucose to glucose utilization in human glioblastoma cells in vitro  

International Nuclear Information System (INIS)

The glucose consumption in tumours in vitro as reflected by uptake of [18F]2-fluoro-2-deoxy-D-glucose (18FDG) using positron emission tomography (PET) is currently under investigation as a measure of tumour response to radiotherapy. The calculation of cerebral metabolic rate of glucose from 18FDG-PET data requires a proportionality factor referred to as the lumped constant. In the present in vitro study, the utilizations of 18FDG and glucose have been measured in a human glioblastoma cell line (86HG-39) as a function of ?-radiation dose with various post-irradiation times and of different fractionation modes. The ratio of utilization of 18FDG to that of glucose (RF/G), assumed to correspond to the lumped constant, was observed to increase 12 and 24 h after single fraction ?-exposure by factors ranging from 1.2 to 1.5 compared with the non-irradiated controls. It decreased after multiple fraction ?-exposure (4 x 2 Gy) by a factor of 0.7 compared with the single fraction schedule (1 x 8 Gy). The results suggest that the affinities of glucose transporters or hexokinase enzyme or both for 18FDG and glucose could be influenced by ?-irradiation in this tumour cell line in vitro. Apparent changes of the glucose consumption determined with PET in human tumours following radiotherapy may, therefore, not be solely due to changes in cellular metabolism or cell number but may also be due to changes iumber but may also be due to changes in RF/G. (author)

341

Cancer Cell Metabolism: One Hallmark, Many Faces  

OpenAIRE

Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. While many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and non-genetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such changes...

Cantor, Jason R.; Sabatini, David M.

2012-01-01

342

RU 486 prevents the acute effects of cortisol on glucose and leucine metabolism.  

Science.gov (United States)

Glucocorticoids have deleterious effects on glucose and protein metabolism. RU 486 is an antiprogestin with antiglucocorticoid activity, which could be used to prevent the undesirable metabolic effects of glucocorticoids. A randomized, controlled, double blind study was performed in eight healthy male volunteers who were tested four times: during the iv infusion of cortisol (2 micrograms/kg.min for 5 h) after the oral ingestion of RU 486 (600 mg) or a placebo, and during the infusion of a normal saline solution with placebo or RU 486 ingestion. During each test, a primed continuous iv infusion of D-[6,6-2H]glucose and [1-13C-]leucine was given for the calculation of hepatic glucose production and plasma leucine appearance rate. 13CO2 enrichment in breath was measured for the calculation of leucine oxidation. Plasma concentrations of cortisol, ACTH, insulin, C-peptide, glucagon, and GH were measured at regular intervals. Compared to saline, cortisol infusion increased plasma glucose 5.5 +/- 0.6 vs. 4.7 +/- 0.4 mmol/L; P < 0.01) and leucine (179 +/- 35 vs. 155 +/- 35 mumol/L; P < 0.01) concentrations as well as the leucine appearance rate (2.24 +/- 0.3 vs. 2.0 +/- 0.28 mumol/kg.min; P < 0.05) and oxidation (0.51 +/- 0.22 vs. 0.39 +/- 0.06 mumol/kg.min; P < 0.01), and there was no change in hepatic glucose production. None of the metabolic changes induced by cortisol were seen when cortisol was administered after the ingestion of RU 486. When RU 486 was given before normal saline infusion, plasma glucose concentrations were transiently lower than those after placebo ingestion, as was the hepatic glucose production. No change in insulin, C-peptide, or glucagon was seen between tests. GH concentrations were higher during cortisol infusion, but not when cortisol was administered after the ingestion of RU 486. The following conclusions were reached. 1) RU 486 can suppress the effects of acute hypercortisolemia on glucose and protein metabolism and GH secretion in man. Long term studies are warranted to explore the potential of antiglucocorticoid molecules as preventive agents of the deleterious effects of chronic glucocorticoid administration. 2) RU 486 is useful molecule for studying the metabolic effects of cortisol in man. PMID:7888013

Garrel, D R; Moussali, R; De Oliveira, A; Lesiège, D; Larivière, F

1995-02-01

343

Glucose metabolism in small subcortical structures in Parkinson's disease  

DEFF Research Database (Denmark)

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) cameras. However, the high-resolution research tomograph (HRRT) PET system has a resolution of 2 mm, sufficient for the investigation of important structures such as the pallidum and thalamic subnuclei.

