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1

Control of pancreatic ? cell regeneration by glucose metabolism.  

Science.gov (United States)

Recent studies revealed a surprising regenerative capacity of insulin-producing ? cells in mice, suggesting that regenerative therapy for human diabetes could in principle be achieved. Physiologic ? cell regeneration under stressed conditions relies on accelerated proliferation of surviving ? cells, but the factors that trigger and control this response remain unclear. Using islet transplantation experiments, we show that ? cell mass is controlled systemically rather than by local factors such as tissue damage. Chronic changes in ? cell glucose metabolism, rather than blood glucose levels per se, are the main positive regulator of basal and compensatory ? cell proliferation in vivo. Intracellularly, genetic and pharmacologic manipulations reveal that glucose induces ? cell replication via metabolism by glucokinase, the first step of glycolysis, followed by closure of K(ATP) channels and membrane depolarization. Our data provide a molecular mechanism for homeostatic control of ? cell mass by metabolic demand. PMID:21459328

Porat, Shay; Weinberg-Corem, Noa; Tornovsky-Babaey, Sharona; Schyr-Ben-Haroush, Rachel; Hija, Ayat; Stolovich-Rain, Miri; Dadon, Daniela; Granot, Zvi; Ben-Hur, Vered; White, Peter; Girard, Christophe A; Karni, Rotem; Kaestner, Klaus H; Ashcroft, Frances M; Magnuson, Mark A; Saada, Ann; Grimsby, Joseph; Glaser, Benjamin; Dor, Yuval

2011-04-01

2

Cell based metabolic barriers to glucose diffusion: macrophages and continuous glucose monitoring.  

Science.gov (United States)

It is assumed that MQ are central to glucose sensor bio-fouling and therefore have a major negative impact on continuous glucose monitoring (CGM) performance in vivo. However to our knowledge there is no data in the literature to directly support or refute this assumption. Since glucose and oxygen (O2) are key to glucose sensor function in vivo, understanding and controlling glucose and O2 metabolic activity of MQ is likely key to successful glucose sensor performance. We hypothesized that the accumulation of MQ at the glucose sensor-tissue interface will act as "Cell Based Metabolic Barriers" (CBMB) to glucose diffusing from the interstitial tissue compartment to the implanted glucose sensor and as such creating an artificially low sensor output, thereby compromising sensor function and CGM. Our studies demonstrated that 1) direct injections of MQ at in vivo sensor implantation sites dramatically decreased sensor output (measured in nA), 2) addition of MQ to glucose sensors in vitro resulted in a rapid and dramatic fall in sensor output and 3) lymphocytes did not affect sensor function in vitro or in vivo. These data support our hypothesis that MQ can act as metabolic barriers to glucose and O2 diffusion in vivo and in vitro. PMID:24461328

Klueh, Ulrike; Frailey, Jackman T; Qiao, Yi; Antar, Omar; Kreutzer, Donald L

2014-03-01

3

Akt Requires Glucose Metabolism to Suppress Puma Expression and Prevent Apoptosis of Leukemic T Cells*  

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The PI3K/Akt pathway is activated in stimulated cells and in many cancers to promote glucose metabolism and prevent cell death. Although inhibition of Akt-mediated cell survival may provide a means to eliminate cancer cells, this survival pathway remains incompletely understood. In particular, unlike anti-apoptotic Bcl-2 family proteins that prevent apoptosis independent of glucose, Akt requires glucose metabolism to inhibit cell death. This glucose dependence may occur in part through metabo...

2011-01-01

4

Sensitization of metformin-cytotoxicity by dichloroacetate via reprogramming glucose metabolism in cancer cells.  

Science.gov (United States)

To investigate sensitization of metformin-cytotoxicity, cancer cells were treated with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK). Metformin-cytotoxicity was mainly dependent on glucose availability and reducing power generated by pentose phosphate pathway, whereas DCA cotreatment enhanced metformin-cytotoxicity via reprogramming glucose metabolism by inhibiting PDK and increasing mitochondrial respiration. DCA cotreatment elicited cell death rather than cell survival despite high glucose and high GSH condition. In conclusion, DCA sensitized metformin-cytotoxicity by reprogramming glucose metabolism in part from aerobic glycolysis to mitochondrial oxidation, evidenced by measurements of glucose consumption, lactate release, and the ratio of oxygen consumption rate/extracellular acidification rate. PMID:24480191

Choi, Yong Won; Lim, In Kyoung

2014-05-01

5

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

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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

Transglutaminase 2 reprogramming of glucose metabolism in mammary epithelial cells via activation of inflammatory signaling pathways.  

Science.gov (United States)

Aberrant glucose metabolism characterized by high levels of glycolysis, even in the presence of oxygen, is an important hallmark of cancer. This metabolic reprogramming referred to as the Warburg effect is essential to the survival of tumor cells and provides them with substrates required for biomass generation. Molecular mechanisms responsible for this shift in glucose metabolism remain elusive. As described herein, we found that aberrant expression of the proinflammatory protein transglutaminase 2 (TG2) is an important regulator of the Warburg effect in mammary epithelial cells. Mechanistically, TG2 regulated metabolic reprogramming by constitutively activating nuclear factor (NF)-?B, which binds to the hypoxia-inducible factor (HIF)-1? promoter and induces its expression even under normoxic conditions. TG2/NF-?B-induced increase in HIF-1? expression was associated with increased glucose uptake, increased lactate production and decreased oxygen consumption by mitochondria. Experimental suppression of TG2 attenuated HIF-1? expression and reversed downstream events in mammary epithelial cells. Moreover, downregulation of p65/RelA or HIF-1? expression in these cells restored normal glucose uptake, lactate production, mitochondrial respiration and glycolytic protein expression. Our results suggest that aberrant expression of TG2 is a master regulator of metabolic reprogramming and facilitates metabolic alterations in epithelial cells even under normoxic conditions. A TG2-induced shift in glucose metabolism helps breast cancer cells to survive under stressful conditions and promotes their metastatic competence. PMID:24477458

Kumar, Santosh; Donti, Taraka R; Agnihotri, Navneet; Mehta, Kapil

2014-06-15

7

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

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

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

2012-01-01

8

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

International Nuclear Information System (INIS)

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

1984-01-01

9

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1984-08-01

10

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

11

Glucagon-insulin interaction on fat cell metabolism using c"1"4 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

1984-01-01

12

Fluorescent microplate cell assay to measure uptake and metabolism of glucose in normal human lung fibroblasts.  

Science.gov (United States)

This is the first report of a fluorimetric microplate assay to assess glucose uptake and metabolism in eukaryotic cells. The assay was carried out incubating normal human lung fibroblasts in the wells of microtiter trays with a fluorescent D-glucose derivative, 2-N-7-(nitrobenz-2-oxa-1,3-diazol-4-yl)amino-2-deoxy-D-glucose (2-NBDG). This dye could be incorporated by glucose transporting systems in living cells. Substrate uptake was determined by analysing the data obtained with a fluorescence microplate reader. Variables studied in the development of the assay included dye concentration and incubation period. We found that this cell assay is very sensitive, reproducible, provides fast results and graphical display of data. It requires small sample volumes and allows handling of a large number of samples simultaneously. Okadaic acid was used to assess this microplate assay in the field of cytotoxicity. This diarrhetic shellfish toxin is a tumour promoter and a specific inhibitor of protein phosphatases 1 and 2A. The exposition of cells to okadaic acid (0.1 nM-1 microM) at different time intervals causes a decrease in intracellular glucose (40-50% over controls). Results obtained with okadaic acid are the starting point to evaluate application of the method to routine toxicity probes. PMID:12020600

Leira, F; Louzao, M C; Vieites, J M; Botana, L M; Vieytes, M R

2002-06-01

13

Exposure to 2,4-dichlorophenoxyacetic acid alters glucose metabolism in immature rat Sertoli cells.  

Science.gov (United States)

The purpose of this study was to determine the effects of 2,4-D, an herbicide used worldwide also known as endocrine disruptor, in Sertoli cell (SC) metabolism. Immature rat SCs were maintained 50h under basal conditions or exposed to 2,4-D (100nM, 10?M and 1mM). SCs exposed to 10?M and 1mM of 2,4-D presented lower intracellular glucose and lactate content. Exposure to 10?M of 2,4-D induced a significant decrease in glucose transporter-3 mRNA levels and phosphofructokinase-1 mRNA levels decreased in cells exposed to 100nM and 10?M of 2,4-D. Exposure to 100nM and 10?M also induced a decrease in lactate dehydrogenase (LDH) mRNA levels while the LDH protein levels were only decreased in cells exposed to 1mM of 2,4-D. Exposure to 2,4-D altered glucose uptake and metabolization in SCs, as well as lactate metabolism and export that may result in impaired spermatogenesis. PMID:23538319

Alves, M G; Neuhaus-Oliveira, A; Moreira, P I; Socorro, S; Oliveira, P F

2013-07-01

14

Potent humanin analog increases glucose-stimulated insulin secretion through enhanced metabolism in the ? cell.  

Science.gov (United States)

Humanin (HN) is a 24-aa polypeptide that offers protection from Alzheimer's disease and myocardial infarction, increases insulin sensitivity, improves survival of ? cells, and delays onset of diabetes. Here we examined the acute effects of HN on insulin secretion and potential mechanisms through which they are mediated. Effects of a potent HN analog, HNGF6A, on glucose-stimulated insulin secretion (GSIS) were assessed in vivo and in isolated pancreatic islets and cultured murine ? cell line (?TC3) in vitro. Sprague-Dawley rats (3 mo old) that received HNGF6A required a significantly higher glucose infusion rate and demonstrated higher insulin levels during hyperglycemic clamps compared to saline controls. In vitro, compared to scrambled peptide controls, HNGF6A increased GSIS in isolated islets from both normal and diabetic mice as well as in ?TC3 cells. Effects of HNGF6A on GSIS were dose dependent, K-ATP channel independent, and associated with enhanced glucose metabolism. These findings demonstrate that HNGF6A increases GSIS in whole animals, from isolated islets and from cells in culture, which suggests a direct effect on the ? cell. The glucose-dependent effects on insulin secretion along with the established effects on insulin action suggest potential for HN and its analogs in the treatment of diabetes. PMID:23995290

Kuliawat, Regina; Klein, Laura; Gong, Zhenwei; Nicoletta-Gentile, Marianna; Nemkal, Anjana; Cui, Lingguang; Bastie, Claire; Su, Kai; Huffman, Derek; Surana, Manju; Barzilai, Nir; Fleischer, Norman; Muzumdar, Radhika

2013-12-01

15

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

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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

16

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-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.)

2004-09-01

17

Cyclin D1-Cdk4 controls glucose metabolism independently of cell cycle progression.  

Science.gov (United States)

Insulin constitutes a principal evolutionarily conserved hormonal axis for maintaining glucose homeostasis; dysregulation of this axis causes diabetes. PGC-1? (peroxisome-proliferator-activated receptor-? coactivator-1?) links insulin signalling to the expression of glucose and lipid metabolic genes. The histone acetyltransferase GCN5 (general control non-repressed protein 5) acetylates PGC-1? and suppresses its transcriptional activity, whereas sirtuin 1 deacetylates and activates PGC-1?. Although insulin is a mitogenic signal in proliferative cells, whether components of the cell cycle machinery contribute to its metabolic action is poorly understood. Here we report that in mice insulin activates cyclin D1-cyclin-dependent kinase 4 (Cdk4), which, in turn, increases GCN5 acetyltransferase activity and suppresses hepatic glucose production independently of cell cycle progression. Through a cell-based high-throughput chemical screen, we identify a Cdk4 inhibitor that potently decreases PGC-1? acetylation. Insulin/GSK-3? (glycogen synthase kinase 3-beta) signalling induces cyclin D1 protein stability by sequestering cyclin D1 in the nucleus. In parallel, dietary amino acids increase hepatic cyclin D1 messenger RNA transcripts. Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5, which then acetylates and inhibits PGC-1? activity on gluconeogenic genes. Loss of hepatic cyclin D1 results in increased gluconeogenesis and hyperglycaemia. In diabetic models, cyclin D1-Cdk4 is chronically elevated and refractory to fasting/feeding transitions; nevertheless further activation of this kinase normalizes glycaemia. Our findings show that insulin uses components of the cell cycle machinery in post-mitotic cells to control glucose homeostasis independently of cell division. PMID:24870244

Lee, Yoonjin; Dominy, John E; Choi, Yoon Jong; Jurczak, Michael; Tolliday, Nicola; Camporez, Joao Paulo; Chim, Helen; Lim, Ji-Hong; Ruan, Hai-Bin; Yang, Xiaoyong; Vazquez, Francisca; Sicinski, Piotr; Shulman, Gerald I; Puigserver, Pere

2014-06-26

18

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

International Nuclear Information System (INIS)

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

1990-01-01

19

Remodeling of Oxidative Energy Metabolism by Galactose Improves Glucose Handling and Metabolic Switching in Human Skeletal Muscle Cells  

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Cultured human myotubes have a low mitochondrial oxidative potential. This study aims to remodel energy metabolism in myotubes by replacing glucose with galactose during growth and differentiation to ultimately examine the consequences for fatty acid and glucose metabolism. Exposure to galactose showed an increased [14C]oleic acid oxidation, whereas cellular uptake of oleic acid uptake was unchanged. On the other hand, both cellular uptake and oxidation of [14C]glucose increased in myotubes e...

2013-01-01

20

Remodelling of oxidative energy metabolism by galactose improves glucose handling and metabolic switching in human skeletal muscle cells  

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Cultured human myotubes have a low mitochondrial oxidative potential. This study aims to remodel energy metabolism in myotubes by replacing glucose with galactose during growth and differentiation to ultimately examine the consequences for fatty acid and glucose metabolism. Exposure to galactose showed an increased [14C]oleic acid oxidation, whereas cellular uptake of oleic acid uptake was unchanged. On the other hand, both cellular uptake and oxidation of [14C]glucose increased in myotubes e...

2013-01-01

 
 
 
 
21

Flow cytometric quantification of glucose-stimulated beta-cell metabolic flux can reveal impaired islet functional potency.  

Science.gov (United States)

The objective of this study was to develop a multiparametric flow cytometry assay to simultaneously quantify isolated pancreatic islet cell viability, apoptosis, and glucose-induced metabolic flux. INS-1 and rat islet beta-cells were stained with fluorescent probes for cell viability (ToPro3), apoptosis (Annexin V and VADFMK), and intracellular calcium (Ca2+(i)) (Fura Red), stimulated with glucose, and analyzed on a FACS Vantage flow cytometer. Glucose-induced metabolic activity was indicated by changes in Fura Red fluorescence and the autofluorescence of the pyridine [NAD(P)H] and flavin (FAD/FMN) nucleotides. Rat islets cultured under conditions of proinflammatory cytokine-induced oxidative stress were evaluated by flow cytometry and transplantation into diabetic mice. INS-1 and rat islet beta-cell health and metabolic activity were quantified in response to elevated glucose dose and inhibitors of glycolysis and mitochondrial function. Changes in metabolite fluorescence were converted to an area under the curve (AUC) value. Rat islets cultured under oxidative stress conditions showed decreased viability, increased apoptosis, and decreased glucose-induced metabolic activity indicated by reduced AUC for pyridine and flavin nucleotides and Ca2+(i). Reduced metabolite AUC measured by flow cytometry correlated with the inability to reverse diabetes in mice. Single cell flow cytometry can simultaneously quantify both overall islet cell health and beta-cell glucose responsiveness as indicators of functional potency. PMID:19364071

Hanson, Matthew S; Steffen, Anja; Danobeitia, Juan S; Ludwig, Barbara; Fernandez, Luis A

2008-01-01

22

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

DEFF Research Database (Denmark)

The enteroendocrine K and L cells are responsible for secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon like-peptide 1 (GLP-1), whereas pancreatic α-cells are responsible for secretion of glucagon. In rodents and humans, dysregulation of the secretion of GIP, GLP-1, and glucagon is associated with impaired regulation of metabolism. This study evaluates the consequences of acute removal of Gip- or Gcg-expressing cells on glucose metabolism. Generation of the two diphtheria toxin receptor cellular knockout mice, TgN(GIP.DTR) and TgN(GCG.DTR), allowed us to study effects of acute ablation of K and L cells and α-cells. Diphtheria toxin administration reduced the expression of Gip and content of GIP in the proximal jejunum in TgN(GIP.DTR) and expression of Gcg and content of proglucagon-derived peptides in both proximal jejunum and terminal ileum as well as content of glucagon in pancreas in TgN(GCG.DTR) compared with wild-type mice. GIP response to oral glucose was attenuated following K cell loss, but oral and intraperitoneal glucose tolerances were unaffected. Intraperitoneal glucose tolerance was impaired following combined L cell and α-cell loss and normal following α-cell loss. Oral glucose tolerance was improved following L cell and α-cell loss and supernormal following α-cell loss. We present two mouse models that allow studies of the effects of K cell or L cell and α-cell loss as well as isolated α-cell loss. Our findings show that intraperitoneal glucose tolerance is dependent on an intact L cell mass and underscore the diabetogenic effects of α-cell signaling. Furthermore, the results suggest that K cells are less involved in acute regulation of mouse glucose metabolism than L cells and α-cells.

Pedersen, J; Ugleholdt, R K

2013-01-01

23

Islet adaptive changes to fructose-induced insulin resistance: beta-cell mass, glucokinase, glucose metabolism, and insulin secretion.  

Science.gov (United States)

Beta-cell mass, hexokinase/glucokinase (HK/GK) activity, glucose metabolism and insulin secretion were studied in the islets of rats with fructose-induced insulin resistance (IR). Normal male Wistar rats were fed a standard commercial diet and water without (control, C) or with 10% fructose-rich diet (FRD) for 3 weeks. Blood glucose (strips), triglyceride (commercial kit), and insulin (RIA) levels were measured at the time of death. Glucose-induced insulin release, glucose metabolism ((14)CO(2) and (3)H(2)O production from D-[U-(14)C]- and D-[5-(3)H]-glucose) and HK/GK activity (G-6-P production), transcription (RT-PCR), protein expression (Western blot), and cellular compartmentalization were measured in isolated islets (collagenase digestion). FRD rats presented normoglycemia but impaired glucose tolerance, hypertriglyceridemia, hyperinsulinemia, and increased HOMA-IR index. In these rats, beta-cell mass decreased significantly by 33%, with a 44% increase in the percentage of apoptotic cells. Glucose-induced insulin release and islet glucose metabolism were higher in FRD rats. While GK activity (total and cytosolic fraction) and protein expression were significantly higher in FRD islets, HK showed no change in any of these parameters. Our results demonstrate that the changes induced by dietary-induced IR upon beta-cell function and mass are strongly conditional on the nutrient model used. In our model (intact animals with impaired glucose tolerance), GK activity increases through mechanisms previously shown only in vitro or under highly hyperglycemic conditions. Such an increase plays a pivotal role in the adaptive increased release of insulin in response to IR, even in the presence of marked beta-cell mass reduction. PMID:19039094

Maiztegui, B; Borelli, M I; Raschia, M A; Del Zotto, H; Gagliardino, J J

2009-02-01

24

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

25

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

2014-01-01

26

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

Tulpule, Ketki

2013-01-01

27

Targeting glucose metabolism in chondrosarcoma cells enhances the sensitivity to doxorubicin through the inhibition of lactate dehydrogenase-A.  

Science.gov (United States)

Chondrosarcoma is a malignant cartilage-forming cancer composed of cells derived from transformed cells that produce cartilage. Conventional chemotherapy and radiotherapy have very limited efficacy in patients with advanced chondrosarcoma. In the present study, we reported a novel therapeutic approach in the treatment of chondrosarcoma cells. We detected that lactate dehydrogenase-A (LDHA) is highly active in chondrosarcoma cells and chondrosarcoma patient samples compared with normal chondrocyte cell lines and primary human chondrocyte. Moreover, chondrosarcoma cells exhibited elevated levels of LDHA expression under doxorubicin treatment. To further explore the mechanisms, we generated doxorubicin-resistant cells from SW1353 chondrosarcoma cell line. Notably, the activity and expression of LDHA are upregulated in doxorubicin-resistant cells. Moreover, our data showed a strong correlation between glucose metabolism and doxorubicin resistance in chondrosarcoma cells; doxorubicin-resistant cells displayed highly activated glucose metabolism and depended more on glucose supply. Finally, we reported a synergistic effect produced by incorporating doxorubicin with glycolysis inhibitors-oxamate in the combined treatment of chondrosarcoma cells in vitro and in vivo. In summary, the present study may aid in the development of new approaches using the combination of chemotherapeutic agents for the treatment of chondrosarcoma patients. PMID:24789077

Hua, Guojun; Liu, Yunpeng; Li, Xiangyong; Xu, Peirong; Luo, Yuchun

2014-06-01

28

Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication.  

Science.gov (United States)

Virus infections trigger metabolic changes in host cells that support the bioenergetic and biosynthetic demands of viral replication. Although recent studies have characterized virus-induced changes in host cell metabolism (Munger et al., 2008; Terry et al., 2012), the molecular mechanisms by which viruses reprogram cellular metabolism have remained elusive. Here, we show that the gene product of adenovirus E4ORF1 is necessary for adenovirus-induced upregulation of host cell glucose metabolism and sufficient to promote enhanced glycolysis in cultured epithelial cells by activation of MYC. E4ORF1 localizes to the nucleus, binds to MYC, and enhances MYC binding to glycolytic target genes, resulting in elevated expression of specific glycolytic enzymes. E4ORF1 activation of MYC promotes increased nucleotide biosynthesis from glucose intermediates and enables optimal adenovirus replication in primary lung epithelial cells. Our findings show how a viral protein exploits host cell machinery to reprogram cellular metabolism and promote optimal progeny virion generation. PMID:24703700

Thai, Minh; Graham, Nicholas A; Braas, Daniel; Nehil, Michael; Komisopoulou, Evangelia; Kurdistani, Siavash K; McCormick, Frank; Graeber, Thomas G; Christofk, Heather R

2014-04-01

29

Glucose metabolism and cardiac hypertrophy  

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The most notable change in the metabolic profile of hypertrophied hearts is an increased reliance on glucose with an overall reduced oxidative metabolism, i.e. a reappearance of the foetal metabolic pattern. In animal models, this change is attributed to the down-regulation of the transcriptional cascades promoting gene expression for fatty acid oxidation and mitochondrial oxidative phosphorylation in adult hearts. Impaired myocardial energetics in cardiac hypertrophy also triggers AMP-activa...

Kolwicz, Stephen C.; Tian, Rong

2011-01-01

30

Mayaro virus infection alters glucose metabolism in cultured cells through activation of the enzyme 6-phosphofructo 1-kinase.  

Science.gov (United States)

Although it is well established that cellular transformation with tumor virus leads to changes on glucose metabolism, the effects of cell infection by non-transforming virus are far to be completely elucidated. In this study, we report the first evidence that cultured Vero cells infected with the alphavirus Mayaro show several alterations on glucose metabolism. Infected cells presented a two fold increase on glucose consumption, accompanied by an increment in lactate production. This increase in glycolytic flux was also demonstrated by a significant increase on the activity of 6-phosphofructo 1-kinase, one of the regulatory enzymes of glycolysis. Analysis of the kinetic parameters revealed that the regulation of 6-phosphofructo 1-kinase is altered in infected cells, presenting an increase in Vmax along with a decrease in Km for fructose-6-phosphate. Another fact contributing to an increase in enzyme activity was the decrease in ATP levels observed in infected cells. Additionally, the levels of fructose 2,6-bisphosphate, a potent activator of this enzyme, was significantly reduced in infected cells. These observations suggest that the increase in PFK activity may be a compensatory cellular response to the viral-induced metabolic alterations that could lead to an impairment of the glycolytic flux and energy production. PMID:15646042

El-Bacha, Tatiana; Menezes, Maíra M T; Azevedo e Silva, Melissa C; Sola-Penna, Mauro; Da Poian, Andrea T

2004-11-01

31

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.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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...

1996-01-01

32

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

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

Bure?n, Jonas

2003-01-01

33

Glucose—a sweet way to die: Metabolic switching modulates tumor cell death  

Digital Repository Infrastructure Vision for European Research (DRIVER)

TRAIL, a putative anticancer cytokine, induces extrinsic cell death by activating the caspase cascade directly (Type I cells) via the death-inducing signaling complex (DISC) or indirectly (Type II cells) by caspase-8 cleavage of Bid and activation of the mitochondrial cell death pathway. Cancer cells are characterized by their dependence on aerobic glycolysis, which, although inefficient in terms of ATP production, facilitates tumor metabolism. Our studies show that TRAIL-induced cell death i...

Macfarlane, Marion; Robinson, Gemma L.; Cain, Kelvin

2012-01-01

34

Pyruvate kinase M2 regulates glucose metabolism by functioning as a coactivator for hypoxia-inducible factor 1 in cancer cells  

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Cancer cells feature altered glucose metabolism that allows their rapid growth. They consume large amounts of glucose to produce lactate, even in the presence of ample oxygen, which is known as the Warburg effect. Pyruvate kinase M2 (PKM2) contributes to the Warburg effect by previously unknown mechanisms. Hypoxia-inducible factor 1 (HIF-1) mediates PKM2 gene transcription and metabolic reprogramming in cancer cells. The recent discovery of novel physical and functional interactions between P...

Luo, Weibo; Semenza, Gregg L.

2011-01-01

35

Dysregulation of Dicer1 in Beta Cells Impairs Islet Architecture and Glucose Metabolism  

Digital Repository Infrastructure Vision for European Research (DRIVER)

microRNAs (miRNAs) play important roles in pancreas development and in regulation of insulin expression in the adult. Here we show that loss of miRNAs activity in beta-cells during embryonic development results in lower beta-cell mass and in impaired glucose tolerance. Dicer1-null cells initially constitute a significant portion of the total beta-cell population. However, during postnatal development, Dicer1-null cells are depleted. Furthermore, wild-type beta cells are repopulating the islet...

Mandelbaum, Amitai D.; Melkman-zehavi, Tal; Oren, Roni; Kredo-russo, Sharon; Nir, Tomer; Dor, Yuval; Hornstein, Eran

2012-01-01

36

PGC-1? integrates glucose metabolism and angiogenesis in multiple myeloma cells by regulating VEGF and GLUT-4.  

Science.gov (United States)

Human peroxisome proliferator-activated receptor-? coactivator 1? (PGC-1?) is a key coactivator in the regulation of gene transcriptional activity in normal tissues. However, it is not clear whether it is involved in the angiogenesis and metabolism of multiple myeloma (MM). The aim of the present study was to investigate the role of PGC-1? in MM. Small interfering RNA (siRNA) was used to inhibit PGC-1? expression in RPMI-8226 cells. An endothelial cell migration assay was performed using transwell chambers and the expression of PGC-1?, estrogen-related receptor-? (ERR-?), vascular endothelial growth factor (VEGF) and glucose transporter-4 (GLUT-4) was tested by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of PGC-1?, ERR-? and GLUT-4 was assayed by western blot analysis. Lastly, RPMI-8226 cell proliferation was evaluated using CCK-8 assay. VEGF and GLUT-4 mRNA levels were decreased in cells treated with siRNA targeting PGC-1?, as was the level of GLUT-4 protein. Endothelial cell migration was significantly reduced when these cells were cultured with culture medium from RPMI-8226 cells treated with siPGC-1?. The proliferation rates at 24 and 48 h were suppressed by PGC-1? inhibition. Our results showed that inhibition of PGC-1? suppresses cell proliferation probably by downregulation of VEGF and GLUT-4. The present study suggests that PGC-1? integrates angiogenesis and glucose metabolism in myeloma through regulation of VEGF and GLUT-4. PMID:24402435

Cao, Dedong; Zhou, Hao; Zhao, Jikai; Jin, Lu; Yu, Wen; Yan, Han; Hu, Yu; Guo, Tao

2014-03-01

37

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 evidence that sepsis disturbed RBC membrane function or metabolism

1990-01-01

38

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

Energy Technology Data Exchange (ETDEWEB)

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

Hotchkiss, R.S.; Song, S.K.; Ling, C.S.; Ackerman, J.J.; Karl, I.E. (Washington Univ. School of Medicine, St. Louis (USA))

1990-01-01

39

Microbial Regulation of Glucose Metabolism and Cell-Cycle Progression in Mammalian Colonocytes  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A prodigious number of microbes inhabit the human body, especially in the lumen of the gastrointestinal (GI) tract, yet our knowledge of how they regulate metabolic pathways within our cells is rather limited. To investigate the role of microbiota in host energy metabolism, we analyzed ATP levels and AMPK phosphorylation in tissues isolated from germfree and conventionally-raised C57BL/6 mice. These experiments demonstrated that microbiota are required for energy homeostasis in the proximal c...

Donohoe, Dallas R.; Wali, Aminah; Brylawski, Bruna P.; Bultman, Scott J.

2012-01-01

40

Arginine supplementation and exposure time affects polyamine and glucose metabolism in primary liver cells isolated from Atlantic salmon.  

Science.gov (United States)

Arginine has been demonstrated to enhance glucose and lipid oxidation in mammals through activation of polyamine turnover. We aimed to investigate how arginine affects energy utilization through polyamine metabolism and whether this effect is time dependent. Primary liver cells were isolated from Atlantic salmon (2.2 kg body weight) fed diets containing 25.5 (low arginine, LA) or 36.1 (high arginine, HA) g arginine/kg dry matter for 12 weeks, to investigate the effect of long-term arginine supplementation. The cells were cultured for 24 h in L-15 medium to which either alpha-difluoromethylornithine (DFMO) or N (1),N (11)-diethylnorspermine (DENSPM) was added. Analysis of the medium by nuclear magnetic resonance revealed significant differences between the two dietary groups as well as between cells exposed to DFMO and DENSPM, with decreased glucose, fumarate and lactate concentrations in media of the HA cells. Liver cells from fish fed the HA diet had higher spermidine/spermine-N1-acetyltransferase protein abundance and lower adenosine triphosphate concentration as compared to the LA-fed fish, while gene expression was not affected by either diet or treatment. Primary liver cells isolated from salmon fed a commercial diet and cultured in L-15 media with or without arginine supplementation (1.82 or 3.63 mM) for 48 h, representing short-term effect of arginine supplementation, showed differential expression of genes for apoptosis and polyamine synthesis due to arginine supplementation or inhibition by DFMO. Overall, arginine concentration and exposure time affected energy metabolism and gene regulation more than inhibition or activation of key enzymes of polyamine metabolism, suggesting a polyamine-independent influence of arginine on cellular energy metabolism and survival. PMID:24500114

Andersen, Synne Marte; Taylor, Richard; Holen, Elisabeth; Aksnes, Anders; Espe, Marit

2014-05-01

 
 
 
 
41

Dysregulation of Dicer1 in Beta Cells Impairs Islet Architecture and Glucose Metabolism  

Science.gov (United States)

microRNAs (miRNAs) play important roles in pancreas development and in regulation of insulin expression in the adult. Here we show that loss of miRNAs activity in beta-cells during embryonic development results in lower beta-cell mass and in impaired glucose tolerance. Dicer1-null cells initially constitute a significant portion of the total beta-cell population. However, during postnatal development, Dicer1-null cells are depleted. Furthermore, wild-type beta cells are repopulating the islets in complex compensatory dynamics. Because loss of Dicer1 is also associated with changes in the distribution of membranous E-cadherin, we hypothesized that E-cadherin activity may play a role in beta cell survival or islet architecture. However, genetic loss of E-cadherin function does not impair islet architecture, suggesting that miRNAs likely function through other or redundant effectors in the endocrine pancreas.

Mandelbaum, Amitai D.; Melkman-Zehavi, Tal; Oren, Roni; Kredo-Russo, Sharon; Nir, Tomer; Dor, Yuval; Hornstein, Eran

2012-01-01

42

Dysregulation of Dicer1 in beta cells impairs islet architecture and glucose metabolism.  

