WorldWideScience
 
 
1

Glucose uptake and metabolism by red blood cells from fish with different extracellular glucose levels.  

Science.gov (United States)

The aim of the present study was to assess whether mechanisms of glucose trafficking by red blood cells (RBCs) relate to species-specific extracellular glucose levels. Atlantic cod (Gadus morhua), Atlantic salmon (Salmo salar), cunner (Tautogolabrus adspersus) and short-horned sculpin (Myoxocephalus scorpius) had plasma glucose levels of 4, 4.1, 1.95 and 0.73 mmol l(-1), respectively. Glucose uptake by isolated RBCs was measured by the initial incorporation of [6-(14)C]-glucose and steady-state glucose metabolism was determined by the production of (3)H(2)O from [2-(3)H]-glucose. Saturation kinetics of glucose uptake and inhibition of both glucose uptake and metabolism by cytochalasin B and phloretin revealed that Atlantic cod, cunner and sculpin RBCs all had a facilitated transport component to glucose trafficking. RBCs from Atlantic salmon showed a linear relationship between glucose uptake and extracellular glucose level, but exhibited clear inhibition of glucose metabolism by cytochalasin B and phloretin, suggesting a component of facilitated glucose transport that is more elusive to detect. The production of (3)H(2)O was linear for at least 6 h and as such presents a rigorous approach to measuring glycolytic rate. Steady-state rates of glucose metabolism were achieved at extracellular levels of approximately 1 mmol l(-1) glucose for RBCs from all species, showing that within-species normal extracellular glucose level is not a primary determinant of the basal level of glycolysis. At physiological levels of extracellular glucose, the ratio of initial glucose uptake to glucose metabolism was 1.5 to 4 for all RBCs, suggesting that there is scope to increase metabolic rate without alteration of the basal glucose uptake capacity. PMID:23038726

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

2012-10-04

2

Geniposide Regulates Glucose-Stimulated Insulin Secretion Possibly through Controlling Glucose Metabolism in INS-1 Cells  

Science.gov (United States)

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

Liu, Jianhui; Guo, Lixia; Yin, Fei; Zhang, Yonglan; Liu, Zixuan; Wang, Yanwen

2013-01-01

3

Excess glucose induces hypoxia-inducible factor-1? in pancreatic cancer cells and stimulates glucose metabolism and cell migration.  

UK PubMed Central (United Kingdom)

Pancreatic cancer patients frequently show hyperglycemia, but it is uncertain whether hyperglycemia stimulates pancreatic cancer cells. We have investigated whether excess glucose induces hypoxia-inducible factor-1? (HIF-1?) and stimulates glucose metabolism and cell migration in pancreatic cancer cells. We studied wild-type (wt) MiaPaCa2 pancreatic cancer cells and a MiaPaCa2 subline (namely si-MiaPaCa2) that had HIF-1?-specific small interfering RNA. Wt-MiaPaCa2 cells are known to be HIF-1?-positive in hypoxia and HIF-1?-negative in normoxia, whereas si-MiaPaCa2 cells are devoid of HIF-1? in both normoxia and hypoxia. We incubated these cells with different amounts of glucose and determined HIF-1? mRNA and protein by real-time polymerase chain reaction and western blotting. We determined glucose consumption, lactate production and intracellular hexokinase-II and ATP to assess glucose metabolisms and determined pyruvate dehydrogenase kinase-1, reactive oxygen species and fumarate to assess mitochondrial activities. Further, we studied cell migration using a Boyden chamber. Excess glucose (16.7-22.2mM) increased HIF-1? in hypoxic wt-MiaPaCa2 cells. HIF-1? expression increased ATP contents and inhibited mitochondrial activities. Extracellular glucose and hypoxia stimulated glucose metabolisms independent of HIF-1?. Excess glucose stimulated the migration of wt- and si-MiaPaCa2 cells in both normoxia and hypoxia. Thus, glucose stimulated cell migration independent of HIF-1?. Nevertheless, hypoxic wt-MiaPaCa2 cells showed greater migrating ability than their si-MiaPaCa2 counterparts. We conclude that (1) excess glucose increases HIF-1? and ATP in hypoxic wt-MiaPaCa2 cells, (2) extracellular glucose and hypoxia regulate glucose metabolisms independent of HIF-1? and (3) glucose stimulates cell migration by mechanisms that are both dependent on HIF-1? and independent of it.

Liu Z; Jia X; Duan Y; Xiao H; Sundqvist KG; Permert J; Wang F

2013-05-01

4

Glucose metabolism by adult hepatocytes in primary culture and by cell lines from rat liver.  

UK PubMed Central (United Kingdom)

The metabolic fate of [U-14C]glucose has been examined in detail in adult rat hepatocytes in primary monolayer culture, as well as in two permanent cell lines--Buffalo rat liver (BRL) and transplantable rat hepatoma (HTC) cells-derived from normal rat liver and from rat hepatoma, respectively. Under defined conditions of incubation, at a glucose concentration of 5.5 mM, the three types of cultured liver cells exhibited pronounced differences in glucose metabolism. Primary cultures, like the intact liver, differed from the cell lines in consuming relatively small amounts of glucose and converting approximately 50% of the total metabolized glucose to lactate. By contrast, the permantent cell lines consumed glucose at a 40-fold greater rate than did primary cultures, converting 80--90% of the carbohydrate to lactate. Oxidative metabolism of glucose carbon also differed among the three types of liver culture. Of the total [U-14C]glucose consumed, primary cultures converted approximately 30% to labeled CO2 per hour, whereas the liver cell lines converted 5--10%. Finally, glucose metabolism in primary culture exhibited adaptation as hepatocytes aged in culture, shifting progressively toward the pattern exhibited by the permanent cell lines. This change occurred over a time course similar to that for other kinds of functional change in hepatocytes in primary culture and thus may be relevant to the general problem of phenotypic alteration in liver cell culture.

Bissell DM; Levine GA; Bissell MJ

1978-03-01

5

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

Directory of Open Access Journals (Sweden)

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

Shiraki Takayuki; Miura Yoshikazu; Sawada Tokihiko; Okada Toshie; Sakuraoka Yuhki; Muto Takashi; Kubota Keiichi

2011-01-01

6

Metabolism of radiolabeled glucose by mouse oocytes and oocyte-cumulus cell complexes.  

Science.gov (United States)

This study was carried out to examine the metabolism of [1-14C]-, [6-14C]-, and [5-3H]glucose by oocyte-cumulus cell complexes (OCC) and denuded oocytes (DO) and to test the hypothesis that metabolism of glucose through the pentose phosphate pathway is associated with meiotic induction. OCC or DO were cultured in hanging drops suspended from the cap of a microfuge tube, with NaOH serving as a trap to collect released 3H2O or 14CO2. Preliminary experiments established that this culture system supports both spontaneous and ligand-induced meiotic maturation. An initial time course experiment (1.5-6 h) showed that hypoxanthine-treated OCC from eCG-primed animals metabolized glucose principally via glycolysis, with an increase to 2.7-fold in response to FSH. Though more [1-14C]glucose was oxidized than [6-14C]glucose, its metabolism was about two orders of magnitude less than that of [5-3H]glucose. Also, FSH significantly increased oxidation of [1-14C]glucose but not [6-14C]glucose, indicating a preferential activation of the pentose phosphate pathway. Pyrroline carboxylate, an activator of the pentose phosphate pathway, increased the activity of this pathway to over 2-fold but failed to affect glucose oxidation through the tricarboxylic acid cycle. Glycolytic metabolism was increased by 25%. The addition of pyruvate to pyruvate-free medium resulted in significant reduction in the metabolism of all three glucose analogues. In OCC retrieved from hCG-injected, primed mice and cultured under hormone-free conditions, metabolic responses were similar to those in FSH-treated complexes cultured in hypoxanthine. DO metabolized glucose, but at a much reduced rate when compared to OCC. Pyruvate reduced the consumption of all three glucose analogues by DO. Pyrroline carboxylate reduced [5-3H]glucose metabolism by DO but had little effect on [1-14C]- and [6-14C]glucose oxidation. These data demonstrate metabolism of glucose by both DO and OCC, but reveal that cumulus cells are more active than the oocyte in this regard. In addition, induction of maturation by FSH, hCG, or pyrroline carboxylate was accompanied by a significant increase in the oxidation of [1-14C]glucose but not [6-14C]glucose by OCC, supporting a proposed role for the pentose phosphate pathway in meiotic induction. PMID:10330104

Downs, S M; Utecht, A M

1999-06-01

7

Metabolism of radiolabeled glucose by mouse oocytes and oocyte-cumulus cell complexes.  