Borghammer, Per; Hansen, SØren B

2012-01-01

344

Modulation of glucose responsiveness of insulinoma beta-cells by graded overexpression of glucokinase.  

Science.gov (United States)

Insulinoma beta-cells capable of overexpressing glucokinase under the control of a doxycycline-dependent transcriptional transactivator were established from parental INS-1 cells. Glucokinase could be maximally induced to a level more than 20 times the basal level after 36 h of culture with doxycycline. Intermediate levels of induction could be achieved by varying doses of, and time of culture with, the inducer. The rate of glycolysis was measured in cells with 3-, 5-, and 8-fold increment in glucokinase activity above the noninduced level. Proportionate increases in glycolytic flux occurred in cells cultured at low physiological glucose concentration. At high glucose concentration, induction of glucokinase in excess of 2-fold above basal resulted in little additional increase in glycolysis. The consequences of graded increases of glucokinase on two physiological glucose effects were investigated. Increments in glucokinase activity were accompanied by a stepwise shift to the left of the dose-response curve for the inductive effect of glucose on the L-type pyruvate kinase mRNA. Similarly, the insulin secretory response to glucose was shifted leftward in glucokinase-induced cells. The following conclusions are drawn: (i) glucokinase is the major rate-limiting enzyme for glycolysis in these cells; (ii) downstream metabolic steps become limiting at high extracellular glucose concentration with moderate increases in glucokinase over the wild-type level; (iii) within limits, glucokinase activity is a determining factor for two types of glucose responses of the beta-cell, the induction of specific gene expression, and insulin release. PMID:9113996

Wang, H; Iynedjian, P B

1997-04-29

345

Single-cell level based approach to investigate bacterial metabolism during batch industrial fermentation  

DEFF Research Database (Denmark)

Escherichia coli fermentations have been studied for decades, but most results are based on average measurements of the whole populations of cells, whilst averaged data can mask the distribution of activities at the sub-population or single-cell level. A population of genetically identical cells can exhibit different phenotypes under specific environmental conditions that show significant differences in physiological parameters from the population average. However, studies concerning segregation of populations into metabolically diversified subpopulations are scarce. Acetate is a product of Escherichia coli overflow metabolism when the bacteria are grown under aerobic conditions and glucose is present in excessive concentrations. Acetate accumulation is of the utmost importance in batch fermentation processes as it is an undesirable byproduct that negatively affects growth, physiology, and performance of Escherichia coli. An insight into glucose and acetate fate on the level of individual cell can provide the type of information which are valuable for the understanding of bacterial metabolism in fermentation process and can shed more light on the differentiation of isogenic fermenting populations into subpopulations expressing metabolically different profiles. The goal of this study was to observe and quantify in situ metabolic response of Escherichia coli at single-cell level and determine activity distribution of glucose and acetate uptake during batch fermentation processes. Pure culture of Escherichia coli MG1655 was used to investigate glucose and acetate metabolism at single-cell level during different stages of glucose batch fermentation process. Uptake of the substrates was observed and measured in situ by quantitative microautoradiography. Sub-populations of Escherichia coli cells expressing different activity levels for the uptake of glucose or acetate were observed. The distribution of these uptake activities changed along the batch fermentation process. The results based on the observation of single cells indicate that heterogeneity exists within bacterial populations and is a result of metabolic diversification of individual cells.

Nierychlo, Marta; Larsen, Poul

346

High-fat/low-carbohydrate diets regulate glucose metabolism via a long-term transcriptional loop.  