Science.gov (United States)

microRNAs (miRNAs) play important roles in pancreas development and in regulation of insulin expression in the adult. Here we show that loss of miRNAs activity in beta-cells during embryonic development results in lower beta-cell mass and in impaired glucose tolerance. Dicer1-null cells initially constitute a significant portion of the total beta-cell population. However, during postnatal development, Dicer1-null cells are depleted. Furthermore, wild-type beta cells are repopulating the islets in complex compensatory dynamics. Because loss of Dicer1 is also associated with changes in the distribution of membranous E-cadherin, we hypothesized that E-cadherin activity may play a role in beta cell survival or islet architecture. However, genetic loss of E-cadherin function does not impair islet architecture, suggesting that miRNAs likely function through other or redundant effectors in the endocrine pancreas. PMID:22991506

Mandelbaum, Amitai D; Melkman-Zehavi, Tal; Oren, Roni; Kredo-Russo, Sharon; Nir, Tomer; Dor, Yuval; Hornstein, Eran

2012-01-01

43

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)

1980-01-01

44

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

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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

45

Glucose Dependency of the Metabolic Pathway of HEK 293 Cells Measured by a Flow-through Type pH/CO2 Sensor System Using ISFETs  

Science.gov (United States)

Our group previously reported the application of a flow-through type pH/CO2 sensor system designed to evaluate the metabolic activity of cultured cells. The sensor system consists of two ion-sensitive field effect transistors (ISFETs), an ISFET to measure the total pH change and an ISFET enclosed within a gas-permeable silicone tube to measure the pH change attributable to CO2. In that study, we used the system to quantitatively analyze metabolic switching induced by glucose concentration changes in three cultured cell types (bovine arterial endothelium cell (BAEC), human umbilical vein endothelium cell (HUVEC), and rat cardiomuscle cell (RCMC)), and to measure the production rates of total carbonate and free lactic acid in the cultured cells. In every cell type examined, a decrease in the glucose concentration led to an increase in total carbonate, a product of cellular respiration, and a decrease of free lactic acid, a product of glycolysis. There were very significant differences among the cell types, however, in the glucose concentrations at the metabolic switching points. We postulated that the cell has a unique switching point on the metabolic pathway from glycolysis to respiration. In this paper we use our sensor system to evaluate the metabolic switching of human embryonic kidney 293 cells triggered by glucose concentration changes. The superior metabolic pathway switched from glycolysis to respiration when the glucose concentration decreased to about 2 mM. This result was very similar to that obtained in our earlier experiments on HUVECs, but far different from our results on the other two cells types, BAECs and RCMCs. This sensor system will be useful for analyzing cellular metabolism for many applications and will yield novel information on different cell types.

Yamada, Akira; Mohri, Satoshi; Nakamura, Michihiro; Naruse, Keiji

46

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

47

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

Science.gov (United States)

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

Jiang, Hua; Yan, Wen-Hua; Li, Chan-Juan; Wang, An-Ping; Dou, Jing-Tao; Mu, Yi-Ming

2014-01-01

48

Elevated white blood cell count is associated with higher risk of glucose metabolism disorders in middle-aged and elderly Chinese people.  

Science.gov (United States)

White blood cell (WBC) count has been associated with diabetic risk, but whether the correlation is independent of other risk factors has hardly been studied. Moreover, very few such studies with large sample sizes have been conducted in Chinese. Therefore, we investigated the relationship between WBC count and glucose metabolism in china. We also examined the relevant variables of WBC count. A total of 9,697 subjects (mean age, 58.0 ± 9.1 years) were recruited. The subjects were classified into four groups, including subjects with normal glucose tolerance, isolated impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus (T2DM). We found that WBC count increased as glucose metabolism disorders exacerbated. WBC count was also positively correlated with waist hip ratio, body mass index, smoking, triglycerides, glycosylated haemoglobin A1c (HbA1c) and 2-h postprandial glucose. In addition, high density lipoprotein and the female gender were inversely correlated with WBC levels. In patients with previously diagnosed T2DM, the course of T2DM was not correlated with WBC count. Our findings indicate that elevated WBC count is independently associated with worsening of glucose metabolism in middle-aged and elderly Chinese. In addition, loss of weight, smoking cessation, lipid-modifying therapies, and control of postprandial plasma glucose and HbA1c may ameliorate the chronic low-grade inflammation. PMID:24852600

Jiang, Hua; Yan, Wen-Hua; Li, Chan-Juan; Wang, An-Ping; Dou, Jing-Tao; Mu, Yi-Ming

2014-05-01

49

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

Directory of Open Access Journals (Sweden)

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

Hua Jiang

2014-05-01

50

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

51

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

International Nuclear Information System (INIS)

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

1989-06-27

52

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  

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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

53

Novel molecular mechanisms of antitumor action of dichloroacetate against T cell lymphoma: Implication of altered glucose metabolism, pH homeostasis and cell survival regulation.  

Science.gov (United States)

Pyruvate dehydrogenase kinase (PDK) inhibits pyruvate dehydrogenase (PDH) activity and thus promotes energetic switch from mitochondrial glucose oxidation to cytoplasmic glycolysis in cancerous cells (a phenomenon known as the 'Warburg effect') for their energy need, which facilitates the cancer progression by resisting induction of apoptosis and promoting tumor metastasis. Thus, in the present investigation, we explored the molecular mechanisms of the tumoricidal action of dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, on cells of a murine T cell lymphoma, designated as Dalton's lymphoma (DL). In vitro treatment of tumor cells with DCA inhibited their survival accompanied by a modulation of the biophysical composition of tumor-conditioned medium with respect to pH, glucose and lactate. DCA treatment also altered expression of HIF1-? and pH regulators: VATPase and MCT1 and production of cytokines: IL-10, IL-6 and IFN-?. Moreover, we also observed an alteration in the expression of other apoptosis and cell survival regulatory molecules: PUMA, GLUT1, Bcl2, p53, CAD, caspase-3 and HSP70. The study discusses the role of novel molecular mechanisms underlying DCA-dependent inhibition of tumor cell survival. This study shows for the first time that DCA-dependent alteration of tumor cell survival involves altered pH homeostasis and glucose metabolism. Thus, these findings will provide a new insight for therapeutic applications of DCA as a novel antineoplastic agent against T cell lymphoma. PMID:22705712

Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra

2012-07-30

54

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

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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

55

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

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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

56

Glucose metabolism in diabetic blood vessels  

International Nuclear Information System (INIS)

Since glycolysis appears to be coupled to active ion transport in vascular smooth muscle, alterations in glucose metabolism may contribute to cellular dysfunction and angiopathy in diabetes. Uptake and utilization of glucose were studied in perfused blood vessels in which pulsatile flow and perfusion pressure were similar to those measured directly in vivo. Thoracic aortae isolated from 8-wk alloxan diabetic (D) and nondiabetic control rabbits were cannulated, tethered, and perfused with oxygenated buffer containing 7 or 25 mM glucose and tracer amounts of glucose-U"-"1"4 C. Norepinephrine (NE) (10"-"6 M) and/or insulin (I) (150 ?U/ml) and albumin (0.2%) were added. NE-induced tension development increased glucose uptake 39% and "1"4CO_2 and lactate production 2.3-fold. With 7 mM glucose, marked decreases in glucose uptake (74%), "1"4CO_2 (68%), lactate (30%), total tissue glycogen (75%), and tissue phospholipids (70%) were observed in D. Addition of I or elevation of exogenous glucose to 25 mM normalized glucose uptake, but had differential effects on the pattern of substrate utilization. Thus, in D, there was a marked depression of vascular glucose metabolism that was partially reversed by addition of low concentrations of insulin or D levels of glucose

1986-03-05

57

Effects of alpha-ketoglutarate on cell growth, glucose, glutamine, lactate and ammonia metabolism in C2C12 cells  

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Background: Nutritional supplement with alpha-ketoglutarate (alpha-KG) can lead to improved exercise tolerance. However, mechanisms underlying the phenomenon have not yet been addressed. The purpose of the study was to investigate the effects of alpha-KG on cell growth in C2C12 cell culture and on the energy metabolism and to explore the potential dose-response of these effects to alpha-KG. Methods: C2C12 cells were cultured in DMEM pretreated with adding alpha-KG. The cells and media were ha...

Yang, Bingquan

2012-01-01

58

Glucose deprivation-induced metabolic oxidative stress and cancer therapy  

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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

59

Glucose metabolism in cultured trophoblasts from human placenta  

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The development of appropriate placental trophoblast isolation and culture techniques enables the study of pathways of glucose utilization by this important cell layer in vitro. Trophoblasts from normal term placentas were isolated and cultured 24 hours and 72 hours in uncoated polystyrene culture tubes or tubes previously coated with a fibrin matrix. Trophoblasts cultured on fibrin are morphologically distinct from those cultured on plastic or other matrices and generally resemble in vivo syncytium. Cells were incubated up to 3 hours with {sup 14}C-labeled glucose and reactions were stopped by addition of perchloric acid. {sup 14}CO{sub 2} production by trophoblasts increased linearly with time however the largest accumulation of label was in organic acids. Trophoblasts cultured in absence of fibrin utilized more glucose and accumulated more {sup 14}C in metabolic products compared to cells cultured on fibrin. Glucose oxidation to CO{sub 2} by the phosphogluconate (PG) pathway was estimated from specific yields of {sup 14}CO{sub 2} from (1-{sup 14}C)-D-glucose and (6-{sup 14}C)-D-glucose. Approximately 6% of glucose oxidation was by the PG pathway when cells were cultured on fibrin compared to approximately 1% by cells cultured in the absence of fibrin. The presence of a fibrin growth matrix appears to modulate the metabolism of glucose by trophoblast from human placenta in vitro.

Moe, A.J.; Farmer, D.R.; Nelson, D.M.; Smith, C.H. (Washington Univ., St. Louis, MO (United States))

1990-02-26

60

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)

1971-02-01

 
 
 
 
61

The Comparison of the 1-C(14)-Glucose and 6-C(14)-Glucose Metabolism of Reticulocyterich and Reticulocyte-Poor Human Red Blood Cells.  

Science.gov (United States)

The production of C(14)O2 from 1-C(14) and 6-C(14)glucose by intact reticulocyterich and reticulocyte-poor human red blood cells was measured. The data are consistent with the hypothesis that reticulocytes contain an operative pentose phosphate pathway bu...

Y. F. Herman C. J. Canfield M. E. Conrad R. H. Herman

1964-01-01

62

Regulation of glucose metabolism and the skeleton.  

Science.gov (United States)

Complex interactions occur among adipose tissue, the central nervous system, bone and pancreas to integrate bone remodelling, glucose, lipid and energy metabolism. Data obtained largely from the judicious use of gain-of-function and loss-of-function genetic mouse models show that leptin, an adipocyte-secreted product, indirectly inhibits bone accrual through a central pathway comprising the hypothalamus and central nervous system. Increased sympathetic output acting via ?2-adrenergic receptors present in osteoblasts decreases bone formation and causes increased bone resorption. Insulin is a key molecular link between bone remodelling and energy metabolism. Insulin signalling in the osteoblasts increases bone formation and resorption as well as the release of undercarboxylated osteocalcin. An increase in the release of bone-derived undercarboxylated osteocalcin into the systemic circulation enables it to act as a circulating hormone to stimulate insulin production and secretion by pancreatic ?-cells and adiponectin by adipocytes. Insulin sensitivity increases, lipolysis and fat accumulation decreases while energy expenditure increases. Whether this model of integrative physiology involving the skeleton, pancreas and adipose tissue, so elegantly demonstrated in rodents, is applicable to humans is controversial. The mouse Esp gene, encoding an intracellular tyrosine phosphatase that negatively regulates insulin signalling in osteoblasts, is a pseudogene in humans, and a homolog for the Esp gene has so far not been identified in humans. A close homologue of Esp, PTP1B, is expressed in human osteoblasts and could take the role of Esp in humans. Data available from the limited number of clinical studies do not provide a sufficient body of evidence to determine whether osteocalcin or undercarboxylated osteocalcin affects glucose metabolism in humans. PMID:21623861

Ng, Kong Wah

2011-08-01

63

Tumor cell metabolism  

Science.gov (United States)

Cancer is a genetic disease that is caused by mutations in oncogenes, tumor suppressor genes and stability genes. The fact that the metabolism of tumor cells is altered has been known for many years. However, the mechanisms and consequences of metabolic reprogramming have just begun to be understood. In this review, an integral view of tumor cell metabolism is presented, showing how metabolic pathways are reprogrammed to satisfy tumor cell proliferation and survival requirements. In tumor cells, glycolysis is strongly enhanced to fulfill the high ATP demands of these cells; glucose carbons are the main building blocks in fatty acid and nucleotide biosynthesis. Glutaminolysis is also increased to satisfy NADPH regeneration, whereas glutamine carbons replenish the Krebs cycle, which produces metabolites that are constantly used for macromolecular biosynthesis. A characteristic feature of the tumor microenvironment is acidosis, which results from the local increase in lactic acid production by tumor cells. This phenomenon is attributed to the carbons from glutamine and glucose, which are also used for lactic acid production. Lactic acidosis also directs the metabolic reprogramming of tumor cells and serves as an additional selective pressure. Finally, we also discuss the role of mitochondria in supporting tumor cell metabolism.

Romero-Garcia, Susana; Lopez-Gonzalez, Jose Sullivan; B?ez-Viveros, Jose Luis; Aguilar-Cazares, Dolores

2011-01-01

64

Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells  

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Selective amino acid restriction targets mitochondria to induce apoptosis of DU145 and PC3 prostate cancer cells. Biochemical assays and flow cytometry were uitilized to analyze the glucose consumption, lactate production, pyruvate dehydrogenase (PDH), nicotinamide adenine dinucleotide (NAD)/NADH and nicotinamide adenine dinucleotide phosphate (NADP)/NADPH ratios, mitochondrial glutathione peroxidase (GPx), manganese superoxide dismutase (SOD), glutathione, reactive oxygen species (ROS) and DNA damage in DU145 and PC prostate cancer cells cultured under various amino acid deprived conditions. Restriction of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln) or methionine (Met) differentially modulated glucose metabolism and PDH and antioxidant enzyme activity in the mitochondria of the two prostate cancer cell lines. In DU145 cells, Gln and Met restriction increased glucose consumption and decreased lactate production, but Tyr/Phe restriction did not. The examined restrictions increased mitochondrial PDH activity and accumulation of ROS. Gln and Met restriction increased GPx activity. Tyr/Phe and Met restriction increased SOD during the first 2 days of the restriction, and the activity returned to the basal level on day 4. All amino acid restrictions decreased reduced glutathione (GSH) and induced mitochondrial DNA damage. In PC3 cells, all amino acid restrictions reduced glucose consumption and lactate production. Gln restriction increased ROS and elevated GPx activity. Tyr/Phe restriction increased SOD activity. The amino acid restriction decreased GSH, but did not cause mitochondrial DNA damage. Specific amino acid dependency differentially regulates glucose metabolism, oxidation-reduction reactions of mitochondria and mitochondrial damage in DU145 and PC3 prostate cancer cell lines.

LIU, XIAOYI; FU, YA-MIN; MEADOWS, GARY G.

2011-01-01

65

Inhibitors of cannabinoid receptors and glucose metabolism.  

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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

66

Glucose metabolism in a rat mammary adenocarcinoma  

International Nuclear Information System (INIS)

Full text: Tumor hypoxia, which decreases therapy response is common in tumors. Glucose metabolism is closely tied to tumor oxygenation and alteration of its metabolism could improve tumor oxygenation. The objective of the study was to compare tissue pharmacokinetics of 14C-2-deoxyglucose (14C2DG) and 14C-glucose in an adenocarcinoma (R3230Ac) and normal control tissue (subcutis:SQ) using a novel fiberoptic scintillation detector. Fischer 344 rats with R3230Ac tumors were anesthetized with Isoflurane and detectors were inserted. Baseline data was acquired for 45 minutes, then 14C2DG or 14C-glucose (i.v.) was injected and data was acquired for 3 hours. After 100mCi of 14C2DG both tissues reached peaks (R3230Ac, 0.4mCi/g; SQ, 0.75mCi/g) 20 minutes post-injection that remained stable for 3 hours. With 200mCi 14C2DG R3230Ac peaked and plateaued at 1.75mCi/g by 50 minutes. SQ peaked (2.25mCi/g) at 20 minutes and decreased to a stable plateau (0.75mCi/g) at 50 minutes. Kinetics of 14C-glucose were different from 14C2DG. R3230Ac and SQ increased over 20 minutes, reaching peaks of 2.4mCi/g and 1.5mCi/g, respectively. A slow decrease followed, but tumor signal (1.25mCi/g) remained higher than SQ (0.5mCi/g). Kinetics of 14C2DG and 14C-glucose were distinctly different. In SQ a wash-in/wash-out effect was observed at 200mCi of 14C2DG. In tumor 14C2DG accumulated to a plateau (1.75mCi/g) that persisted out to 3 hours. 14C-glucose signal declined below 14C2DG signal in both tissues, suggesting they both metabolize 14C-glucose and excrete 14C-containing metabolites. PET can assess flouride-deoxyglucose uptake in tumors, which is analogous to our 14C2DG studies. However, PET cannot provide data on glucose metabolism and excretion because there is not a metabolizable fluorinated-glucose analogue that is imageable by PET. In summary, this novel detector has the unique capability to evaluate real-time accumulation, metabolism, and excretion of radiolabeled glucose in tissues before and after metabolic manipulation

2003-08-17

67

Glucose metabolism and NADH recycling by Treponema hyodysenteriae, the agent of swine dysentery.  

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Glucose metabolism and the mechanisms of NADH oxidation by Treponema hyodysenteriae were studied. Under an N2 atmosphere, washed cell suspensions of the spirochete consumed glucose and produced acetate, butyrate, H2, and CO2. Approximately twice as much H2 as CO2 was produced. Determinations of radioactivity in products of [14C]glucose and [14C]pyruvate metabolism and analyses of enzyme activities in cell lysates revealed that glucose was catabolized to pyruvate via the Embden-Meyerhof-Parnas...

Stanton, T. B.

1989-01-01

68

Hypothalamic control of energy and glucose metabolism.  

Science.gov (United States)

The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM. PMID:21695389

Sisley, Stephanie; Sandoval, Darleen

2011-09-01

69

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

1991-01-01

70

Specific role of impaired glucose metabolism and diabetes mellitus in endothelial progenitor cell characteristics and function.  

Science.gov (United States)

The disease burden of diabetes mellitus (DM) and its associated cardiovascular complications represent a growing and major global health problem. Recent studies suggest that circulating exogenous endothelial progenitor cells (EPCs) play an important role in endothelial repair and neovascularization at sites of injury or ischemia. Both experimental and clinical studies have demonstrated that hyperglycemia related to DM can induce alterations to EPCs. The reduction and dysfunction of EPCs related to DM correlate with the occurrence and severity of microvascular and macrovascular complications, suggesting a close mechanistic link between EPC dysfunction and impaired vascular function/repair in DM. These alterations to EPCs, likely mediated by multiple pathophysiological mechanisms, including inflammation, oxidative stress, and alterations in Akt and the nitric oxide pathway, affect EPCs at multiple stages: differentiation and mobilization in the bone marrow, trafficking and survival in the circulation, and homing and neovascularization. Several different therapeutic approaches have consequently been proposed to reverse the reduction and dysfunction of EPCs in DM and may represent a novel therapeutic approach to prevent and treat DM-related cardiovascular complications. PMID:24743430

Yiu, Kai-Hang; Tse, Hung-Fat

2014-06-01

71

p-Coumaric acid modulates glucose and lipid metabolism via AMP-activated protein kinase in L6 skeletal muscle cells.  

Science.gov (United States)

p-Coumaric acid (3-[4-hydroxyphenyl]-2-propenoic acid) is a ubiquitous plant metabolite with antioxidant, anti-inflammatory, and anticancer properties. In this study, we examined whether p-coumaric acid modulates glucose and lipid metabolism via AMP-activated protein kinase (AMPK) in L6 skeletal muscle cells. p-Coumaric acid increased the phosphorylation of AMPK in a dose-dependent manner in differentiated L6 skeletal muscle cells. It also increased the phosphorylation of acetyl-CoA carboxylase (ACC) and the expression of CPT-1 mRNA and PPAR?, suggesting that it promotes the ?-oxidation of fatty acids. Also, it suppressed oleic acid-induced triglyceride accumulation, and enhanced 2-NBDG uptake in differentiated L6 muscle cells. Pretreatment with compound C inhibited AMPK activation, reduced ACC phosphorylation and 2-NBDG uptake, and increased triglyceride accumulation. However, p-coumaric acid counterbalanced the inhibitory effects of compound C. Taken together, these results suggest that p-coumaric acid modulates glucose and lipid metabolism via AMPK activation in L6 skeletal muscle cells and that it has potentially beneficial effects in improving or treating metabolic disorders. PMID:23485470

Yoon, Seon-A; Kang, Seong-Il; Shin, Hye-Sun; Kang, Seung-Woo; Kim, Jeong-Hwan; Ko, Hee-Chul; Kim, Se-Jae

2013-03-22

72

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

International Nuclear Information System (INIS)

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

1992-10-01

73

Overlapping and distinct roles of Aspergillus fumigatus UDP-glucose 4-epimerases in galactose metabolism and the synthesis of galactose-containing cell wall polysaccharides.  

Science.gov (United States)

The cell wall of Aspergillus fumigatus contains two galactose-containing polysaccharides, galactomannan and galactosaminogalactan, whose biosynthetic pathways are not well understood. The A. fumigatus genome contains three genes encoding putative UDP-glucose 4-epimerases, uge3, uge4, and uge5. We undertook this study to elucidate the function of these epimerases. We found that uge4 is minimally expressed and is not required for the synthesis of galactose-containing exopolysaccharides or galactose metabolism. Uge5 is the dominant UDP-glucose 4-epimerase in A. fumigatus and is essential for normal growth in galactose-based medium. Uge5 is required for synthesis of the galactofuranose (Galf) component of galactomannan and contributes galactose to the synthesis of galactosaminogalactan. Uge3 can mediate production of both UDP-galactose and UDP-N-acetylgalactosamine (GalNAc) and is required for the production of galactosaminogalactan but not galactomannan. In the absence of Uge5, Uge3 activity is sufficient for growth on galactose and the synthesis of galactosaminogalactan containing lower levels of galactose but not the synthesis of Galf. A double deletion of uge5 and uge3 blocked growth on galactose and synthesis of both Galf and galactosaminogalactan. This study is the first survey of glucose epimerases in A. fumigatus and contributes to our understanding of the role of these enzymes in metabolism and cell wall synthesis. PMID:24257745

Lee, Mark J; Gravelat, Fabrice N; Cerone, Robert P; Baptista, Stefanie D; Campoli, Paolo V; Choe, Se-In; Kravtsov, Ilia; Vinogradov, Evgeny; Creuzenet, Carole; Liu, Hong; Berghuis, Albert M; Latgé, Jean-Paul; Filler, Scott G; Fontaine, Thierry; Sheppard, Donald C

2014-01-17

74

Comparison of spheroids formed by rat glioma stem cells and neural stem cells reveals differences in glucose metabolism and promising therapeutic applications.  

Science.gov (United States)

Cancer stem cells (CSCs) are thought to be partially responsible for cancer resistance to current therapies and tumor recurrence. Dichloroacetate (DCA), a compound capable of shifting metabolism from glycolysis to glucose oxidation, via an inhibition of pyruvate dehydrogenase kinase was used. We show that DCA is able to shift the pyruvate metabolism in rat glioma CSCs but has no effect in rat neural stem cells. DCA forces CSCs into oxidative phosphorylation but does not trigger the production of reactive oxygen species and consecutive anti-cancer apoptosis. However, DCA, associated with etoposide or irradiation, induced a Bax-dependent apoptosis in CSCs in vitro and decreased their proliferation in vivo. The former phenomenon is related to DCA-induced Foxo3 and p53 expression, resulting in the overexpression of BH3-only proteins (Bad, Noxa, and Puma), which in turn facilitates Bax-dependent apoptosis. Our results demonstrate that a small drug available for clinical studies potentiates the induction of apoptosis in glioma CSCs. PMID:22782899

Morfouace, Marie; Lalier, Lisenn; Bahut, Muriel; Bonnamain, Virginie; Naveilhan, Philippe; Guette, Catherine; Oliver, Lisa; Gueguen, Naig; Reynier, Pascal; Vallette, Francois M

2012-09-28

75

Abnormal Glucose Metabolism in Heterozygous Mutant Mice for a Type I Receptor Required for BMP Signaling  

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BMPRIA and its high-affinity ligand BMP4 have recently been shown to be expressed in the ?-cells of the pancreas. Here, we report the abnormalities of heterozygous mice for Bmpr1a in glucose metabolism during the course of intraperitoneal glucose tolerance test. The heterozygous mice had increased blood glucose levels throughout the first 2.5 h after the administration of glucose. Analysis of glucose-stimulated insulin secretion (GSIS) indicates that insulin secretion in the heterozygous mic...

Scott, Gregory J.; Ray, Manas K.; Ward, Toni; Mccann, Kelly; Peddada, Shyamal; Jiang, Fang-xu; Mishina, Yuji

2009-01-01

76

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-β) 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-β, 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

77

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

78

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

Science.gov (United States)

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. PMID:24051182

Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra

2013-11-15

79

The Acute Effects of Low-Dose TNF- α on Glucose Metabolism and β -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- α . TNF- α has been shown to impair peripheral insulin signaling in vitro and in vivo. However, it is unclear whether TNF- α may also affect endogenous glucose production (EGP) during fasting and glucose-stimulated insulin secretion (GSIS) in vivo. We hypothesized that low-dose TNF- α would increase EGP and attenuate GSIS. Recombinant human TNF- α 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- α 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- α did not affect EGP during the basal period. Our results indicate that TNF- αacutely 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- α increasing clearance of insulin from plasma without impairing beta-cell function or hepatic insulin sensitivity

Ibfeldt, T; Fischer, Christian Philip

2014-01-01

80

Metabolic reprogramming of macrophages: glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype.  

Science.gov (United States)

Glucose is a critical component in the proinflammatory response of macrophages (M?s). However, the contribution of glucose transporters (GLUTs) and the mechanisms regulating subsequent glucose metabolism in the inflammatory response are not well understood. Because M?s contribute to obesity-induced inflammation, it is important to understand how substrate metabolism may alter inflammatory function. We report that GLUT1 (SLC2A1) is the primary rate-limiting glucose transporter on proinflammatory-polarized M?s. Furthermore, in high fat diet-fed rodents, M?s in crown-like structures and inflammatory loci in adipose and liver, respectively, stain positively for GLUT1. We hypothesized that metabolic reprogramming via increased glucose availability could modulate the M? inflammatory response. To increase glucose uptake, we stably overexpressed the GLUT1 transporter in RAW264.7 M?s (GLUT1-OE M?s). Cellular bioenergetics analysis, metabolomics, and radiotracer studies demonstrated that GLUT1 overexpression resulted in elevated glucose uptake and metabolism, increased pentose phosphate pathway intermediates, with a complimentary reduction in cellular oxygen consumption rates. Gene expression and proteome profiling analysis revealed that GLUT1-OE M?s demonstrated a hyperinflammatory state characterized by elevated secretion of inflammatory mediators and that this effect could be blunted by pharmacologic inhibition of glycolysis. Finally, reactive oxygen species production and evidence of oxidative stress were significantly enhanced in GLUT1-OE M?s; antioxidant treatment blunted the expression of inflammatory mediators such as PAI-1 (plasminogen activator inhibitor 1), suggesting that glucose-mediated oxidative stress was driving the proinflammatory response. Our results indicate that increased utilization of glucose induced a ROS-driven proinflammatory phenotype in M?s, which may play an integral role in the promotion of obesity-associated insulin resistance. PMID:24492615

Freemerman, Alex J; Johnson, Amy R; Sacks, Gina N; Milner, J Justin; Kirk, Erin L; Troester, Melissa A; Macintyre, Andrew N; Goraksha-Hicks, Pankuri; Rathmell, Jeffery C; Makowski, Liza

2014-03-14

 
 
 
 
81

The role of obestatin in glucose and lipid metabolism.  

Science.gov (United States)

Obestatin is a 23 amino acid peptide encoded by the ghrelin gene, which, like ghrelin, is mainly produced by the stomach, as well as by a wide range of other tissues. Obestatin remains a controversial peptide, as the initial finding of its binding to the orphan receptor GPR39 and the inhibitory effect on food intake has been questioned. In fact, to date, its biological effects are still largely unknown, although it is becoming clear that obestatin is a pleiotropic hormone, exerting a variety of effects in different cell types and tissues. Indeed, besides regulating cell proliferation and survival, obestatin has been shown to regulate glucose and lipid metabolism, both in vitro, in pancreatic ?-cells and adipocytes, and in vivo in rodents. Furthermore, its positive effects on glucose homeostasis, combined with the anti-inflammatory actions, make this peptide appealing as a candidate for treating metabolic disorders such as insulin resistance and diabetes. PMID:23950037

Gargantini, E; Grande, C; Trovato, L; Ghigo, E; Granata, R

2013-12-01

82

Steroid receptor coactivator-3 regulates glucose metabolism in bladder cancer cells through coactivation of hypoxia inducible factor 1?.  

Science.gov (United States)

Cancer cell proliferation is a metabolically demanding process, requiring high glycolysis, which is known as "Warburg effect," to support anabolic growth. Steroid receptor coactivator-3 (SRC-3), a steroid receptor coactivator, is overexpressed and/or amplified in multiple cancer types, including non-steroid targeted cancers, such as urinary bladder cancer (UBC). However, whether SRC-3 regulates the metabolic reprogramming for cancer cell growth is unknown. Here, we reported that overexpression of SRC-3 accelerated UBC cell growth, accompanied by the increased expression of genes involved in glycolysis. Knockdown of SRC-3 reduced the UBC cell glycolytic rate under hypoxia, decreased tumor growth in nude mice, with reduction of proliferating cell nuclear antigen and lactate dehydrogenase expression levels. We further revealed that SRC-3 could interact with hypoxia inducible factor 1? (HIF1?), which is a key transcription factor required for glycolysis, and coactivate its transcriptional activity. SRC-3 was recruited to the promoters of HIF1?-target genes, such as glut1 and pgk1. The positive correlation of expression levels between SRC-3 and Glut1 proteins was demonstrated in human UBC patient samples. Inhibition of glycolysis through targeting HK2 or LDHA decelerated SRC-3 overexpression-induced cell growth. In summary, overexpression of SRC-3 promoted glycolysis in bladder cancer cells through HIF1? to facilitate tumorigenesis, which may be an intriguing drug target for bladder cancer therapy. PMID:24584933

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

2014-04-18

83

Dichloroacetate shifts the metabolism from glycolysis to glucose oxidation and exhibits synergistic growth inhibition with cisplatin in HeLa cells.  

Science.gov (United States)

The unique bioenergetic feature of cancer, aerobic glycolysis or the Warburg effect, is an attractive therapeutic target for cancer therapy. Reversing the glycolytic phenotype may trigger apoptosis in tumor cells. Recently, dichloroacetate (DCA) was proven to produce significant cytotoxic effects in certain tumor cells through this distinct mechanism. In this study, the effect of DCA on the metabolism of cervical cancer HeLa cells was explored and its synergistic growth inhibition with cisplatin was also evaluated. The intracellular changes in HeLa cells following DCA exposure were analyzed through cell viability, intracellular H2O2 and pH levels, mitochondrial membrane potential (MMP), expression of apoptotic proteins and Kv1.5 channel, and intracellular-free Ca2+ concentration ([Ca2+]i). For the evaluation of combination chemotherapy, HeLa cells were treated with a combination of DCA and cisplatin at various concentrations for 48 h. Cell viability was determined by CCK-8 assay and the synergy of the two agents was evaluated using the R index method. DCA shifted the metabolism of HeLa cells from aerobic glycolysis to glucose oxidation as shown by the increased intracellular H2O2 and pH levels. The change of the metabolism modality led to a drop in MMP and the increase of apoptotic proteins (caspase 3 and 9). The increased Kv1.5 expression and decreased [Ca2+]i established a positive feedback loop that resulted in reduced tonic inhibition of caspases. Combination chemotherapy of DCA and cisplatin exhibited a significant synergy in inhibiting the proliferation of HeLa cells. The specific apoptotic mechanism of DCA as distinguished from the cisplatin may be partly responsible for the synergy and further in vivo study on combination chemotherapy of the two agents in cervical cancer xenografts in mice is warranted. PMID:21132264

Xie, Jing; Wang, Bing-Shun; Yu, De-Hong; Lu, Qin; Ma, Jian; Qi, Hong; Fang, Chao; Chen, Hong-Zhuan

2011-02-01

84

Engineering of glycerol-stimulated insulin secretion in islet beta cells. Differential metabolic fates of glucose and glycerol provide insight into mechanisms of stimulus-secretion coupling.  