UK PubMed Central (United Kingdom)

This study was carried out to examine the metabolism of [1-14C]-, [6-14C]-, and [5-3H]glucose by oocyte-cumulus cell complexes (OCC) and denuded oocytes (DO) and to test the hypothesis that metabolism of glucose through the pentose phosphate pathway is associated with meiotic induction. OCC or DO were cultured in hanging drops suspended from the cap of a microfuge tube, with NaOH serving as a trap to collect released 3H2O or 14CO2. Preliminary experiments established that this culture system supports both spontaneous and ligand-induced meiotic maturation. An initial time course experiment (1.5-6 h) showed that hypoxanthine-treated OCC from eCG-primed animals metabolized glucose principally via glycolysis, with an increase to 2.7-fold in response to FSH. Though more [1-14C]glucose was oxidized than [6-14C]glucose, its metabolism was about two orders of magnitude less than that of [5-3H]glucose. Also, FSH significantly increased oxidation of [1-14C]glucose but not [6-14C]glucose, indicating a preferential activation of the pentose phosphate pathway. Pyrroline carboxylate, an activator of the pentose phosphate pathway, increased the activity of this pathway to over 2-fold but failed to affect glucose oxidation through the tricarboxylic acid cycle. Glycolytic metabolism was increased by 25%. The addition of pyruvate to pyruvate-free medium resulted in significant reduction in the metabolism of all three glucose analogues. In OCC retrieved from hCG-injected, primed mice and cultured under hormone-free conditions, metabolic responses were similar to those in FSH-treated complexes cultured in hypoxanthine. DO metabolized glucose, but at a much reduced rate when compared to OCC. Pyruvate reduced the consumption of all three glucose analogues by DO. Pyrroline carboxylate reduced [5-3H]glucose metabolism by DO but had little effect on [1-14C]- and [6-14C]glucose oxidation. These data demonstrate metabolism of glucose by both DO and OCC, but reveal that cumulus cells are more active than the oocyte in this regard. In addition, induction of maturation by FSH, hCG, or pyrroline carboxylate was accompanied by a significant increase in the oxidation of [1-14C]glucose but not [6-14C]glucose by OCC, supporting a proposed role for the pentose phosphate pathway in meiotic induction.

Downs SM; Utecht AM

1999-06-01

8

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

International Nuclear Information System (INIS)

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

2007-01-01

9

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

10

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

11

Immune cell-mediated inflammation and the early improvements in glucose metabolism after gastric banding surgery.  

UK PubMed Central (United Kingdom)

AIMS/HYPOTHESIS: The contribution of immune cells to the inflammasome that characterises type 2 diabetes mellitus and obesity is under intense research scrutiny. We hypothesised that early changes in glucose metabolism following gastric banding surgery may relate to systemic inflammation, particularly cell-mediated immunity. METHODS: Obese participants (BMI 43.4?±?4.9 kg/m(2), n?=?15) with diabetes or impaired glucose tolerance (IGT) underwent laparoscopic adjustable gastric banding surgery. Measurements taken before, and at 2 and 12 weeks after surgery included: fasting glucose, glucose levels 2 h after a 75 g oral load, glucose incremental AUC, oral glucose insulin sensitivity index (OGIS), circulating immune cell numbers and activation, and adipokine levels. Subcutaneous and visceral adipose tissue were collected at surgery, and macrophage number and activation measured. RESULTS: There were significant reductions in fasting and 2 h glucose, as well as improved OGIS at 2 and 12 weeks. At 12 weeks, 80% of the diabetic participants reverted to normal glucose tolerance or IGT, and all IGT participants had normalised glucose tolerance. The 12 week fall in fasting glucose was significantly related to baseline lymphocyte and T lymphocyte numbers, and to granulocyte activation, but also to the magnitude of the 12 week reduction in lymphocyte and T lymphocyte numbers and TNF-? levels. In a model that explained 75% of the variance in the change in fasting glucose, the 12 week change in T lymphocytes was independently associated with the 12 week fall in fasting glucose. CONCLUSIONS/INTERPRETATION: Rapid improvements in glucose metabolism after gastric banding surgery are related to reductions in circulating pro-inflammatory immune cells, specifically T lymphocytes. The contribution of immune cell-mediated inflammation to glucose homeostasis in type 2 diabetes and its improvement after bariatric surgery require further investigation.

Samaras K; Viardot A; Botelho NK; Jenkins A; Lord RV

2013-09-01

12

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

Energy Technology Data Exchange (ETDEWEB)

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

Tsacopoulos, M.; Evequoz-Mercier, V.; Perrottet, P.; Buchner, E.

1988-11-01

13

Glucose metabolism is altered after loss of L cells and ?-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 ?-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 ?-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 ?-cell loss and normal following ?-cell loss. Oral glucose tolerance was improved following L cell and ?-cell loss and supernormal following ?-cell loss. We present two mouse models that allow studies of the effects of K cell or L cell and ?-cell loss as well as isolated ?-cell loss. Our findings show that intraperitoneal glucose tolerance is dependent on an intact L cell mass and underscore the diabetogenic effects of ?-cell signaling. Furthermore, the results suggest that K cells are less involved in acute regulation of mouse glucose metabolism than L cells and ?-cells.

Pedersen, J; Ugleholdt, R K

2013-01-01

14

Glucose-Induced Metabolic Memory in Schwann Cells: Prevention by PPAR Agonists.  

Science.gov (United States)

A major barrier in reversing diabetic complications is that molecular and pathologic effects of elevated glucose persist despite normalization of glucose, a phenomenon referred to as metabolic memory. In the present studies we have investigated the effects of elevated glucose on Schwann cells, which are implicated in diabetic neuropathy. Using quantitative PCR arrays for glucose and fatty acid metabolism, we have found that chronic (>8 wk) 25 mM high glucose induces a persistent increase in genes that promote glycolysis, while inhibiting those that oppose glycolysis and alternate metabolic pathways such as fatty acid metabolism, the pentose phosphate pathway, and trichloroacetic acid cycle. These sustained effects were associated with decreased peroxisome proliferator-activated receptor (PPAR)? binding and persistently increased reactive oxygen species, cellular NADH, and altered DNA methylation. Agonists of PPAR? and PPAR? prevented select effects of glucose-induced gene expression. These observations suggest that Schwann cells exhibit features of metabolic memory that may be regulated at the transcriptional level. Furthermore, targeting PPAR may prevent metabolic memory and the development of diabetic complications. PMID:23709088

Kim, Esther S; Isoda, Fumiko; Kurland, Irwin; Mobbs, Charles V

2013-05-24

15

Regulation of glutamine and glucose metabolism by cell volume in lymphocytes and macrophages.  

UK PubMed Central (United Kingdom)

The effects of osmotically and sucrose-induced cell volume changes on glutamine and glucose metabolism were investigated in rat lymphocytes and macrophages incubated for 10-60 min at 37 degrees C in Krebs-Henseleit bicarbonate buffer (pH 7.4). Decreasing extracellular osmolarity from 336 to 286 mOsmol by decreasing medium NaCl from 119 to 94 mM increased cell volume and the rates of glutamine metabolism and glycolysis in both cell types. Conversely, increasing extracellular osmolarity from 286 to 386 mOsmol by the addition of 50 and 100 mM D-mannitol progressively decreased both cell volume and the rates of glutamine and glucose metabolism in lymphocytes and macrophages. At the same medium osmolarity of 336 mOsmol, the rates of glutamine metabolism and glycolysis were greater with the addition of 50 mM sucrose than with that of 25 mM NaCl. The sucrose-induced increase in cell volume, which is due to the uptake of sucrose by lymphocytes and macrophages via pinocytosis, is associated with enhanced rates of glutamine metabolism and glycolysis. Our findings suggest that cell volume change may be a hitherto unrecognized mechanism for regulating metabolism in lymphocytes and macrophages. The enhanced glutamine and glucose metabolism in these cells in response to mitogenic stimulation or immunological activation may result, at least in part, from the concomitant increase in cell volume.

Wu G; Flynn NE

1995-04-01

16

Nonlinear scaling analysis of glucose metabolism in normal and cancer cells.  

Science.gov (United States)

Cancer progression is commonly accompanied by an altered glucose metabolism. In general, spatially resolved imaging of glucose metabolism and its subtle alterations might provide valuable diagnostic information in vivo. A classical example is positron emission tomography that exploits this feature in obtaining preferential accumulation of fluorescent analog of glucose in tumors, thereby achieving an imaging contrast. We report a novel scaling analysis of glucose metabolism in mammary epithelial (NMuMG) cells by detrended fluctuation analysis of Cerulean (cyan fluorescent protein variant) fluorescence. Fluorescence fluctuations of Cerulean are reasoned to be indicative of dynamic pH changes associated with glucose metabolism. Normal parental cells and the spontaneously transformed (cancerous) NMuMG cells displayed robust scaling exponent that reflects nonrandom fluctuations in Cerulean fluorescence. Acute dependence of cancer cells on glycolysis as compared with normal cells is exploited to yield a statistically significant difference in scaling exponent, thereby providing discrimination between normal and cancer cells in vitro. By careful design of experiments in vivo, the proposed scaling approach might even have diagnostic potential for early detection of cancer lesions in small animal models. PMID:18601543

Ramanujan, V Krishnan; Herman, Brian A

17

Nonlinear scaling analysis of glucose metabolism in normal and cancer cells.  

UK PubMed Central (United Kingdom)

Cancer progression is commonly accompanied by an altered glucose metabolism. In general, spatially resolved imaging of glucose metabolism and its subtle alterations might provide valuable diagnostic information in vivo. A classical example is positron emission tomography that exploits this feature in obtaining preferential accumulation of fluorescent analog of glucose in tumors, thereby achieving an imaging contrast. We report a novel scaling analysis of glucose metabolism in mammary epithelial (NMuMG) cells by detrended fluctuation analysis of Cerulean (cyan fluorescent protein variant) fluorescence. Fluorescence fluctuations of Cerulean are reasoned to be indicative of dynamic pH changes associated with glucose metabolism. Normal parental cells and the spontaneously transformed (cancerous) NMuMG cells displayed robust scaling exponent that reflects nonrandom fluctuations in Cerulean fluorescence. Acute dependence of cancer cells on glycolysis as compared with normal cells is exploited to yield a statistically significant difference in scaling exponent, thereby providing discrimination between normal and cancer cells in vitro. By careful design of experiments in vivo, the proposed scaling approach might even have diagnostic potential for early detection of cancer lesions in small animal models.