Science.gov (United States)

Insulin sensitivity is characterized by insulin-stimulated glucose metabolism in skeletal muscle. We hypothesized that carbohydrate metabolism and storage might be under transcriptional control. To test this hypothesis, we fed insulin-sensitive males (glucose disposal rate, 14.7 +/- 4.1 mg/kg fat-free mass [FFM] per minute) an isoenergetic high-fat/low-carbohydrate diet (HF/LCD) for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarrays revealed a total of 369 genes of 18861 genes on the arrays were differentially regulated in response to diet (Bonferonni adjusted P PFKFB3), pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4), and glycogen synthase 1 (muscle). In a separate experiment, we fed C57Bl/6J mice an HF/LCD for 3 weeks and found that the same glucose metabolism genes were changed by approximately 70% on average. Fructose-2,6-biphosphatase 3 and pyruvate dehydrogenase kinase, isoenzyme 4 increased and glycogen synthase 1 (muscle) decreased. Combined, these results suggest a mechanism whereby HF/LCD regulates the genes necessary for glucose utilization and storage vis-á-vis transcriptional control. PMID:17046547

Sparks, Lauren M; Xie, Hui; Koza, Robert A; Mynatt, Randall; Bray, George A; Smith, Steven R

2006-11-01

347

Assessment of metabolic status in young Japanese females using postprandial glucose and insulin levels.  

Science.gov (United States)

Lifestyle-related diseases develop through the accumulation of undesirable lifestyle habits both prior to the onset of disease as well as during normal healthy life. Accordingly, early detection of, and intervention in, metabolic disorders is desirable, but is hampered by the lack of an established evaluation index for young individuals. The purpose of this study was to investigate the utility of a biomarker of health in young female subjects. The subjects were young healthy Japanese females in whom energy expenditure was measured for a period of 210 min after a test meal. In addition, ?plasma glucose and ?serum insulin were calculated from the fasting and 30 min values. ?Plasma glucose and ?serum insulin levels varied widely compared to fasting levels. Both the area under the curve of carbohydrate oxidation rate and serum free fatty acid levels were higher in individuals in the high ?plasma glucose group. Moreover, ?plasma glucose was higher in individuals in the high ?serum insulin group than in the low ?serum insulin group. We conclude that nutritional balanced liquid loading test using ?plasma glucose and ?serum insulin as the evaluation index is useful for the detection of primary metabolic disorders in young females. PMID:24895484

Sakuma, Masae; Sasaki, Megumi; Katsuda, Sayaka; Kobayashi, Kana; Takaya, Chiaki; Umeda, Minako; Arai, Hidekazu

2014-05-01

348

Similarities of cerebral glucose metabolism in Alzheimer's and Parkinsonian dementia  

International Nuclear Information System (INIS)

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 ofex useful in the differential diagnosis of early dementia

349

Metabolic engineering of Rhizopus oryzae: effects of overexpressing pyc and pepc genes on fumaric acid biosynthesis from glucose.  

Science.gov (United States)

Fumaric acid, a dicarboxylic acid used as a food acidulant and in manufacturing synthetic resins, can be produced from glucose in fermentation by Rhizopus oryzae. However, the fumaric acid yield is limited by the co-production of ethanol and other byproducts. To increase fumaric acid production, overexpressing endogenous pyruvate carboxylase (PYC) and exogenous phosphoenolpyruvate carboxylase (PEPC) to increase the carbon flux toward oxaloacetate were investigated. Compared to the wild type, the PYC activity in the pyc transformants increased 56%-83%, whereas pepc transformants exhibited significant PEPC activity (3-6 mU/mg) that was absent in the wild type. Fumaric acid production by the pepc transformant increased 26% (0.78 g/g glucose vs. 0.62 g/g for the wild type). However, the pyc transformants grew poorly and had low fumaric acid yields (<0.05 g/g glucose) due to the formation of large cell pellets that limited oxygen supply and resulted in the accumulation of ethanol with a high yield of 0.13-0.36 g/g glucose. This study is the first attempt to use metabolic engineering to modify the fumaric acid biosynthesis pathway to increase fumaric acid production in R. oryzae. PMID:22814110

Zhang, Baohua; Skory, Christopher D; Yang, Shang-Tian

2012-09-01

350

A comparison of glucose metabolism and related hormonal parameters in two strains of mice having differing hepatic glucokinase activities.  