Science.gov (United States)

Insulin secretion from beta cells in the islets of Langerhans can be stimulated by a number of metabolic fuels, including glucose and glyceraldehyde, and is thought to be mediated by metabolism of the secretagogues and an attendant increase in the ATP:ADP ratio. Curiously, glycerol fails to stimulate insulin secretion, even though it has been reported that islets contain abundant glycerol kinase activity and oxidize glycerol efficiently. We have reinvestigated this point and find that rat islets and the well differentiated insulinoma cell line INS-1 contain negligible glycerol kinase activity. A recombinant adenovirus containing the bacterial glycerol kinase gene (AdCMV-GlpK) was constructed and used to express the enzyme in islets and INS-1 cells, resulting in insulin secretion in response to glycerol. In AdCMV-GlpK-treated INS-1 cells a greater proportion of glycerol is converted to lactate and a lesser proportion is oxidized compared with glucose. The two fuels are equally potent as insulin secretagogues, despite the fact that oxidation of glycerol at its maximally effective dose (2-5 mM) occurs at a rate that is similar to the rate of glucose oxidation at its basal, nonstimulatory concentration (3 mM). We also investigated the possibility that glycerol may signal via expansion of the glycerol phosphate pool to allow enhanced fatty acid esterification and formation of complex lipids. Addition of Triacsin-C, an inhibitor of long-chain acyl-CoA synthetase, to AdCMV-GlpK-treated INS-1 cells did not inhibit glycerol-stimulated insulin secretion despite the fact that it blocked glycerol incorporation into cellular lipids. We conclude from these studies that glycerol kinase expression is sufficient to activate glycerol signaling in beta cells, showing that the failure of normal islets to respond to this substrate is due to a lack of this enzyme activity. Further, our studies show that glycerol signaling is not linked to esterification or oxidation of the substrate, but is likely mediated by its metabolism in the glycerol phosphate shuttle and/or the distal portion of the glycolytic pathway, either of which can lead to production of ATP and an increased ATP:ADP ratio. PMID:9228030

Noel, R J; Antinozzi, P A; McGarry, J D; Newgard, C B

1997-07-25

85

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

International Nuclear Information System (INIS)

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

2011-08-01

86

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2011-08-15

87

Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production  

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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

88

Glucose transporters and ATP-gated K+ (KATP) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells.  

Science.gov (United States)

Although the heteromeric combination of type 1 taste receptors 2 and 3 (T1r2 + T1r3) is well established as the major receptor for sugars and noncaloric sweeteners, there is also evidence of T1r-independent sweet taste in mice, particularly so for sugars. Before the molecular cloning of the T1rs, it had been proposed that sweet taste detection depended on (a) activation of sugar-gated cation channels and/or (b) sugar binding to G protein-coupled receptors to initiate second-messenger cascades. By either mechanism, sugars would elicit depolarization of sweet-responsive taste cells, which would transmit their signal to gustatory afferents. We examined the nature of T1r-independent sweet taste; our starting point was to determine if taste cells express glucose transporters (GLUTs) and metabolic sensors that serve as sugar sensors in other tissues. Using RT-PCR, quantitative PCR, in situ hybridization, and immunohistochemistry, we determined that several GLUTs (GLUT2, GLUT4, GLUT8, and GLUT9), a sodium-glucose cotransporter (SGLT1), and two components of the ATP-gated K(+) (K(ATP)) metabolic sensor [sulfonylurea receptor (SUR) 1 and potassium inwardly rectifying channel (Kir) 6.1] were expressed selectively in taste cells. Consistent with a role in sweet taste, GLUT4, SGLT1, and SUR1 were expressed preferentially in T1r3-positive taste cells. Electrophysiological recording determined that nearly 20% of the total outward current of mouse fungiform taste cells was composed of K(ATP) channels. Because the overwhelming majority of T1r3-expressing taste cells also express SUR1, and vice versa, it is likely that K(ATP) channels constitute a major portion of K(+) channels in the T1r3 subset of taste cells. Taste cell-expressed glucose sensors and K(ATP) may serve as mediators of the T1r-independent sweet taste of sugars. PMID:21383163

Yee, Karen K; Sukumaran, Sunil K; Kotha, Ramana; Gilbertson, Timothy A; Margolskee, Robert F

2011-03-29

89

Glucose metabolism during bovine preimplantation development: analysis of gene expression in single oocytes and embryos.  

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Glucose metabolism of the bovine embryo is low during the first cleavages and increases sharply after the major resumption of the genome (8-16 cells). The mRNA level for genes involved in glucose metabolism was tested by RT-PCR on individual oocytes and embryos at different stages of development. These genes were: glucose transport GLUT-1, hexokinase (HK), glucose-6-phosphatase-dehydrogenase (G6PDH), and glucose-phosphate-isomerase (GPI); actin was used as a reference transcript. RT-PCR resul...

Lequarre?, Anne-sophie; Grisart, B.; Schuurbiers, N.; Moreau, B.; Massip, A.; Dessy, F.

1997-01-01

90

Simvastatin Inhibits Glucose Metabolism and Legumain Activity in Human Myotubes  

Science.gov (United States)

Simvastatin, a HMG-CoA reductase inhibitor, is prescribed worldwide to patients with hypercholesterolemia. Although simvastatin is well tolerated, side effects like myotoxicity are reported. The mechanism for statin-induced myotoxicity is still poorly understood. Reports have suggested impaired mitochondrial dysfunction as a contributor to the observed myotoxicity. In this regard, we wanted to study the effects of simvastatin on glucose metabolism and the activity of legumain, a cysteine protease. Legumain, being the only known asparaginyl endopeptidase, has caspase-like properties and is described to be involved in apoptosis. Recent evidences indicate a regulatory role of both glucose and statins on cysteine proteases in monocytes. Satellite cells were isolated from the Musculus obliquus internus abdominis of healthy human donors, proliferated and differentiated into polynuclear myotubes. Simvastatin with or without mevalonolactone, farnesyl pyrophosphate or geranylgeranyl pyrophosphate were introduced on day 5 of differentiation. After 48 h, cells were either harvested for immunoblotting, ELISA, cell viability assay, confocal imaging or enzyme activity analysis, or placed in a fuel handling system with [14C]glucose or [3H]deoxyglucose for uptake and oxidation studies. A dose-dependent decrease in both glucose uptake and oxidation were observed in mature myotubes after exposure to simvastatin in concentrations not influencing cell viability. In addition, simvastatin caused a decrease in maturation and activity of legumain. Dysregulation of glucose metabolism and decreased legumain activity by simvastatin points out new knowledge about the effects of statins on skeletal muscle, and may contribute to the understanding of the myotoxicity observed by statins.

Smith, Robert; Solberg, Rigmor; Jacobsen, Linn L?kken; Voreland, Anette Larsen; Rustan, Arild Christian; Thoresen, G. Hege; Johansen, Harald Thidemann

2014-01-01

91

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

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

2011-01-01

92

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

93

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

94

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

95

Utilization of dietary glucose in the metabolic syndrome  

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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 prepa...

Alemany Marià

2011-01-01

96

Persistent impaired glucose metabolism in a zebrafish hyperglycemia model.  

Science.gov (United States)

Diabetes mellitus (DM) affects over 10% of the world's population. Hyperglycemia is the main feature for the diagnosis of this disease. The zebrafish (Danio rerio) is an established model organism for the study of various metabolic diseases. In this paper, hyperglycemic zebrafish, when immersed in a 111 mM glucose solution for 14 days, developed increased glycation of proteins from the eyes, decreased mRNA levels of insulin receptors in the muscle, and a reversion of high blood glucose level after treatment with anti-diabetic drugs (glimepiride and metformin) even after 7 days of glucose withdrawal. Additionally, hyperglycemic zebrafish developed an impaired response to exogenous insulin, which was recovered after 7 days of glucose withdrawal. These data suggest that the exposure of adult zebrafish to high glucose concentration is able to induce persistent metabolic changes probably underlined by a hyperinsulinemic state and impaired peripheral glucose metabolism. PMID:24704522

Capiotti, Katiucia Marques; Antonioli, Régis; Kist, Luiza Wilges; Bogo, Maurício Reis; Bonan, Carla Denise; Da Silva, Rosane Souza

2014-05-01

97

A review of metabolism of labeled glucoses for use in measuring glucose recycling  

International Nuclear Information System (INIS)

The fate of tritium from each carbon of D-glucose and the metabolism of L-glucose and 2-deoxy-D-glucose are known. Differences in metabolism of labeled glucoses can be used to quantify physical and chemical recycling of glucose. Only physical recycling is measured by [1-3H]-L-glucose, whereas [U-14C]-D-glucose measures total recycling. The difference between [1-3H]-L-glucose and [U-14C]-D-glucose, therefore, is chemical recycling. Recycling from extracellular binding sites and hepatic glucose 6-phosphate can be measured by difference between [1,2-3H]-2-deoxy-D-glucose and [1-3H]-L-glucose, and the difference in irreversible loss of the two will measure extrahepatic uptake of D-glucose. Recycling via Cori-alanine cycle plus CO2 is the difference in irreversible loss measured by using [6-3H]-glucose and [U-14C]-D-glucose. Recycling via the hexose monophosphate pathway can be determined by difference in irreversible loss between [1-3H]-D-glucose and [6-3H]-D-glucose. Recycling via CO2 and glycerol must be measured directly with [U-14C]glucose, bicarbonate, and glycerol. Recycling via hepatic glycogen can be estimated by subtracting all other measured chemical recycling from total chemical recycling. This review describes means to quantify glucose recycling in vivo, enabling studies of mechanisms for conservation and utilization of glucose. 54 references

1990-01-01

98

Experimental evidence and isotopomer analysis of mixotrophic glucose metabolism in the marine diatom Phaeodactylum tricornutum  

Science.gov (United States)

Background Heterotrophic fermentation using simple sugars such as glucose is an established and cost-effective method for synthesizing bioproducts from bacteria, yeast and algae. Organisms incapable of metabolizing glucose have limited applications as cell factories, often despite many other advantageous characteristics. Therefore, there is a clear need to investigate glucose metabolism in potential cell factories. One such organism, with a unique metabolic network and a propensity to synthesize highly reduced compounds as a large fraction of its biomass, is the marine diatom Phaeodactylum tricornutum (Pt). Although Pt has been engineered to metabolize glucose, conflicting lines of evidence leave it unresolved whether Pt can natively consume glucose. Results Isotope labeling experiments in which Pt was mixotrophically grown under light on 100% U-13C glucose and naturally abundant (~99% 12C) dissolved inorganic carbon resulted in proteinogenic amino acids with an average 13C-enrichment of 88%, thus providing convincing evidence of glucose uptake and metabolism. The dissolved inorganic carbon was largely incorporated through anaplerotic rather than photosynthetic fixation. Furthermore, an isotope labeling experiment utilizing 1-13C glucose and subsequent metabolic pathway analysis indicated that (i) the alternative Entner-Doudoroff and Phosphoketolase glycolytic pathways are active during glucose metabolism, and (ii) during mixotrophic growth, serine and glycine are largely synthesized from glyoxylate through photorespiratory reactions rather than from 3-phosphoglycerate. We validated the latter result for mixotrophic growth on glycerol by performing a 2-13C glycerol isotope labeling experiment. Additionally, gene expression assays showed that known, native glucose transporters in Pt are largely insensitive to glucose or light, whereas the gene encoding cytosolic fructose bisphosphate aldolase 3, an important glycolytic enzyme, is overexpressed in light but insensitive to glucose. Conclusion We have shown that Pt can use glucose as a primary carbon source when grown in light, but cannot use glucose to sustain growth in the dark. We further analyzed the metabolic mechanisms underlying the mixotrophic metabolism of glucose and found isotopic evidence for unusual pathways active in Pt. These insights expand the envelope of Pt cultivation methods using organic substrates. We anticipate that they will guide further engineering of Pt towards sustainable production of fuels, pharmaceuticals, and platform chemicals.

2013-01-01

99

The effect of vagal nerve blockade using electrical impulses on glucose metabolism in nondiabetic subjects  

Science.gov (United States)

Purpose Vagal interruption causes weight loss in humans and decreases endogenous glucose production in animals. However, it is unknown if this is due to a direct effect on glucose metabolism. We sought to determine if vagal blockade using electrical impulses alters glucose metabolism in humans. Patients and methods We utilized a randomized, cross-over study design where participants were studied after 2 weeks of activation or inactivation of vagal nerve blockade (VNB). Seven obese subjects with impaired fasting glucose previously enrolled in a long-term study to examine the effect of VNB on weight took part. We used a standardized triple-tracer mixed meal to enable measurement of the rate of meal appearance, endogenous glucose production, and glucose disappearance. The 550 kcal meal was also labeled with 111In-diethylene triamine pentaacetic acid (DTPA) to measure gastrointestinal transit. Insulin action and ?-cell responsivity indices were estimated using the minimal model. Results Integrated glucose, insulin, and glucagon concentrations did not differ between study days. This was also reflected in a lack of effect on ?-cell responsivity and insulin action. Furthermore, fasting and postprandial endogenous glucose production, integrated meal appearance, and glucose disposal did not differ in the presence or absence of VNB. Similarly, gastric emptying and colonic transit were unchanged by VNB. Conclusion In this pilot study in nondiabetic humans, electrical vagal blockade had no acute effects on glucose metabolism, insulin secretion and action, or gastric emptying. It remains to be determined if more pronounced effects would be observed in diabetic subjects.

Sathananthan, Matheni; Ikramuddin, Sayeed; Swain, James M; Shah, Meera; Piccinini, Francesca; Dalla Man, Chiara; Cobelli, Claudio; Rizza, Robert A; Camilleri, Michael; Vella, Adrian

2014-01-01

100

Effects of fluctuating glucose levels on neuronal cells in vitro.  

Science.gov (United States)

There is increasing evidence for glucose fluctuation playing a role in the damaging effects of diabetes on various organs, including the brain. We aimed to study the effects of glycaemic variation (GV) upon mitochondrial activity using an in vitro human neuronal model. The metabolic disturbance of GV in neuronal cells, was mimicked via exposure of neuroblastoma cells SH-SY5Y to constant glucose or fluctuating (i.e. 6 h cycles) for 24 and 48 h. Mitochondrial dehydrogenase activity was determined via MTT assay. Cell mitochondrial activity (MTT) was moderately decreased in constant high glucose, but markedly decreased following 24 and 48 h of cyclical glucose fluctuations. Glucose transport determined via 2-deoxy-D-[1-(14)C] glucose uptake was regulated in an exaggerated manner in response to glucose variance, accompanied by modest changes in GLUT 1 mRNA abundance. Osmotic components of these glucose effects were investigated in the presence of the osmotic-mimics mannitol and L: -glucose. Both treatments showed that fluctuating osmolality did not result in a significant change in mitochondrial activity and had no effects on (14)Cglucose uptake, suggesting that adverse effects on mitochondrial function were specifically related to metabolically active glucose fluctuations. Apoptosis gene expression showed that both intrinsic and extrinsic apoptotic pathways were modulated by glucose variance, with two major response clusters corresponding to (i) glucose stress-modulated genes, (ii) glucose mediated osmotic stress-modulated genes. Gene clustering analysis by STRING showed that most of the glucose stress-modulated genes were components of the intrinsic/mitochondrial apoptotic pathway including Bcl-2, Caspases and apoptosis executors. On the other hand the glucose mediated osmotic stress-modulated genes were mostly within the extrinsic apoptotic pathway, including TNF receptor and their ligands and adaptors/activators/initiators of apoptosis. Fluctuating glucose levels have a greater adverse effect on neuronal cell energy regulation mechanisms than either sustained high or low glucose levels. PMID:22565596

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

2012-08-01

 
 
 
 
101

Glucose metabolism in adult survivors of severe acute malnutrition.  

Science.gov (United States)

Context and Objectives: The clinical syndromes of severe acute malnutrition may have early life origins because children with marasmus have lower birth weight than those with kwashiorkor. We hypothesized that resultant metabolic effects may persist into adulthood. We investigated whether marasmus survivors (MS) are more insulin resistant and glucose intolerant than kwashiorkor survivors (KS). Research Design and Setting: This was a case-control study in Jamaican adults. Subjects: We performed oral glucose tolerance tests on 191 adults (aged 17-50 y; 52% male; body mass index 24.2 ± 5.5 kg/m(2)). There were 43 MS; 38 KS; 70 age-, sex-, and body mass index-matched community controls; and 40 age- and birth weight-matched controls. Measurements: We measured insulin sensitivity with the whole-body insulin sensitivity index, and ?-cell function with the insulinogenic index and the oral disposition index. Results: Fasting glucose was comparable across groups, but glucose intolerance was significantly more common in MS (19%) than in KS (3%), community controls (11%), and birth weight-matched controls (10%). The whole-body insulin sensitivity index was lower in MS than KS (P = .06) but similar between MS and controls. The insulinogenic index and oral disposition index were lower in MS compared with all three groups (P < .01). Conclusions: Marasmus survivors tend to be less insulin sensitive, but have significantly lower insulin secretion and are more glucose intolerant compared with kwashiorkor survivors and controls. This suggests that poor nutrition in early life causes ?-cell dysfunction, which may predispose to the development of diabetes. PMID:24517147

Francis-Emmanuel, Patrice M; Thompson, Debbie S; Barnett, Alan T; Osmond, Clive; Byrne, Christopher D; Hanson, Mark A; Gluckman, Peter D; Forrester, Terrence E; Boyne, Michael S

2014-06-01

102

Effects of sex steroid hormones on sertoli cells metabolic pathways  

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Developing germ cells use lactate, derived from glucose metabolism of Sertoli cells (SCs), as their main energy source. Androgens and estrogens have been implicated in the modulation of testicular cells energy metabolism, particularly in SCs. The goal of the present study was to shed light on the effects of sex steroid hormones on glucose metabolic pathways in rat SCs. The mRNA levels of glucose transporters 1 and 3 (GLUT1 and GLUT3), phosphofructokinase 1 (PFK1) and lactate dehydrogenase cha...

Martins, Ana Catarina Dias

2012-01-01

103

The effect of ascorbate, 2-deoxy-D-glucose and dichloroacetate on the growth and the glucose metabolism of neuroblastoma cells with or without N-myc-amplification  

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For decades there has been a controversy on the benefit of using ascorbate (AA) in cancer therapy. Lately, three articles in PNAS by Marc Levine et al. (NIH) generated new interest in the use of high dose ascorbate: First, high doses of ascorbate were shown to be cytotoxic to human lymphoma and mamma carcinoma cell lines in vitro. Cytotoxicity was mediated by H2O2 (Chen et al. 2005). Secondly, ascorbyl radical and H2O2 could be detected in the extracellular fluid of rats after intravenous app...

2010-01-01

104

Glucose metabolism in a patient with hyperthyroidism and an insulinoma.  

Science.gov (United States)

A 67-year-old woman was admitted in hypoglycemic coma, with fever and signs of hyperthyroidism. Diagnosis was made of both an insulinoma and subacute ("De Quervain") thyroiditis. This rare coincidence of two diseases with opposite effects on serum glucose levels, offered a rare opportunity to study glucose metabolism in this peculiar physiopathological situation. During the day abnormally high postprandial blood glucose levels were seen, pointing to the glucose intolerance usually seen in the hyperthyroid state. During the night and after prolonged fasting, however, hypoglycemia predominated, consistent with the clinical picture typical of an insulinoma. After resection of the insulinoma and spontaneous healing of hyperthyroidism, glucose metabolism reverted to normal. As shown in this case, concurrent hyperthyroidism and an insulinoma may lead to consecutive episodes of glucose intolerance and hypoglycemia within the same 24-hour period. PMID:7941923

Verhelst, J; Stockman, D; De Foer, F; Mahler, C

1994-01-01

105

FGF19 Regulates Cell Proliferation, Glucose and Bile Acid Metabolism via FGFR4-Dependent and Independent Pathways  

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Fibroblast growth factor 19 (FGF19) is a hormone-like protein that regulates carbohydrate, lipid and bile acid metabolism. At supra-physiological doses, FGF19 also increases hepatocyte proliferation and induces hepatocellular carcinogenesis in mice. Much of FGF19 activity is attributed to the activation of the liver enriched FGF Receptor 4 (FGFR4), although FGF19 can activate other FGFRs in vitro in the presence of the coreceptor ?Klotho (KLB). In this report, we investigate the role of FGFR...

2011-01-01

106

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

1989-01-01

107

Abnormal glucose metabolism in patients treated with antipsychotics.  

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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...

2007-01-01

108

A link between sleep loss, glucose metabolism and adipokines  

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The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolis...

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

2011-01-01

109

Metabolic state of glioma stem cells and nontumorigenic cells  

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Gliomas contain a small number of treatment-resistant glioma stem cells (GSCs), and it is thought that tumor regrowth originates from GSCs, thus rendering GSCs an attractive target for novel treatment approaches. Cancer cells rely more on glycolysis than on oxidative phosphorylation for glucose metabolism, a phenomenon used in 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography imaging of solid cancers, and targeting metabolic pathways in cancer cells has become a topic of considerab...

Vlashi, Erina; Lagadec, Chann; Vergnes, Laurent; Matsutani, Tomoo; Masui, Kenta; Poulou, Maria; Popescu, Ruxandra; Della Donna, Lorenza; Evers, Patrick; Dekmezian, Carmen; Reue, Karen; Christofk, Heather; Mischel, Paul S.; Pajonk, Frank

2011-01-01

110

Mechanism of Insulin-resistant Glucose Transport Activity in the Enlarged Adipose Cell of the Aged, Obese Rat: RELATIVE DEPLETION OF INTRACELLULAR GLUCOSE TRANSPORT SYSTEMS  

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The effects of increasing cell size on glucose transport activity and metabolism and on the concentrations of glucose transport systems in both the plasma and low density microsomal membranes in isolated adipose cells from the aging rat model of obesity have been examined. Glucose transport activity was assessed by measuring l-arabinose transport and the concentration of glucose transport systems estimated by measuring specific d-glucose-inhibitable cytochalasin B-binding. Basal glucose trans...

Hissin, Paul J.; Foley, James E.; Wardzala, Lawrence J.; Karnieli, Eddy; Simpson, Ian A.; Salans, Lester B.; Cushman, Samuel W.

1982-01-01

111

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

112

[Bone Metabolism and Cardiovascular Function Update. Effects of antiosteoporotic agents on glucose and lipid metabolism].  

Science.gov (United States)

At present, antiosteoporotic agents that might affect glucose and/or lipid metabolism include bisphosphonates, Selective Estrogen Receptor Modulators ; SERMs and activated vitamin D. Bisphosphonates have little, if any, effect on lipid metabolism, while they are suggested to improve glucose metabolism, via osteocalcin or adiponectin. SERMs are shown to decrease serum triglycerides and LDL cholesterol levels, and increase HDL cholesterol level. To date, SERMs are not proven to reduce the risk of coronary events. From nutritional point of view, studies suggest that vitamin D may improve lipid and glucose metabolism, whereas its therapeutic effect on lifestyle related diseases is unknown. PMID:24976061

Kondo, Mai; Mizuno, Yuzo

2014-07-01

113

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

Directory of Open Access Journals (Sweden)

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

Yamanoi,Yasuhiro

1984-10-01

114

The effects of hypoglycin on glucose metabolism in the rat  

International Nuclear Information System (INIS)

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

1978-02-15

115

Glucose regulates hypothalamic long-chain fatty acid metabolism via AMP-activated kinase (AMPK) in neurons and astrocytes.  

Science.gov (United States)

Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance. PMID:24240094

Taïb, Bouchra; Bouyakdan, Khalil; Hryhorczuk, Cécile; Rodaros, Demetra; Fulton, Stephanie; Alquier, Thierry

2013-12-27

116

A link between sleep loss, glucose metabolism and adipokines  

Directory of Open Access Journals (Sweden)

Full Text Available The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-? (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

2011-10-01

117

A link between sleep loss, glucose metabolism and adipokines  

Scientific Electronic Library Online (English)

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

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

118

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

119

Metabolism of tritiated D-glucose in rat erythrocytes  

International Nuclear Information System (INIS)

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

1991-01-01

120

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

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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 1,000 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/...

Bauer, J. E.; Capone, D. G.

1985-01-01

 
 
 
 
121

In vivo imaging of glucose uptake and metabolism in tumors.  

Science.gov (United States)

Tumors have a greater reliance on anaerobic glycolysis for energy production than normal tissues. We developed a noninvasive method for imaging glucose uptake in vivo that is based on magnetic resonance imaging and allows the uptake of unlabeled glucose to be measured through the chemical exchange of protons between hydroxyl groups and water. This method differs from existing molecular imaging methods because it permits detection of the delivery and uptake of a metabolically active compound in physiological quantities. We show that our technique, named glucose chemical exchange saturation transfer (glucoCEST), is sensitive to tumor glucose accumulation in colorectal tumor models and can distinguish tumor types with differing metabolic characteristics and pathophysiologies. The results of this study suggest that glucoCEST has potential as a useful and cost-effective method for characterizing disease and assessing response to therapy in the clinic. PMID:23832090

Walker-Samuel, Simon; Ramasawmy, Rajiv; Torrealdea, Francisco; Rega, Marilena; Rajkumar, Vineeth; Johnson, S Peter; Richardson, Simon; Gonçalves, Miguel; Parkes, Harold G; Arstad, Erik; Thomas, David L; Pedley, R Barbara; Lythgoe, Mark F; Golay, Xavier

2013-08-01

122

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

123

Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism.  

Science.gov (United States)

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

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

2011-01-01

124

Sirtuin 1 stabilization by HuR represses TNF-?- and glucose-induced E-selectin release and endothelial cell adhesiveness in vitro: relevance to human metabolic syndrome.  

Science.gov (United States)

Chronic inflammation and hyperglycaemia, typical features of metabolic diseases, trigger endothelial damage and release of E-selectin, a marker of endothelial activation. In the present study, we investigated molecular pathways involved in the regulation of endothelial cell activation induced by tumour necrosis factor-? (TNF-?) and high glucose. In cultured human umbilical vein endothelial cells (HUVECs), we studied the role of HuR, an ELAV (embryonic lethal, abnormal vision, Drosophila) family RNA-binding protein, and Sirtuin 1 (SIRT1) on E-selectin release and cell adhesion at different glucose concentrations. HuR expression and binding to SIRT1 were also analysed ex vivo in peripheral blood mononuclear cells (PBMCs) of subjects with and without the metabolic syndrome (MS), by immunoprecipitation (IP) of the ribonucleoprotein (RNP) complex. We found that SIRT1 overexpression prevented TNF-?- and high-glucose-dependent nuclear factor-?B (NF-?B)-p65 acetylation, E-selectin promoter activity, E-selectin release and adhesion of THP-1 cells to HUVECs. The same was mimicked by HuR overexpression, which binds and stabilizes SIRT1 mRNA. Importantly, in PBMCs of individuals with MS compared with those without, SIRT1 expression was lower, and the ability of HuR to bind SIRT1 mRNA was significantly reduced, while plasma E-selectin was increased. We conclude that post-transcriptional stabilization of SIRT1 by HuR represses inflammation- and hyperglycaemia-induced E-selectin release and endothelial cell activation. Therefore, increasing SIRT1 expression represents a strategy to counter the accelerated vascular disease in metabolic disorders. PMID:24702436

Ceolotto, Giulio; De Kreutzenberg, Saula Vigili; Cattelan, Arianna; Fabricio, Aline S C; Squarcina, Elisa; Gion, Massimo; Semplicini, Andrea; Fadini, Gian Paolo; Avogaro, Angelo

2014-10-01

125

Examining glucose transport in single vascular smooth muscle cells with a fluorescent glucose analog.  

Science.gov (United States)

Changes in vascular smooth muscle glucose transport are thought to contribute to the pathogenesis of vascular disease in conditions such as diabetes, yet no single-cell assay for glucose uptake by VSM exists. Therefore, we examined the uptake of the fluorescent glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) in isolated pig vascular smooth muscle cells (VSMC) using digital imaging microscopy. Uptake of 2-NBDG by VSMC was inhibited by D-glucose but not by L-glucose, suggesting that 2-NBDG enters VSMC via glucose transporters. Uptake of 2-NBDG was linear in the presence of 10 mM D-glucose (n=6, R2=0.9408) but not in its absence (n=4, R2=0.9993), indicating that 2-NBDG is not metabolized and accumulates within the cells. 2-NBDG fluorescence in VSMC was often non-uniform and appeared to represent binding of 2-NBDG to some cytoplasmic component. The present study demonstrates that 2-NBDG is a useful tool for examining vascular smooth muscle glucose uptake at the single cell level. PMID:10783904

Lloyd, P G; Hardin, C D; Sturek, M

1999-01-01

126

Glucose metabolism in rats submitted to skeletal muscle denervation  

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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...

Wilton Marlindo Santana Nunes; Maria Alice Rostom de Mello

2005-01-01

127

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.

128

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

129

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

130

Abnormalities of glucose metabolism in spontaneously hypertensive rats  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english Abnormalities in glucose metabolism and insulin action are frequently detected in patients with essential hypertension. Spontaneously hypertensive rats (SHR) have been used as an experimental model to understand this pathological condition. The objective of the present study was to assess glucose me [...] tabolism and insulin action in SHR and Wistar rats under fed and fasting conditions. Peripheral glucose utilization was estimated by kinetic studies with [6-³H]-glucose and gluconeogenetic activity was measured during continuous [14C]-bicarbonate infusion. Plasma glucose levels were higher in the SHR group. Plasma insulin levels in the fed state were higher in the SHR group (99.8 ± 6.5 µM) than in the control group (70.4 ± 3.6 µM). Muscle glycogen content was reduced in SHR compared to control under the various experimental conditions. Peripheral glucose utilization was slightly lower in the SHR group in the fed state (8.72 ± 0.55 vs 9.52 ± 0.80 mg kg-1 min-1 in controls). Serum free fatty acid levels, hepatic glycogen levels, hepatic phosphoenolpyruvate carboxykinase activity and gluconeogenetic activity were similar in the two groups. The presence of hyperglycemia and hyperinsulinemia and the slightly reduced peripheral glucose utilization suggest the presence of resistance to the action of insulin in peripheral tissues of SHR. Hepatic gluconeogenesis does not seem to contribute to the metabolic alterations detected in these animals.

L.M.F.B., Gouveia; I.C., Kettelhut; M.C., Foss.

131

Obstructive Sleep Apnea and Abnormal Glucose Metabolism  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Obstructive sleep apnea (OSA) is a chronic disorder that is prevalent, especially in subjects with obesity or diabetes. OSA is related to several metabolic abnormalities, including diabetes, insulin resistance, hypertension, and cardiovascular diseases. Although Koreans are less obese than Caucasians, the prevalence of OSA is comparable in both groups. Thus, the impact of OSA on metabolism may be similar. Many epidemiologic and experimental studies have demonstrated that OSA is associated wit...

Kim, Nan Hee

2012-01-01

132

Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Selective amino acid restriction targets mitochondria to induce apoptosis of DU145 and PC3 prostate cancer cells. Biochemical assays and flow cytometry were uitilized to analyze the glucose consumption, lactate production, pyruvate dehydrogenase (PDH), nicotinamide adenine dinucleotide (NAD)/NADH and nicotinamide adenine dinucleotide phosphate (NADP)/NADPH ratios, mitochondrial glutathione peroxidase (GPx), manganese superoxide dismutase (SOD), glutathione, reactive oxygen species (ROS) and D...

Liu, Xiaoyi; Fu, Ya-min; Meadows, Gary G.

2011-01-01

133

Regional glucose metabolism using PETT in normal and psychiatric populations  

International Nuclear Information System (INIS)

The metabolism of "1"8F-2-deoxy-2-fluoro-D-glucose ("1"8FDG) in 150 subjects including normals, schizophrenics, senile dementias, and primary affective disorders was studied. Some of the data analyzed to date are discussed

1982-05-08

134

Changes induced by sucrose administration on glucose metabolism in pancreatic islets in normal hamsters.  