Ramanujan VK; Herman BA

2008-05-01

18

Glucose metabolism in uremia.  

UK PubMed Central (United Kingdom)

Formation of CO2 from uniformly labeled 14C-glucose was measured in liver slices from uremic and normal rats. Both CO2 formation and lactate concentration were decreased in the uremic liver slices suggesting an inhibition of glucose oxidation. In addition, a net loss of glucose from the medium in the uremic preparation and a net gain in the normal controls suggested that there was increased nonoxidative utilization in the uremic liver. Such changes could not be explained by differences in glucose availability consequent to alterations in glycogen degradation. The most likely explanation is diversion of glucose into other biosynthetic pathways such as the synthesis of amino acids. In this regard, synthesis of glutamine appeared to be enhanced in uremia. Thus, products of carbohydrate metabolism may provide a potential mechanism for disposition of ammonia and synthesis of amino acids in uremia.

Quintanilla A; Shambaugh GE 3rd; Gibson TP; Craig R

1980-07-01

19

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

UK PubMed Central (United Kingdom)

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

Fendt SM; Bell EL; Keibler MA; Davidson SM; Wirth GJ; Fiske B; Mayers JR; Schwab M; Bellinger G; Csibi A; Patnaik A; Blouin MJ; Cantley LC; Guarente L; Blenis J; Pollak MN; Olumi AF; Vander Heiden MG; Stephanopoulos G

2013-07-01

20

New aspects of an old drug--diclofenac targets MYC and glucose metabolism in tumor cells.  

UK PubMed Central (United Kingdom)

Non-steroidal anti-inflammatory drugs such as diclofenac exhibit potent anticancer effects. Up to now these effects were mainly attributed to its classical role as COX-inhibitor. Here we show novel COX-independent effects of diclofenac. Diclofenac significantly diminished MYC expression and modulated glucose metabolism resulting in impaired melanoma, leukemia, and carcinoma cell line proliferation in vitro and reduced melanoma growth in vivo. In contrast, the non-selective COX inhibitor aspirin and the COX-2 specific inhibitor NS-398 had no effect on MYC expression and glucose metabolism. Diclofenac significantly decreased glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 1 (MCT1) gene expression in line with a decrease in glucose uptake and lactate secretion. A significant intracellular accumulation of lactate by diclofenac preceded the observed effect on gene expression, suggesting a direct inhibitory effect of diclofenac on lactate efflux. While intracellular lactate accumulation impairs cellular proliferation and gene expression, it does not inhibit MYC expression as evidenced by the lack of MYC regulation by the MCT inhibitor ?-cyano-4-hydroxycinnamic acid. Finally, in a cell line with a tetracycline-regulated c-MYC gene, diclofenac decreased proliferation both in the presence and absence of c-MYC. Thus, diclofenac targets tumor cell proliferation via two mechanisms, that is inhibition of MYC and lactate transport. Based on these results, diclofenac holds potential as a clinically applicable MYC and glycolysis inhibitor supporting established tumor therapies.

Gottfried E; Lang SA; Renner K; Bosserhoff A; Gronwald W; Rehli M; Einhell S; Gedig I; Singer K; Seilbeck A; Mackensen A; Grauer O; Hau P; Dettmer K; Andreesen R; Oefner PJ; Kreutz M

2013-01-01

 
 
 
 
21

JC Virus T-Antigen Regulates Glucose Metabolic Pathways in Brain Tumor Cells  

Science.gov (United States)

Recent studies have reported the detection of the human neurotropic virus, JCV, in a significant population of brain tumors, including medulloblastomas. Accordingly, expression of the JCV early protein, T-antigen, which has transforming activity in cell culture and in transgenic mice, results in the development of a broad range of tumors of neural crest and glial origin. Evidently, the association of T-antigen with a range of tumor-suppressor proteins, including p53 and pRb, and signaling molecules, such as ?-catenin and IRS-1, plays a role in the oncogenic function of JCV T-antigen. We demonstrate that T-antigen expression is suppressed by glucose deprivation in medulloblastoma cells and in glioblastoma xenografts that both endogenously express T-antigen. Mechanistic studies indicate that glucose deprivation-mediated suppression of T-antigen is partly influenced by 5?-activated AMP kinase (AMPK), an important sensor of the AMP/ATP ratio in cells. In addition, glucose deprivation-induced cell cycle arrest in the G1 phase is blocked with AMPK inhibition, which also prevents T-antigen downregulation. Furthermore, T-antigen prevents G1 arrest and sustains cells in the G2 phase during glucose deprivation. On a functional level, T-antigen downregulation is partially dependent on reactive oxygen species (ROS) production during glucose deprivation, and T-antigen prevents ROS induction, loss of ATP production, and cytotoxicity induced by glucose deprivation. Additionally, we have found that T-antigen is downregulated by the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), and the pentose phosphate inhibitors, 6-aminonicotinamide and oxythiamine, and that T-antigen modulates expression of the glycolytic enzyme, hexokinase 2 (HK2), and the pentose phosphate enzyme, transaldolase-1 (TALDO1), indicating a potential link between T-antigen and metabolic regulation. These studies point to the possible involvement of JCV T-antigen in medulloblastoma proliferation and the metabolic phenotype and may enhance our understanding of the role of viral proteins in glycolytic tumor metabolism, thus providing useful targets for the treatment of virus-induced tumors.

Noch, Evan; Sariyer, Ilker Kudret; Gordon, Jennifer; Khalili, Kamel

2012-01-01

22

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

International Nuclear Information System (INIS)

[en] 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.)

2004-01-01

23

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

Energy Technology Data Exchange (ETDEWEB)

Amino acid imaging is increasingly being used for assessment of brain tumor malignancy, extent of disease, and prognosis. This study explores the relationship between proliferative activity, amino acid transport, and glucose metabolism in three glioma cell lines (U87, Hs683, C6) at different phases of growth in culture. Growth phase was characterized by direct cell counting, proliferation index determined by flow cytometry, and [{sup 3}H]thymidine (TdR) accumulation, and was compared with the uptake of two non-metabolized amino acids ([{sup 14}C]aminocyclopentane carboxylic acid (ACPC) and [{sup 14}C]aminoisobutyric acid (AIB)), and [{sup 18}F]fluorodeoxyglucose (FDG). Highly significant relationships between cell number (density), proliferation index, and TdR accumulation rate were observed in all cell lines (r>0.99). Influx (K{sub 1}) of both ACPC and AIB was directly related to cell density, and inversely related to the proliferation index and TdR accumulation in all cell lines. The volume of distribution (V{sub d}) for ACPC and AIB was lowest during rapid growth and highest during the near-plateau growth phase in all cell lines. FDG accumulation in Hs683 and C6 cells was unaffected by proliferation rate, growth phase, and cell density, whereas FDG accumulation was correlated with TdR accumulation, growth phase, and cell density in U87 cells. This study demonstrates that proliferation rate and glucose metabolism are not necessarily co-related in all glioma cell lines. The values of K{sub 1} and V{sub d} for ACPC and AIB under different growth conditions suggest that these tumor cell lines can up-regulate amino acid transporters in their cell membranes when their growth conditions become adverse and less than optimal. (orig.)

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

2004-09-01

24

Effects of glucose availability on expression of the key genes involved in synthesis of milk fat, lactose and glucose metabolism in bovine mammary epithelial cells.  

UK PubMed Central (United Kingdom)

As the main precursor for lactose synthesis, large amounts of glucose are required by lactating dairy cows. Milk yield greatly depends on mammary lactose synthesis due to its osmoregulatory property for mammary uptake of water. Thus, glucose availability to the mammary gland could be a potential regulator of milk production. In the present study, the effect of glucose availability on expression of the key genes involved in synthesis of milk fat, lactose and glucose metabolism in vitro was investigated. Bovine mammary epithelial cells (BMEC) were treated for 12 h with various concentrations of glucose (2.5, 5, 10 or 20 mmol/L). The higher concentrations of glucose (10-20 mmol/L) did not affect the mRNA expression of acetyl-CoA carboxylase, diacyl glycerol acyl transferase, glycerol-3 phosphate acyl transferase and ?-lactalbumin, whereas fatty acid synthase, sterol regulatory element binding protein-1 and beta-1, 4-galactosyl transferase mRNA expression increased at 10 mmol/L and then decreased at 20 mmol/L. The content of lactose synthase increased with increasing concentration of glucose, with addition of highest value at 20 mmol/L of glucose. Moreover, the increased glucose concentration stimulated the activities of pyruvate kinase and glucose-6-phosphate dehydrogenase, and elevated the energy status of the BMEC. Therefore, it was deduced that after increasing glucose availability, the extra absorbed glucose was partitioned to entering the synthesis of milk fat and lactose by the regulation of the mRNA expression of key genes, promoting glucose metabolism by glycolysis and pentose phosphate pathway as well as energy status. These results indicated that the sufficient availability of glucose in BMEC may promote glucose metabolism, and affect the synthesis of milk composition.