Science.gov (United States)

Parameters of glucose metabolism in the livers of two inbred strains of mice, C3H/He and C58, which have high- and low-glucokinase activities respectively, have been determined. Unlike insulin concentrations, the plasma glucagon concentrations are similar in the two strains. Certain of the numbers of insulin receptors per hepatocyte cell surface area were higher in starved than fed animals of the same strain but affinities were the same, while only small differences in receptor numbers were found between the strains in starved animals. The difference in glucokinase activity, determined spectrophotometrically and confirmed by measurements of detritiation of [2-3H]glucose by hepatocytes incubated in vitro, does not apparently influence the minimal rate of glucose recycling as measured by the relative loss of 3H and 14C from [2-3H, U-14C]glucose. The development profiles for the two strains show a marked developmental difference arising around 20 days after birth. PMID:3004807

James, P A; Walker, D G

1985-01-01

351

Glucose and lactate metabolism in the awake and stimulated rat: a 13C-NMR study  

Science.gov (United States)

Glucose is the major energetic substrate for the brain but evidence has accumulated during the last 20 years that lactate produced by astrocytes could be an additional substrate for neurons. However, little information exists about this lactate shuttle in vivo in activated and awake animals. We designed an experiment in which the cortical barrel field (S1BF) was unilaterally activated during infusion of both glucose and lactate (alternatively labeled with 13C) in rats. At the end of stimulation (1 h) both S1BF areas were removed and analyzed by HR-MAS NMR spectroscopy to compare glucose and lactate metabolism in the activated area vs. the non-activated one. In combination with microwave irradiation HR-MAS spectroscopy is a powerful technical approach to study brain lactate metabolism in vivo. Using in vivo 14C-2-deoxyglucose and autoradiography we confirmed that whisker stimulation was effective since we observed a 40% increase in glucose uptake in the activated S1BF area compared to the ipsilateral one. We first determined that lactate observed on spectra of biopsies did not arise from post-mortem metabolism. 1H-NMR data indicated that during brain activation there was an average 2.4-fold increase in lactate content in the activated area. When [1-13C]glucose + lactate were infused 13C-NMR data showed an increase in 13C-labeled lactate during brain activation as well as an increase in lactate C3-specific enrichment. This result demonstrates that the increase in lactate observed on 1H-NMR spectra originates from newly synthesized lactate from the labeled precursor ([1-13C]glucose). It also shows that this additional lactate does not arise from an increase in blood lactate uptake since it would otherwise be unlabeled. These results are in favor of intracerebral lactate production during brain activation in vivo which could be a supplementary fuel for neurons. PMID:23755012

Sampol, Denys; Ostrofet, Eugène; Jobin, Marie-Lise; Raffard, Gérard; Sanchez, Stéphane; Bouchaud, Véronique; Franconi, Jean-Michel; Bonvento, Gilles; Bouzier-Sore, Anne-Karine

2013-01-01

352

Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints  

International Nuclear Information System (INIS)

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.)

353

Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints  

Energy Technology Data Exchange (ETDEWEB)

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.)

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

354

Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients.  

Science.gov (United States)

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients. PMID:25294128

Stender, Johan; Kupers, Ron; Rodell, Anders; Thibaut, Aurore; Chatelle, Camille; Bruno, Marie-Aurélie; Gejl, Michael; Bernard, Claire; Hustinx, Roland; Laureys, Steven; Gjedde, Albert

2015-01-01

355

Early Metabolic Flare in Squamous Cell Carcinoma after Chemotherapy is a Marker of Treatment Sensitivity In Vitro  

International Nuclear Information System (INIS)