Science.gov (United States)

We correlated the changes in glucose-induced insulin secretion with those observed in glucose metabolism and hexokinase/glucokinase activity in islets from normal sucrose-fed hamsters. Blood glucose and insulin levels were measured in normal male hamsters fed with (S5) or without (C5) 10% sucrose in the drinking water for 5 weeks. Isolated islets (collagenase digestion) from both groups of animals were used to study insulin secretion, (14)CO(2) and (3)H(2)O production from D-[U-(14)C]-glucose and D-[5-(3)H]-glucose respectively, with 3.3 or 16.7 mM glucose in the medium, and hexokinase/glucokinase activity (fluorometric assay) in islet homogenates. Whereas S5 and C5 animals had comparable normal blood glucose levels, S5 showed higher insulin levels than C5 hamsters (2.3+/-0.1 vs 0.6+/-0.03 ng/ml, P<0.001). Islets from S5 hamsters released significantly more insulin than C5 islets in the presence of low and high glucose (3.3 mM glucose: 0.77+/-0.04 vs 0.20+/-0.06 pg/ng DNA/min, P<0.001; 16.7 mM glucose: 2.77+/-0.12 vs 0.85+/-0.06 pg/ng DNA/min, P<0.001) and produced significantly higher amounts of (14)CO(2) and (3)H(2)O at both glucose concentrations ((14)CO(2): 3.3 mM glucose: 0.27+/-0.01 vs 0.18+/-0.01, P<0.001; 16.7 mM glucose: 1.44+/-0.15 vs 0.96+/-0.08, P<0.02; (3)H(2)O: 3.3 mM glucose: 0.31+/-0.02 vs 0.15+/-0.01, P<0.001; 16.7 mM glucose: 1.46+/-0.20 vs 0.76+/-0.05 pmol glucose/ng DNA/min, P<0.005). The hexokinase K(m) and V(max) values from S5 animals were significantly higher than those from C5 ones (K(m): 100.14+/-7.01 vs 59.90+/- 3.95 microM, P<0.001; V(max): 0.010+/-0.0005 vs 0.008+/- 0.0006 pmol glucose/ng DNA/min, P<0.02). Conversely, the glucokinase K(m) value from S5 animals was significantly lower than in C5 animals (K(m): 15.31+/-2.64 vs 35.01+/-1.65 mM, P<0.001), whereas V(max) figures were within a comparable range in both groups (V(max): 0.048+/-0.009 vs 0.094+/-0.035 pmol glucose/ng DNA/min, not significant). The glucose phosphorylation ratio measured at 1 and 100 mM (hexokinase/glucokinase ratio) was significantly higher in S5 (0.26+/-0.02) than in C5 animals (0.11+/-0.01, P<0.005), and it was attributable to an increase in the hexokinase activity in S5 animals. In conclusion, sucrose administration increased the hexokinase/glucokinase activity ratio in the islets, which would condition the increase in glucose metabolism by beta-cells, and in beta-cell sensitivity and responsiveness to glucose. These results support the concept that increased hexokinase rather than glucokinase activity causes the beta-cell hypersensitivity to glucose, hexokinase being metabolically more active than glucokinase to up-regulate beta-cell function. PMID:11739021

Massa, M L; Borelli, M I; Del Zotto, H; Gagliardino, J J

2001-12-01

135

Cerebral glucose metabolism in the course of subacute sclerosing panencephalitis  

Energy Technology Data Exchange (ETDEWEB)

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

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

1989-01-01

136

Cerebral glucose metabolism in the course of subacute sclerosing panencephalitis  

International Nuclear Information System (INIS)

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

1989-01-01

137

Miniaturised glucose-oxygen biofuel cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Miniaturized glucose-oxygen biofuel cells are useful to power implantable medical devices such as biosensors. They are small, more biocompatible and run continuously on glucose and oxygen, providing cleaner energy at neutral environment. A typical glucose-oxygen biofuel cell consists of an anode with glucose oxidase (GOx) and a cathode with various oxygen reducing catalysts. This thesis describes experimental investigations of the major issues of such systems, viz.: complex ele...

Kikuchi, Yoko

2010-01-01

138

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

2013-03-22

139

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

140

Paricalcitol does not improve glucose metabolism in patients with stage 3-4 chronic kidney disease.  

Science.gov (United States)

Patients with chronic kidney disease are often insulin resistant and glucose intolerant--abnormalities that promote cardiovascular disease. Administration of 1,25-dihydroxyvitamin D (calcitriol) has improved glucose metabolism in patients with end-stage renal disease. We conducted a randomized, placebo-controlled clinical trial to test whether paricalcitol, a 1,25-dihydroxyvitamin D analog, changes glucose tolerance in earlier stages of chronic kidney disease. In a crossover design, 22 nondiabetic patients with estimated glomerular filtration rates of stage 3-4 chronic kidney disease and fasting plasma glucose of 100-125 mg/dl were given daily oral paricalcitol for 8 weeks and matching placebo for 8 weeks, separated by an 8-week washout period. The order of interventions was random and blinded to both participants and investigators. Paricalcitol significantly reduced serum concentrations of parathyroid hormone, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D while significantly increasing serum concentrations of fibroblast growth factor-23 and 24,25-dihydroxyvitamin D. Paricalcitol, however, had no significant effect on glucose tolerance (the primary outcome measure), insulin sensitivity, beta-cell insulin response, plasma free fatty acid suppression, or urinary F2-isoprostane excretion. Thus, despite substantial effects on vitamin D metabolism, paricalcitol did not improve glucose metabolism in nondiabetic patients with stage 3-4 chronic kidney disease. PMID:22913981

de Boer, Ian H; Sachs, Michael; Hoofnagle, Andrew N; Utzschneider, Kristina M; Kahn, Steven E; Kestenbaum, Bryan; Himmelfarb, Jonathan

2013-02-01

 
 
 
 
141

Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors.  

Science.gov (United States)

Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca(2+)]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P wortmannin (50 nM; OT: P = 0.03; VP: P ? 0.002). Inactivating K ATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P < 0.003; VP: P < 0.05). These results suggest that insulin activation of PI3K increases glucokinase-mediated ATP production inducing closure of K ATP channels, opening of voltage-sensitive calcium channels, and stimulation of oxytocin and vasopressin release. The findings are consistent with SON oxytocin and vasopressin neurons functioning as glucose and "metabolic" sensors to participate in appetite regulation. PMID:24477542

Song, Zhilin; Levin, Barry E; Stevens, Wanida; Sladek, Celia D

2014-04-01

142

Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Notwithstanding previous studies supporting independent associations between obstructive sleep apnea (OSA and prevalence of diabetes, the underlying pathogenesis of impaired glucose regulation in OSA remains unclear. We explored mechanisms linking OSA with prediabetes/diabetes and associated biomarker profiles. We hypothesized that OSA is associated with distinct alterations in glucose homeostasis and biomarker profiles in subjects with normal (NGM and impaired glucose metabolism (IGM. Methods Forty-five severely obese adults (36 women without certain comorbidities/medications underwent anthropometric measurements, polysomnography, and blood tests. We measured fasting serum glucose, insulin, selected cytokines, and calculated homeostasis model assessment estimates of insulin sensitivity (HOMA-IS and pancreatic beta-cell function (HOMA-B. Results Both increases in apnea-hypopnea index (AHI and the presence of prediabetes/diabetes were associated with reductions in HOMA-IS in the entire cohort even after adjustment for sex, race, age, and BMI (P = 0.003. In subjects with NGM (n = 30, OSA severity was associated with significantly increased HOMA-B (a trend towards decreased HOMA-IS independent of sex and adiposity. OSA-related oxyhemoglobin desaturations correlated with TNF-? (r=-0.76; P = 0.001 in women with NGM and with IL-6 (rho=-0.55; P = 0.035 in women with IGM (n = 15 matched individually for age, adiposity, and AHI. Conclusions OSA is independently associated with altered glucose homeostasis and increased basal beta-cell function in severely obese adults with NGM. The findings suggest that moderate to severe OSA imposes an excessive functional demand on pancreatic beta-cells, which may lead to their exhaustion and impaired secretory capacity over time. The two distinct biomarker profiles linking sleep apnea with NGM and IGM via TNF-? and IL-6 have been discerned in our study to suggest that sleep apnea and particularly nocturnal oxyhemoglobin desaturations are associated with chronic metabolic fluxes and specific cytokine stressors that reflect links between sleep apnea and glucose metabolism. The study may help illuminate potential mechanisms for glucose dysregulation in OSA, and resolve some controversy over the associations of OSA with TNF-? and IL-6 in previous studies.

Hill Nathan R

2010-12-01

143

[Impaired glucose metabolism in patients with ischaemic heart disease].  

Science.gov (United States)

Patients with ischaemic heart disease commonly have an impaired glucose tolerance. On the 2004 congress of the ESC, the 75-75-rule was announced, indicating that 75% of all diabetics die of cardiovascular complications, and that 75% of all patients with myocardial infarction have diabetes or an (often undiagnosed) impaired glucose tolerance. Data of our "Esslinger Koronarregister" confirm that diabetics and in particular women with diabetes have a higher mortality both after STEMI and NSTEMI. During acute myocardial infarction, a higher blood glucose level strongly correlates with increased mortality. This increased blood glucose level on the one hand is due to preexisting diabetes mellitus or metabolic syndrome, but on the other hand may be a marker of larger myocardial damage with excess katecholamine release. Recent data indicate that intensive glucose control results in a reduction of cardiovascular risk, e. g. the risk of sudden cardiac death. The data presented show that an early intervention in preclinical diabetics aiming at normalization of blood glucose control is necessary in order to reduce cardiovascular mortality. PMID:16598558

Leschke, M; Schwenk, B; Bollinger, C; Faehling, M

2006-01-01

144

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

145

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

1990-01-01

146

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

147

Positron emission tomography and subcortical glucose metabolism in schizophrenia.  

Science.gov (United States)

Our previous observation of a disturbed subcortical-to-cortical gradient of activity in schizophrenia was further elucidated by examining glucose metabolism in three subcortical structures: lenticular nucleus, caudate nucleus, and thalamus. Local cerebral glucose metabolism was determined with 18F-fluorodeoxyglucose using positron emission tomography (PET) in a sample of 20 unmedicated schizophrenics and 18 normal volunteers. Repeated evaluations were performed for 12 schizophrenics following treatment with psychotropic medications and for 11 controls. Unmedicated schizophrenics had lower cortical and caudate absolute metabolic rates. Subcortical-to-cortical ratios for the lenticular nucleus and thalamus were increased in schizophrenics compared with controls, reflecting a preservation of activity in these structures relative to decreased cortical metabolism. When patients were grouped by length of medication-free period before the initial study, there was a trend for patients who had been medication free less than 6 months to have higher subcortical ratios. However, there were no consistent effects of medication in the subsample of patients whose PET studies were repeated following treatment. The results demonstrate relative hypermetabolism in structures implicated in dopamine pathways. An understanding of the physiological significance of this finding awaits the combined measurement of metabolic activity and neuroreceptors in schizophrenics. PMID:2899331

Resnick, S M; Gur, R E; Alavi, A; Gur, R C; Reivich, M

1988-04-01

148

Cerebral glucose metabolism in Parkinson's disease  

Energy Technology Data Exchange (ETDEWEB)

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.

Martin, W.R.W.; Beckman, J.H.; Calne, D.B.; Adam, M.J.; Harrop, R.; Rogers, J.G.; Ruth, T.J.; Sayre, C.I.; Pate, B.D. (British Columbia Univ., Vancouver (Canada). TRIUMF Facility)

1984-02-01

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.

Nielsen, Morten Frost; Tvede, Michael

2013-01-01

150

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

1986-01-01

151

Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

152

Heterogeneous cerebral glucose metabolism in normal pressure hydrocephalus.  

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The regional cerebral metabolic rate for glucose (rCMRglu) has never been investigated in large consecutive groups of patients with normal pressure hydrocephalus (NPH), a potentially treatable form of dementia with an unpredictable outcome after shunt surgery. Using PET and 18F-2-fluorodeoxyglucose, rCMRglu was studied in 18 patients who fulfilled hydrodynamic criteria for NPH and in whom a biopsy of the frontal cortex was obtained. When compared with an age matched group of 11 healthy subjec...

1995-01-01

153

GSM mobile phone radiation suppresses brain glucose metabolism  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

DEFF Research Database (Denmark)

The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI RFLP) were established using polymerase chain reaction and restriction enzyme digests. The effect of genotypes on lipid levels and on glucose, insulin, and HOMA (i.e., calculated parameters of beta-cell function and insulin resistance) was assessed by multivariate analyses of variance correcting for the effect of gender, age, glucose tolerance status, and body mass index. The effect of genotype on the risk of having impaired glucose metabolism was calculated by logistic regression analysis. Finally, linkage between allele sharing and physiological parameters was calculated by the new Haseman-Elston method. The allele frequencies of all five polymorphisms were similar to those previously reported for Caucasian populations. The L2711P (MvaI RFLP) polymorphism influenced LDL-cholesterol and LDL-to-HDL measures (p = 0.04 and 0.03, respectively), while the R3611Q (MspI RFLP) polymorphism had an effect on the insulin-to-glucose ratio (p = 0.04), and E4154K (EcoRI RFLP) influenced HOMAbeta (p = 0.04). Significant interactions were observed between genotype in T71I (ApaLI RFLP), A591V (AluI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI RFLP) and glucose tolerance on lipid-related parameters (0.03 < p < 0.004), and between genotype in L2712P (MvaI RFLP) and E4154K (EcoRI RFLP) and gender on lipid and glucose-related parameters (0.02 < p < 0.003). No genotypes were significantly associated with impaired glucose tolerance measured by logistic regression. Likewise, no effect of allele sharing in the five polymorphisms was seen in the dizygotic twins. The effect of the polymorphisms on lipid and glucose parameters could be mediated through linkage to genes with known effect on glucose metabolism or through free fatty acids exerting their effect on glucose metabolism.

Bentzen, Joan; Poulsen, Pernille

2003-01-01

155

Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue  

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The control of lipid and glucose metabolism is closely linked. The nuclear receptors liver X receptor (LXR)? and LXR? have been implicated in gene expression linked to lipid homeostasis; however, their role in glucose metabolism is not clear. We demonstrate here that the synthetic LXR agonist GW3965 improves glucose tolerance in a murine model of diet-induced obesity and insulin resistance. Analysis of gene expression in LXR agonist-treated mice reveals coordinate regulation of genes involv...

2003-01-01

156

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

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

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

2012-01-01

157

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

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The MIG1 gene was disrupted in a haploid laboratory strain (B224) and in an industrial polyploid strain (DGI 342) of Saccharomyces cerevisiae. The alleviation of glucose repression of the expression of MAL genes and alleviation of glucose control of maltose metabolism were investigated in batch cultivations on glucose-maltose mixtures. In the MIG1-disrupted haploid strain, glucose repression was partly alleviated; i.e., maltose metabolism was initiated at higher glucose concentrations than in...

Klein, C. J.; Olsson, L.; Rønnow, B.; Mikkelsen, J. D.; Nielsen, J.

1996-01-01

158

The deoxyglucose method adapted for studies of glucose metabolism in the early chick embryo.  

Science.gov (United States)

14C-2-deoxyglucose (DG), currently employed in in vivo studies of brain glucose metabolism, has been used for determination of glucose consumption in the in vitro developing chick embryo. DG, presented in traces, accumulates in the embryo in proportion with incubation time. Analysis of tissue homogenates shows that the accumulated radioactivity is due to both phosphorylated (DGP) and nonphosphorylated DG. As it is only the radioactivity originating from the DGP that is proportional to glucose utilization, the nonphosphorylated DG must be washed out. The washout shows two distinct kinetics: a fast one corresponding to DG that has entered the cells but has not yet been phosphorylated and a slow one that is probably due to a dephosphorylated DGP coming from a different cellular compartment. On the basis of these results the optimal experimental conditions have been defined, allowing quantitative studies of glucose metabolism during the first day of development of the chicken embryo. From 18 to 24 hr of incubation (end of gastrulation), total glucose consumption increases from 50 nmol X h-1 at stage 3-4 to 90 nmol X h-1 at stage 6-7. This increase mainly reflects the growth of the blastodisc. Comparison with the values of O2 uptake measured at the same period of development suggests that only a fraction of the glucose consumed is oxidized, the major part being converted aerobically to lactate. PMID:3972908

Baroffio, A; Kucera, P

1985-04-01

159

Molecular mechanism of hepatitis C virus-induced glucose metabolic disorders  

Directory of Open Access Journals (Sweden)

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

IkuoShoji

2012-01-01

160

Comparative effects of quinine and quinidine on glucose metabolism in healthy volunteers.  

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1. To investigate the relative effects of quinine and quinidine on glucose metabolism, 11 healthy males aged 17-32 years were given three separate 1 h intravenous infusions; normal saline alone, quinine dihydrochloride 10 mg base kg-1 body weight (BW) in normal saline, and quinidine dihydrochloride 10 mg base kg-1 BW in normal saline. A constant infusion of 5 mg glucose kg-1 ideal BW min-1 was given for 1 h before and during each study. 2. Assessment of pancreatic beta cell function and tissu...

Davis, Tm; Karbwang, J.; Looareesuwan, S.; Turner, Rc; White, Nj

1990-01-01

 
 
 
 
161

Glucose ameliorates the metabolic profile and mitochondrial function of platelet concentrates during storage in autologous plasma  

Science.gov (United States)

Background It is essential that the quality of platelet metabolism and function remains high during storage in order to ensure the clinical effectiveness of a platelet transfusion. New storage conditions and additives are constantly evaluated in order to achieve this. Using glucose as a substrate is controversial because of its potential connection with increased lactate production and decreased pH, both parameters triggering the platelet lesion during storage. Materials and methods In this study, we analysed the morphological status and metabolic profile of platelets stored for various periods in autologous plasma enriched with increasing glucose concentrations (13.75, 27.5 and 55 mM). After 0, 2, 4, 6 and 8 days, high energy phosphates (ATP, GTP, ADP, AMP), oxypurines (hypoxanthine, xanthine, uric acid), lactate, pH, mitochondrial function, cell lysis and morphology, were evaluated. Results The data showed a significant dose-dependent improvement of the different parameters in platelets stored with increasing glucose, compared to what detected in controls. Interestingly, this phenomenon was more marked at the highest level of glucose tested and in the period of time generally used for platelet transfusion (0–6 days). Conclusion These results indicate that the addition of glucose during platelet storage ameliorates, in a dose-dependent manner, the biochemical parameters related to energy metabolism and mitochondrial function. Since there was no correspondence between glucose addition, lactate increase and pH decrease in our experiments, it is conceivable that platelet derangement during storage is not directly caused by glucose through an increase of anaerobic glycolysis, but rather to a loss of mitochondrial functions caused by reduced substrate availability.

Amorini, Angela M.; Tuttobene, Michele; Tomasello, Flora M.; Biazzo, Filomena; Gullotta, Stefano; De Pinto, Vito; Lazzarino, Giuseppe; Tavazzi, Barbara

2013-01-01

162

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)

1992-11-01

163

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.

2012-01-06

164

Testing the role of myeloid cell glucose flux in inflammation and atherosclerosis.  

Science.gov (United States)

Inflammatory activation of myeloid cells is accompanied by increased glycolysis, which is required for the surge in cytokine production. Although in vitro studies suggest that increased macrophage glucose metabolism is sufficient for cytokine induction, the proinflammatory effects of increased myeloid cell glucose flux in vivo and the impact on atherosclerosis, a major complication of diabetes, are unknown. We therefore tested the hypothesis that increased glucose uptake in myeloid cells stimulates cytokine production and atherosclerosis. Overexpression of the glucose transporter GLUT1 in myeloid cells caused increased glycolysis and flux through the pentose phosphate pathway but did not induce cytokines. Moreover, myeloid-cell-specific overexpression of GLUT1 in LDL receptor-deficient mice was ineffective in promoting atherosclerosis. Thus, increased glucose flux is insufficient for inflammatory myeloid cell activation and atherogenesis. If glucose promotes atherosclerosis by increasing cellular glucose flux, myeloid cells do not appear to be the key targets. PMID:24726364

Nishizawa, Tomohiro; Kanter, Jenny E; Kramer, Farah; Barnhart, Shelley; Shen, Xia; Vivekanandan-Giri, Anuradha; Wall, Valerie Z; Kowitz, Jason; Devaraj, Sridevi; O'Brien, Kevin D; Pennathur, Subramaniam; Tang, Jingjing; Miyaoka, Robert S; Raines, Elaine W; Bornfeldt, Karin E

2014-04-24

165

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

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

2010-01-01

166

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

167

Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival.  

Science.gov (United States)

The serine/threonine kinase Akt is a component of many receptor signal transduction pathways and can prevent cell death following growth factor withdrawal. Here, we show that Akt inhibition of cell death is not dependent on new protein translation. Instead, Akt inhibition of cell death requires glucose hydrolysis through glycolysis. Akt was found to regulate multiple steps in glycolysis via posttranscriptional mechanisms that included localization of the glucose transporter, Glut1, to the cell surface and maintenance of hexokinase function in the absence of extrinsic factors. To test the role of glucose uptake and phosphorylation in growth factor-independent survival, cells were transfected with Glut1 and hexokinase 1 (Glut1/HK1) cells. Glut1/HK1 cells accumulated Glut1 on the cell surface and had high glucose uptake capacity similar to that of cells with constitutively active Akt (mAkt). Unlike mAkt-expressing cells, however, they did not consume more glucose, did not maintain prolonged phosphofructokinase-1 protein levels and activity, and did not maintain pentose phosphate shuttle activity in the absence of growth factor. Nevertheless, expression of Glut1 and HK1 promoted increased cytosolic NADH and NADPH levels relative to those of the control cells upon growth factor withdrawal, prevented activation of Bax, and promoted growth factor-independent survival. These data indicate that Bax conformation is sensitive to glucose metabolism and that maintaining glucose uptake and phosphorylation can promote cell survival in the absence of growth factor. Furthermore, Akt required glucose and the ability to perform glycolysis to prevent Bax activation. The prevention of Bax activation by posttranscriptional regulation of glucose metabolism may, therefore, be a required aspect of the ability of Akt to maintain long-term cell survival in the absence of growth factors. PMID:14517300

Rathmell, Jeffrey C; Fox, Casey J; Plas, David R; Hammerman, Peter S; Cinalli, Ryan M; Thompson, Craig B

2003-10-01

168

Cerebral glucose metabolic abnormality in patients with congenital scoliosis  

Energy Technology Data Exchange (ETDEWEB)

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

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

2007-07-01

169

GSK-3ß and Control of Glucose Metabolism and Insulin Action in Human Skeletal Muscle  

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The involvement of the ß-isoform of Glycogen Synthase Kinase (GSK-3) in glucose metabolism and insulin action was investigated in cultured human skeletal muscle cells. A 60% reduction in GSK-3ß protein expression was attained by treatment with siRNA; GSK-3? expression was unaltered. GSK-3ß knockdown did not influence total glycogen synthase (GS) activity, but increased the phosphorylation-dependent activity (fractional velocity – FV) in the basal state. Insulin responsiveness of GSFV wa...

Ciaraldi, T. P.; Carter, L.; Mudaliar, S.; Henry, R. R.

2010-01-01

170

Glucose metabolism in brain tumor as studied by positron-emission tomography  

Energy Technology Data Exchange (ETDEWEB)

Although high rates of glycolysis have been correlated with malignancy in glioma on the basis of PET findings using 18-F-deoxyglucose, these results indicate only the activity of hexokinase in the tumor cells; they do not demonstrate what kinds of systems of glycolysis increase. In this report, the differences in the activities of systems of glycolysis on both benign and malignant tumors were studied by means of PET using /sup 11/C-glucose and /sup 11/C-pyruvate administration, along with PET studies of r-CBF, r-OEF and r-CMRO/sub 2/. At a benign glioma, the uptake of /sup 11/C-glucose was lower than in normal brain tissue, with lower r-CBF, r-OEF, and r-CMRO/sub 2/ values. Many malignant tumors and cases of meningioma showed increases in glucose uptake with lower oxygen metabolism. On the other hand, the activities of /sup 11/C-pyruvate in both benign and malignant tumors were increased 34 - 131 % relative to normal brain tissue, and there was no difference between benign and malignant tumors. According to these findings, it might be concluded that benign and malignant tumors have mainly an anerobic glycolytic pathway. However, the findings of the alternation of /sup 11/C-glucose uptake suggest that, in addition to the anerobic glycolytic pathway, an alternative metabolic pathway of glucose, such as a pentose-phosphate pathway or an amino-acid-utilizing pathway, may also be present.

Tsukiyama, Takashi; Tsubokawa, Takashi; Kido, Goro; Kumakawa, Hitoshi; Iio, Masaaki; Hara, Toshihiko.

1988-06-01

171

Glucose metabolism in brain tumor as studied by positron-emission tomography  

International Nuclear Information System (INIS)

Although high rates of glycolysis have been correlated with malignancy in glioma on the basis of PET findings using 18-F-deoxyglucose, these results indicate only the activity of hexokinase in the tumor cells; they do not demonstrate what kinds of systems of glycolysis increase. In this report, the differences in the activities of systems of glycolysis on both benign and malignant tumors were studied by means of PET using 11C-glucose and 11C-pyruvate administration, along with PET studies of r-CBF, r-OEF and r-CMRO2. At a benign glioma, the uptake of 11C-glucose was lower than in normal brain tissue, with lower r-CBF, r-OEF, and r-CMRO2 values. Many malignant tumors and cases of meningioma showed increases in glucose uptake with lower oxygen metabolism. On the other hand, the activities of 11C-pyruvate in both benign and malignant tumors were increased 34 - 131 % relative to normal brain tissue, and there was no difference between benign and malignant tumors. According to these findings, it might be concluded that benign and malignant tumors have mainly an anerobic glycolytic pathway. However, the findings of the alternation of 11C-glucose uptake suggest that, in addition to the anerobic glycolytic pathway, an alternative metabolic pathway of glucose, such as a pentose-phosphate pathway or an amino-acid-utilizing pathway, may also be present. (author)

1988-01-01

172

Transient stimulation of glucose metabolism by insulin in the 1-day chick embryo.  

Science.gov (United States)

Effects of insulin upon glucose metabolism were investigated in chick embryos explanted in vitro during the first 30 h of incubation. Insulin stimulated the glucose consumption of the chick gastrula (18 h) and neurula (24 h), but had no effect on the late blastula (0 h:laying) and on the stage of six to eight somites (30 h). The increase in glucose consumption concerned both the embryonic area pellucida (AP) and extraembryonic area opaca (AO). AP responded to a greater extent (50%) and at a lower range of concentrations (0.1-1.0 ng/ml) than AO (30%; 1-100 ng/ml). Insulin had no effect on the oxygen consumption of blastoderms, whereas it stimulated the aerobic lactate production (approximately 70% of the additional glucose consumption was converted to lactate). The nanomolar range of stimulating concentrations suggests that insulin has a specific effect in the chick embryo, and that it could modulate glucose metabolism in ovo as well. The transient sensitivity of the embryo to insulin is discussed in relation to behavior of mesodermal cells. PMID:3517013

Baroffio, A; Raddatz, E; Markert, M; Kucera, P

1986-05-01

173

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

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

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

2008-01-01

174

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-"1"4C)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 ("1"4C)glucose metabolism averaged 1.7 x 10"-"2"1 and 0.5 x 10"-"2"1 mol/min per cell for aerobic and anaerobic sediment slurries, respectively; ("3H)thymidine incorporation rates averaged 43 x 10"-"2"4 and 9 x 10"-"2"4 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 ("1"4C)glucose metabolism; and (iii) the toxicity of the pollutants increased in the following order: anthracene, p,p'-dichlorodiphenyltrichloroethane, naphthalene, and pentachlorophenol

1985-01-01

175

Metabolic engineering of Escherichia coli for (2S)-pinocembrin production from glucose by a modular metabolic strategy.  

Science.gov (United States)

Flavonoids are valuable natural products widely used in human health and nutrition. Recent advances in synthetic biology and metabolic engineering have yielded improved strain titers and yields. However, current fermentation strategies often require supplementation of expensive phenylpropanoic precursors in the media and separate evaluation of each strategy in turn as part of the flavonoid pathway, implicitly assuming the modifications are additive. In this study, an Escherichia coli fermentation system was developed to bypass both of these problems. An eight-step pathway, consisting of 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (DAHPS), chorismate mutase/prephenate dehydratase (CM/PDT), phenylalanine ammonia lyase (PAL), 4-coumarate:CoA ligase (4CL), chalcone synthase (CHS), chalcone isomerase (CHI), malonate synthetase, and malonate carrier protein, was assembled on four vectors in order to produce the flavonoid precursor (2S)-pinocembrin directly from glucose. Furthermore, a modular metabolic strategy was employed to identify conditions that optimally balance the four pathway modules. Once this metabolic balance was achieved, such strains were capable of producing 40.02mg/L (2S)-pinocembrin directly from glucose. These results were attained by culturing engineered cells in minimal medium without additional precursor supplementation. The fermentation platform described here paves the way for the development of an economical process for microbial production of flavonoids directly from glucose. PMID:23246524

Wu, Junjun; Du, Guocheng; Zhou, Jingwen; Chen, Jian

2013-03-01

176

Demographic and metabolic characteristics of individuals with progressive glucose tolerance  

Directory of Open Access Journals (Sweden)

Full Text Available 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 pairs 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 < 0.02 with a similar insulin sensitivity index and a lower disposition index (3.9 ± 0.2 vs 4.1 ± 0.2 µmol·kg-1·min-1 ; P < 0.05 vs non-progressors. After 9 years, both groups presented similar increases in weight and fasting blood glucose levels and progressors had an increased glycemic response at 120 min (P < 0.05 and reduced early insulin response to OGTT (progressors, 1st: 2.10 ± 0.34 vs 2nd: 1.87 ± 0.25 pmol/mmol; non-progressors, 1st: 2.15 ± 0.28 vs 2nd: 2.03 ± 0.39 pmol/mmol; P < 0.05. Theses data suggest that ?-cell dysfunction might be a risk factor for type 2 diabetes mellitus.

A.L. Mendes

2009-03-01

177

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

Jacobsen, Siv Hesse; Bojsen-Møller, KN

2013-01-01

178

Glucose and Fatty Acid Metabolism in a 3 Tissue In-Vitro Model Challenged with Normo- and Hyperglycaemia  

Science.gov (United States)

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

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

2012-01-01

179

Petasin Activates AMP-Activated Protein Kinase and Modulates Glucose Metabolism.  

Science.gov (United States)

Petasin (1), a natural product found in plants of the genus Petasites, has beneficial medicinal effects, such as antimigraine and antiallergy activities. However, whether or not 1 modulates metabolic diseases is unknown. In this study, the effects of 1 on AMP-activated protein kinase (AMPK), which is considered a pharmacological target for treating metabolic diseases, are described. It was found that an extract of Petasites japonicus produces an increase in the phosphorylation of AMPK in vitro, and the main active compound 1 was isolated. When this compound was administered orally to mice, activation of AMPK in the liver, skeletal muscle, and adipose tissue was observed. Moreover, pretreatment with 1 enhanced glucose tolerance following the administration of a glucose solution to normal mice. The mechanism by which 1 activates AMPK was subsequently investigated, and an increased intracellular AMP/ATP ratio in the cultured cells treated with 1 occurred. In addition, treatment with petasin inhibited mitochondrial respiratory chain complex I. Taken together, the present results indicated that 1 modulates glucose metabolism and activates AMPK through the inhibition of mitochondrial respiration. The preclinical data suggested that petasin (1) could be useful for the treatment of metabolic diseases in humans. PMID:24871354

Adachi, Yusuke; Kanbayashi, Yayoi; Harata, Ikue; Ubagai, Risa; Takimoto, Tetsuya; Suzuki, Katsuya; Miwa, Tetsuya; Noguchi, Yasushi

2014-06-27

180

UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets  

DEFF Research Database (Denmark)

Uncoupling Protein 2 (UCP2) is expressed in the pancreatic β-cell, where it partially uncouples the mitochondrial proton gradient, decreasing both ATP-production and glucose-stimulated insulin secretion (GSIS). Increased glucose levels up-regulate UCP2 mRNA and protein levels, but the mechanism for UCP2 up-regulation in response to increased glucose is unknown. The aim was to examine the effects of glucokinase (GK) deficiency on UCP2 mRNA levels and to characterize the interaction between UCP2 and GK with regard to glucose-stimulated insulin secretion in pancreatic islets. UCP2 mRNA expression was reduced in GK+/â?? 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 UCP2â??/â?? and GK+/â?? islets compared with GK+/â?? islets and UCP2 deficiency improved glucose tolerance of GK+/â?? mice. Accordingly, UCP2 deficiency increased ATP-levels of GK+/â?? 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

 
 
 
 
181

Modeling of Xanthophyllomyces dendrorhous growth on glucose and overflow metabolism in batch and fed-batch cultures for astaxanthin production.  