Liu H; Zhao K; Liu J

2013-01-01

25

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

26

Pioglitazone acutely reduces insulin secretion and causes metabolic deceleration of the pancreatic beta-cell at submaximal glucose concentrations.  

UK PubMed Central (United Kingdom)

Thiazolidinediones (TZDs) have beneficial effects on glucose homeostasis via enhancement of insulin sensitivity and preservation of beta-cell function. How TZDs preserve beta-cells is uncertain, but it might involve direct effects via both peroxisome proliferator-activated receptor-gamma-dependent and -independent pathways. To gain insight into the independent pathway(s), we assessed the effects of short-term (glucose-induced insulin secretion (GIIS), AMP-activated protein kinase (AMPK) activation, and beta-cell metabolism in INS 832/13 beta-cells and rat islets. Pio caused a right shift in the dose-dependence of GIIS, such that insulin release was reduced at intermediate glucose but unaffected at either basal or maximal glucose concentrations. This was associated in INS 832/13 cells with alterations in energy metabolism, characterized by reduced glucose oxidation, mitochondrial membrane polarization, and ATP levels. Pio caused AMPK phosphorylation and its action on GIIS was reversed by the AMPK inhibitor compound C. Pio also reduced palmitate esterification into complex lipids and inhibited lipolysis. As for insulin secretion, the alterations in beta-cell metabolic processes were mostly alleviated at elevated glucose. Similarly, the antidiabetic agents and AMPK activators metformin and berberine caused a right shift in the dose dependence of GIIS. In conclusion, Pio acutely reduces glucose oxidation, energy metabolism, and glycerolipid/fatty acid cycling of the beta-cell at intermediate glucose concentrations. We suggest that AMPK activation and the metabolic deceleration of the beta-cell caused by Pio contribute to its known effects to reduce hyperinsulinemia and preserve beta-cell function and act as an antidiabetic agent.

Lamontagne J; Pepin E; Peyot ML; Joly E; Ruderman NB; Poitout V; Madiraju SR; Nolan CJ; Prentki M

2009-08-01

27

Endocrine control of oleic acid and glucose metabolism in rainbow trout (Oncorhynchus mykiss) muscle cells in culture.  

Science.gov (United States)

The effects of insulin and IGF-I on fatty acid (FA) and glucose metabolism were examined using oleic acid or glucose as tracers in differentiated rainbow trout (Oncorhynchus mykiss) myotubes. Insulin and IGF-I significantly reduced the production of CO(2) from oleic acid with respect to the control values. IGF-I also significantly reduced the production of acid-soluble products (ASP) and the concentration of FA in the medium, while cellular triacylglycerols (TAG) tended to increase. Only insulin produced a significant accumulation of glycogen inside the cells in glucose distribution experiments. Incubation with catecholamines did not affect oleic acid metabolism. Cells treated with rapamycin [a target of rapamycin (TOR) inhibitor] significantly increased the oxidation of oleic acid to CO(2) and ASP, while the accumulation of TAG diminished. Rosiglitazone (a peroxisome proliferator-activated receptor gamma agonist) and etomoxir (a CPT-1 inhibitor) produced a severe and significant reduction in the production of CO(2) and ASP. Rosiglitazone and etomoxir also produced a significant accumulation of FA outside and inside the cells, respectively. No significant effects of these drugs on glucose distribution were observed. These data indicate that insulin and IGF-I act as anabolic hormones in trout myotubes in both oleic acid and glucose metabolism, although glucose oxidation appears to be less sensitive than FA oxidation to insulin and IGF-I. The use of rapamycin, etomoxir, and rosiglitazone may help us to understand the mechanisms of regulation of lipid metabolism in fish. PMID:20484701

Sánchez-Gurmaches, Joan; Cruz-Garcia, Lourdes; Gutiérrez, Joaquím; Navarro, Isabel

2010-05-19

28

Endocrine control of oleic acid and glucose metabolism in rainbow trout (Oncorhynchus mykiss) muscle cells in culture.  

UK PubMed Central (United Kingdom)

The effects of insulin and IGF-I on fatty acid (FA) and glucose metabolism were examined using oleic acid or glucose as tracers in differentiated rainbow trout (Oncorhynchus mykiss) myotubes. Insulin and IGF-I significantly reduced the production of CO(2) from oleic acid with respect to the control values. IGF-I also significantly reduced the production of acid-soluble products (ASP) and the concentration of FA in the medium, while cellular triacylglycerols (TAG) tended to increase. Only insulin produced a significant accumulation of glycogen inside the cells in glucose distribution experiments. Incubation with catecholamines did not affect oleic acid metabolism. Cells treated with rapamycin [a target of rapamycin (TOR) inhibitor] significantly increased the oxidation of oleic acid to CO(2) and ASP, while the accumulation of TAG diminished. Rosiglitazone (a peroxisome proliferator-activated receptor gamma agonist) and etomoxir (a CPT-1 inhibitor) produced a severe and significant reduction in the production of CO(2) and ASP. Rosiglitazone and etomoxir also produced a significant accumulation of FA outside and inside the cells, respectively. No significant effects of these drugs on glucose distribution were observed. These data indicate that insulin and IGF-I act as anabolic hormones in trout myotubes in both oleic acid and glucose metabolism, although glucose oxidation appears to be less sensitive than FA oxidation to insulin and IGF-I. The use of rapamycin, etomoxir, and rosiglitazone may help us to understand the mechanisms of regulation of lipid metabolism in fish.

Sánchez-Gurmaches J; Cruz-Garcia L; Gutiérrez J; Navarro I

2010-08-01

29

Drosophila adiponectin receptor in insulin producing cells regulates glucose and lipid metabolism by controlling insulin secretion.  

UK PubMed Central (United Kingdom)

Adipokines secreted from adipose tissue are key regulators of metabolism in animals. Adiponectin, one of the adipokines, modulates pancreatic beta cell function to maintain energy homeostasis. Recently, significant conservation between Drosophila melanogaster and mammalian metabolism has been discovered. Drosophila insulin like peptides (Dilps) regulate energy metabolism similarly to mammalian insulin. However, in Drosophila, the regulatory mechanism of insulin producing cells (IPCs) by adipokine signaling is largely unknown. Here, we describe the discovery of the Drosophila adiponectin receptor and its function in IPCs. Drosophila adiponectin receptor (dAdipoR) has high homology with the human adiponectin receptor 1. The dAdipoR antibody staining revealed that dAdipoR was expressed in IPCs of larval and adult brains. IPC- specific dAdipoR inhibition (Dilp2>dAdipoR-Ri) showed the increased sugar level in the hemolymph and the elevated triglyceride level in whole body. Dilps mRNA levels in the Dilp2>dAdipoR-Ri flies were similar with those of controls. However, in the Dilp2>dAdipoR-Ri flies, Dilp2 protein was accumulated in IPCs, the level of circulating Dilp2 was decreased, and insulin signaling was reduced in the fat body. In ex vivo fly brain culture with the human adiponectin, Dilp2 was secreted from IPCs. These results indicate that adiponectin receptor in insulin producing cells regulates insulin secretion and controls glucose and lipid metabolism in Drosophila melanogaster. This study demonstrates a new adipokine signaling in Drosophila and provides insights for the mammalian adiponectin receptor function in pancreatic beta cells, which could be useful for therapeutic application.

Kwak SJ; Hong SH; Bajracharya R; Yang SY; Lee KS; Yu K

2013-01-01

30

Oxidative metabolism: glucose versus ketones.  

UK PubMed Central (United Kingdom)

The coupling of upstream oxidative processes (glycolysis, beta-oxidation, CAC turnover) to mitochondrial oxidative phosphorylation (OXPHOS) under the driving conditions of energy demand by the cell results in the liberation of free energy as ATP. Perturbations in glycolytic CAC or OXPHOS can result in pathology or cell death. To better understand whole body energy expenditure during chronic ketosis, we used a diet-induced rat model of ketosis to determine if high-fat-carbohydrate-restricted "ketogenic" diet results in changes in total energy expenditure (TEE). Consistent with previous reports of increased energy expenditure in mice, we hypothesized that rats fed ketogenic diet for 3 weeks would result in increased resting energy expenditure due to alterations in metabolism associated with a "switch" in energy substrate from glucose to ketone bodies. The rationale is ketone bodies are a more efficient fuel than glucose. Indirect calorimetric analysis revealed a moderate increase in VO2 and decreased VCO2 and heat with ketosis. These results suggest ketosis induces a moderate uncoupling state and less oxidative efficiency compared to glucose oxidation.

Prince A; Zhang Y; Croniger C; Puchowicz M

2013-01-01

31

Oxidative metabolism: glucose versus ketones.  