Early metabolic response with a decrease in glucose demand after cytotoxic treatment has been reported to precede tumor volume shrinkage. However, preclinical studies report of a very early rise in metabolism, a flare, following treatment. To elucidate these observations, we performed an experimental study on early metabolic response with sequential analysis of metabolic changes. Three squamous cell carcinoma cell lines and one non tumorigenic cell line were exposed to cisplatin. The uptake of the fluorescent glucose analogue 2-NBDG was examined at days 1-6 using fluorescence microscopy. The relation between 2-NBDG-uptake and cell survival was evaluated. The tumor cells exhibited a high uptake of 2-NBDG, whereas the uptake in the nonmalignant cells was low. The more cisplatin sensitive cell lines exhibited a more pronounced metabolic flare than the less sensitive cell line. A metabolic flare was a very early sign of treatment response and potentially it could be used as an early marker of treatment sensitivity.

356

Pathways of glucose metabolism by rough and smooth variants of Bacillus stearothermophilus.  

Science.gov (United States)

The radiorespirometric method was used to study the pathways of glucose metabolism in the rough and smooth variants of Bacillus stearothermophilus NCA 1518. The Embden-Meyerhof (EM) pathway was more active in the smooth variant than in the rough variant. The participation of the hexose monophosphate shunt (HMP) and EM pathways in the smooth variant was calculated as 4.2 and 95.8%, respectively. The rough variant utilized glucose via the EM pathway exclusively or in combination with a pathway other than the HMP pathway. The estimated efficiency of the tricarboxylic acid system in the rough and smooth variants was 81.3 and 4.9%, respectively. PMID:6035046

Hill, W M; Fields, M L; Tweedy, B G

1967-05-01

357

Hormone and glucose metabolic effects of compound cyproterone acetate in women with polycystic ovarian syndrome  

International Nuclear Information System (INIS)

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)

358

The Fragile X proteins Fmrp and Fxr2p cooperate to regulate glucose metabolism in mice.  

Science.gov (United States)

Fragile X syndrome results from loss of FMR1 expression. Individuals with the disorder exhibit not only intellectual disability, but also an array of physical and behavioral abnormalities, including sleep difficulties. Studies in mice demonstrated that Fmr1, along with its paralog Fxr2, regulate circadian behavior, and that their absence disrupts expression and cycling of essential clock mRNAs in the liver. Recent reports have identified circadian genes to be essential for normal metabolism. Here we describe the metabolic defects that arise in mice mutated for both Fmr1 and Fxr2. These mice have reduced fat deposits compared with age- and weight-matched controls. Several metabolic markers show either low levels in plasma or abnormal circadian cycling (or both). Insulin levels are consistently low regardless of light exposure and feeding conditions, and the animals are extremely sensitive to injected insulin. Glucose production from introduced pyruvate and glucagon is impaired and the mice quickly clear injected glucose. These mice also have higher food intake and higher VO2 and VCO2 levels. We analyzed liver expression of genes involved in glucose homeostasis and found several that are expressed differentially in the mutant mice. These results point to the involvement of Fmr1 and Fxr2 in maintaining the normal metabolic state in mice. PMID:25552647

Lumaban, Jeannette G; Nelson, David L

2015-04-15

359

Glucose transporter expression and glucose metabolism in a model of hibernating myocardium in pigs  

International Nuclear Information System (INIS)

We were able to present results on GLUT expression in an exemplary hibernating heart in order to test the hypothesis of a differentially regulated GLUT profile responsible for increased FDG uptake. The herein reported animal fulfilled all following criteria characterizing hibernation: - A complete occlusion of the LAD after 28 days. - Dysfunctionality but viability of the LV LAD territory as characterized by wall motion abnormality and a metabolic mismatch situation. - No histopathological signs of infarction. (orig.)