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An astaxanthin-producing yeast Xanthophyllomyces dendrorhous ENM5 was cultivated in a liquid medium containing 50 g/L glucose as the major carbon source in stirred fermentors (1.5-L working volume) in fully aerobic conditions. Ethanol was produced during the exponential growth phase as a result of overflow metabolism or fermentative catabolism of glucose by yeast cells. After accumulating to a peak of 3.5 g/L, the ethanol was consumed by yeast cells as a carbon source when glucose in the culture was nearly exhausted. High initial glucose concentrations and ethanol accumulation in the culture had inhibitory effects on cell growth. Astaxanthin production was partially associated with cell growth. Based on these culture characteristics, we constructed a modified Monod kinetic model incorporating substrate (glucose) and product (ethanol) inhibition to describe the relationship of cell growth rate with glucose and ethanol concentrations. This kinetic model, coupled with the Luedeking-Piret equation for the astaxanthin production, gave satisfactory prediction of the biomass production, glucose consumption, ethanol formation and consumption, and astaxanthin production in batch cultures over 25-75 g/L glucose concentration ranges. The model was also applied to fed-batch cultures to predict the optimum feeding scheme (feeding glucose and corn steep liquor) for astaxanthin production, leading to a high volumetric yield (28.6 mg/L) and a high productivity (5.36 mg/L/day). PMID:18683256

Liu, Yuan-Shuai; Wu, Jian-Yong

2008-12-01

182

The role of the pancreatic endocannabinoid system in glucose metabolism.  

Science.gov (United States)

The endogenous cannabinoid system participates in the regulation of energy homeostasis, and this fact led to the identification of a new group of therapeutic agents for complicated obesity and diabetes. Cannabinoid receptor antagonists are now realities in clinical practice. The use of such antagonists for reducing body weight gain, lowering cholesterol and improving glucose homeostasis is based on the ability of the endocannabinoids to coordinately regulate energy homeostasis by interacting with central and peripheral targets, including adipose tissue, muscle, liver and endocrine pancreas. In this review we will analyse the presence of this system in the main cell types of the islets of Langerhans, as well as the physiological relevance of the endocannabinoids and parent acylethanolamides in hormone secretion and glucose homeostasis. We will also analyse the impact that these findings may have in clinical practice and the potential outcome of new therapeutic strategies for modulating glucose homeostasis and insulin/glucagon secretion. PMID:19285263

Bermúdez-Silva, Francisco J; Suárez Pérez, Juan; Nadal, Angel; Rodríguez de Fonseca, Fernando

2009-02-01

183

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

Science.gov (United States)

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

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

1995-04-15

184

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

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

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

2012-01-01

185

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

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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

186

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.)

1991-01-01

187

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

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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 int...

Cescon, Marzia; Johansson, Rolf

2012-01-01

188

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

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

Pei Dee

2007-01-01

189

Influence of castration-induced testosterone and estradiol deficiency on obesity and glucose metabolism in male Göttingen minipigs.  

Science.gov (United States)

Low testosterone and estradiol concentrations are predictive for the development of the metabolic syndrome in men and women, respectively. The aim of this study was to investigate the influence of sex hormone deficiency on food intake, body weight, body composition and glucose metabolism in male Göttingen minipigs. Five adult male Göttingen minipigs were studied before castration (pre-cast), 10-18 days (post-cast 1) and 10-11 weeks (post-cast 2) after castration. Parameters of interest were food intake, body weight, body fat percentage and sex hormone concentrations. Furthermore glucose tolerance, glucagon suppression, insulin resistance, beta cell function and disposition index were evaluated by oral and intravenous glucose tolerance tests. Castration led to almost complete disappearance of circulating testosterone and estradiol and secondarily to increased food intake, body weight and body fat percentage. Ten-eighteen days sex hormone deficiency (post-cast 1) did not significantly change any of the investigated metabolic parameters compared to pre-cast levels. Ten weeks after castration (post-cast 2) significant insulin resistance, glucose intolerance and hyperglucagonemia was found, and the beta cell function and the disposition index both were decreased. In conclusion, castration-induced sex hormone deficiency in male Göttingen minipigs results in hyperphagia, obesity and disturbed glucose metabolism, which are some of the features typical for the human metabolic syndrome. PMID:20420845

Christoffersen, Berit Oestergaard; Gade, Laust Peter; Golozoubova, Valeria; Svendsen, Ove; Raun, Kirsten

2010-10-01

190

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

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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

191

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease?  

Science.gov (United States)

Unlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD.

Dunn, Laura; Allen, George FG.; Mamais, Adamantios; Ling, Helen; Li, Abi; Duberley, Kate E.; Hargreaves, Iain P.; Pope, Simon; Holton, Janice L.; Lees, Andrew; Heales, Simon J.; Bandopadhyay, Rina

2014-01-01

192

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease.  

Science.gov (United States)

Unlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD. PMID:24300239

Dunn, Laura; Allen, George Fg; Mamais, Adamantios; Ling, Helen; Li, Abi; Duberley, Kate E; Hargreaves, Iain P; Pope, Simon; Holton, Janice L; Lees, Andrew; Heales, Simon J; Bandopadhyay, Rina

2014-05-01

193

Immobilization of Whole Cells Containing Glucose Isomerase.  

Science.gov (United States)

Various procedures for construction of secondary cellulose acetate membranes with entrapped whole cells (containing glucose isomerase) have been developed and studied. Different effects on the behavior of the constructed membranes were noted and reported....

B. J. Chen

1974-01-01

194

Assessment of Regional Glucose Metabolism in Aging Brain and Dementia with Positron-Emission Tomography.  

Science.gov (United States)

This paper explores the alterations in regional glucose metabolism that occur in elderly subjects and those with senile dementia compared to normal young volunteers. Results showed a tendency for the frontal regions to have a lower metabolic rate in patie...

M. Reivich A. Alavi S. Ferris D. Christman J. Fowler

1981-01-01

195

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

1990-01-01

196

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

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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

197

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

1986-01-01

198

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

Energy Technology Data Exchange (ETDEWEB)

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.

Meglasson, M.D.; Manning, C.D.; Najafi, H.; Matschinsky, F.M.

1986-12-01

199

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

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

1998-01-01

200

Regulation of glucose utilization in adipose cells and muscle after long-term experimental hyperinsulinemia in rats.  

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The effects of chronic insulin administration on the metabolism of isolated adipose cells and muscle were studied. Adipose cells from 2 and 6 wk insulin-treated and control rats, fed either chow or chow plus sucrose, were prepared, and insulin binding, 3-O-methylglucose transport, glucose metabolism, and lipolysis were measured at various insulin concentrations. After 2 wk of treatment, adipose cell size and basal glucose transport and metabolism were unaltered, but insulin-stimulated transpo...

Wardzala, L. J.; Hirshman, M.; Pofcher, E.; Horton, E. D.; Mead, P. M.; Cushman, S. W.; Horton, E. S.

1985-01-01

 
 
 
 
201

Berberine Improves Glucose Metabolism through Induction of Glycolysis  

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

2008-01-01

202

JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1?-mediated glucose metabolism.  

Science.gov (United States)

JMJD5, a Jumonji C domain-containing dioxygenase, is important for embryonic development and cancer growth. Here, we show that JMJD5 is up-regulated by hypoxia and is crucial for hypoxia-induced cell proliferation. JMJD5 interacts directly with pyruvate kinase muscle isozyme (PKM)2 to modulate metabolic flux in cancer cells. The JMJD5-PKM2 interaction resides at the intersubunit interface region of PKM2, which hinders PKM2 tetramerization and blocks pyruvate kinase activity. This interaction also influences translocation of PKM2 into the nucleus and promotes hypoxia-inducible factor (HIF)-1?-mediated transactivation. JMJD5 knockdown inhibits the transcription of the PKM2-HIF-1? target genes involved in glucose metabolism, resulting in a reduction of glucose uptake and lactate secretion in cancer cells. JMJD5, along with PKM2 and HIF-1?, is recruited to the hypoxia response element site in the lactate dehydrogenase A and PKM2 loci and mediates the recruitment of the latter two proteins. Our data uncover a mechanism whereby PKM2 can be regulated by factor-binding-induced homo/heterooligomeric restructuring, paving the way to cell metabolic reprogram. PMID:24344305

Wang, Hung-Jung; Hsieh, Ya-Ju; Cheng, Wen-Chi; Lin, Chun-Pu; Lin, Yu-shan; Yang, So-Fang; Chen, Chung-Ching; Izumiya, Yoshihiro; Yu, Jau-Song; Kung, Hsing-Jien; Wang, Wen-Ching

2014-01-01

203

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

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

2010-01-01

204

Development of fluorescent glucose bioprobes and their application on real-time and quantitative monitoring of glucose uptake in living cells.  

Science.gov (United States)

We developed a novel fluorescent glucose bioprobe, GB2-Cy3, for the real-time and quantitative monitoring of glucose uptake in living cells. We synthesized a series of fluorescent glucose analogues by adding Cy3 fluorophores to the ?-anomeric position of D-glucose through various linkers. Systematic and quantitative analysis of these Cy3-labeled glucose analogues revealed that GB2-Cy3 was the ideal fluorescent glucose bioprobe. The cellular uptake of this probe competed with the cellular uptake of D-glucose in the media and was mediated by a glucose-specific transport system, and not by passive diffusion. Flow cytometry and fluorescence microscopy analyses revealed that GB2-Cy3 is ten times more sensitive than 2-NBDG, a leading fluorescent glucose bioprobe. GB2-Cy3 can also be utilized for the quantitative flow cytometry monitoring of glucose uptake in metabolically active C2C12 myocytes under various treatment conditions. As opposed to a glucose uptake assay performed by using radioisotope-labeled deoxy-D-glucose and a scintillation counter, GB2-Cy3 allows the real-time monitoring of glucose uptake in living cells under various experimental conditions by using fluorescence microscopy or confocal laser scanning microscopy (CLSM). Therefore, we believe that GB2-Cy3 can be utilized in high-content screening (HCS) for the discovery of novel therapeutic agents and for making significant advances in biomedical studies and diagnosis of various diseases, especially metabolic diseases. PMID:21207611

Lee, Hyang Yeon; Lee, Jae Jeong; Park, Jongmin; Park, Seung Bum

2011-01-01

205

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

Science.gov (United States)

Control of energy metabolism is an essential process for life. In insects, egg formation (oogenesis) and embryogenesis is dependent on stored molecules deposited by the mother or transcribed later by the zygote. In oviparous insects the egg becomes an isolated system after egg laying with all energy conversion taking place during embryogenesis. Previous studies in a few vector species showed a strong correlation of key morphogenetic events and changes in glucose metabolism. Here, we investigate glycogen and glucose metabolism in the red flour beetle Tribolium castaneum, an insect amenable to functional genomic studies. To examine the role of the key enzymes on glycogen and glucose regulation we cloned and analyzed the function of glycogen synthase kinase 3 (GSK-3) and hexokinase (HexA) genes during T. castaneum embryogenesis. Expression analysis via in situ hybridization shows that both genes are expressed only in the embryonic tissue, suggesting that embryonic and extra-embryonic cells display different metabolic activities. dsRNA adult female injection (parental RNAi) of both genes lead a reduction in egg laying and to embryonic lethality. Morphological analysis via DAPI stainings indicates that early development is impaired in Tc-GSK-3 and Tc-HexA1 RNAi embryos. Importantly, glycogen levels are upregulated after Tc-GSK-3 RNAi and glucose levels are upregulated after Tc-HexA1 RNAi, indicating that both genes control metabolism during embryogenesis and oogenesis, respectively. Altogether our results show that T. castaneum embryogenesis depends on the proper control of glucose and glycogen. PMID:23750237

Fraga, Amanda; Ribeiro, Lupis; Lobato, Mariana; Santos, Vitória; Silva, José Roberto; Gomes, Helga; da Cunha Moraes, Jorge Luiz; de Souza Menezes, Jackson; de Oliveira, Carlos Jorge Logullo; Campos, Eldo; da Fonseca, Rodrigo Nunes

2013-01-01

206

Heterogeneous cerebral glucose metabolism in normal pressure hydrocephalus.  

Science.gov (United States)

The regional cerebral metabolic rate for glucose (rCMRglu) has never been investigated in large consecutive groups of patients with normal pressure hydrocephalus (NPH), a potentially treatable form of dementia with an unpredictable outcome after shunt surgery. Using PET and 18F-2-fluorodeoxyglucose, rCMRglu was studied in 18 patients who fulfilled hydrodynamic criteria for NPH and in whom a biopsy of the frontal cortex was obtained. When compared with an age matched group of 11 healthy subjects, the patients with NPH showed a significant rCMRglu reduction in all cortical and subcortical regions of interest. Individual metabolic patterns, however, disclosed a large topographical heterogeneity. Furthermore, histopathological examination identified Alzheimer's disease or cerebrovascular disease in six cases, and no parenchymal disease or non-specific degenerative processes in the remaining 12. After separating the patients according to the histological diagnosis, the rCMRglu patterns were still heterogeneous, the abnormalities ranging from focal to diffuse in both subgroups. After shunt operation, 11 patients did not improve or worsened clinically. Six patients improved; of those, two had Alzheimer changes and two cerebrovascular changes in their biopsy. The metabolic pattern of these six patients did not differ from the rest of the NPH group. The results indicate that the NPH syndrome may be non-specifically associated with different degenerative disorders. The metabolic heterogeneity, together with the heterogeneous histopathological findings, indicate the necessity of reevaluating the pathogenesis of the NPH syndrome, and may account for the high variability in the success rate of shunt surgery series. PMID:7500099

Tedeschi, E; Hasselbalch, S G; Waldemar, G; Juhler, M; Høgh, P; Holm, S; Garde, L; Knudsen, L L; Klinken, L; Gjerris, F

1995-12-01

207

Unmasking Glucose Metabolism Alterations in Stable Renal Transplant Recipients: A Multicenter Study  

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Background and objectives: Emerging information indicates that glucose metabolism alterations are common after renal transplantation and are associated with carotid atheromatosis. The aims of this study were to investigate the prevalence of different glucose metabolism alterations in stable recipients as well as the factors related to the condition.

Delgado, Patricia; Diaz, Juan Manuel; Silva, Irene; Osorio, Jose? M.; Osuna, Antonio; Baye?s, Beatriz; Lauzurica, Ricardo; Arellano, Edgar; Campistol, Jose Maria; Dominguez, Rosa; Go?mez-alamillo, Carlos; Ibernon, Meritxell; Moreso, Francisco; Benitez, Rocio; Lampreave, Ildefonso

2008-01-01

208

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

International Nuclear Information System (INIS)

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

1992-12-01

209

Comparative energetics of glucose and xylose metabolism in ethanologenic recombinant Escherichia coli B  

Energy Technology Data Exchange (ETDEWEB)

This study compared the anaerobic catabolism of glucose and xylose by a patented, recombinant ethanologenic Escherichia coli B 11303:pLOI297 in terms of overall yields of cell mass (growth), energy (ATP), and end product (ethanol). Batch cultivations were conducted with pH-controlled stirred-tank bioreactors using both a nutritionally rich, complex medium (Luria broth) and a defined salts minimal medium and growth-limiting concentrations of glucose or xylose. The value of {Upsilon}{sub ATP} was determined to be 9.28 and 8.19 g dry wt cells/mol ATP in complex and minimal media, respectively. Assuming that the nongrowth-associated energy demand is similar for glucose and xylose, the mass-based growth yield ({Upsilon}{sub x/s}, g dry wt cells/g sugar) should be proportional to the net energy yield from sugar metabolism. The value of {Upsilon}{sub x/s} was reduced, on average, by about 50% (from 0.096 g/g glu to 0.051 g/g xyl) when xylose replaced glucose as the growth-limiting carbon and energy source. It was concluded that this observation is consistent with the theoretical difference in net energy (ATP) yield associated with anaerobic catabolism of glucose and xylose when differences in the mechanisms of energy-coupled transport of each sugar are taken into account. In a defined salts medium, the net ATP yield was determined to be 2.0 and 0.92 for glucose and xylose, respectively.

Lawford, H.G.; Rousseau, J.D. [Univ. of Toronto, Ontario (Canada)

1995-12-31

210

Tumor necrosis factor- (TNF- in glutathione (GSH-depleted rats. A possible link to impaired glucose metabolism  

Directory of Open Access Journals (Sweden)

Full Text Available Rats: treated with the glutathione depleting agent, allyl alcohol (AlAl (1 mmol/kg was found to induce a marked increase in serum TNF- 45 minutes post treatment. This increase is suggested to play a critical role in the development of impaired glucose metabolism and glucose intolerance in AlAl-treated rats. Impaired glucose metabolism was evidenced by the significant increase in serum creatinine, urea and blood urea nitrogen accounting for accelerated glycolysis and breakdown of creatinine phosphate. These are the metabolic consequences of the activation of a back up system for the generation of ATP when the primary energy forming pathway is impaired. Meanwhile, the present data show a significant decrease in the serum levels of triglycerides and cholesterol in AlAl-treated rats that was accompanied with a concomitant increase in their liver levels indicating the development of fatty livers in these rats. Due to the strong link between TNF- and the GSH status and to the well established role of TNF- in causing insulin resistance, which is potentiated by fat accumulation in different tissues, it is concluded that the combination of TNF- overproduction, GSH depletion and lipid accumulation in the liver caused by AlAl treatment, cooperate making cells more sensitive to AlAl poisoning, therefore, imposing a potent negative impact on glucose metabolism. Added to the deleterious effects of TNF- , enhanced lipid peroxidation observed in AlAl- treated rats suggests possible alterations in the rates of glucose transport and metabolism which may further contribute to AlAl-induced impairment in glucose metabolism. Conclusion: Finally, the selective effect of TNF- in inhibiting insulin secretion give an additional support to its hypothesized role in initiating glucose intolerance in GSH-depleted rats

Sohair A. Moustafa

2008-12-01

211

Defects in pancreatic development and glucose metabolism in SMN-depleted mice independent of canonical spinal muscular atrophy neuromuscular pathology.  

Science.gov (United States)

Spinal muscular atrophy (SMA) is characterized by motor neuron loss, caused by mutations or deletions in the ubiquitously expressed survival motor neuron 1 (SMN1) gene. We recently identified a novel role for Smn protein in glucose metabolism and pancreatic development in both an intermediate SMA mouse model (Smn(2B/-)) and type I SMA patients. In the present study, we sought to determine if the observed metabolic and pancreatic defects are SMA-dependent. We employed a line of heterozygous Smn-depleted mice (Smn(+/-)) that lack the hallmark SMA neuromuscular pathology and overt phenotype. At 1 month of age, pancreatic/metabolic function of Smn(+/-)mice is indistinguishable from wild type. However, when metabolically challenged with a high-fat diet, Smn(+/-)mice display abnormal localization of glucagon-producing ?-cells within the pancreatic islets and increased hepatic insulin and glucagon sensitivity, through increased p-AKT and p-CREB, respectively. Further, aging results in weight gain, an increased number of insulin-producing ? cells, hyperinsulinemia and increased hepatic glucagon sensitivity in Smn(+/-)mice. Our study uncovers and highlights an important function of Smn protein in pancreatic islet development and glucose metabolism, independent of canonical SMA pathology. These findings suggest that carriers of SMN1 mutations and/or deletions may be at an increased risk of developing pancreatic and glucose metabolism defects, as even small depletions in Smn protein may be a risk factor for diet- and age-dependent development of metabolic disorders. PMID:24497575

Bowerman, Melissa; Michalski, John-Paul; Beauvais, Ariane; Murray, Lyndsay M; DeRepentigny, Yves; Kothary, Rashmi

2014-07-01

212

Defects in pancreatic development and glucose metabolism in SMN-depleted mice independent of canonical spinal muscular atrophy neuromuscular pathology  

Science.gov (United States)

Spinal muscular atrophy (SMA) is characterized by motor neuron loss, caused by mutations or deletions in the ubiquitously expressed survival motor neuron 1 (SMN1) gene. We recently identified a novel role for Smn protein in glucose metabolism and pancreatic development in both an intermediate SMA mouse model (Smn2B/?) and type I SMA patients. In the present study, we sought to determine if the observed metabolic and pancreatic defects are SMA-dependent. We employed a line of heterozygous Smn-depleted mice (Smn+/?) that lack the hallmark SMA neuromuscular pathology and overt phenotype. At 1 month of age, pancreatic/metabolic function of Smn+/?mice is indistinguishable from wild type. However, when metabolically challenged with a high-fat diet, Smn+/?mice display abnormal localization of glucagon-producing ?-cells within the pancreatic islets and increased hepatic insulin and glucagon sensitivity, through increased p-AKT and p-CREB, respectively. Further, aging results in weight gain, an increased number of insulin-producing ? cells, hyperinsulinemia and increased hepatic glucagon sensitivity in Smn+/?mice. Our study uncovers and highlights an important function of Smn protein in pancreatic islet development and glucose metabolism, independent of canonical SMA pathology. These findings suggest that carriers of SMN1 mutations and/or deletions may be at an increased risk of developing pancreatic and glucose metabolism defects, as even small depletions in Smn protein may be a risk factor for diet- and age-dependent development of metabolic disorders.

Bowerman, Melissa; Michalski, John-Paul; Beauvais, Ariane; Murray, Lyndsay M.; DeRepentigny, Yves; Kothary, Rashmi

2014-01-01

213

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

DEFF Research Database (Denmark)

PURPOSE: 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 ([(18)F]FAZA), a promising but not well-characterised hypoxia-specific tracer, and fluorodeoxyglucose ([(18)F]FDG) in four carcinoma cell lines. METHODS: 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 ([(18)F]FDG + [(18)F]FAZA) or re-incubated in tracer-free oxygenated medium and then measured ([(18)F]FAZA). Next, we tested the reliability of [(18)F]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. RESULTS: Three hours of anoxia strongly stimulated [(18)F]FAZA retention with anoxic-to-oxic uptake ratios typically above 30. Three out of four cell lines displayed similar selectivity of [(18)F]FDG versus glucose, but oxic uptake and anoxic-to-oxic uptake ratio of [(18)F]FDG varied considerably. Although less pronounced, [(18)F]FAZA also showed superior in vivo hypoxia specificity compared with [(18)F]FDG. CONCLUSIONS: [(18)F]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 [(18)F]FDG as a surrogate marker for hypoxia is questionable due to large variations in baseline (oxic) glucose metabolism and magnitudes of the Pasteur effects.

Busk, Morten; Horsman, Michael R

2008-01-01

214

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

Energy Technology Data Exchange (ETDEWEB)

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 ([{sup 18}F]FAZA), a promising but not well-characterised hypoxia-specific tracer, and fluorodeoxyglucose ([{sup 18}F]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 ([{sup 18}F]FDG+[{sup 18}F]FAZA) or re-incubated in tracer-free oxygenated medium and then measured ([{sup 18}F]FAZA). Next, we tested the reliability of [{sup 18}F]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 [{sup 18}F]FAZA retention with anoxic-to-oxic uptake ratios typically above 30. Three out of four cell lines displayed similar selectivity of [{sup 18}F]FDG versus glucose, but oxic uptake and anoxic-to-oxic uptake ratio of [{sup 18}F]FDG varied considerably. Although less pronounced, [{sup 18}F]FAZA also showed superior in vivo hypoxia specificity compared with [{sup 18}F]FDG. [{sup 18}F]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 [{sup 18}F]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.)

Busk, Morten; Horsman, Michael R.; Overgaard, Jens [Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus C (Denmark); Jakobsen, Steen [Aarhus University Hospital, PET Centre, Aarhus (Denmark); Bussink, Johan; Kogel, Albert van der [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands)

2008-12-15

215

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 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

1995-01-01

216

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

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

2013-01-01

217

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

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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 ...

Carbó Roxana; Guarner Verónica

2010-01-01

218

Decreased Insulin Receptors but Normal Glucose Metabolism in Duchenne Muscular Dystrophy  

Science.gov (United States)

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

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

1982-04-01

219

Relationship between fatty liver and glucose metabolism: A cross-sectional study in 571 obese children  

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BACKGROUND AND AIMS: Early onset type 2 diabetes mellitus (T2DM) is associated with obesity, insulin resistance and impaired beta-cell function. Non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for T2DM. We investigated the relationship between NAFLD and glucose metabolism in a large sample of obese children. METHODS AND RESULTS: A total of 571 obese children (57% males and 43% females) aged 8-18 years were consecutively studied at a tertiary care centre specialised...

Bedogni, G.; Gastaldelli, A.; Manco, M.; Col, A.; Agosti, F.; Tiribelli, C.; Sartorio, A.

2011-01-01

220

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.)

1976-01-01

 
 
 
 
221

Cerebral glucose metabolism after portacaval shunting in the rat. Patterns of metabolism and implications for the pathogenesis of hepatic encephalopathy.  

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The regional cerebral metabolic rate for glucose was measured in normal and portacaval shunted rats and the effects of unilateral carotid infusions of "threshold" amounts of ammonia were assessed. 8 wk after shunting the glucose metabolic rate was increased in all 20 brain regions sampled. Effects on subcortical and phylogenetically older regions of the brain were most pronounced with a 74% increase observed in the reticular formation at the collicular level. Increases in the cerebral cortex ...

Lockwood, A. H.; Ginsberg, M. D.; Rhoades, H. M.; Gutierrez, M. T.

1986-01-01

222

Trypanosoma cruzi infection alters glucose metabolism at rest and during exercise without modifying the morphology of pancreatic islets in rats.  

Science.gov (United States)

This study investigated the effects of Trypanosoma cruzi infection on pancreatic morphology and glucose metabolism at rest and during exercise. Wistar rats were randomized into control (CG=10) and infected (IG=10) groups. The IG animals were inoculated with T. cruzi Y strain (300,000 trypomastigotes/50 g). After 9 weeks, the animals were subjected to glucose (OGTT) and insulin (ITT) tolerance tests and a treadmill running protocol. Blood glucose, lactate and time to fatigue were determined. After euthanasia, the pancreases were removed for morphological and biochemical analyses. The IG presented abnormal glucose kinetics in OGTT and a similar glucose curve in ITT compared to the CG. During the exercise test, the IG showed anticipation of time to fatigue. At the point of fatigue, no difference was found in blood glucose and lactate between the groups. There was a significant correlation between lactate levels and the time to fatigue. The IG presented marked pancreatic inflammation, fibrosis and protein oxidation. The number of ? cells in the IG animals was not reduced. T. cruzi infection impaired pancreas morphology and glucose metabolism at rest and during exercise in rats, which could constitute an additional mechanism in the induction of exercise intolerance in Chagas' disease. PMID:22749578

Novaes, Rômulo D; Gonçalves, Reggiani V; Penitente, Arlete R; Talvani, André; Neves, Clóvis A; Natali, Antônio J; Maldonado, Izabel R S C

2012-08-15

223

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

224

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

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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

225

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

Scientific Electronic Library Online (English)

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

André Belico de, Vasconcelos; Patrícia Castanheira de, Souza; Fabiana Cristina, Varago; Monique de Albuquerque, Lagares; Marcelo Matos, Santoro.

226

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

Energy Technology Data Exchange (ETDEWEB)

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 10{sup 7} cells/ml by {sup 1}H-, {sup 19}F-, {sup 31}P-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 {alpha}- and {beta}-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 {alpha} and {beta}-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 disaccharides were observed. Thus, in contrast to UDP-Glc, UDP-DG, Glc6P and DG6P, UDP-FDG and FDG6P are not good substrates for trehalose-6-P synthetase. The effect of DG and FDG on the cell growth in standard nutrient media was also investigated at 37 deg C. The cell growth was found to be completely inhibited upon addition of 1 mM FDG and only slowed down in the presence of 1 mM DG. In the latter case, the doubling time {tau} 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. (Abstract Truncated)

Tran-Dinh, S.; Courtois, A.; Wietzerbin, J. [CEA Centre d`Etudes de Saclay, 91-Gif-sur-Yvette (France). Dept. de Biologie Cellulaire et Moleculaire; Bouet, F. [CEA Centre d`Etudes de Saclay, 91 -Gif-sur-Yvette (France). Direction des Sciences du Vivant; Herve, M. [CEA Centre d`Etudes de Saclay, 91 Gif-sur-Yvette (France). Dept. de Biologie Cellulaire et Moleculaire (France)]|[Paris-13 Univ., 93 -Saint-Denis (France)

1995-12-31

227

Inhibition of murine splenic T lymphocyte proliferation by 2-deoxy-D-glucose-induced metabolic stress  

Science.gov (United States)

Female Swiss-Webster mice were injected with the glucose analogue 2-deoxy-D-glucose (2-DG), which when administered to rodents induces acute periods of metabolic stress. A single or multiple injections of 2-DG invoked a stress response, as evidenced by increases in serum corticosterone levels. The influence of this metabolic stressor on the blastogenic potential of splenic T lymphocytes was then examined. It was found that one, two, or three injections of 2-DG resulted in depressed T cell proliferative responses, with an attenuation of the effect occurring by the fifth injection. The 2-DG-induced inhibition of T cell proliferation was not attributable to 2-DG-induced cytolysis, as in vitro incubation of naive T cells with varying concentrations of 2-DG did not result in a reduction in cell number or viability, and flow cytometric analysis demonstrated that percentages of CD3, CD4, and CD8 splenic T cells were not altered as a result of 2-DG-induced stress. Incubating naive T cells in varying concentrations of 2-DG resulted in a dose-dependent inhibition of T cell blastogenic potential. Following in vivo exposure to 2-DG, T cell proliferation did not return to normal levels until 3 days after the cessation of 2-DG injections. Administering the beta-adrenergic receptor antagonist propranolol did not reverse the inhibited lymphoproliferation in 2-DG-treated mice. The inhibition in T cell proliferation was not observed, however, in mice that had been adrenalectomized or hypophysectomized and injected with 2-DG.(ABSTRACT TRUNCATED AT 250 WORDS).

Miller, E. S.; Klinger, J. C.; Akin, C.; Koebel, D. A.; Sonnenfeld, G.

1994-01-01

228

LIPOCALIN 13 REGULATION OF GLUCOSE AND LIPID METABOLISM IN OBESITY  

Science.gov (United States)

Summary Lipocalin (LCN) family members are small secreted proteins that bind to small hydrophobic molecules via their characteristic central ?-barrels. A couple of LCN family members, including major urinary protein 1 (MUP1), retinol-binding protein 4 (RBP4), LCN2, and LCN13, have been reported to regulate insulin sensitivity and nutrient metabolism. LCN13 is expressed by multiple tissues, including the liver, pancreas, epididymis, and skeletal muscle, and is secreted into the bloodstream in mice. Obesity is associated with a downregulation of LCN13 expression and lower levels of circulating LCN13. LCN13 therapies overcome LCN13 deficiency in mice with either genetic or dietary obesity, leading to an improvement in hyperglycemia, hyperinsulinemia, insulin resistance, glucose intolerance, and hepatic steatosis. In hepatocytes, LCN13 directly suppresses hepatic gluconeogenesis and lipogenesis but increases fatty acid ? oxidation. LCN13 also enhances insulin sensitivity in adipocytes. The potential mechanisms of the anti-diabetes and anti-steatosis actions of LCN13 are discussed.

Zhou, Yingjiang; Rui, Liangyou

2014-01-01

229

Demographic and metabolic characteristics of individuals with progressive glucose tolerance  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 pairs 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...

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

2009-01-01

230

Glucose metabolism in obese and lean adolescents with polycystic ovary syndrome.  