Science.gov (United States)

The coupling of upstream oxidative processes (glycolysis, beta-oxidation, CAC turnover) to mitochondrial oxidative phosphorylation (OXPHOS) under the driving conditions of energy demand by the cell results in the liberation of free energy as ATP. Perturbations in glycolytic CAC or OXPHOS can result in pathology or cell death. To better understand whole body energy expenditure during chronic ketosis, we used a diet-induced rat model of ketosis to determine if high-fat-carbohydrate-restricted "ketogenic" diet results in changes in total energy expenditure (TEE). Consistent with previous reports of increased energy expenditure in mice, we hypothesized that rats fed ketogenic diet for 3 weeks would result in increased resting energy expenditure due to alterations in metabolism associated with a "switch" in energy substrate from glucose to ketone bodies. The rationale is ketone bodies are a more efficient fuel than glucose. Indirect calorimetric analysis revealed a moderate increase in VO2 and decreased VCO2 and heat with ketosis. These results suggest ketosis induces a moderate uncoupling state and less oxidative efficiency compared to glucose oxidation. PMID:23852511

Prince, Allison; Zhang, Yifan; Croniger, Colleen; Puchowicz, Michelle

2013-01-01

32

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 t...

Burén, Jonas

33

Regulation of glucose metabolism in Thiobacillus intermedius.  

UK PubMed Central (United Kingdom)

Glucose-yeast extract or glucose-casein hydrolysate-grown Thiobacillus intermedius cells, which use glucose for energy generation, possess high specific activities of the Entner-Doudoroff pathway and related enzymes, 6-phosphogluconate dehydrase, 2-keto-3-deoxy-6-phosphogluconate aldolase, glucokinase, and glucose-6-phosphate dehydrogenase, but low activities of enzymes unique to the pentose shunt and Embden-Meyerhof pathways. Although the synthesis of the latter enzymes remains largely unaffected by the growth environment, that of the former is stimulated by glucose. Radiorespirometric measurements demonstrate an early and parallel respiration of glucose carbon atoms one and four in glucose-casein hydrolysate broth. It is concluded that the Entner-Doudoroff pathway performs an energetic role in glucose metabolism by T. intermedius with the pentose shunt and Embden-Meyerhof pathways functioning mainly in biosynthesis. The presence of thiosulfate in the growth medium inhibits the synthesis of the Entner-Doudoroff pathway and related enzymes. In addition, both thiosulfate and glucose inhibit the synthesis of the Krebs cycle enzymes, nicotinamide adenine dinucleotide phosphate-linked isocitrate and alpha-ketoglutarate dehydrogenases. Thus, repression of enzymes is of significance in the adaptation of T. intermedius to its nutritional environment. The activity of glucose-6-phosphate dehydrogenase of T. intermedius is inhibited by adenosine triphosphate. Such a control could afford the organism a mechanism to regulate the flow of glucose into major energetic and biosynthetic routes.

Matin A; Rittenberg SC

1970-10-01

34

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

Science.gov (United States)

In this study we characterized (3)H-2-deoxy-d-glucose ((3)H -DG) uptake by the estrogen receptor (ER)-positive MCF7 and the ER-negative MDA-MB-231 human breast cancer cell lines and investigated the effect of quercetin (QUE) and epigallocatechin gallate (EGCG) upon (3)H-DG uptake, glucose metabolism and cell viability and proliferation. In both MCF7 and MDA-MB-231 cells (3)H-DG uptake was (a) time-dependent, (b) saturable with similar capacity (Vmax) and affinity (Km), (c) potently inhibited by cytochalasin B, an inhibitor of the facilitative glucose transporters (GLUT), (d) sodium-independent and (e) slightly insulin-stimulated. This suggests that (3)H-DG uptake by both cell types is mediated by members of the GLUT family, including the insulin-responsive GLUT4 or GLUT12, while being independent of the sodium-dependent glucose transporter (SGLT1). QUE and EGCG markedly and concentration-dependently inhibited (3)H-DG uptake by MCF7 and by MDA-MB-231 cells, and both compounds blocked lactate production by MCF7 cells. Additionally, a 4h-treatment with QUE or EGCG decreased MCF7 cell viability and proliferation, an effect that was more potent when glucose was available in the extracellular medium. Our results implicate QUE and EGCG as metabolic antagonists in breast cancer cells, independently of estrogen signalling, and suggest that these flavonoids could serve as therapeutic agents/adjuvants even for ER-negative breast tumors. PMID:23664836

Moreira, Liliana; Araújo, Isabel; Costa, Tito; Correia-Branco, Ana; Faria, Ana; Martel, Fátima; Keating, Elisa

2013-05-09

35

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

UK PubMed Central (United Kingdom)

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

Moreira L; Araújo I; Costa T; Correia-Branco A; Faria A; Martel F; Keating E

2013-07-01

36

Enzymes of glucose metabolism in Frankia sp.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Enzymes of glucose metabolism were assayed in crude cell extracts of Frankia strains HFPArI3 and HFPCcI2 as well as in isolated vesicle clusters from Alnus rubra root nodules. Activities of the Embden-Meyerhof-Parnas pathway enzymes glucokinase, phosphofructokinase, and pyruvate kinase were found in...

Lopez, M F; Torrey, J G

37

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

Science.gov (United States)

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

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

2013-04-21

38

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

UK PubMed Central (United Kingdom)

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

Dai Q; Yin Y; Liu W; Wei L; Zhou Y; Li Z; You Q; Lu N; Guo Q

2013-07-01

39

Glucose metabolism and antidepressant medication.  

UK PubMed Central (United Kingdom)

Impaired glucose tolerance is observed in depressed patients, and patients suffering from depression have an increased risk to develop diabetes mellitus. In depressed and diabetic patients, studies have shown both a beneficial effect of antidepressants on glucose homeostasis and the opposite. This review aims to structure the conflicting data and focuses on the question, which effect specific antidepressants have on glucose homeostasis. We therefore performed a systematic review of all available studies referenced in Medline from 1960 to 2011. We included antidepressant agents indexed in the Anatomical Therapeutic Chemical (ATC) classification system of the WHO in 2011 and searched for studies investigating their effects on glucose metabolism in clinical samples as well as in healthy subjects. Of 876 studies screened we included 66. Most studies had small sample sizes and lacked a placebo group limiting conclusions about antidepressant effects on glucose tolerance. However, some evidence points to beneficial effects on glucose homeostasis of hydrazine-type monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs). In case of SSRIs, the effect is more pronounced in diabetic patients or patients with comorbid depression and diabetes mellitus. Noradrenegic substances (and possibly also dualacting antidepressants), in contrast, may deteriorate glucose tolerance. They can be used in depressed patients when favorable effects on mood outweigh adverse metabolic effects, but in depressed diabetics this can be at the expense of worsening of glycemic control. The effects of other antidepressants, like bupropione, mirtazapine or newer agents, require further investigation before reliable conclusions can be made. The synthesis of the findings is discussed in light of the specific pharmacodynamic properties of the antidepressants as well as the pathophysiological changes in depression and impaired glucose homeostasis, including animal studies.

Hennings JM; Schaaf L; Fulda S

2012-01-01

40

MicroRNA 33 regulates glucose metabolism.  

UK PubMed Central (United Kingdom)

Metabolic diseases are characterized by the failure of regulatory genes or proteins to effectively orchestrate specific pathways involved in the control of many biological processes. In addition to the classical regulators, recent discoveries have shown the remarkable role of small noncoding RNAs (microRNAs [miRNAs]) in the posttranscriptional regulation of gene expression. In this regard, we have recently demonstrated that miR-33a and miR33b, intronic miRNAs located within the sterol regulatory element-binding protein (SREBP) genes, regulate lipid metabolism in concert with their host genes. Here, we show that miR-33b also cooperates with SREBP1 in regulating glucose metabolism by targeting phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC), key regulatory enzymes of hepatic gluconeogenesis. Overexpression of miR-33b in human hepatic cells inhibits PCK1 and G6PC expression, leading to a significant reduction of glucose production. Importantly, hepatic SREBP1c/miR-33b levels correlate inversely with the expression of PCK1 and G6PC upon glucose infusion in rhesus monkeys. Taken together, these results suggest that miR-33b works in concert with its host gene to ensure a fine-tuned regulation of lipid and glucose homeostasis, highlighting the clinical potential of miR-33a/b as novel therapeutic targets for a range of metabolic diseases.

Ramírez CM; Goedeke L; Rotllan N; Yoon JH; Cirera-Salinas D; Mattison JA; Suárez Y; de Cabo R; Gorospe M; Fernández-Hernando C

2013-08-01

 
 
 
 
41

[Glucose metabolic changes in stress].  

UK PubMed Central (United Kingdom)

Provision of a better understanding of the pathogenic pathways underlying injured sugar metabolism during stress should ideally translate into a more rational approach to the provision of nutritional support. Patients with burns, trauma, severe injuries or infections commonly develop a hypermetabolic state that is associated with several changes in carbohydrate metabolism. The hypermetabolic state is induced either by the area of injury and by organs involved in the immunologic response to stress; further it determines a glycemic milieu which will be directed toward satisfaction of the requirements for glucose as an energy support.

Foia L; Costuleanu N; Trandafirescu M; Saila V; Pavel M

1999-07-01

42

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

43

Regulation of glucose transport and metabolism in Thiobacillus novellus.  