360

Glucose transporter expression and glucose metabolism in a model of hibernating myocardium in pigs  

Energy Technology Data Exchange (ETDEWEB)

We were able to present results on GLUT expression in an exemplary hibernating heart in order to test the hypothesis of a differentially regulated GLUT profile responsible for increased FDG uptake. The herein reported animal fulfilled all following criteria characterizing hibernation: - A complete occlusion of the LAD after 28 days. - Dysfunctionality but viability of the LV LAD territory as characterized by wall motion abnormality and a metabolic mismatch situation. - No histopathological signs of infarction. (orig.)

Egert, S.; Praus, A. [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik; Nimz, C.; Schwaiger, M. [Technische Univ. Muenchen (Germany). Inst. fuer Experimentelle Onkologie und Therapieforschung

2004-08-01

361

The multiple connections between pRB and cell metabolism  

OpenAIRE

The pRB tumor suppressor is traditionally seen as an important regulator of the cell cycle. pRB represses the transcriptional activation of a diverse set of genes by the E2F transcription factors and prevents inappropriate S-phase entry. Advances in our understanding of pRB have documented roles that extend beyond the cell cycle and this review summarizes recent studies that link pRB to the control of cell metabolism. pRB has been shown to regulate glucose tolerance, mitogenesis, glutathione ...

Nicolay, Brandon N.; Dyson, Nicholas J.

2013-01-01

362

Glucose metabolite glyoxal induces senescence in telomerase-immortalized human mesenchymal stem cells  

OpenAIRE

Abstract Background Various by-products of the cellular metabolism, such as reactive carbonyl species (RCS) are potentially harmful to cells and tissues, and play a role in many physiological and pathological processes. Among various RCS is the highly reactive dicarbonyl glyoxal (GO), which is a natural physiological metabolite produced by the auto-oxidation of glucose, and can form covalent adducts known as advanced glycation endproducts (AGE). We have previously reported that GO accelerates...

Larsen Simon; Kassem Moustapha; Is, Rattan Suresh

2012-01-01

363

Normalization of Obesity-Associated Insulin Resistance through Immunotherapy: CD4+ T Cells Control Glucose Homeostasis  

OpenAIRE

Progressive obesity and its associated metabolic syndromes represent a globally growing challenge, yet mechanistic understanding and current therapeutics are unsatisfactory. We discovered that CD4+ T-lymphocytes, resident in visceral adipose tissue (VAT), control insulin-resistance in diet-induced obese (DIO) mice and likely humans. DIO VAT-associated T cells display biased TCR-V? repertoires suggesting antigen-specific expansion. CD4+ T-lymphocyte control of glucose homeostasis is compromis...

Winer, Shawn; Chan, Yin; Paltser, Geoffrey; Truong, Dorothy; Tsui, Hubert; Bahrami, Jasmine; Dorfman, Ruslan; Wang, Yongqian; Zielenski, Julian; Mastronardi, Fabrizio; Maezawa, Yuko; Drucker, Daniel; Engleman, Edgar; Winer, Daniel; Dosch, H. -michael

2009-01-01

364

Calcium co-regulates oxidative metabolism and ATP synthase-dependent respiration in pancreatic beta cells.  

Science.gov (United States)

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

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

2014-03-28

365

Metabolic measurements in cell culture and tissue constructs  

Science.gov (United States)

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.Â#

Rolfe, P.

2008-10-01

366

Generalized decrease in brain glucose metabolism during fasting in humans studied by PET  

International Nuclear Information System (INIS)

In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged

367

1H- and 13C-NMR spectroscopic study of glucose metabolism in eggs of Angiostrongylus cantonensis during their development  

International Nuclear Information System (INIS)

1H- and 13C-nuclear magnetic resonance (NMR) spectroscopy was used to study aerobic glucose metabolism in eggs of Angiostrongylus cantonensis in an NCTC-109 medium supplemented with fetal calf serum. Without any pretreatment of the spent medium, we were able to identify and quantitate, by NMR, the end-products of glucose metabolism in eggs after cultivation for 2, 4, and 8 days. We demonstrated that A. cantonensis eggs took up glucose rapidly; among the major end products were found lactic acid, acetic acid and alanine. The eggs are parasitic in a sense that the energy metabolism in them is dependent mainly upon the energy source presentin outer medium. (author)