Science.gov (United States)

Data on glucose metabolism in Asian adolescents with polycystic ovary syndrome (PCOS) are limited. Glucose metabolism assessment using an oral glucose tolerance test (OGTT) in obese and lean Thai adolescents with PCOS, and a comparison between the two groups were done. Thirty-one patients (19 obese, 12 lean) were enrolled. Their median (range) age was 14.9 (11.0-21.0) years. Eighteen patients had abnormal glucose metabolism (13 hyperinsulinemia, 4 impaired glucose tolerance, and 1 diabetes). Compared between obese [median (range) BMI Z-score, 1.6 (1.2-2.6)] and lean [median (range) BMI Z-score, 0.1 (-1.4 to 0.6)] patients, the frequencies of each abnormal OGTT category, areas under the curves of glucose and insulin levels, and insulinogenic index were not different; however, insulin resistance was greater in the obese group. In conclusion, a high proportion of our adolescents with PCOS had abnormal glucose metabolism. Therefore, OGTT should be performed in adolescents with PCOS for the early detection of abnormal glucose metabolism. PMID:23314524

Poomthavorn, Preamrudee; Chaya, Weerapong; Mahachoklertwattana, Pat; Sukprasert, Matchuporn; Weerakiet, Sawaek

2013-01-01

231

Role of sleep duration in the regulation of glucose metabolism and appetite.  

Science.gov (United States)

Sleep curtailment has become a common behavior in modern society. This review summarizes the current laboratory evidence indicating that sleep loss may contribute to the pathophysiology of diabetes mellitus and obesity. Experimentally induced sleep loss in healthy volunteers decreases insulin sensitivity without adequate compensation in beta-cell function, resulting in impaired glucose tolerance and increased diabetes risk. Lack of sleep also down-regulates the satiety hormone leptin, up-regulates the appetite-stimulating hormone ghrelin, and increases hunger and food intake. Taken together with the epidemiologic evidence for an association between short sleep and the prevalence or incidence of diabetes mellitus and/or obesity, these results support a role for reduced sleep duration in the current epidemic of these metabolic disorders. Screening for habitual sleep patterns in patients with "diabesity" is therefore of great importance. Studies are warranted to investigate the putative therapeutic impact of extending sleep in habitual short sleepers with metabolic disorders. PMID:21112019

Morselli, Lisa; Leproult, Rachel; Balbo, Marcella; Spiegel, Karine

2010-10-01

232

Role of sleep duration in the regulation of glucose metabolism and appetite  

Science.gov (United States)

Sleep curtailment has become a common behavior in modern society. This review summarizes the current laboratory evidence indicating that sleep loss may contribute to the pathophysiology of diabetes mellitus and obesity. Experimentally-induced sleep loss in healthy volunteers decreases insulin sensitivity without adequate compensation in beta-cell function, resulting in impaired glucose tolerance and increased diabetes risk. Lack of sleep also down-regulates the satiety hormone leptin, up-regulates the appetite-stimulating hormone ghrelin, and increases hunger and food intake. Taken together with the epidemiologic evidence for an association between short sleep and the prevalence or incidence of diabetes mellitus and/or obesity, these results support a role for reduced sleep duration in the current epidemic of these metabolic disorders. Screening for habitual sleep patterns in patients with “diabesity” is therefore of great importance. Studies are warranted to investigate the putative therapeutic impact of extending sleep in habitual short sleepers with metabolic disorders.

Morselli, Lisa; Leproult, Rachel; Balbo, Marcella

2010-01-01

233

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

Energy Technology Data Exchange (ETDEWEB)

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).

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

1992-11-01

234

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 alkalosis

1989-01-01

235

Regional glucose metabolism in acute head injury as determined by positron emission tomography  

International Nuclear Information System (INIS)

The effects of head injury on regional glucose metabolism, as determined by PET, were investigated. The data described demonstrate the potential usefulness of PET in identifying functional and biochemical derangements that occur with head injury. (author). 6 refs

1988-10-01

236

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1981-01-01

237

Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels  

International Nuclear Information System (INIS)

Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either [6-14C]glucose or [1-14C]oleic acid and the incorporation of radioactivity into 14CO2, lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO2 was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to 14CO2 was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO2 and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously

1987-01-01

238

Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels  

Energy Technology Data Exchange (ETDEWEB)

Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either (6-/sup 14/C)glucose or (1-/sup 14/C)oleic acid and the incorporation of radioactivity into /sup 14/CO/sub 2/, lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO/sub 2/ was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to /sup 14/CO/sub 2/ was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO/sub 2/ and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously.

Hingorani, V.; Brecher, P.

1987-05-01

239

Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels.  

Science.gov (United States)

Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either [6-14C]glucose or [1-14C]oleic acid and the incorporation of radioactivity into 14CO2, lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO2 was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to 14CO2 was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO2 and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously. PMID:3578513

Hingorani, V; Brecher, P

1987-05-01

240

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

 
 
 
 
241

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

DEFF Research Database (Denmark)

We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp (HI), 40 mU/m(2) x min], 3-(3)H-glucose, indirect calorimetry, and iv glucose tolerance test. Free fatty acid concentrations were similar during basal steady state but 3.7- to 13-fold higher during clamps. P-glucagon increased and the insulin/glucagon ratio decreased at both LI and HI during Intralipid infusion. At LI, glucose oxidation decreased by 10%, whereas glucose disposal, glycolytic flux, glucose storage, and glucose production were not significantly altered. At HI, glucose disposal, and glucose oxidation decreased by 12% and 24%, respectively, during Intralipid infusion. Glycolytic flux, glucose storage, and glucose production were unchanged. Insulin secretion rates increased in response to Intralipid infusion, but disposition indices (DI = insulin action.insulin secretion) were unchanged. In conclusion, a 24-h low-grade Intralipid infusion caused insulin resistance in the oxidative (but not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes.

Jensen, Christine B; Storgaard, Heidi

2003-01-01

242

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

DEFF Research Database (Denmark)

We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp (HI), 40 mU/m(2) x min], 3-(3)H-glucose, indirect calorimetry, and iv glucose tolerance test. Free fatty acid concentrations were similar during basal steady state but 3.7- to 13-fold higher during clamps. P-glucagon increased and the insulin/glucagon ratio decreased at both LI and HI during Intralipid infusion. At LI, glucose oxidation decreased by 10%, whereas glucose disposal, glycolytic flux, glucose storage, and glucose production were not significantly altered. At HI, glucose disposal, and glucose oxidation decreased by 12% and 24%, respectively, during Intralipid infusion. Glycolytic flux, glucose storage, and glucose production were unchanged. Insulin secretion rates increased in response to Intralipid infusion, but disposition indices (DI = insulin action.insulin secretion) were unchanged. In conclusion, a 24-h low-grade Intralipid infusion caused insulin resistance in the oxidative (but not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes.

Jensen, Christine B; Storgaard, Heidi

2003-01-01

243

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

Kennes, C.; Veiga, M. C.; Dubourguier, H. C.; Touzel, J. P.; Albagnac, G.; Naveau, Henry; Nyns, Edmond-jacques

1991-01-01

244

Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer's disease  

Digital Repository Infrastructure Vision for European Research (DRIVER)

It has been established for a long time that brain glucose metabolism is impaired in Alzheimer's disease. Recent studies have demonstrated that impaired brain glucose metabolism precedes the appearance of clinical symptoms, implying its active role in the development of Alzheimer's disease. However, the molecular mechanism by which this impairment contributes to the disease is not known. In this study, we demonstrated that protein O-GlcNAcylation, a common post-translational modification of n...

Liu, Fei; Shi, Jianhua; Tanimukai, Hitoshi; Gu, Jinhua; Gu, Jianlan; Grundke-iqbal, Inge; Iqbal, Khalid; Gong, Cheng-xin

2009-01-01

245

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

246

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

Pin, Carmen; Garci?a Fernando, Gonzalo D.; Ordo?n?ez, Juan A.

2002-01-01

247

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2004-01-01

248

Histamine Regulation in Glucose and Lipid Metabolism via Histamine Receptors : Model for Nonalcoholic Steatohepatitis in Mice  

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Histamine has been proposed to be an important regulator of energy intake and expenditure. The aim of this study was to evaluate histamine regulation of glucose and lipid metabolism and development of nonalcoholic steatohepatitis (NASH) with a hyperlipidemic diet. Histamine regulation of glucose and lipid metabolism, adipocytokine production, and development of hyperlipidemia-induced hepatic injury were studied in histamine H1 (H1R?/?) and H2 (H2R?/?) receptor knockout and wild-type m...

Wang, Ke-yong; Tanimoto, Akihide; Yamada, Sohsuke; Guo, Xin; Ding, Yan; Watanabe, Teruo; Watanabe, Takeshi; Kohno, Kimitoshi; Hirano, Ken-ichi; Tsukada, Hideo; Sasaguri, Yasuyuki

2010-01-01

249

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

Energy Technology Data Exchange (ETDEWEB)

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

Finan, A.; Cleary, M.P.

1986-03-05

250

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

International Nuclear Information System (INIS)

DHEA has been shown to competitively inhibit the pentose phosphate shunt (PPS) enzyme glucose-6-phosphate dehydrogenase (G6PD) when added in vitro to supernatants or homogenates prepared from mammalian tissues. However, no consistent effect on G6PD activity has been determined in tissue removed from DHEA-treated rats. To explore the effects of DHEA on PPS, glucose utilization was measured in hepatocytes from lean and obese male Zucker rats (8 wks of age) following 1 wk of DHEA treatment (0.6% in diet). Incubation of isolated hepatocytes from treated lean Zucker rats with either [1-"1"4C] glucose or [6-"1"4C] glucose resulted in significant decreases in CO_2 production and total glucose utilization. DHEA-lean rats also had lowered fat pad weights. In obese rats, there was no effect of 1 wk of treatment on either glucose metabolism or fat pad weight. The calculated percent contribution of the PPS to glucose metabolism in hepatocytes was not changed for either DHEA-lean or obese rats when compared to control rats. In conclusion, 1 wk of DHEA treatment lowered overall glucose metabolism in hepatocytes of lean Zucker rats, but did not selectively affect the PPS. The lack of an effect of short-term treatment in obese rats may be due to differences in their metabolism or storage/release of DHEA in tissues in comparison to lean rats

1986-03-05

251

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

252

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

2013-10-11

253

Glucose metabolism in relation to perfusion in patients with ischaemic heart disease  

International Nuclear Information System (INIS)

In order to correlate myocardial perfusion and residual metabolism in patients with coronary artery disease, the regional metabolic rate of glucose (rMRGlu) was compared with regional perfusion under glucose loading state (GL) and fasting state (FA). Fluorine-18 deoxyglucose dynamic scan was obtained in ten patients after oral GL and in 16 patients under FA. rMRGlu in seven segments was calculated using Patlak graphic analysis for comparison with normalized percent uptake of nitrogen-13 ammonia at rest in each segment. When perfusion was less than 45%, no segment showed an increase in rMRGlu (? 0.3 ?mol/min/g) under either FA (0/6 segment) or GL (0/8 segments), indicating a certain threshold of perfusion for maintenance of glucose metabolism. When perfusion exceeded 45%, rMRGlu was higher in GL (0.37 ± 0.18 ?mol/min/g) than FA (0.15 ± 0.12 ?mol/min/g, P < 0.001) but there was very wide scatter of rMRGlu values under both states. Thus, both myocardium with preserved and myocardium with reduced glucose metabolism may exist when the perfusion exceeds 45%. In conclusion, a minimum threshold of perfusion for the maintenance of glucose metabolism may exist under both FA and GL. Below the threshold, irreversible damage may occur in the myocardium. Above the threshold, quantitative analysis of glucose metabolism should play an important role in differentiating reversibly injured myocardium from necrotic myocardium. (orig.)

1994-04-01

254

The glucose-deprivation network counteracts lapatinib-induced toxicity in resistant ErbB2-positive breast cancer cells  

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This study implicates the glucose deprivation response in breast cancer cell resistance to lapatinib and high relapse rates in Her2-positive patients. Identification of these compensatory networks suggests novel strategies to target cancer signaling and metabolism.

Komurov, Kakajan; Tseng, Jen-te; Muller, Melissa; Seviour, Elena G.; Moss, Tyler J.; Yang, Lifeng; Nagrath, Deepak; Ram, Prahlad T.

2012-01-01

255

Glucose uptake rates of single E. coli cells grown in glucose-limited chemostat cultures.  

Science.gov (United States)

To evaluate the extent to which single-cell glucose uptake rates determine the overall specific growth rate of a culture, dilute chemostat cultures of Escherichia coli BL21 were grown in defined medium under glucose limitation. The glucose uptake dynamics of the cell population was examined at the single-cell level using the fluorescent glucose analog, 2-NBDG. Between dilution rates of 0.12 h(-1) and 0.40 h(-1), mean cellular protein content and steady-state, extracellular glucose concentrations increased with increasing dilution rate. However, the distribution of 2-NBDG uptake rates in the population remained constant over the range of dilution rates studied. This indicates that the growth of cells in continuous culture is not limited by the maximum rate of uptake of glucose but by the availability of glucose for transport. The work represents an example of how quantitative flow cytometry can be applied to gain detailed insight into microbial growth physiology. PMID:11000435

Natarajan, A; Srienc, F

2000-09-01

256

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

Directory of Open Access Journals (Sweden)

Full Text Available Objective ?To investigate the protein expression of transcriptional coactivator p300, acetylated histone H3 (Ac-H3 and Ac-H4 in human renal mesangial cell (HMCs as imitative "metabolic memory" in vitro, and explore the potential role of convergence point of p300. Methods ?The HMCs were divided into the following groups: ? High glucose metabolic memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d, high glucose group (HG, 25mmol/L D-glucose×2d, memory groups (M1, M2, M3, 25mmol/L D-glucose×2days + 5.5mmol/L D-glucose×3d, 6d or 9d, persisting normal glucose group (NG, 5.5mmol/L D-glucose×9d. ? Advanced glycation end products memory model: normal glucose group (NG, 5.5mmol/ L D-glucose×2d, NG+AGEs group (AGEs, 5.5mmol/L D-glucose+250µg/ml AGEs×2d; AGEs memory group (AGEs-M, 5.5mmol/L D-glucose + 250µg/ml AGEs×2d + 5.5mmol/L D-glucose×3d; BSA control group (NG+BSA, 5.5mmol/L D-glucose + 250µg/ml BSA×2d. ? H2O2 was used to simulate oxidative stress memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d, NG+H2O2 group (H2O2, 5.5mmol/L D-glucose +100µmol/L H2O2×30min; H2O2 memory group [(5.5mmol/ L D-glucose + 100µmol/L H2O2×30min + 5.5mmol/L D-glucose×3d]; normal glucose control group (NG3, 5.5mmol/L D-glucose×3d. ? Transfection with PKC?2 memory model: normal glucose group (NG, 5.5mmol/L D-glucose×2d; high glucose group (HG, 25mmol/L D-glucose×2d; memory group (M, 25mmol/L D-glucose×2d + 5.5mmol/L D-glucose×3d; Ad5-null memory group (HN, 25mmol/L D-glucose + Ad5-null×2d + 5.5mmol/L D-glucose×3d; PKC?2 memory group (PO, 25mmol/L D-glucose + Ad5-PKC?2×2d + 5.5mmol/L D-glucose×3d; inhibitor of PKC?2 memory group (PI, 25mmol/L D-glucose×2d + 10µmol/L CGP53353 + 5.5mmol/L D-glucose×3d. The expression of intracellular reactive oxygen species (ROS was detected by fluorescence microscope and fluorescence microplate reader. The expression levels of p300, Ac-H3, Ac-H4 and PKC?2 proteins were determined by Western blotting. Results ?The expression levels of p300, Ac-H3 and Ac-H4 protein in HG group increased, being 2.15, 1.93 and 1.87 fold of those in group NG (P<0.05, accompanying with the up-regulation of PKC?2 protein and ROS levels in HG group. The p300, Ac-H3, Ac-H4, PKC?2 protein expression and ROS levels in M1, M2, M3 group were higher than those in NG group, and was 1.75, 1.49, 1.47, 1.98 and 1.48 fold higher in M3 group than in NG group. The protein expressions of p300, Ac-H3 and Ac-H4 in AGEs group were increased by 1.73, 1.08 and 1.05 folds, and in AGE-M group increased by 1.47, 0.95 and 1.03 folds of that in control group (P<0.05. The protein expression levels of p300, Ac-H3 and Ac-H4 in H2O2 group increased by 1.03, 0.85 and 0.79 folds of those in control group (P<0.05. However, no significantly difference in these indices was found between H2O2-M and control groups. The protein expression levels of p300, Ac-H3 and Ac-H4 in PO group increased more obviously by 1.25, 1.06 and 1.10 folds of those in M group (P<0.05. However, the elective PKC?2 inhibitor CGP53353 could lower those indices significantly. Conclusion ?Persistent activation of transcriptional coactivator p300 and apparent modification may be normalized in HMCs. p300 may be the convergent point of glucose-induced metabolic "memory" stimulations.

Hong SU

2013-03-01

257

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

258

Hexokinase-mitochondrial interactions regulate glucose metabolism differentially in adult and neonatal cardiac myocytes  

Science.gov (United States)

In mammalian tumor cell lines, localization of hexokinase (HK) isoforms to the cytoplasm or mitochondria has been shown to control their anabolic (glycogen synthesis) and catabolic (glycolysis) activities. In this study, we examined whether HK isoform differences could explain the markedly different metabolic profiles between normal adult and neonatal cardiac tissue. We used a set of novel genetically encoded optical imaging tools to track, in real-time in isolated adult (ARVM) and neonatal (NRVM) rat ventricular myocytes, the subcellular distributions of HKI and HKII, and the functional consequences on glucose utilization. We show that HKII, the predominant isoform in ARVM, dynamically translocates from mitochondria and cytoplasm in response to removal of extracellular glucose or addition of iodoacetate (IAA). In contrast, HKI, the predominant isoform in NRVM, is only bound to mitochondria and is not displaced by the above interventions. In ARVM, overexpression of HKI, but not HKII, increased glycolytic activity. In neonatal rat ventricular myocytes (NVRM), knockdown of HKI, but not HKII, decreased glycolytic activity. In conclusion, differential interactions of HKI and HKII with mitochondria underlie the different metabolic profiles of ARVM and NRVM, accounting for the markedly increased glycolytic activity of NRVM.

Calmettes, Guillaume; John, Scott A.

2013-01-01

259

The use of /sup 11/C-glucose and positron emission tomography to measure brain glucose metabolism  

International Nuclear Information System (INIS)

To measure regional cerebral metabolism of glucose (CMRGlu) with positron emission tomography (PET), but avoid the potential problems inherent in the use of /sup 18/F-fluoro-deoxyglucose, (e.g. regional variation in regional rate constants and instability of the ''lumped constant''), the authors have developed a method using uniformly labeled /sup 11/C-glucose. The method employs a 4-compartment model that accounts for vascular tracer, transport of tracer in and out of the extravascular space, metabolism of tracer, and the production of labeled carbon dioxide, which is free to leave the tissue with blood flow. The differential equations for this model, when solved for CMRGlu, yield CMRGlu=k/sub 1/ . k/sub 3/ . CBF . C/sub B//[k/sub 1/ . k/sub 3/+CBF/CBV . (k/sub 2/+k/sub 3/)] where CBF and CBV are cerebral blood flow and volume, C/sub B/ is unlabeled blood glucose content, k/sub 1/ and k/sub 2/ are transport rate constants and k/sub 3/ is the metabolism rate constant. The authors have begun implementing this technique in baboons and human subjects by first measuring regional CBV and CBF with extant PET methods, then after injection of 20-40mCi of U-/sup 11/C-glucose, estimating the rate constants from 40 sequential PET scans taken over 20 minutes. Resulting white-to-gray matter range in CMRGlu for one typical human subject was 2.9 to 6.3 mg/(min . 100 mg). Oxygen metabolism (CMRO/sub 2/) was also measured at the same sitting with PET and the molar ratio of CMRO/sub 2//CMRGlu ranged from 5.8 to 6.4 as would be expected. These results demonstrate that it may be feasible to avoid the difficulties of an analogue tracer in the measurement of CMRGlu by using /sup 11/C-glucose

1985-05-01

260

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

Science.gov (United States)

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

Klein, C J; Olsson, L; R?nnow, B; Mikkelsen, J D; Nielsen, J

1996-01-01

 
 
 
 
261

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

DEFF Research Database (Denmark)

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

Klein, Christopher; Olsson, Lisbeth

1996-01-01

262

Investigation of 18F-2-deoxyglucose for the measure of myocardial glucose metabolism  

International Nuclear Information System (INIS)

18F labeled 2-deoxyglucose (18FDG) was studied as a glucose analog. Myocardial uptake and retention, blood clearance, species (dog, monkey, man) dependence and effect of diet on uptake were investigated. Normal myocardial uptake of 18FDG was 3 to 4% in dog and monkey and 1 to 4% of injected dose in man compared to brain uptake of 2% in dog, 5 to 6% in monkey and 4 to 8% in man. The metabolic rate (MR) for glucose in non-fasting (glycolytic state) was 2.8 times greater than in fasting (ketogenic state). Human subjects showed higher myocardial uptake after a normal meal than after meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t1/2 of 0.2 to 0.3 min followed by a t1/2 of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had a t1/2 of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. High image contrast ratios between heart and blood (dog 3.5/1; man 14/1), heart and lung (dog 9/1; man 20/1), heart and liver (dog 15/1; man 10/1) were found with the ECAT positron tomograph. 18FDG was found to be rapidly taken up by the myocardium without any significant tissue clearance over a 4 hour period. 18FDG is transported, phosphorylated to 18FDG-6-PO4 and trapped in myocardial cells in the same manner as has been found for brain and exhibits excellent imaging properties. Determination of glucose and FFA MR in vivo with ECT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man

1977-01-01

263

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

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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...

2007-01-01

264

Regulation of glucose and glycogen metabolism during and after exercise  

DEFF Research Database (Denmark)

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

Jensen, Thomas Elbenhardt; Richter, Erik

2012-01-01

265

Bcl-2 and Bcl-xL Suppress Glucose Signaling in Pancreatic ?-Cells  

Science.gov (United States)

B-cell lymphoma 2 (Bcl-2) family proteins are established regulators of cell survival, but their involvement in the normal function of primary cells has only recently begun to receive attention. In this study, we demonstrate that chemical and genetic loss-of-function of antiapoptotic Bcl-2 and Bcl-xL significantly augments glucose-dependent metabolic and Ca2+ signals in primary pancreatic ?-cells. Antagonism of Bcl-2/Bcl-xL by two distinct small-molecule compounds rapidly hyperpolarized ?-cell mitochondria, increased cytosolic Ca2+, and stimulated insulin release via the ATP-dependent pathway in ?-cell under substimulatory glucose conditions. Experiments with single and double Bax–Bak knockout ?-cells established that this occurred independently of these proapoptotic binding partners. Pancreatic ?-cells from Bcl-2?/? mice responded to glucose with significantly increased NAD(P)H levels and cytosolic Ca2+ signals, as well as significantly augmented insulin secretion. Inducible deletion of Bcl-xL in adult mouse ?-cells also increased glucose-stimulated NAD(P)H and Ca2+ responses and resulted in an improvement of in vivo glucose tolerance in the conditional Bcl-xL knockout animals. Our work suggests that prosurvival Bcl proteins normally dampen the ?-cell response to glucose and thus reveals these core apoptosis proteins as integrators of cell death and physiology in pancreatic ?-cells.

Luciani, Dan S.; White, Sarah A.; Widenmaier, Scott B.; Saran, Varun V.; Taghizadeh, Farnaz; Hu, Xiaoke; Allard, Michael F.; Johnson, James D.

2013-01-01

266

Bcl-2 and Bcl-xL suppress glucose signaling in pancreatic ?-cells.  

Science.gov (United States)

B-cell lymphoma 2 (Bcl-2) family proteins are established regulators of cell survival, but their involvement in the normal function of primary cells has only recently begun to receive attention. In this study, we demonstrate that chemical and genetic loss-of-function of antiapoptotic Bcl-2 and Bcl-x(L) significantly augments glucose-dependent metabolic and Ca(2+) signals in primary pancreatic ?-cells. Antagonism of Bcl-2/Bcl-x(L) by two distinct small-molecule compounds rapidly hyperpolarized ?-cell mitochondria, increased cytosolic Ca(2+), and stimulated insulin release via the ATP-dependent pathway in ?-cell under substimulatory glucose conditions. Experiments with single and double Bax-Bak knockout ?-cells established that this occurred independently of these proapoptotic binding partners. Pancreatic ?-cells from Bcl-2(-/-) mice responded to glucose with significantly increased NAD(P)H levels and cytosolic Ca(2+) signals, as well as significantly augmented insulin secretion. Inducible deletion of Bcl-x(L) in adult mouse ?-cells also increased glucose-stimulated NAD(P)H and Ca(2+) responses and resulted in an improvement of in vivo glucose tolerance in the conditional Bcl-x(L) knockout animals. Our work suggests that prosurvival Bcl proteins normally dampen the ?-cell response to glucose and thus reveals these core apoptosis proteins as integrators of cell death and physiology in pancreatic ?-cells. PMID:22933114

Luciani, Dan S; White, Sarah A; Widenmaier, Scott B; Saran, Varun V; Taghizadeh, Farnaz; Hu, Xiaoke; Allard, Michael F; Johnson, James D

2013-01-01

267

Photoelectrochemical oxidation of glucose for sensing and fuel cell applications.  

Science.gov (United States)

We report the photoelectrochemical oxidation of glucose at an anatase TiO2 modified electrode for unique sensing application. Furthermore, electricity was extracted with a dual-functional photoelectrochemical glucose fuel cell. PMID:23900400

Yan, Yiming; Fang, Jianmei; Yang, Zhiyu; Qiao, Jinshuo; Wang, Zhenhua; Yu, Qiyao; Sun, Kening

2013-10-01

268

Butyrate and glucose metabolism by colonocytes in experimental colitis in mice  

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BACKGROUND/AIMS—Impaired colonocyte metabolism of butyrate has been implicated in the aetiopathogenesis of ulcerative colitis. Colonocyte butyrate metabolism was investigated in experimental colitis in mice.?METHODS—Colitis was induced in Swiss outbred white mice by oral administration of 4% dextran sulphate sodium (DSS). Colonocytes isolated from colitic and normal control mice were incubated with [14C]butyrate or glucose, and production of 14CO2, as well as of intermediate metabol...

Ahmad, M.; Krishnan, S.; Ramakrishna, B.; Mathan, M.; Pulimood, A.; Murthy, S.

2000-01-01

269

Increased Glucose Metabolism and Glycerolipid Formation by Fatty Acids and GPR40 Receptor Signaling Underlies the Fatty Acid Potentiation of Insulin Secretion.  

Science.gov (United States)

Acute fatty acid (FA) exposure potentiates glucose-stimulated insulin secretion in ? cells through metabolic and receptor-mediated effects. We assessed the effect of fatty acids on the dynamics of the metabolome in INS-1 cells following exposure to [U-(13)C]glucose to assess flux through metabolic pathways. Metabolite profiling showed a fatty acid-induced increase in long chain acyl-CoAs that were rapidly esterified with glucose-derived glycerol-3-phosphate to form lysophosphatidic acid, mono- and diacylglycerols, and other glycerolipids, some implicated in augmenting insulin secretion. Glucose utilization and glycolytic flux increased, along with a reduction in the NADH/NAD(+) ratio, presumably by an increase in conversion of dihydroxyacetone phosphate to glycerol-3-phosphate. The fatty acid-induced increase in glycolysis also resulted in increases in tricarboxylic cycle flux and oxygen consumption. Inhibition of fatty acid activation of FFAR1/GPR40 by an antagonist decreased glycerolipid formation, attenuated fatty acid increases in glucose oxidation, and increased mitochondrial FA flux, as evidenced by increased acylcarnitine levels. Conversely, FFAR1/GPR40 activation in the presence of low FA increased flux into glycerolipids and enhanced glucose oxidation. These results suggest that, by remodeling glucose and lipid metabolism, fatty acid significantly increases the formation of both lipid- and TCA cycle-derived intermediates that augment insulin secretion, increasing our understanding of mechanisms underlying ? cell insulin secretion. PMID:24675078

El-Azzouny, Mahmoud; Evans, Charles R; Treutelaar, Mary K; Kennedy, Robert T; Burant, Charles F

2014-05-01

270

Increased visual cortex glucose metabolism contralateral to angioma in children with Sturge-Weber syndrome.  

Science.gov (United States)

Functional reorganization after focal brain injury can lead to altered cerebral metabolism of glucose. Sturge-Weber syndrome (SWS) with unilateral involvement is a clinical model for evaluating the effects of early focal brain injury on brain metabolism and function. In this study, 2-deoxy-2[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) was used to measure glucose metabolism in cortex and basal ganglia, both ipsilateral and contralateral to the angioma, in 17 children (eight males, nine females; age range 1y 8mo-10y 4mo; mean 5y 7mo [SD 2y 11mo]) with unilateral SWS and epilepsy. The PET findings were compared with those of a control group of 11 age-matched children (four males, seven females; age range 3y-10y 8mo; mean 6y [SD 2y 10mo]) with partial epilepsy but normal magnetic resonance imaging and PET scans. In the SWS group, visual and parietal cortex showed decreased glucose metabolism on the side of the angioma (p=0.001) but increased metabolism on the contralateral side (p=0.002). In particular, glucose metabolism was very high in contralateral visual cortex of childrenwith SWS, showing severe occipital hypometabolism on the side of the angioma. Eight children with visual field defect showed increased metabolism in the contralateral visual cortex (p=0.012). These findings indicate that early, severe unilateral cortical damage in SWS may induce increased glucose metabolism in the contralateral visual cortex, probably reflecting reorganization. PMID:17635199

Batista, Carlos E A; Juhasz, C; Muzik, O; Chugani, D C; Chugani, H T

2007-08-01

271

Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance.  

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The effect of graded, physiologic hyperinsulinemia (+5, +15, +30, +70, +200 microU/ml) on oxidative and nonoxidative pathways of glucose and FFA metabolism was examined in nine lean non-insulin dependent diabetic patients (NIDDM) and in eight age- and weight-matched control subjects. Glucose and FFA metabolism were assessed using stepwise insulin clamp in combination with indirect calorimetry and infusion of [3H]3-glucose/[14C]palmitate. The basal rate of hepatic glucose production (HGP) was ...

1989-01-01

272

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

1991-01-01

273

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

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

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

2003-01-01

274

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)

2006-06-01

275

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.

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

2013-01-01

276

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; Angeloni, Cristina; Leoncini, Emanuela; Dalla Sega, Francesco Vieceli; Prata, Cecilia; Fiorentini, Diana; Hrelia, Silvana

2013-01-01

277

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

International Nuclear Information System (INIS)

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

2002-10-01

278

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

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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

279

Apolipoprotein E, not fibrillar ?-amyloid, reduces cerebral glucose metabolism in normal aging.  

Science.gov (United States)

The ?4 allele of the polymorphic apolipoprotein E gene is associated with increased risk of Alzheimer's disease (AD), deposition of ?-amyloid (A?), and reduction in cerebral glucose metabolism in asymptomatic people. Although ApoE4 may exert an effect on AD risk through amyloidogenic pathways, whether its effect on glucose metabolism is related to A? is unknown. To answer this question, we examined data from 175 cognitively normal older people (mean age, 77; 87 men, 88 women) in the Alzheimer's disease neuroimaging initiative studied concurrently with [(18)F]flurodeoxyglucose (FDG) positron emission tomography measures of glucose metabolism and the radiotracer [(18)F]florbetapir, an imaging agent which labels fibrillar A? in vivo. Based on a threshold value of florbetapir uptake determined in separate samples, subjects were categorized as florbetapir+ or florbetapir-. Glucose metabolism was measured as a continuous variable in a group of regions of interest (ROIs) selected a priori based on their involvement in AD, and also by using a whole-brain voxelwise approach. Among this sample, 29% of subjects were florbetapir+ and 23% were ApoE4 carriers. As expected, there was a significant association between ApoE4 genotype and florbetapir positivity. Florbetapir status, however, was not significantly associated with glucose metabolism, but the ApoE4 genotype was associated with lower metabolism in both voxelwise and ROI approaches. These results show that ApoE genotype, and not aggregated fibrillar forms of A?, contributes to reduced glucose metabolism in aging and adds to a growing list of neural consequences of ApoE that do not appear to be related to A?. PMID:23238736

Jagust, William J; Landau, Susan M

2012-12-12

280

Staphylococcus epidermidis glucose uptake in biofilm versus planktonic cells  

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The aim of this work was to compare the glucose uptake of biofilms formed by four different Staphylococcus epidermidis strains as well as to compare between sessile and planktonic cells of the same strain. Biofilm cells showed a lower level of glucose uptake compared to planktonic cells. Moreover, glucose uptake by cells in the sessile form was strongly influenced by biofilm composition. Therefore, this work helps to confirm the phenotypic variability of S. epidermidis...