UK PubMed Central (United Kingdom)

To investigate the physiological basis of decreased rate of glucose utilization by Thiobacillus novellus in a mixotrophic environment (R. C. Perez and A. Matin, J. Bacteriol. 142:633-638, 1980), its glucose transport system was characterized and the modulation of this system as well as enzymes of glucose metabolism by the growth environment was examined. Uptake of 2-deoxy-d-glucose by cell suspensions was almost abolished by respiratory chain inhibitors, and the sugar accumulated unchanged inside the cells against a concentration gradient: its transport is probably linked to the proton electrochemical gradient. The glucose transport system, as well as several enzymes of glucose metabolism, had a high specific activity in heterotrophic cells, intermediate activity in mixotrophic cells, and low activity in autotrophic cells; thus, they are induced by glucose but repressed by thiosulfate, its metabolites, or both. Thiosulfate and sulfite inhibited the glucose transport system uncompetitively and noncompetitively, respectively (apparent K(i) = 3.1 x 10(-2) M and 3.3 x 10(-7) M, respectively) and also inhibited glucose-6-phosphate dehydrogenase activity. Thus, the rate of glucose utilization in mixotrophic environments decreased because thiosulfate and its metabolites repress as well as inhibit the glucose transport system and enzymes of glucose metabolism. The significance of this and other regulatory phenomena that come into play in such environments is discussed.

Matin A; Schleiss M; Perez RC

1980-05-01

44

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

11C-choline and 18F-FAMT are known to correlate with tumor cell proliferation and amino acid metabolism. We investigated the ability of 11C-Choline and 18F-FAMT PET in diagnosis of musculoskeletal tumors in thirty-six patients in comparison of 18F-FDG PET. 11C-Choline and 18F-FDG PET were posi...

Tian, Mei; Zhang, Hong; Endo, Keigo

45

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

46

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

47

Chromium improves glucose uptake and metabolism through upregulating the mRNA levels of IR, GLUT4, GS, and UCP3 in skeletal muscle cells.  

UK PubMed Central (United Kingdom)

The aim of this study was to evaluate the impact of three different chromium forms as chromic chloride (CrCl), chromium picolinate (CrPic), and a newly synthesized complex of chromium chelated with small peptides (CrSP) on glucose uptake and metabolism in vitro. In cultured skeletal muscle cells, chromium augmented insulin-stimulated glucose uptake and metabolism as assessed by a reduced glucose concentration of culture medium. At the molecular level, insulin significantly increased the mRNA levels of insulin receptor (IR), glucose transporter 4 (GLUT4), glycogen synthase (GS), and uncoupling protein-3 (UCP3), and these impacts can be enhanced by the addition of chromium, especially in the form of CrSP. Collectively, results of this study demonstrate that chromium improves glucose uptake and metabolism through upregulating the mRNA levels of IR, GLUT4, GS, and UCP3 in skeletal muscle cells, and CrSP has higher efficacy on glucose uptake and metabolism compared to the forms of CrCl and CrPic.

Qiao W; Peng Z; Wang Z; Wei J; Zhou A

2009-11-01

48

Bone marrow stromal cell transplantation enhances recovery of local glucose metabolism after cerebral infarction in rats: a serial 18F-FDG PET study.  

UK PubMed Central (United Kingdom)

UNLABELLED: This study aimed to assess whether (18)F-FDG PET could serially monitor the beneficial effects of bone marrow stromal cells (BMSC) on cerebral glucose metabolism when transplanted into the infarct brain of rats. METHODS: The BMSC from green fluorescent protein transgenic rats or vehicle was stereotactically transplanted into the ipsilateral striatum at 7 d after permanent middle cerebral artery occlusion of rats. Local glucose metabolism was semiquantitatively measured at 6 and 35 d after ischemia using (18)F-FDG PET. Motor function was serially evaluated throughout the experiments. At 35 d after ischemia, immunohistochemistry was performed to evaluate the phenotype of BMSC and their effects on the expression of brain-type glucose transporters. RESULTS: BMSC transplantation not only enhanced functional recovery but also promoted the recovery of glucose utilization in the periinfarct area when stereotactically transplanted at 1 wk after ischemia. The engrafted cells were widely distributed, and most expressed a neuron-specific protein, NeuN. BMSC transplantation also prevented the pathologic upregulation of glucose transporters in the periinfarct neocortex. CONCLUSION: The present findings strongly suggest that the BMSC may enhance functional recovery by promoting the recovery of local glucose metabolism in the periinfarct area when directly transplanted into the infarct brain at clinically relevant timing. The BMSC also inhibit the pathologic upregulation of brain-isoform glucose transporters type 1 and 3. (18)F-FDG PET may be a valuable modality to scientifically prove the beneficial effects of BMSC transplantation on the host brain in clinical situations.

Miyamoto M; Kuroda S; Zhao S; Magota K; Shichinohe H; Houkin K; Kuge Y; Tamaki N

2013-01-01

49

FGF19 regulates cell proliferation, glucose and bile acid metabolism via FGFR4-dependent and independent pathways.  

Science.gov (United States)

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 FGFR4 in mediating FGF19 activity by using Fgfr4 deficient mice as well as a variant of FGF19 protein (FGF19v) which is specifically impaired in activating FGFR4. Our results demonstrate that FGFR4 activation mediates the induction of hepatocyte proliferation and the suppression of bile acid biosynthesis by FGF19, but is not essential for FGF19 to improve glucose and lipid metabolism in high fat diet fed mice as well as in leptin-deficient ob/ob mice. Thus, FGF19 acts through multiple receptor pathways to elicit pleiotropic effects in regulating nutrient metabolism and cell proliferation. PMID:21437243

Wu, Ai-Luen; Coulter, Sally; Liddle, Christopher; Wong, Anne; Eastham-Anderson, Jeffrey; French, Dorothy M; Peterson, Andrew S; Sonoda, Junichiro

2011-03-18

50

FGF19 regulates cell proliferation, glucose and bile acid metabolism via FGFR4-dependent and independent pathways.  

UK PubMed Central (United Kingdom)

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 FGFR4 in mediating FGF19 activity by using Fgfr4 deficient mice as well as a variant of FGF19 protein (FGF19v) which is specifically impaired in activating FGFR4. Our results demonstrate that FGFR4 activation mediates the induction of hepatocyte proliferation and the suppression of bile acid biosynthesis by FGF19, but is not essential for FGF19 to improve glucose and lipid metabolism in high fat diet fed mice as well as in leptin-deficient ob/ob mice. Thus, FGF19 acts through multiple receptor pathways to elicit pleiotropic effects in regulating nutrient metabolism and cell proliferation.

Wu AL; Coulter S; Liddle C; Wong A; Eastham-Anderson J; French DM; Peterson AS; Sonoda J

2011-01-01

51

Glucose Metabolism Measured by [18F]Fluorodeoxyglucose Positron Emission Tomography Is Independent of PTEN/AKT Status in Human Colon Carcinoma Cells1  

Science.gov (United States)

The phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most altered in cancer, leading to a range of cellular responses including enhanced proliferation, survival, and metabolism, and is thus an attractive target for anticancer drug development. Stimulation of the PI3K pathway can be initiated by alterations at different levels of the signaling cascade including growth factor receptor activation, as well as mutations in PIK3CA, PTEN, and AKT genes frequently found in a broad range of cancers. Given its role in glucose metabolism, we investigated the utility of [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG PET) as a pharmacodynamic biomarker of PI3K pathway-induced glucose metabolism. PTEN deletion in human colon carcinoma cells led to constitutive AKT activation but did not confer a phenotype of increased cell proliferation or glucose metabolism advantage in vivo relative to isogenic tumors derived from cells with a wild-type allele. This was not due to the activation context, that is, phosphatase activity, per se because PIK3CA activation in xenografts derived from the same lineage failed to increase glucose metabolism. Acute inhibition of PI3K activity by LY294002, and hence decreased activated AKT expression, led to a significant reduction in tumor [18F]FDG uptake that could be explained at least in part by decreased membrane glucose transporter 1 expression. The pharmacodynamic effect was again independent of PTEN status. In conclusion, [18F]FDG PET is a promising pharmacodynamic biomarker of PI3K pathway inhibition; however, its utility to detect glucose metabolism is not directly linked to the magnitude of activated AKT protein expression.

Nguyen, Quang-De; Perumal, Meg; Waldman, Todd A; Aboagye, Eric O

2011-01-01

52

[Hormonal regulation of glucose metabolism in islands of Langerhans  

UK PubMed Central (United Kingdom)

Insulin secretion and glucose metabolism were simultaneously studied in isolated islets obtained from normal, endocrine-deficient (adrenalectomized, ovariectomized and radiothyroidectomized) rats as well as from this latter group of rats previously submitted to specific substitutive therapy. The islets from all the endocrine-deficient rats showed clear and similar changes in both the insulin secretion and the metabolism of glucose, being the correlation between the degree of these two alterations highly significant. All the above mentioned abnormalities were corrected by the administration of the corresponding substitutive therapy. These results suggest that the hormones involved in this study could modify the B cell insulin secretion by changing their capacity to metabolize glucose.

Borelli MI; Cortizo AM; de Gagliardino EE; García ME; Gagliardino JJ

1985-01-01

53

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

UK PubMed Central (United Kingdom)

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

Mayer A; Von Wallbrunn A; Vaupel P

2010-08-01

54

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

Science.gov (United States)

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

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

2010-08-01

55

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

Directory of Open Access Journals (Sweden)

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

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

2012-01-01

56

Glucose metabolism in injured tissue: A longitudinal study  

International Nuclear Information System (INIS)

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

1990-01-01

57

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

Directory of Open Access Journals (Sweden)

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

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

2010-01-01

58

Comparison of cell proliferation, protein, and glucose metabolism in musculoskeletal tumors in a PET study.  