368

Regulation of. beta. -cell glucose transporter gene expression  

Energy Technology Data Exchange (ETDEWEB)

It has been postulated that a glucose transporter of {beta} cells (GLUT-2) may be important in glucose-stimulated insulin secretion. To determine whether this transporter is constitutively expressed or regulated, the authors subjected conscious unrestrained Wistar rats to perturbations in glucose homeostasis and quantitated {beta}-cell GLUT-2 mRNA by in situ hybridization. After 3 hr of hypoglycemia, GLUT-2 and proinsulin mRNA signal densities were reduced by 25% of the level in control rats. After 4 days, GLUT-2 and proinsulin mRNA densities were reduced by 85% and 65%, respectively. After 12 days of hypoglycemia, the K{sub m} for 3-O-methyl-D-glucose transport in isolated rat islets, normally 18-20 mM, was 2.5 mM. This provides functional evidence of a profound reduction of high K{sub m} glucose transporter in {beta} cells. In contrast, GLUT-2 was only slightly reduced by hypoglycemia in liver. To determine the effect of prolonged hyperglycemia, they also infused animals with 50% (wt/vol) glucose for 5 days. Hyperglycemic clamping increased GLUT-2 mRNA by 46% whereas proinsulin mRNA doubled. They conclude that GLUT-2 expression in {beta} cells, but not liver, is subject to regulation by certain perturbations in blood glucose homeostasis.

Chen, Ling; Alam, Tausif; Johnson, J.H.; Unger, R.H. (Univ. of Texas Southwestern Medical Center, Dallas (USA) Department of Veterans Affairs Medical Center, Dallas, TX (USA)); Hughes, S.; Newgard, C.B. (Univ. of Texas Southwestern Medical Center, Dallas (USA))

1990-06-01

369

Melphalan metabolism in cultured cells  

International Nuclear Information System (INIS)

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

370

Cell metabolism: an essential link between cell growth and apoptosis  

OpenAIRE

Growth factor-stimulated or cancerous cells require sufficient nutrients to meet the metabolic demands of cell growth and division. If nutrients are insufficient, metabolic checkpoints are triggered that lead to cell cycle arrest and the activation of the intrinsic apoptotic cascade through a process dependent on the Bcl-2 family of proteins. Given the connections between metabolism and apoptosis, the notion of targeting metabolism to induce cell death in cancer cells has recently garnered mu...

Mason, Emily F.; Rathmell, Jeffrey C.

2010-01-01

371

Effect of high glucose on gene expression in mesangial cells: upregulation of the thiol pathway is an adaptational response.  

Science.gov (United States)

Pathological alterations in glomerular mesangial cells play a critical role in the development of diabetic nephropathy, the leading cause of end-stage renal disease. Molecular mechanisms mediating such alterations, however, remain to be fully understood. The present study first examined the effect of high glucose on the mRNA expression profile in rat mesangial cells using cDNA microarray. Based on variation-weighted criteria and with a false discovery rate of 4.3%, 459 of 17,664 cDNA elements examined were found to be upregulated and 151 downregulated by exposure to 25 mM d-glucose for 5 days. A large number of differentially expressed genes belonged to several functional categories, indicating high glucose had a profound effect on mesangial cell proliferation, protein synthesis, energy metabolism, and, somewhat unexpectedly, protein sorting and the cytoskeleton. Interestingly, several thiol antioxidative genes (glutathione peroxidase 1, peroxiredoxin 6, and thioredoxin 2) were found by microarray and confirmed by real-time PCR to be upregulated by high glucose. These changes suggested that the oxidative stress known to be induced in mesangial cells by high glucose might be buffered by upregulation of the thiol antioxidative pathway. Upregulation of thiol antioxidative genes also occurred in high-glucose-treated human mesangial cells and in glomeruli isolated from rats after 1 wk of streptozotocin-induced diabetes, but not in human proximal tubule cells. High glucose slightly increased lipid peroxidation and decreased the amount of reduced thiols in rat and human mesangial cells. Disruption of the thiol antioxidative pathway by two different thiol-oxidizing agents resulted in a three- to fivefold increase in high-glucose-induced lipid peroxidation. In summary, the present study provided a global view of the short-term effect of high glucose on mesangial cells at the level of mRNA expression and identified the upregulation of the thiol antioxidative pathway as an adaptational response of mesangial cells to high glucose. PMID:15039483