Sousa, Cla?udia; Henriques, Mariana; Azeredo, Joana; Teixeira, P.; Oliveira, R.

2008-01-01

 
 
 
 
281

Metabolic fuel homeostasis in golden hamsters: effects of fasting, refeeding, glucose, and insulin.  

Science.gov (United States)

Experiments were conducted to investigate possible metabolic correlates of the unusual ingestive behavior of hamsters after food deprivation. A hypothesis of metabolic refractoriness predicts that hamsters, unlike rats, should not show changes in plasma metabolic fuels, adipose tissue, or liver after fasting and subsequent refeeding. This hypothesis was discredited by findings that fasted hamsters, like rats, have increased plasma ketones and free fatty acids and decreased liver glycogen. On refeeding, hamsters showed rapid reversal of these changes, with supranormal glycogen content and apparent fatty acid synthesis in liver. Additional studies examined the metabolic responses of hamsters and rats to exogenous insulin or glucose administration. Incorporation of 3H2O into liver fatty acids was greatly elevated in rats by both insulin and glucose, but in hamsters only insulin was effective. Some of these metabolic differences may help our understanding of the unusual refractoriness of hamster food intake to various stimuli. PMID:6377929

Rowland, N

1984-07-01

282

Prolonged Sleep Restriction Affects Glucose Metabolism in Healthy Young Men  

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Full Text Available This study identifies the effects of sleep restriction and subsequent recovery sleep on glucose homeostasis, serum leptin levels, and feelings of subjective satiety. Twenty-three healthy young men were allocated to a control group (CON or an experimental (EXP group. After two nights of 8?h in bed (baseline, BL, EXP spent 4?h in bed for five days (sleep restriction, SR, followed by two nights of 8?h (recovery, REC. CON spent 8?h in bed throughout the study. Blood samples were taken after the BL, SR, and REC period. In EXP, insulin and insulin-to-glucose ratio increased after SR. IGF-1 levels increased after REC. Leptin levels were elevated after both SR and REC; subjective satiety remained unaffected. No changes were observed in CON. The observed increase of serum IGF-1 and insulin-to-glucose ratio indicates that sleep restriction may result in an increased risk to develop type 2 diabetes.

Ari Hirvonen

2010-01-01

283

Risk of Glucose Intolerance and Diabetes in Hemipancreatectomized Donors Selected for Normal Preoperative Glucose Metabolism  

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OBJECTIVE—Hemipancreatectomy (HPx) for the purpose of organ donation has been associated with a 25% risk of developing abnormal glucose tolerance or diabetes in the year after surgery. Since 1997, the University of Minnesota has imposed criteria to prevent potential donors with clinical features associated with an increased diabetes risk from undergoing HPx. We recently assessed glucose tolerance in hemipancreatectomized donors selected since the adoption of the new criteria to determine wh...

Kumar, Anjali F.; Gruessner, Rainer W. G.; Seaquist, Elizabeth R.

2008-01-01

284

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

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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

285

Berberine Improves Glucose Metabolism in Diabetic Rats by Inhibition of Hepatic Gluconeogenesis  

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Berberine (BBR) is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French). It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK) and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyp...

Xia, Xuan; Yan, Jinhua; Shen, Yunfeng; Tang, Kuanxiao; Yin, Jun; Zhang, Yanhua; Yang, Dongjie; Liang, Hua; Ye, Jianping; Weng, Jianping

2011-01-01

286

Brain glucose and acetoacetate metabolism: a comparison of young and older adults.  

Science.gov (United States)

The extent to which the age-related decline in regional brain glucose uptake also applies to other important brain fuels is presently unknown. Ketones are the brain's major alternative fuel to glucose, so we developed a dual tracer positron emission tomography protocol to quantify and compare regional cerebral metabolic rates for glucose and the ketone, acetoacetate. Twenty healthy young adults (mean age, 26 years) and 24 healthy older adults (mean age, 74 years) were studied. In comparison with younger adults, older adults had 8 ± 6% (mean ± SD) lower cerebral metabolic rates for glucose in gray matter as a whole (p = 0.035), specifically in several frontal, temporal, and subcortical regions, as well as in the cingulate and insula (p ? 0.01, false discovery rate correction). The effect of age on cerebral metabolic rates for acetoacetate in gray matter did not reach significance (p = 0.11). Rate constants (min(-1)) of glucose (Kg) and acetoacetate (Ka) were significantly lower (-11 ± 6%; [p = 0.005], and -19 ± 5%; [p = 0.006], respectively) in older adults compared with younger adults. There were differential effects of age on Kg and Ka as seen by significant interaction effects in the caudate (p = 0.030) and post-central gyrus (p = 0.023). The acetoacetate index, which expresses the scaled residuals of the voxel-wise linear regression of glucose on ketone uptake, identifies regions taking up higher or lower amounts of acetoacetate relative to glucose. The acetoacetate index was higher in the caudate of young adults when compared with older adults (p ? 0.05 false discovery rate correction). This study provides new information about glucose and ketone metabolism in the human brain and a comparison of the extent to which their regional use changes during normal aging. PMID:24388785

Nugent, Scott; Tremblay, Sebastien; Chen, Kewei W; Ayutyanont, Napatkamon; Roontiva, Auttawut; Castellano, Christian-Alexandre; Fortier, Melanie; Roy, Maggie; Courchesne-Loyer, Alexandre; Bocti, Christian; Lepage, Martin; Turcotte, Eric; Fulop, Tamas; Reiman, Eric M; Cunnane, Stephen C

2014-06-01

287

High glucose inhibits glucose-6-phosphate dehydrogenase, leading to increased oxidative stress and ?-cell apoptosis  

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Patients with type 2 diabetes lose ? cells, but the underlying mechanisms are incompletely understood. Glucose-6-phosphate dehydrogenase (G6PD) is the principal source of the major intracellular reductant, NADPH, which is required by many enzymes, including enzymes of the antioxidant pathway. Previous work from our laboratory has shown that high glucose impairs G6PD activity in endothelial and kidney cells, which leads to decreased cell survival. Pancreatic ? cells are highly sensitive to i...

Zhang, Zhaoyun; Liew, Chong Wee; Handy, Diane E.; Zhang, Yingyi; Leopold, Jane A.; Hu, Ji; Guo, Lili; Kulkarni, Rohit N.; Loscalzo, Joseph; Stanton, Robert C.

2010-01-01

288

PINK1 deficiency in ?-cells increases basal insulin secretion and improves glucose tolerance in mice  

Science.gov (United States)

The Parkinson's disease (PD) gene, PARK6, encodes the PTEN-induced putative kinase 1 (PINK1) mitochondrial kinase, which provides protection against oxidative stress-induced apoptosis. Given the link between glucose metabolism, mitochondrial function and insulin secretion in ?-cells, and the reported association of PD with type 2 diabetes, we investigated the response of PINK1-deficient ?-cells to glucose stimuli to determine whether loss of PINK1 affected their function. We find that loss of PINK1 significantly impairs the ability of mouse pancreatic ?-cells (MIN6 cells) and primary intact islets to take up glucose. This was accompanied by higher basal levels of intracellular calcium leading to increased basal levels of insulin secretion under low glucose conditions. Finally, we investigated the effect of PINK1 deficiency in vivo and find that PINK1 knockout mice have improved glucose tolerance. For the first time, these combined results demonstrate that loss of PINK1 function appears to disrupt glucose-sensing leading to enhanced insulin release, which is uncoupled from glucose uptake, and suggest a key role for PINK1 in ?-cell function.

Deas, Emma; Piipari, Kaisa; Machhada, Asif; Li, Abi; Gutierrez-del-Arroyo, Ana; Withers, Dominic J.; Wood, Nicholas W.; Abramov, Andrey Y.

2014-01-01

289

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

DEFF Research Database (Denmark)

Using C-13-labeled glucose fed to the facultative alkalophilic Bacillus clausii producing the alkaline serine protease Savinase, the intracellular fluxes were quantified in continuous cultivation and in batch cultivation on a minimal medium. The flux through the pentose phosphate pathway was found to increase with increasing specific growth rate but at a much lower level than previously reported for Bacillus subtilis. Two futile cycles in the pyruvate metabolism were included in the metabolic network. A substantial flux in the futile cycle involving malic enzyme was estimated, whereas only a very small or zero flux through PEP carboxykinase was estimated, indicating that the latter enzyme was not active during growth on glucose. The uptake of the amino acids in a semirich medium containing 15 of the 20 amino acids normally present in proteins was estimated using fully labeled glucose in batch cultivations. It was found that leucine, isoleucine, and phenylalanine were taken up from the medium and not synthesized de novo from glucose. In contrast, serine and threonine were completely synthesized from other metabolites and not taken up from the medium. Valine, proline, and lysine were partly taken up from the medium and partly synthesized from glucose. The metabolic network analysis was extended to include analysis of growth on the semirich medium containing amino acids, and the metabolic flux distribution on this medium was estimated and compared with growth on minimal medium.

Christiansen, Torben; Christensen, Bjarke

2002-01-01

290

Beyond Warburg effect - dual metabolic nature of cancer cells  

Science.gov (United States)

Warburg effect is a dominant phenotype of most cancer cells. Here we show that this phenotype depends on its environment. When cancer cells are under regular culture condition, they show Warburg effect; whereas under lactic acidosis, they show a nonglycolytic phenotype, characterized by a high ratio of oxygen consumption rate over glycolytic rate, negligible lactate production and efficient incorporation of glucose carbon(s) into cellular mass. These two metabolic modes are intimately interrelated, for Warburg effect generates lactic acidosis that promotes a transition to a nonglycolytic mode. This dual metabolic nature confers growth advantage to cancer cells adapting to ever changing microenvironment.

Xie, Jiansheng; Wu, Hao; Dai, Chunyan; Pan, Qiangrong; Ding, Zonghui; Hu, Danqing; Ji, Bingyan; Luo, Yan; Hu, Xun

2014-01-01

291

A real time simulation model of glucose-insulin metabolism for type 1 diabetes patients.  

Science.gov (United States)

In this paper, a simulation model of glucose-insulin metabolism for Type 1 diabetes patients is presented. The proposed system is based on the combination of Compartmental Models (CMs) and artificial Neural Networks (NNs). This model aims at the development of an accurate system, in order to assist Type 1 diabetes patients to handle their blood glucose profile and recognize dangerous metabolic states. Data from a Type 1 diabetes patient, stored in a database, have been used as input to the hybrid system. The data contain information about measured blood glucose levels, insulin intake, and description of food intake, along with the corresponding time. The data are passed to three separate CMs, which produce estimations about (i) the effect of Short Acting (SA) insulin intake on blood insulin concentration, (ii) the effect of Intermediate Acting (IA) insulin intake on blood insulin concentration, and (iii) the effect of carbohydrate intake on blood glucose absorption from the gut. The outputs of the three CMs are passed to a Recurrent NN (RNN) in order to predict subsequent blood glucose levels. The RNN is trained with the Real Time Recurrent Learning (RTRL) algorithm. The resulted blood glucose predictions are promising for the use of the proposed model for blood glucose level estimation for Type 1 diabetes patients. PMID:17282172

Mougiakakou, S; Prountzou, K; Nikita, K

2005-01-01

292

Cortical and subcortical glucose metabolism in childhood epileptic encephalopathies  

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OBJECTIVES— Nearly one third of children with cryptogenic epileptic encephalopathies have been reported to have focal cortical defects on 18fluorodeoxyglucose (FDG) PET. As diffuse cortical dysfunction and involvement of subcortical structures, particularly the thalami, is postulated to underlie the propensity to seizures in these conditions, the aim was to determine the frequency of bilateral and diffuse cortical metabolic defects and of subcortical metabolic abnormali...

Ferrie, C.; Marsden, P.; Maisey, M.; Robinson, R.

1997-01-01

293

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

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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

294

Dynamics of glucose uptake by single Escherichia coli cells.  

Science.gov (United States)

The fluorescent glucose analog, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), was used to measure rates of glucose uptake by single Escherichia coli cells. When cell populations were exposed to the glucose analog, 2-NBDG was actively transported and accumulated in single cells to a steady-state level that depended upon its extracellular concentration, the glucose transport capacity of the cells, and the intracellular degradation rate. The dependence upon substrate concentration could be described according to Michaelis-Menten kinetics with apparent saturation constant KM = 1.75 microM, and maximum 2-NBDG uptake rate= 197 molecules/cell-second. Specificity of glucose transporters to the analog was confirmed by inhibition of uptake of 2-NBDG by D-glucose, 3-o-methyl glucose, and D-glucosamine, and lack of inhibition by L-glucose. Inhibition of 2-NBDG uptake by D-glucose was competitive in nature. The assay for 2-NBDG uptake is extremely sensitive such that the presence of even trace amounts of D-glucose in the culture medium (approximately 0.2 microM) is detectable. The rates of single-cell analog uptake were found to increase proportionally with cell size as measured by microscopy or single-cell light scattering intensity. The assay was used to identify and isolate mutant cells with altered glucose uptake characteristics. A mathematical model was developed to provide a theoretical basis for estimating single-cell glucose uptake rates from single-cell 2-NBDG uptake rates. The assay provides a novel means of estimating the instantaneous rates of nutrient depletion in the growth environment during a batch cultivation. PMID:10937825

Natarajan, A; Srienc, F

1999-10-01

295

Clinical correlates of basal hepatic glucose output and metabolic clearance rate of glucose using glucose-C-peptide-body mass indexes in ambulatory type 2 diabetic patients.  

Science.gov (United States)

The use of glucose (G)--C-peptide (C)--body mass indexes (BMI) as clinical determinants of likely response to oral sulphonylurea agents in type 2 diabetic patients have been suggested by some investigators. The relationships between these clinical parameters are usually expressed as scores (C/G, G/BMI and C/BMI scores). Based on this approach, we have determined the significance of these clinical scores using isotopically-derived basal glucose fluxes (D[3-3H]glucose technique) in 26 subjects (10 type 2 diabetics and 16 nondiabetics) with a broad range (72-346 mg/dl) of fasting serum glucose (FSG) and BMI (19-39 kg/m2). The basal hepatic glucose output (HGO) correlated positively with FSG, BMI and G/BMI score and negatively with C/G score in the diabetic patients. We found no significant relationships between basal HGO and most of these parameters except FSG and G/BMI in the normal subjects. The basal metabolic clearance rate of glucose (MCR) significantly correlated, but inversely, with FSG and G/BMI score, but not with the C/G score or BMI in the diabetic patients. In the normal subjects, MCR significantly, but negatively, correlated with the BMI, but not with FSG, C/G or G/BMI scores. Neither basal HGO nor MCR correlated with fasting serum C-peptide, duration of diabetes or daily insulin dose. As a group, the basal HGO correlated positively with FSG, BMI and G/BMI scores but negatively with C/G Score. However, the basal MCR correlated negatively with FSG, BMI and G/BMI scores but positively with C/G score. In summary, the present cross-sectional study provides additional information on the determinants of fasting serum glucose levels in type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3665344

Osei, K; Holland, G C

1987-08-01

296

SAICAR Stimulates Pyruvate Kinase Isoform M2 and Promotes Cancer Cell Survival in Glucose -Limited Conditions  

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Pyruvate kinase isoform M2 (PKM2) plays an important role in the growth and metabolic reprogramming of cancer cells in stress conditions. Here, we report that SAICAR (succinylaminoimidazolecarboxamide ribose-5?-phosphate, an intermediate of the de novo purine nucleotide synthesis pathway) specifically stimulates PKM2. Upon glucose starvation, cellular SAICAR concentration increases in an oscillatory manner and stimulates PKM2 activity in cancer cells. Changes in SAICAR levels in cancer cell...

Keller, Kirstie E.; Tan, Irene S.; Lee, Young-sam

2012-01-01

297

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)

1984-01-01

298

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

299

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

Energy Technology Data Exchange (ETDEWEB)

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

Schelbert, H.R.; Phelps, M.E.

1980-06-01

300

The continuous infusion of acylated ghrelin enhances growth hormone secretion and worsens glucose metabolism in humans  

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CONTEXT: Acylated ghrelin (AG) has been discovered as a natural ligand of the GH secretagogue receptor type 1a and is now recognized as an important orexigenic factor. Besides stimulation of GH secretion and appetite, it exerts other central and peripheral actions including modulation of insulin secretion, glucose and lipid metabolism. OBJECTIVE: To define the effects of the continuous iv infusion of AG in humans with particular attention to metabolic parameters. MATERIALS AND METHODS: We stu...

Ghigo, Ezio; Muccioli, Giampiero; Broglio, Fabio; Granata, Riccarda

2008-01-01

 
 
 
 
301

Regulation of renal brush-border glucose transport in response to metabolic dysregulation  

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Diabetic nephropathy is a consequence of hyperglycaemia-induced renal cell damage and a major contributor to end-stage renal disease in later stages of diabetes. Previous studies, in type I diabetes, observed PKC-?I-dependent GLUT2 recruitment to the proximal tubule brush-border membrane (BBM) as a direct result of elevated plasma glucose. The up-regulation of glucose transporters at the proximal tubule BBM causes a rise in intracellular glucose concentration; tubular injury in diabetic neph...

Chichger, H.

2011-01-01

302

Pancreatic GLP-1 receptor activation is sufficient for incretin control of glucose metabolism in mice  

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Glucagon-like peptide-1 (GLP-1) circulates at low levels and acts as an incretin hormone, potentiating glucose-dependent insulin secretion from islet ? cells. GLP-1 also modulates gastric emptying and engages neural circuits in the portal region and CNS that contribute to GLP-1 receptor–dependent (GLP-1R–dependent) regulation of glucose homeostasis. To elucidate the importance of pancreatic GLP-1R signaling for glucose homeostasis, we generated transgenic mice that expressed the human GL...

Lamont, Benjamin J.; Li, Yazhou; Kwan, Edwin; Brown, Theodore J.; Gaisano, Herbert; Drucker, Daniel J.

2012-01-01

303

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

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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

304

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

Science.gov (United States)

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

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

2010-03-30

305

Cancer cell metabolism regulates extracellular matrix degradation by invadopodia.  

Science.gov (United States)

Transformed cancer cells have an altered metabolism, characterized by a shift towards aerobic glycolysis, referred to as 'the Warburg phenotype'. A change in flux through mitochondrial OXPHOS and cytosolic pathways for ATP production and a gain of capacity for biomass production in order to sustain the needs for altered growth and morphodynamics are typically involved in this global rewiring of cancer cell metabolism. Characteristically, these changes in metabolism are accompanied by enhanced uptake of nutrients like glucose and glutamine. Here we focus on the relationship between cell metabolism and cell dynamics, in particular the formation and function of invadopodia, specialized structures for focal degradation of the extracellular matrix. Since we recently found presence of enzymes that are active in glycolysis and associated pathways in invadopodia, we hypothesize that metabolic adaptation and invadopodia formation are linked processes. We give an overview on the background for this idea and show for the first time that extracellular matrix degradation by invadopodia can be differentially manipulated, without effects on cell proliferation, by use of metabolic inhibitors or changes in nutrient composition of cell culture media. We conclude that cell metabolism and carbohydrate availability, especially pyruvate, are involved in fuelling of invadopodia formation and activity. PMID:23306026

van Horssen, Remco; Buccione, Roberto; Willemse, Marieke; Cingir, Sahika; Wieringa, Bé; Attanasio, Francesca

2013-03-01

306

Pancreatic Metabolism, Blood Flow, and ?-Cell Function in Obese Humans.  

Science.gov (United States)

Context: Glucolipotoxicity is believed to induce pancreatic ?-cell dysfunction in obesity. Previously, it has not been possible to study pancreatic metabolism and blood flow in humans. Objective: The objective of the study was to investigate whether pancreatic metabolism and blood flow are altered in obesity using positron emission tomography (PET). In the preclinical part, the method was validated in animals. Design: This was a cross-sectional study. Setting: The study was conducted in a clinical research center. Participants: Human studies consisted of 52 morbidly obese and 25 healthy age-matched control subjects. Validation experiments were done with rodents and pigs. Interventions: PET and magnetic resonance imaging studies using a glucose analog ([(18)F]fluoro-2-deoxy-d-glucose), a palmitate analog [14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid], and radiowater ([(15)O]H2O) were performed. In animals, a comparison between ex vivo and in vivo data was performed. Main Outcome Measures: Pancreatic glucose/fatty acid (FA) uptake, fat accumulation, and blood flow parameters of ?-cell function were measured. Results: PET proved to be a feasible method to measure pancreatic metabolism. Compared with healthy participants, obese participants had elevated pancreatic FA uptake (P < .0001), more fat accumulation (P = .0001), lowered glucose uptake both during fasting and euglycemic hyperinsulinemia, and blunted blood flow (P < .01) in the pancreas. Blood flow, FA uptake, and fat accumulation were negatively associated with multiple markers of ?-cell function. Conclusions: Obesity leads to changes in pancreatic energy metabolism with a substrate shift from glucose to FAs. In morbidly obese humans, impaired pancreatic blood flow may contribute to ?-cell dysfunction and in the pathogenesis of type 2 diabetes. PMID:24527718

Honka, Henri; Hannukainen, Jarna C; Tarkia, Miikka; Karlsson, Henry; Saunavaara, Virva; Salminen, Paulina; Soinio, Minna; Mikkola, Kirsi; Kudomi, Nobu; Oikonen, Vesa; Haaparanta-Solin, Merja; Roivainen, Anne; Parkkola, Riitta; Iozzo, Patricia; Nuutila, Pirjo

2014-06-01

307

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

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Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle. PMID:24567902

Dyar, Kenneth A; Ciciliot, Stefano; Wright, Lauren E; Biensø, Rasmus S; Tagliazucchi, Guidantonio M; Patel, Vishal R; Forcato, Mattia; Paz, Marcia I P; Gudiksen, Anders; Solagna, Francesca; Albiero, Mattia; Moretti, Irene; Eckel-Mahan, Kristin L; Baldi, Pierre; Sassone-Corsi, Paolo; Rizzuto, Rosario; Bicciato, Silvio; Pilegaard, Henriette; Blaauw, Bert; Schiaffino, Stefano

2014-02-01

308

High glucose induces DNA damage in cultured human endothelial cells.  

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Morphologic and functional abnormalities of vascular endothelium are well recognized in diabetes. In view of our previous finding that high glucose concentrations accelerate death and hamper replication of cultured human endothelial cells, we have investigated in the same model the possibility that exposure to high glucose may result in DNA damage. DNA from human endothelial cells--but not from fibroblasts--exposed to 30 mM glucose for 9-14 d manifested an accelerated rate of unwinding in alk...

Lorenzi, M.; Montisano, D. F.; Toledo, S.; Barrieux, A.

1986-01-01

309

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 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

2002-11-15

310

The characteristics of cortical glucose metabolism in amblyopia  

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Cortical metabolism of amblyopia patients was investigated with F-18-FDG PET and Statistical Parametric Mapping (SPM) and quantificiation based on volume of interest (VOI) by statistical probabilistic anatomical map (SPAM). In 9 amblyopic patients (12{+-}7 years ) and 20 normal subjects (23{+-}2 years), F-18-FDG PET scans were peformed in amblyopic patients after amblyopic eye or sound eye was patch-closed during PET studies. SPM was done with SPM96. By multiplying SPAM to FDG images, counts of 98 VOI's were calculated and compared with 3 S. D. range of those of normal subjects. On SPM, cortical metabolism decreased (p<0.05) in occipital lobe (Ba 17, 18, 19), superior partietal lobe (Ba 7), and inferior temporal lobe (BA 37, 20). FDG uptake of gyri of occuipital lobe was decreased in 2 and increased in 2, and was normal in the other 5. FDG uptake of gyri of parietal, frontal, and temporal lobes were decreased in FDG uptake on these VOIs. We conclude that cortical metabolism in occipital lobe and extraoccipital lobes was variable but was consistent regardless of visual input during PET studies in amblyopic patients. SPM and quantification of functional images using SPAM could reveal subtle differences or changes according to visual input. The significance of metabolic changes of extraoccipital lobes should be studies further.

Ahn, Ji Young [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of); Lee, Dong Soo; Chung, June Key; Shin, Seung Ai; Lee, Myung Chul [College of Medicine, Ewha Womans Univ., Seoul (Korea, Republic of)

2000-07-01

311

The characteristics of cortical glucose metabolism in amblyopia  

International Nuclear Information System (INIS)

Cortical metabolism of amblyopia patients was investigated with F-18-FDG PET and Statistical Parametric Mapping (SPM) and quantificiation based on volume of interest (VOI) by statistical probabilistic anatomical map (SPAM). In 9 amblyopic patients (12±7 years ) and 20 normal subjects (23±2 years), F-18-FDG PET scans were peformed in amblyopic patients after amblyopic eye or sound eye was patch-closed during PET studies. SPM was done with SPM96. By multiplying SPAM to FDG images, counts of 98 VOI's were calculated and compared with 3 S. D. range of those of normal subjects. On SPM, cortical metabolism decreased (p<0.05) in occipital lobe (Ba 17, 18, 19), superior partietal lobe (Ba 7), and inferior temporal lobe (BA 37, 20). FDG uptake of gyri of occuipital lobe was decreased in 2 and increased in 2, and was normal in the other 5. FDG uptake of gyri of parietal, frontal, and temporal lobes were decreased in FDG uptake on these VOIs. We conclude that cortical metabolism in occipital lobe and extraoccipital lobes was variable but was consistent regardless of visual input during PET studies in amblyopic patients. SPM and quantification of functional images using SPAM could reveal subtle differences or changes according to visual input. The significance of metabolic changes of extraoccipital lobes should be studies further

2000-11-18

312

Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis.  

Science.gov (United States)

Berberine (BBR) is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French). It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK) and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS) was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1), sterol regulatory element-binding protein 1c (SREBP1) and carbohydrate responsive element-binding protein (ChREBP) were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP) level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway. PMID:21304897

Xia, Xuan; Yan, Jinhua; Shen, Yunfeng; Tang, Kuanxiao; Yin, Jun; Zhang, Yanhua; Yang, Dongjie; Liang, Hua; Ye, Jianping; Weng, Jianping

2011-01-01

313

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

1987-09-01

314

The effect of liver microsomal enzyme inducing and inhibiting drugs on insulin mediated glucose metabolism in man.  

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The effects of hepatic microsomal enzyme inducing (phenobarbitone and flumecinol), and inhibiting (cimetidine) drugs, and placebo treatment on insulin mediated glucose metabolism (M) were investigated in 29 healthy volunteers. Phenobarbitone (50 mg for 10 days) increased M (30%), metabolic clearance rate of glucose (MCRg), and antipyrine clearance rate (33%). Fasting immunoreactive insulin (IRI) decreased while fasting blood glucose (BG) remained unaltered. Flumecinol, another inducer, tested...

Lahtela, J. T.; Gachalyi, B.; Eksyma?, S.; Ha?ma?la?inen, A.; Sotaniemi, E. A.

1986-01-01

315

Regulators of glucose and lipid metabolism in skeletal muscle and serum : implications for obesity and type 2 diabetes  

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Type 2 diabetes mellitus (T2DM) has become a growing worldwide problem of public health importance. Insulin resistance is commonly associated with obesity and a key factor mediating the progression to T2DM. The failure of insulin-sensitive peripheral tissues to respond to insulin results in an increase in serum glucose levels that leads to an impaired homeostatic state. Skeletal muscle plays a crucial role in maintaining glucose metabolism. Impairments in both glucose and lipid metabolism ari...

2012-01-01

316

Impaired kisspeptin signaling decreases metabolism and promotes glucose intolerance and obesity.  

Science.gov (United States)

The neuropeptide kisspeptin regulates reproduction by stimulating gonadotropin-releasing hormone (GnRH) neurons via the kisspeptin receptor KISS1R. In addition to GnRH neurons, KISS1R is expressed in other brain areas and peripheral tissues, which suggests that kisspeptin has additional functions beyond reproduction. Here, we studied the energetic and metabolic phenotype in mice lacking kisspeptin signaling (Kiss1r KO mice). Compared with WT littermates, adult Kiss1r KO females displayed dramatically higher BW, leptin levels, and adiposity, along with strikingly impaired glucose tolerance. Conversely, male Kiss1r KO mice had normal BW and glucose regulation. Surprisingly, despite their obesity, Kiss1r KO females ate less than WT females; however, Kiss1r KO females displayed markedly reduced locomotor activity, respiratory rate, and energy expenditure, which were not due to impaired thyroid hormone secretion. The BW and metabolic phenotype in Kiss1r KO females was not solely reflective of absent gonadal estrogen, as chronically ovariectomized Kiss1r KO females developed obesity, hyperleptinemia, reduced metabolism, and glucose intolerance compared with ovariectomized WT females. Our findings demonstrate that in addition to reproduction, kisspeptin signaling influences BW, energy expenditure, and glucose homeostasis in a sexually dimorphic and partially sex steroid-independent manner; therefore, alterations in kisspeptin signaling might contribute, directly or indirectly, to some facets of human obesity, diabetes, or metabolic dysfunction. PMID:24937427

Tolson, Kristen P; Garcia, Christian; Yen, Stephanie; Simonds, Stephanie; Stefanidis, Aneta; Lawrence, Alison; Smith, Jeremy T; Kauffman, Alexander S

2014-07-01

317

Diabetes-Related Symptom Distress in Association With Glucose Metabolism and Comorbidity  

Science.gov (United States)

OBJECTIVE—The purpose of this study was to determine the associations between diabetes-related symptom distress, glucose metabolism status, and comorbidities of type 2 diabetes. RESEARCH DESIGN AND METHODS—This was a cross-sectional sample of 281 individuals with normal glucose metabolism (NGM), 181 individuals with impaired glucose metabolism (IGM), and 107 subjects with type 2 diabetes. We used the revised type 2 Diabetes Symptom Checklist (DSC-R) to assess diabetes-related symptom distress. RESULTS—The total symptom distress score (range 0–100) was relatively low for diabetic subjects (mean ± SD 8.4 ± 9.4), although it was significantly different from that for subjects with IGM (6.5 ± 7.1) and NGM (6.1 ± 7.9) (F = 3.1, 2 d.f., P = 0.046). Ischemic heart disease was associated with elevated DSC-R scores on three subscales, whereas depression showed higher symptom distress levels across all DSC-R domains. CONCLUSIONS—Worsening glucose metabolism is associated with increasing diabetes-related symptom distress. This relationship is attenuated by ischemic heart disease and particularly by depression.

Adriaanse, Marcel C.; Pouwer, Frans; Dekker, Jacqueline M.; Nijpels, Giel; Stehouwer, Coen D.; Heine, Robert J.; Snoek, Frank J.

2008-01-01

318

Glucose metabolism transporters and epilepsy: only GLUT1 has an established role.  