UK PubMed Central (United Kingdom)

¹¹C-choline and ¹?F-FAMT are known to correlate with tumor cell proliferation and amino acid metabolism. We investigated the ability of ¹¹C-Choline and ¹?F-FAMT PET in diagnosis of musculoskeletal tumors in thirty-six patients in comparison of ¹?F-FDG PET. ¹¹C-Choline and ¹?F-FDG PET were positive in all the malignant tumors (n = 13), whereas ¹?F-FAMT was positive in 11 tumors. The mean SUVs for malignant tumors were significantly higher than those for benign lesions in all three tracers imaging. A moderate correlation was found between ¹¹C-Choline and ¹?F-FDG (r = 0.540, P < .05), or ¹?F-FAMT and FDG (r = 0.596, P < .05). The diagnostic sensitivity and specificity for malignancy were 91.7% and 71.4%, respectively, using ¹¹C-choline with a SUV cut-off of 2.69. The sensitivity and specificity of ¹?F-FAMT for malignancy were 66.7% and 85.7%, respectively, using a SUV cut-off of 1.26. For ¹?F-FDG, using a SUV cut-off of 2.77, the sensitivity and specificity were 83.3% and 71.4%, respectively. According to ROC analysis, the ROC curves for ¹¹C-Choline, ¹?F-FAMT, and ¹?F-FDG were 0.855, 0.734, and 0.847, respectively. ¹¹C-Choline PET is superior in the visualization of musculoskeletal tumors with high contrast imaging, whereas the combination of ¹?F-FAMT and ¹?F-FDG PET provides valuable information for the preoperative planning in patients with musculoskeletal tumors.

Tian M; Zhang H; Endo K

2011-01-01

59

Enzymes of glucose metabolism in Frankia sp.  

UK PubMed Central (United Kingdom)

Enzymes of glucose metabolism were assayed in crude cell extracts of Frankia strains HFPArI3 and HFPCcI2 as well as in isolated vesicle clusters from Alnus rubra root nodules. Activities of the Embden-Meyerhof-Parnas pathway enzymes glucokinase, phosphofructokinase, and pyruvate kinase were found in Frankia strain HFPArI3 and glucokinase and pyruvate kinase were found in Frankia strain HFPCcI2 and in the vesicle clusters. An NADP+-linked glucose 6-phosphate dehydrogenase and an NAD-linked 6-phosphogluconate dehydrogenase were found in all of the extracts, although the role of these enzymes is unclear. No NADP+-linked 6-phosphogluconate dehydrogenase was found. Both dehydrogenases were inhibited by adenosine 5-triphosphate, and the apparent Km's for glucose 6-phosphate and 6-phosphogluconate were 6.86 X 10(-4) and 7.0 X 10(-5) M, respectively. In addition to the enzymes mentioned above, an NADP+-linked malic enzyme was detected in the pure cultures but not in the vesicle clusters. In contrast, however, the vesicle clusters had activity of an NAD-linked malic enzyme. The possibility that this enzyme resulted from contamination from plant mitochondria trapped in the vesicle clusters could not be discounted. None of the extracts showed activities of the Entner-Doudoroff enzymes or the gluconate metabolism enzymes gluconate dehydrogenase or gluconokinase. Propionate- versus trehalose-grown cultures of strain HFPArI3 showed similar activities of most enzymes except malic enzyme, which was higher in the cultures grown on the organic acid. Nitrogen-fixing cultures of strain HFPArI3 showed higher specific activities of glucose 6-phosphate and 6-phosphogluconate dehydrogenases and phosphofructokinase than ammonia-grown cultures.

Lopez MF; Torrey JG

1985-04-01

60

Enzymes of glucose metabolism in Frankia sp.  

Science.gov (United States)

Enzymes of glucose metabolism were assayed in crude cell extracts of Frankia strains HFPArI3 and HFPCcI2 as well as in isolated vesicle clusters from Alnus rubra root nodules. Activities of the Embden-Meyerhof-Parnas pathway enzymes glucokinase, phosphofructokinase, and pyruvate kinase were found in Frankia strain HFPArI3 and glucokinase and pyruvate kinase were found in Frankia strain HFPCcI2 and in the vesicle clusters. An NADP+-linked glucose 6-phosphate dehydrogenase and an NAD-linked 6-phosphogluconate dehydrogenase were found in all of the extracts, although the role of these enzymes is unclear. No NADP+-linked 6-phosphogluconate dehydrogenase was found. Both dehydrogenases were inhibited by adenosine 5-triphosphate, and the apparent Km's for glucose 6-phosphate and 6-phosphogluconate were 6.86 X 10(-4) and 7.0 X 10(-5) M, respectively. In addition to the enzymes mentioned above, an NADP+-linked malic enzyme was detected in the pure cultures but not in the vesicle clusters. In contrast, however, the vesicle clusters had activity of an NAD-linked malic enzyme. The possibility that this enzyme resulted from contamination from plant mitochondria trapped in the vesicle clusters could not be discounted. None of the extracts showed activities of the Entner-Doudoroff enzymes or the gluconate metabolism enzymes gluconate dehydrogenase or gluconokinase. Propionate- versus trehalose-grown cultures of strain HFPArI3 showed similar activities of most enzymes except malic enzyme, which was higher in the cultures grown on the organic acid. Nitrogen-fixing cultures of strain HFPArI3 showed higher specific activities of glucose 6-phosphate and 6-phosphogluconate dehydrogenases and phosphofructokinase than ammonia-grown cultures. PMID:3980434

Lopez, M F; Torrey, J G

1985-04-01

 
 
 
 
61

Anomeric specificity of glucose metabolism in the pentose cycle  

Energy Technology Data Exchange (ETDEWEB)

The production of TH2O from alpha- and beta-D-(5-TH)glucose and that of UCO2 from either alpha- and beta-D-(1- UC) or alpha- and beta-D-(6- UC)glucose were measured in rat pancreatic islets and tumoral insulin-producing cells incubated at 7 degrees C. The ratio in UCO2 output from D-(1- UC)glucose/D-(6- UC)glucose, the fraction of glucose metabolism occurring through the pentose cycle, and the flow rate through such a cycle were always higher in the presence of beta- than alpha-D-glucose. This indicates that the anomeric specificity of glucose-6-phosphate dehydrogenase is operative in intact islet cells.

Malaisse, W.J.; Giroix, M.H.; Sener, A.

1985-11-25

62

Glucose deprivation-induced metabolic oxidative stress and cancer therapy  

Directory of Open Access Journals (Sweden)

Full Text Available Cancer cells (vs. normal cells) demonstrate evidence of oxidative stress, increased glycolysis, and increased pentose cycle activity. The oxidative stress in cancer cells has been hypothesized to arise from mitochondrial dysfunction leading to increased levels of hydroperoxides, and cancer cells have been proposed to compensate for this defect by increasing glucose metabolism. Glucose metabolism has also been shown to play a role in hydroperoxide detoxification via the formation of pyruvate (from glycolysis) and NADPH (from the pentose cycle). Furthermore, in cancer cells, glucose deprivation as well as treatment with 2-deoxyglucose (2?DG) has been shown to induce oxidative stress and cytotoxicity. Additionally, transformed cells have been shown to be more susceptible to glucose deprivation (and 2DG-)-induced cytotoxicity and oxidative stress than untransformed cells. These results support the hypothesis that cancer cells have a defect in mitochondrial respiration leading to increased steady state levels of O 2· - and H 2 O2 , and glucose metabolism is increased to compensate for this defect. The application of these findings to developing cancer therapies using 2DG combined with inhibitors of hydroperoxide metabolism to induce radio/chemosensitization is discussed, as well as the possibility that FDG-PET imaging may predict tumor responses to these therapies.

Simons Andrean; Mattson David; Dornfeld Ken; Spitz Douglas

2009-01-01

63

Glucose metabolism in cultured trophoblasts from human placenta  

International Nuclear Information System (INIS)

[en] 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 14C-labeled glucose and reactions were stopped by addition of perchloric acid. 14CO2 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 14C in metabolic products compared to cells cultured on fibrin. Glucose oxidation to CO2 by the phosphogluconate (PG) pathway was estimated from specific yields of 14CO2 from [1-14C]-D-glucose and [6-14C]-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

1990-02-26

64

Glucose metabolism in cultured trophoblasts from human placenta  

Energy Technology Data Exchange (ETDEWEB)

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

65

In vitro differentiation of unrestricted somatic stem cells into functional hepatic-like cells displaying a hepatocyte-like glucose metabolism.  