Morrison, Jolean; Knoll, Kristen; Hessner, Martin J; Liang, Mingyu

2004-05-19

372

Simultaneous catabolite repression between glucose and toluene metabolism in Pseudomonas putida is channeled through different signaling pathways.  

Science.gov (United States)

Pseudomonas putida KT2440(pWW0) can use toluene via the TOL plasmid-encoded catabolic pathways and can use glucose via a series of three peripheral chromosome-encoded routes that convert glucose into 6-phosphogluconate (6PG), namely, the glucokinase pathway, in which glucose is transformed to 6PG through the action of glucokinase and glucose-6-phosphate dehydrogenase. Alternatively, glucose can be oxidized to gluconate, which can be phosphorylated by gluconokinase to 6PG or oxidized to 2-ketogluconate, which, in turn, is converted into 6PG. Our results show that KT2440 metabolizes glucose and toluene simultaneously, as revealed by net flux analysis of [(13)C]glucose. Determination of glucokinase and gluconokinase activities in glucose metabolism, gene expression assays using a fusion of the promoter of the Pu TOL upper pathway to 'lacZ, and global transcriptomic assays revealed simultaneous catabolite repression in the use of these two carbon sources. The effect of toluene on glucose metabolism was directed to the glucokinase branch and did not affect gluconate metabolism. Catabolite repression of the glucokinase pathway and the TOL pathway was triggered by two different catabolite repression systems. Expression from Pu was repressed mainly via PtsN in response to high levels of 2-dehydro-3-deoxygluconate-6-phosphate, whereas repression of the glucokinase pathway was channeled through Crc. PMID:17616587

del Castillo, Teresa; Ramos, Juan L

2007-09-01

373

Fluorodeoxyglucose rate constants, lumped constant, and glucose metabolic rate in rabbit heart  

International Nuclear Information System (INIS)

The isolated arterial perfused rabbit interventricular septum was used to measure myocardial metabolic rate for glucose (MMRGlc) and rate constants and lumped constant (LC) for the glucose analogue [18F]fluorodeoxyglucose (FDG) using a tracer kinetic model. FDG was delivered by constant infusion during coincidence counting of tissue 18F radioactivity. The MMRGlc was measured by the Fick method. Control septa were paced at 72 beats/min and perfused at 1.5 ml/min with oxygenated perfusate containing 5.6 mM glucose and 5 mU/ml insulin. The following conditions were tested: 3.0 and 4.5 ml/min; insulin increased to 25 mU/ml; insulin omitted; 2.8 mM and 11.2 mM glucose; 144 beats/min and 96 paired stimuli/min; and anoxia. Under all conditions studied the phosphorylation (hexokinase) reaction was rate limiting relative to transport. Compared with control conditions, the phosphorylation rate constant was significantly increased with 2.8 mM glucose as well as in anoxia. With 4.5 ml/min and 11.2 mM glucose, conditions that should increase glucose flux into tissue without increasing demand, the phosphorylation rate constant decreased significantly. With 11.2 mM glucose, 96 paired stimuli/min, and anoxia without insulin, a significant increase in the hydrolysis rate of FDG 6-phosphate was observed and suggests that hydrolysis is also an important mechanism for regulating the MMRGlc. Increased transport rate constants were observed with increased flow rates, were observed with increased flow rates, 96 paired stimuli/min, and anoxia at 96 beats/min. The LC was not significantly different from control in 11 of 14 conditions studied. Therefore, under most conditions in average LC can be used to calculate MMRGlc estimates