Science.gov (United States)

The availability of glucose, and its glycolytic product lactate, for cerebral energy metabolism is regulated by specific brain transporters. Inadequate energy delivery leads to neurologic impairment. Haploinsufficiency of the glucose transporter GLUT1 causes a characteristic early onset encephalopathy, and has recently emerged as an important cause of a variety of childhood or later-onset generalized epilepsies and paroxysmal exercise-induced dyskinesia. We explored whether mutations in the genes encoding the other major glucose (GLUT3) or lactate (MCT1/2/3/4) transporters involved in cerebral energy metabolism also cause generalized epilepsies. A cohort of 119 cases with myoclonic astatic epilepsy or early onset absence epilepsy was screened for nucleotide variants in these five candidate genes. No epilepsy-causing mutations were identified, indicating that of the major energetic fuel transporters in the brain, only GLUT1 is clearly associated with generalized epilepsy. PMID:24483274

Hildebrand, Michael S; Damiano, John A; Mullen, Saul A; Bellows, Susannah T; Oliver, Karen L; Dahl, Hans-Henrik M; Scheffer, Ingrid E; Berkovic, Samuel F

2014-02-01

319

External Qi of Yan Xin Qigong induces cell death and gene expression alterations promoting apoptosis and inhibiting proliferation, migration and glucose metabolism in small-cell lung cancer cells  

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Small-cell lung cancer (SCLC) is a highly malignant carcinoma with poor long-term survival. Effective treatment remains highly demanded. In the present study, we demonstrated that External Qi of Yan Xin Qigong (YXQ-EQ) exerted potent cytotoxic effect towards SCLC cell line NCI-H82 via induction of apoptosis. Global gene expression profiling identified 39 genes whose expression was altered by YXQ-EQ in NCI-82 cells. Among them, semi-quantitative RT-PCR and real-time qPCR analyses confirmed tha...

Yan, Xin; Li, Feng; Dozmorov, Igor; Frank, Mark Barton; Dao, Ming; Centola, Michael; Cao, Wei; Hu, Dan

2012-01-01

320

Modeling the pancreatic ?-cell: dual mechanisms of glucose suppression of glucagon secretion.  

Science.gov (United States)

The mechanism by which glucose induces insulin secretion in ?-cells is fairly well understood. Despite years of research, however, the mechanism of glucagon secretion in ?-cells is still not well established. It has been proposed that glucose regulates glucagon secretion by decreasing the conductance of either outward ATP-dependent potassium channels (K(ATP)) or an inward store-operated current (SOC). We have developed a mathematical model based on mouse data to test these hypotheses and found that both mechanisms are possible. Glucose metabolism closes K(ATP) channels, which depolarizes the cell but paradoxically reduces calcium influx by inactivating voltage-dependent calcium and sodium channels and decreases secretion. Glucose metabolism also activates SERCA pumps, which fills the endoplasmic reticulum and hyperpolarizes the cells by reducing the inward current through SOC channels and again suppresses glucagon secretion. We find further that the two mechanisms can combine to account for the nonmonotonic dependence of secretion on glucose observed in some studies, an effect that cannot be obtained with either mechanism alone. PMID:24507615

Watts, Margaret; Sherman, Arthur

2014-02-01

 
 
 
 
321

Positron emission tomography to study the effect of eye closure and optic nerve damage on human cerebral glucose metabolism.  

Science.gov (United States)

We used 18F-2-fluoro-2-deoxyglucose and positron emission tomography to evaluate the effect of visual deprivation on brain glucose metabolism. In experiment 1, we compared local cerebral metabolic rates for glucose in seven normal volunteers studied with eyes closed to 11 age- and sex-matched normal volunteers studied with eyes open. Whole brain metabolism was similar in the two groups, and region/whole brain analysis of metabolic data showed that metabolism in the calcarine posterior cortex was decreased by 14% (P less than .05) with eye closure. Glucose metabolism in other regions was not different between the two groups. In experiment 2, we compared glucose metabolism in six patients with severe bilateral optic neuropathies to 12 age- and sex-matched normal controls. Whole brain glucose metabolism was unchanged in the optic neuropathy group compared to controls. However, statistically significant reductions in glucose metabolism in the optic neuropathy group were found in anterior calcarine cortex (17%), posterior calcarine cortex (27%), peristriate cortex (27%), and lateral occipital cortex (15%). The metabolic effects of damage to the pregeniculate visual system went well beyond those of simple eye closure. PMID:2787961

Kiyosawa, M; Bosley, T M; Kushner, M; Jamieson, D; Alavi, A; Savino, P J; Sergott, R C; Reivich, M

1989-08-15

322

A metabolic mechanism for the detrimental effect of exogenous glucose during cardiac storage.  

Science.gov (United States)

The purpose of this study was to clarify the metabolic events that explain why supplemental glucose is detrimental during cardiac storage. Four solutions were used to flush and store porcine hearts: St. Thomas Hospital Solution (STHS), University of Wisconsin (UW) solution, and UW + 90 mM histidine, and UW + 90 mM histidine + 11 mM glucose. Despite equivalent increases in lactate in the two histidine-buffered groups throughout 10 h of storage, glycogen utilization was evident in the group without supplemental glucose. The presence of glucose resulted in a reduction in energy production, presumably mediated by direct inhibition of glycogenolysis. Furthermore, UW + histidine was the only group to show consistent improvements in ATP and total adenylates. It was concluded that inclusion of the buffering agent, histidine, to UW solution promotes anaerobic energy production as a result, in part, of preserved high levels of the regulatory control enzyme, phosphofructokinase. PMID:12859530

Pulis, Randy P; Wu, Beatrice M; Zhu, Jay Z; Castillo, Erika G; Kneteman, Norman M; Churchill, Thomas A

2003-08-01

323

[2,4-13C]?-hydroxybutyrate Metabolism in Astrocytes and C6 Glioblastoma Cells  

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This study was undertaken to determine if the ketogenic diet could be useful for glioblastoma patients. The hypothesis tested was whether glioblastoma cells can metabolize ketone bodies. Cerebellar astrocytes and C6 glioblastoma cells were incubated in glutamine and serum free medium containing [2,4-13C]?-hydroxybutyrate (BHB) with and without glucose. Furthermore, C6 cells were incubated with [1-13C]glucose in the presence and absence of BHB. Cell extracts were analyzed by mass spectrometry...

Eloqayli, Haytham; Melø, Torun M.; Haukvik, Anne; Sonnewald, Ursula

2011-01-01

324

Allozymes of glucose-6-phosphate isomerase differentially modulate pentose-shunt metabolism in the sea anemone Metridium senile.  

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We tested the hypothesis that kinetic differences among allelic variants of glucose-6-phosphate isomerase (GPI; D-glucose-6-phosphate ketol-isomerase, EC 5.3.1.9) from the sea anemone Metridium senile differentially modulate glucose metabolism at the glycolysis-pentose-shunt branch point. Fractional contribution of pentose shunt and absolute flux of glucose in glycolysis were measured in fasted or fed anemones acclimated to 5 degrees C or 15 degrees C. When fed, anemones of genotype Gpiss rou...

Zamer, W. E.; Hoffmann, R. J.

1989-01-01

325

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

326

Improvement of glucose metabolism in patients with type II diabetes after treatment with a hemodialysate.  

Science.gov (United States)

Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Previous studies have shown that Actovegin, a hemodialysate of calf blood, which has been used for treatment of circulatory disorders for many years, improves glucose tolerance in NIDDM without affecting insulin levels; in vitro studies found an improvement of insulin-stimulated glucose uptake in adipocytes. This pilot study was initiated to see whether this compound augments insulin sensitivity after repeated treatment. Ten patients with NIDDM received the hemodialysate (Actovegin 2.000 pro infusions, 500 ml as daily infusions) over a period of 10 days. A hyperinsulinaemic, isoglycaemic glucose-clamp was done on day 0 and day 11; oral glucose tolerance test (oGTT) was done on day -4 and day 12. Parenteral administration of the hemodialysate markedly augmented insulin stimulated glucose disposal (glucose infusion rate and metabolic clearance rate) by more than 80% (p < 0.003 day 11 vs. day 0). Although tested 44 h after the last infusion, oGTT also improved significantly, as documented by the diminished area under the curve (AUC) for glucose, whereas the AUC for insulin remained unchanged. This is the first clinical study to show that parenteral administration of the tested hemodialysate results in a significant increase of insulin-stimulated glucose disposal in NIDDM. The exact mode of action of the hemodialysate in improving insulin sensitivity is currently not known. The hemodialysate possibly acts via a supplementation of inositol-phosphate-oligosaccharides (IPO), as in experimental studies IPOs isolated from the hemodialysate improved glucose uptake in adipocytes in an insulin-independent manner. Further studies are needed to elucidate the underlying mechanisms. PMID:8901147

Jacob, S; Dietze, G J; Machicao, F; Kuntz, G; Augustin, H J

1996-03-01

327

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

Energy Technology Data Exchange (ETDEWEB)

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.

Alavi, A.; Chawluk, J.; Hurtig, H.; Dann, R.; Rosen, M.; Kushner, M.; Silver, F.; Reivich, M.

1985-05-01

328

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

Energy Technology Data Exchange (ETDEWEB)

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.

Ratib, O.; Phelps, M.E.; Huang, S.C.; Henze, E.; Selin, C.E.; Schelbert, H.R.

1981-01-01

329

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

1981-01-01

330

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

1996-02-01

331

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

Energy Technology Data Exchange (ETDEWEB)

Cerebral blood flow (CBF), oxygen metabolism (CMRO{sub 2}), 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 CMRO{sub 2} 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.

Shishido, F. [Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubota-machi, Akita-city 010 (Japan)]|[Department of Radiology, Fukushima Medical College, 1 Hikarigaoka, Fukushima-city 960-12 (Japan); Uemura, K. [Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubota-machi, Akita-city 010 (Japan); Inugami, A. [Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubota-machi, Akita-city 010 (Japan); Tomura, N. [Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubota-machi, Akita-city 010 (Japan); Higano, S. [Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubota-machi, Akita-city 010 (Japan); Fujita, H. [Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubota-machi, Akita-city 010 (Japan); Sasaki, H. [Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubota-machi, Akita-city 010 (Japan); Kanno, I. [Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubota-machi, Akita-city 010 (Japan); Murakami, M. [Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubota-machi, Akita-city 010 (Japan); Watahiki, Y. [Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubota-machi, Akita-city 010 (Japan)]|[Department of Neurology, Research Institute for Brain and Blood Vessels-Akita, 6-10 Senshukubota-machi, Akita-city 010 (Japan); Nagata, K.

1996-02-01

332

TGR5: A Novel Target for Weight Maintenance and Glucose Metabolism  

Science.gov (United States)

TGR5, an emerging G protein-coupled receptor, was identified as a membrane receptor for bile acids. The expression of TGR5 and its function are distinct from the previously identified nuclear bile acid receptor, farnesoid X receptor (FXR). These two bile acid receptors complement with each other for maintaining bile acid homeostasis and mediating bile acid signaling. Both receptors are also shown to play roles in regulating inflammation and glucose metabolism. An interesting finding for TGR5 is its role in energy metabolism. The discovery of TGR5 expression in brown adipocyte tissues (BATs) and the recent demonstration of BAT in adult human body suggest a potential approach to combat obesity by targeting TGR5 to increase thermogenesis. We summarize here the latest finding of TGR5 research, especially its role in energy metabolism and glucose homeostasis.

Chen, Xiaosong; Lou, Guiyu; Meng, Zhipeng; Huang, Wendong

2011-01-01

333

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

Science.gov (United States)

Summary: 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 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

334

MicroRNA-451 Regulates LKB1/AMPK Signaling and Allows Adaptation to Metabolic Stress in Glioma Cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

To sustain tumor growth, cancer cells must be able to adapt to fluctuations in energy availability. We have identified a single microRNA that controls glioma cell proliferation, migration, and responsiveness to glucose deprivation. Abundant glucose allows relatively high miR-451 expression, promoting cell growth. In low glucose, miR-451 levels decrease, slowing proliferation but enhancing migration and survival. This allows cells to survive metabolic stress and seek out favorable growth condi...

Godlewski, Jakub; Nowicki, Michal O.; Bronisz, Agnieszka; Nuovo, Gerard; Palatini, Jeff; Lay, Michael; Brocklyn, James; Ostrowski, Michael C.; Chiocca, E. Antonio; Lawler, Sean E.

2010-01-01

335

The effects of antihypertensive drugs on chromium status, glucose metabolism, and antioxidant and inflammatory indices in spontaneously hypertensive rats.  

Science.gov (United States)

The long-term use of hypotensive drugs may cause side effects, including impaired glucose metabolism and mineral status. This study tested the hypothesis that some hypotensive drugs can affect tissular chromium levels and indices of glucose metabolic and antioxidant potential in rats. The experiment was performed on 40 male spontaneously hypertensive rats (SHRs), which were assigned to five groups: control (C), with perindopril (PR), with metoprolol (MT), with indapamide (ID), and with amlodipine (AM). All rats were provided ad libitum standard diet (with or without drugs) and distilled water for 45 days. Glucose and insulin levels, along with total antioxidant status (TAS) and concentrations of TNF-alpha and C-reactive protein, were assayed in serum. Chromium concentrations in the liver and kidney were determined using the flame atomic absorption spectrometry method. Detailed statistical analysis was performed using Statistica for Windows 10.0 (StatSoft, Poland). One-way analysis of variance (ANOVA), followed by a post hoc Tukey test, was used to compare the data between groups. Treatment with indapamide and amlodipine resulted in significantly higher chromium concentrations in the liver and kidney (AM) of the rats, compared with the control group. A markedly higher concentration of glucose was found in the ID group. Treatment with amlodipine significantly increased TAS levels in serum and decreased TNF-alpha concentration in serum of the rats. A significant positive correlation between chromium concentration in tissues and serum TAS level was observed, as was a significant negative correlation between chromium concentration in the kidneys, and TNF-alpha and glucose levels in serum. In conclusion, the administration of amlodipine may lead to an increase in chromium accumulation in the internal organs, which is associated with increased antioxidant status and suppression of the inflammatory response of cells in SHRs. PMID:24249586

Suliburska, Joanna; Krejpcio, Zbigniew; Staniek, Halina; Król, Ewelina; Bogdanski, Pawel; Kupsz, Justyna; Hertig, Iwona

2014-01-01

336

Role of NADH shuttles in glucose-induced insulin secretion from fetal beta-cells.  

Science.gov (United States)

The NADH shuttle system, which transports the substrate for oxidative metabolism directly from the cytosol to the mitochondrial electron transport chain, has been shown to be essential for glucose-induced activation of mitochondrial metabolism and insulin secretion in adult beta-cells. We examined the role of these shuttles in the fetal beta-cell, which is immature in being unable to secrete insulin in response to glucose. The activity and concentration of the two key enzymes of the NADH shuttles, mitochondrial glycerol phosphate dehydrogenase (mGPDH) and mitochondrial malate dehydrogenase (mMDH), were eight- and threefold lower, respectively, in fetal compared with adult rat islets. Likewise, mGPDH and mMDH activity was fivefold lower in islet-like cell clusters (ICCs) and sevenfold lower in purified beta-cells compared with adult islets in the pig. The low level of enzyme activity was a result of low gene expression of the mitochondrial enzymes in the fetal beta-cells. Increasing NADH shuttle activity by transduction of fetal rat islets with mGPDH cDNA enabled the fetal islets to secrete insulin when stimulated with glucose. We concluded that the immaturity of the NADH shuttles contributes to the inability of fetal beta-cells to secrete insulin in response to glucose. PMID:12351438

Tan, Cynthia; Tuch, Bernard E; Tu, Jian; Brown, Shane A

2002-10-01

337

A Drosophila orphan G protein-coupled receptor BOSS functions as a glucose-responding receptor: loss of boss causes abnormal energy metabolism.  

Science.gov (United States)

Glucose, one of the most important nutrients for animals, acts as a regulatory signal that controls the secretion of hormones, such as insulin, by endocrine tissues. However, how organisms respond to extracellular glucose and how glucose controls nutrient homeostasis remain unknown. Here, we show that a putative Drosophila melanogaster G protein-coupled receptor, previously identified as Bride of sevenless (BOSS), responds to extracellular glucose and regulates sugar and lipid metabolism. We found that BOSS was expressed in the fat body, a nutrient-sensing tissue equivalent to mammalian liver and adipose tissues, and in photoreceptor cells. Boss null mutants had small bodies, exhibited abnormal sugar and lipid metabolism (elevated circulating sugar and lipid levels, impaired lipid mobilization to oenocytes), and were sensitive to nutrient deprivation stress. These phenotypes are reminiscent of flies defective in insulin signaling. Consistent with these findings are the observations that boss mutants had reduced PI3K activity and phospho-AKT levels, which indicates that BOSS is required for proper insulin signaling. Because human G protein-coupled receptor 5B and the seven-transmembrane domain of BOSS share the same sequence, our results also have important implications for glucose metabolism in humans. Thus, our study provides insight not only into the basic mechanisms of metabolic regulation but also into the pathobiological basis for diabetes and obesity. PMID:18832180

Kohyama-Koganeya, Ayako; Kim, Yeon-Jeong; Miura, Masayuki; Hirabayashi, Yoshio

2008-10-01

338

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 of early dementia

1985-05-01

339

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

Science.gov (United States)

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

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

2013-10-01

340

The Lin28/let-7 axis regulates glucose metabolism  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 resistanc...

Zhu, H.; Shyh-chang, N.; Segre, A. V.; Shinoda, G.; Shah, S. P.; Einhorn, W. S.; Takeuchi, A.; Engreitz, J. M.; Hagan, J. P.; Kharas, M. G.; Urbach, A.; Thornton, J. E.; Triboulet, R.; Gregory, R. I.; Hottenga, J. J.

2011-01-01

 
 
 
 
341

Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion.  

Science.gov (United States)

Postprandial insulin release is regulated by glucose, but other circulating nutrients may target beta cells and potentiate glucose-stimulated insulin secretion via distinct signaling pathways. We demonstrate that fructose activates sweet taste receptors (TRs) on beta cells and synergizes with glucose to amplify insulin release in human and mouse islets. Genetic ablation of the sweet TR protein T1R2 obliterates fructose-induced insulin release and its potentiating effects on glucose-stimulated insulin secretion in vitro and in vivo. TR signaling in beta cells is triggered, at least in part, in parallel with the glucose metabolic pathway and leads to increases in intracellular calcium that are dependent on the activation of phospholipase C (PLC) and transient receptor potential cation channel, subfamily M, member 5 (TRPM5). Our results unveil a pathway for the regulation of insulin release by postprandial nutrients that involves beta cell sweet TR signaling. PMID:22315413

Kyriazis, George A; Soundarapandian, Mangala M; Tyrberg, Björn

2012-02-21

342

Altered regional brain glucose metabolism in Duchenne muscular dystrophy: a pet study.  

Science.gov (United States)

The basis for cognitive impairment in Duchenne muscular dystrophy (DMD) is not well understood but may be related to abnormal expression of dystrophin in brain. The aim of this study was to determine whether regional brain glucose metabolism is altered in children with DMD and whether such metabolic disturbances are localized to regions shown to be normally rich in dystrophin expression. Ten boys (mean age, 11.8 years) with DMD and 17 normal adults as a control group (mean age, 27.6 years) underwent 2-deoxy-2[(18)F]fluoro-D-glucose positron emission tomography (PET) and neuropsychological evaluation. The PET data were analyzed by statistical parametric mapping (SPM). The SPM analysis showed five clusters of decreased glucose metabolism in children with DMD, including the medial temporal structures and cerebellum bilaterally and the sensorimotor and lateral temporal cortex on the right side. At the voxel level, significant glucose hypometabolism was found in the right postcentral and middle temporal gyri, uncus, and VIIIB cerebellar lobule, as well as in the left hippocampal gyrus and cerebellar lobule. The neuropsychological profile of the DMD group revealed borderline nonverbal intellectual functioning, impaired manual dexterity bilaterally, borderline cognitive functioning, and internalizing behavioral difficulties. Our findings demonstrate region-specific hypometabolism, as well as cognitive and behavioral deficits in DMD children. As the regions showing hypometabolism on PET include those normally rich in dystrophin expression, it will be important to determine whether the hypometabolic regions also show cytoarchitectural abnormalities related to the lack of dystrophin. PMID:12362416

Lee, Joon Soo; Pfund, Zoltán; Juhász, Csaba; Behen, Michael E; Muzik, Otto; Chugani, Diane C; Nigro, Michael A; Chugani, Harry T

2002-10-01

343

Factor analysis of regional cerebral glucose metabolic rates in healthy men  

Energy Technology Data Exchange (ETDEWEB)

Cerebral glucose utilization measured with fluorine-18-fluoro-2-deoxy-D-glucose is characterized by considerable variability both among different persons and for the same person examined on different occasions. The goal of this study was to explore whether some regions of the brain were more variable than others with respect to glucose utilization and whether there was a pattern in their covariance. The global and regional cerebral utilization of glucose was measured in 12 healthy young volunteers on 3 or 4 occasions. In all, 24 regions were examined. The interrelation of the glucose utilization rates of the brain regions was investigated by factor analysis of the metabolic rates. Some 70% of the total variance was attributable to only 1 factor, while 80% of the total variance could be attributed to 2 factors. Regions making up the first factor were the frontal and temporal cortex, cingulate gyrus, caudate nucleus, thalamus and putamen. These regions are functionally related to the limbic system. Regions of the second factor were the parietal cortex, occipital cortex and cerebellum, regions more clearly related to sensory and motor functions. The 2-factor pattern was highly reproducible, being found with different algorithms for factor extraction and rotation. Under resting conditions, the variance of cerebral metabolism seems to be primarily related to regions which are closely involved with the limbic system. Cortical regions involved primarily in motor and sensory functions have less influence on the variance. (orig.).

Szabo, Z.; Camargo, E.E.; Sostre, S.; Shafique, I.; Sadzot, B.; Links, J.M.; Dannals, R.F.; Wagner, H.N. Jr. (Johns Hopkins Medical Institutions, Baltimore, MA (United States). Div. of Nuclear Medicine Johns Hopkins Medical Institutions, Baltimore, MA (United States). Div. of Radiation Health Sciences)

1992-07-01

344

Culture environment regulates amino acid turnover and glucose utilisation in human ES cells.  

Science.gov (United States)

Human embryonic stem (ES) cells have been proposed as a renewable source of pluripotent cells that can be differentiated into various cell types for use in research, drug discovery and in the emerging area of regenerative medicine. Exploitation of this potential will require the development of ES cell culture conditions that promote pluripotency and a normal cell metabolism, and quality control parameters that measure these outcomes. There is, however, relatively little known about the metabolism of pluripotent cells or the impact of culture environment and differentiation on their metabolic pathways. The effect of two commonly used medium supplements and cell differentiation on metabolic indicators in human ES cells were examined. Medium modifications and differentiation were compared in a chemically defined and feeder-independent culture system. Adding serum increased glucose utilisation and altered amino acid turnover by the cells, as well as inducing a small proportion of the cells to differentiate. Cell differentiation could be mitigated by inhibiting p38 mitogen-activated protein kinase (p38 MAPK activity). The addition of Knockout Serum Replacer also increased glucose uptake and changed amino acid turnover by the cells. These changes were distinct from those induced by serum and occurred in the absence of detectable differentiation. Induction of differentiation by bone morphogenetic protein 4 (BMP4), in contrast, did not alter metabolite turnover. Deviations from metabolite turnover by ES cells in fully defined medium demonstrated that culture environment can alter metabolite use. The challenge remains to understand the impact of metabolic changes on long-term cell maintenance and the functionality of derived cell populations. PMID:23759283

Rathjen, Joy; Yeo, Christine; Yap, Charlotte; Tan, Boon Siang Nicholas; Rathjen, Peter D; Gardner, David K

2014-06-01

345

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

346

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.

347

Toward homosuccinate fermentation: metabolic engineering of Corynebacterium glutamicum for anaerobic production of succinate from glucose and formate.  

Science.gov (United States)

Previous studies have demonstrated the capability of Corynebacterium glutamicum for anaerobic succinate production from glucose under nongrowing conditions. In this work, we have addressed two shortfalls of this process, the formation of significant amounts of by-products and the limitation of the yield by the redox balance. To eliminate acetate formation, a derivative of the type strain ATCC 13032 (strain BOL-1), which lacked all known pathways for acetate and lactate synthesis (?cat ?pqo ?pta-ackA ?ldhA), was constructed. Chromosomal integration of the pyruvate carboxylase gene pyc(P458S) into BOL-1 resulted in strain BOL-2, which catalyzed fast succinate production from glucose with a yield of 1 mol/mol and showed only little acetate formation. In order to provide additional reducing equivalents derived from the cosubstrate formate, the fdh gene from Mycobacterium vaccae, coding for an NAD(+)-coupled formate dehydrogenase (FDH), was chromosomally integrated into BOL-2, leading to strain BOL-3. In an anaerobic batch process with strain BOL-3, a 20% higher succinate yield from glucose was obtained in the presence of formate. A temporary metabolic blockage of strain BOL-3 was prevented by plasmid-borne overexpression of the glyceraldehyde 3-phosphate dehydrogenase gene gapA. In an anaerobic fed-batch process with glucose and formate, strain BOL-3/pAN6-gap accumulated 1,134 mM succinate in 53 h with an average succinate production rate of 1.59 mmol per g cells (dry weight) (cdw) per h. The succinate yield of 1.67 mol/mol glucose is one of the highest currently described for anaerobic succinate producers and was accompanied by a very low level of by-products (0.10 mol/mol glucose). PMID:22389371

Litsanov, Boris; Brocker, Melanie; Bott, Michael

2012-05-01

348

Both acyl and des-acyl ghrelin regulate adiposity and glucose metabolism via central nervous system ghrelin receptors.  

Science.gov (United States)

Growth hormone secretagogue receptors (GHSRs) in the central nervous system (CNS) mediate hyperphagia and adiposity induced by acyl ghrelin (AG). Evidence suggests that des-AG (dAG) has biological activity through GHSR-independent mechanisms. We combined in vitro and in vivo approaches to test possible GHSR-mediated biological activity of dAG. Both AG (100 nmol/L) and dAG (100 nmol/L) significantly increased inositol triphosphate formation in human embryonic kidney-293 cells transfected with human GHSR. As expected, intracerebroventricular infusion of AG in mice increased fat mass (FM), in comparison with the saline-infused controls. Intracerebroventricular dAG also increased FM at the highest dose tested (5 nmol/day). Chronic intracerebroventricular infusion of AG or dAG increased glucose-stimulated insulin secretion (GSIS). Subcutaneously infused AG regulated FM and GSIS in comparison with saline-infused control mice, whereas dAG failed to regulate these parameters even with doses that were efficacious when delivered intracerebroventricularly. Furthermore, intracerebroventricular dAG failed to regulate FM and induce hyperinsulinemia in GHSR-deficient (Ghsr(-/-)) mice. In addition, a hyperinsulinemic-euglycemic clamp suggests that intracerebroventricular dAG impairs glucose clearance without affecting endogenous glucose production. Together, these data demonstrate that dAG is an agonist of GHSR and regulates body adiposity and peripheral glucose metabolism through a CNS GHSR-dependent mechanism. PMID:24062249

Heppner, Kristy M; Piechowski, Carolin L; Müller, Anne; Ottaway, Nickki; Sisley, Stephanie; Smiley, David L; Habegger, Kirk M; Pfluger, Paul T; Dimarchi, Richard; Biebermann, Heike; Tschöp, Matthias H; Sandoval, Darleen A; Perez-Tilve, Diego

2014-01-01

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

High glucose concentrations attenuate hypoxia-inducible factor-1? expression and signaling in non-tumor cells  

International Nuclear Information System (INIS)

Hypoxia-inducible factor (HIF) is the major transcription factor mediating adaption to hypoxia e.g. by enhancing glycolysis. In tumor cells, high glucose concentrations are known to increase HIF-1? expression even under normoxia, presumably by enhancing the concentration of tricarboxylic acid cycle intermediates, while reactions of non-tumor cells are not well defined. Therefore, we analyzed cellular responses to different glucose concentrations in respect to HIF activation comparing tumor to non-tumor cells. Using cells derived from non-tumor origin, we show that HIF-1? accumulation was higher under low compared to high glucose concentrations. Low glucose allowed mRNA expression of HIF-1 target genes like adrenomedullin. Transfection of C2C12 cells with a HIF-1? oxygen-dependent degradation domaine-GFP fusion protein revealed that prolyl hydroxylase (PHD) activity is impaired at low glucose concentrations, thus stabilizing the fusion protein. Mechanistic considerations suggested that neither O2 redistribution nor an altered redox state explains impaired PHD activity in the absence of glucose. In order to affect PHD activity, glucose needs to be metabolized. Amino acids present in the medium also diminished HIF-1? expression, while the addition of fatty acids did not. This suggests that glucose or amino acid metabolism increases oxoglutarate concentrations, which enhances PHD activity in non-tumor cells. Tumor cells deprived of glutamine showed HIF-1? accumulation in the absence of glucose, proposing that enhanced glutaminolysis observed in many tumors enables these cells to compensate reduced oxoglutarate production in the absence of glucose.

2010-04-15

351

High glucose concentrations attenuate hypoxia-inducible factor-1{alpha} expression and signaling in non-tumor cells  

Energy Technology Data Exchange (ETDEWEB)

Hypoxia-inducible factor (HIF) is the major transcription factor mediating adaption to hypoxia e.g. by enhancing glycolysis. In tumor cells, high glucose concentrations are known to increase HIF-1{alpha} expression even under normoxia, presumably by enhancing the concentration of tricarboxylic acid cycle intermediates, while reactions of non-tumor cells are not well defined. Therefore, we analyzed cellular responses to different glucose concentrations in respect to HIF activation comparing tumor to non-tumor cells. Using cells derived from non-tumor origin, we show that HIF-1{alpha} accumulation was higher under low compared to high glucose concentrations. Low glucose allowed mRNA expression of HIF-1 target genes like adrenomedullin. Transfection of C{sub 2}C{sub 12} cells with a HIF-1{alpha} oxygen-dependent degradation domaine-GFP fusion protein revealed that prolyl hydroxylase (PHD) activity is impaired at low glucose concentrations, thus stabilizing the fusion protein. Mechanistic considerations suggested that neither O{sub 2} redistribution nor an altered redox state explains impaired PHD activity in the absence of glucose. In order to affect PHD activity, glucose needs to be metabolized. Amino acids present in the medium also diminished HIF-1{alpha} expression, while the addition of fatty acids did not. This suggests that glucose or amino acid metabolism increases oxoglutarate concentrations, which enhances PHD activity in non-tumor cells. Tumor cells deprived of glutamine showed HIF-1{alpha} accumulation in the absence of glucose, proposing that enhanced glutaminolysis observed in many tumors enables these cells to compensate reduced oxoglutarate production in the absence of glucose.

Dehne, Nathalie, E-mail: dehne@biochem.uni-frankfurt.de [Institute of Biochemistry I/ZAFES (Germany); Hintereder, Gudrun, E-mail: Gudrun.Hintereder@kgu.de [Zentrallabor, Goethe-University, 60590 Frankfurt am Main (Germany); Bruene, Bernhard, E-mail: bruene@pathobiochemie1.de [Institute of Biochemistry I/ZAFES (Germany)

2010-04-15

352

Action of irbesartan on blood pressure and glucose/lipid metabolism, in hemodialysis patients with hypertension  

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Full Text Available Akira Onishi,1 Yoshiyuki Morishita,1 Minami Watanabe,1 Akihiko Numata,1 Mikio Tezuka,2 Kosuke Okuda,3 Sadao Tsunematsu,4 Yasuhiro Sugaya,5 Shinichi Hashimoto,5 Eiji Kusano11Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, Japan; 2Kurosu Hospital, Tochigi, Japan; 3Okuda Clinic, Tochigi, Japan; 4Yuki Clinic, Ibaraki, Japan; 5Ninomiya Central Clinic, Tochigi, JapanBackground: Irbesartan has been reported to have beneficial effects on glucose/lipid metabolism in addition to an antihypertensive effect; however, such effects have not been clarified in hemodialysis (HD patients. We investigated the effects of irbesartan on blood pressure (BP as well as glucose/lipid metabolism, in HD patients with hypertension.Methods: Seventeen HD patients with hypertension, aged 62.7 ± 12.5 years, were treated with daily oral administration of 50 to 100 mg of irbesartan for 12 weeks. Then, the changes of BP as well as glucose metabolism (random serum glucose level and serum glycosylated hemoglobin [HbA1c] level and lipid metabolism (serum low-density lipoprotein cholesterol [LDL-chol] level, serum high-density lipoprotein cholesterol [HDL-chol] level, and serum triglyceride [TG] level were evaluated.Results: Irbesartan significantly reduced systolic BP (154.9 ± 12.8 to 139.4 ± 13.1 mmHg (P < 0.01 and diastolic BP (78.9 ± 9.1 to 72.2 ± 9.7 mmHg, P < 0.01. It also reduced LDL-