UK PubMed Central (United Kingdom)

The hepatic-like phenotype resulting from in vitro differentiation of unrestricted somatic stem cells (USSC) derived from human umbilical cord blood (CB) was analyzed with regard to functional and metabolic aspects. USSC can be differentiated into cells of all three germ layers in vitro and in vivo and, although they share many features with mesenchymal stroma cells (MSC), can be distinguished from these by their expression of DLK1 as well as a restricted adipogenic differentiation potential. For the differentiation procedure described herein, a novel three-stage differentiation protocol resembling embryonic developmental processes of hepatic endoderm was applied. Hepatic pre-induction was performed by activinA and FGF4 resulting in enhanced SOX17 and FOXA2 expression. Further differentiation was achieved sequentially by retinoic acid, FGF4, HGF, EGF, and OSM resulting in a hepatic endodermal identity, characterized by the expression of AFP and HNF1alpha. Thereafter, expression of G6PC, ARG1, FBP1, and HNF4alpha was observed, thus indicating progressive differentiation. Functional studies concerning albumin secretion, urea formation, and cytochrome-p450-3A4 (CYP3A4) enzyme activity confirmed the hepatic-like phenotype. In order to characterize the differentiated cells at a metabolic level, USSC were incubated with [1-(13)C]glucose. By tracing the fate of the molecule's label via isotopomer analysis using (13)C NMR spectroscopy, formation of both glycogen and some gluconeogenetic activity could be observed providing evidence of a hepatocyte-like glucose metabolism in differentiated USSC. In conclusion, the results of the present study indicate that USSC represent a stem cell source with a substantial hepatic differentiation capacity which hold the potential for clinical applications.

Waclawczyk S; Buchheiser A; Flögel U; Radke TF; Kögler G

2010-11-01

66

Hepatic glucose sensing is required to preserve ? cell glucose competence  

Science.gov (United States)

Liver glucose metabolism plays a central role in glucose homeostasis and may also regulate feeding and energy expenditure. Here we assessed the impact of glucose transporter 2 (Glut2) gene inactivation in adult mouse liver (LG2KO mice). Loss of Glut2 suppressed hepatic glucose uptake but not glucose output. In the fasted state, expression of carbohydrate-responsive element-binding protein (ChREBP) and its glycolytic and lipogenic target genes was abnormally elevated. Feeding, energy expenditure, and insulin sensitivity were identical in LG2KO and control mice. Glucose tolerance was initially normal after Glut2 inactivation, but LG2KO mice exhibited progressive impairment of glucose-stimulated insulin secretion even though ? cell mass and insulin content remained normal. Liver transcript profiling revealed a coordinated downregulation of cholesterol biosynthesis genes in LG2KO mice that was associated with reduced hepatic cholesterol in fasted mice and reduced bile acids (BAs) in feces, with a similar trend in plasma. We showed that chronic BAs or farnesoid X receptor (FXR) agonist treatment of primary islets increases glucose-stimulated insulin secretion, an effect not seen in islets from Fxr–/– mice. Collectively, our data show that glucose sensing by the liver controls ? cell glucose competence and suggest BAs as a potential mechanistic link.

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

2013-01-01

67

Glucose metabolism in a rat mammary adenocarcinoma  

International Nuclear Information System (INIS)

[en] 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

2003-01-01

68

Glucose and fructose metabolism in Zymomonas anaerobia.  

UK PubMed Central (United Kingdom)

Isotopic and enzymic evidence indicates that Zymomonas anaerobia ferments glucose via the Entner-Doudoroff pathway. The molar growth yields with glucose (5.89) and fructose (5.0) are lower than those for the related organism Zymomonas mobilis and the observed linear growth suggests that energetically uncoupled growth occurs. A survey of enzymes of carbohydrate metabolism revealed the presence of weak phosphofructokinase and fructose 1,6-diphosphate aldolase activities but phosphoketolase, transketolase and transaldolase were not detected. Fermentation balances for glucose and fructose are reported; acetaldehyde accumulated in both fermentations, to a greater extent with fructose which also yielded glycerol and dihydroxyacetone as minor products.

McGill DJ; Dawes EA

1971-12-01

69

Role of glucose signaling in yeast metabolism  

Energy Technology Data Exchange (ETDEWEB)

The conversion of glucose to ethanol and carbon dioxide by yeast was the first biochemical pathway to be studied in detail. The initial observation that this process is catalyzed by an extract of yeast led to the discovery of enzymes and coenzymes and laid the foundation for modern biochemistry. In this article, knowledge concerning the relation between uptake of and signaling by glucose in the yeast Saccharomyces cerevisiae is reviewed and compared to the analogous process in prokaryotes. It is concluded that (much) more fundamental knowledge concerning these processes is required before rational redesign of metabolic fluxes from glucose in yeast can be achieved.

Dam, K. van [Univ. of Amsterdam (Netherlands). E.C. Slater Inst.

1996-10-05

70

Glucose metabolism in bone marrow cells and granulocytes of adult mice after X-ray (5 Gy) irradiation: relationship to cell functionality  

International Nuclear Information System (INIS)

Our experiments focused on the metabolic implications of the residual haemopoietic damage in adult mice given 5 Gy X-rays. Bone marrow cells from irradiated mice exhibited an increase in protein synthesis and a decrease in ATP levels, which could be related to the enhancement of the proliferative activity of haemopoietic precursor cells. However, the kinetic parameters (Vmax and Km) of glucose uptake, the glycolytic flux and the hexose monophosphate (HMP) shunt activity were similar to those found in the control group. On the other hand, a reduction of glucose uptake (Vmax) was found in both resting and stimulated granulocytes from irradiated mice. This reduction was accompanied by a decrease in the glycolytic rate and ATP levels. However, HMP shunt activity was similar in resting granulocytes in both the control and the irradiated mice. The stimulation by PMA produced a significantly higher increase in the activity of the pathway in granulocytes from the irradiated mice and was in accordance with the enhancement of superoxide anion production that has been previously described in these cells. (Author).

1997-01-01

71

Glucose metabolism in bone marrow cells and granulocytes of adult mice after X-ray (5 Gy) irradiation: relationship to cell functionality  

Energy Technology Data Exchange (ETDEWEB)

Our experiments focused on the metabolic implications of the residual haemopoietic damage in adult mice given 5 Gy X-rays. Bone marrow cells from irradiated mice exhibited an increase in protein synthesis and a decrease in ATP levels, which could be related to the enhancement of the proliferative activity of haemopoietic precursor cells. However, the kinetic parameters (V{sub max} and K{sub m}) of glucose uptake, the glycolytic flux and the hexose monophosphate (HMP) shunt activity were similar to those found in the control group. On the other hand, a reduction of glucose uptake (V{sub max}) was found in both resting and stimulated granulocytes from irradiated mice. This reduction was accompanied by a decrease in the glycolytic rate and ATP levels. However, HMP shunt activity was similar in resting granulocytes in both the control and the irradiated mice. The stimulation by PMA produced a significantly higher increase in the activity of the pathway in granulocytes from the irradiated mice and was in accordance with the enhancement of superoxide anion production that has been previously described in these cells. (Author).

Gaitan, S.; Escribano, S.; Sancho, P. [Universidad Complutense de Madrid (Spain). Facultad de Veterinaria; Cuenllas, E.; Tejero, C. [Universidad de Alcala de Henares, Madrid (Spain). Dept. de Bioquimica y Biologia Molecular

1997-03-01

72

Glucose metabolism in advanced lung cancer patients.  

Science.gov (United States)

Although it is generally accepted that altered nutrient intake and metabolism are responsible for the progressive loss of body weight observed in most advanced cancer patients, there is still considerable controversy regarding the contributory role of changes in both resting energy expenditure (REE) and glucose metabolism. Several studies suggest increases in both REE and glucose appearance in advanced cancer patients compared with healthy control subjects, whereas others revealed no changes in either metabolic parameter. We measured REE with indirect calorimetry and glucose kinetics with a primed constant infusion of D-[U-14C]glucose and D-[6-3H]glucose over the last 4 h of a 24-h fast in 32 advanced lung cancer patients immediately after diagnosis and before any chemotherapy or radiotherapy and in 19 healthy volunteer subjects. REE for the lung cancer group was not significantly different from that in the control group (1535.8 +/- 78.0 vs. 1670.2 +/- 53.9 kcal/day, respectively, p = 0.151). When REE was expressed as a function of body weight, or lean body mass, no differences between the two groups were observed. The rate of glucose appearance was 9.88 +/- 0.36 mumol.kg-1.min-1 in the cancer patients and 10.15 +/- 0.53 mumol.kg-1.min-1 in control subjects (p = 0.667), of which 50.4 versus 58.2%, respectively, was oxidized. The amount of glucose recycled was 13.54 +/- 1.22% in cancer patients and 15.08 +/- 0.99% in control subjects (p = 0.394). The amount of VCO2 from direct oxidation of glucose was 23.39 +/- 0.74% in cancer patients and 27.45 +/- 1.36% in control subjects (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1498456

Richards, E W; Long, C L; Nelson, K M; Pinkston, J A; Navari, R M; Geiger, J W; Gandy, R E; Blakemore, W S

73

[Clinical and metabolic features of subjects with glucose intolerance and high fasting glucose levels].  

UK PubMed Central (United Kingdom)

BACKGROUND: Subjects with glucose intolerance or high fasting glucose levels have a higher cardiovascular risk and frequently become diabetic. AIM: To assess clinical and metabolic characteristics of patients with glucose intolerance or high fasting glucose levels. MATERIAL AND METHODS: Fasting and post glucose load serum glucose and insulin levels were measured in 1404 people, aged 42,0 +/- 14,2 years (81% women) with high diabetic risk. We categorized subjects in different alterations of blood glucose, according to 2006 American Diabetes Association categories. Insulin resistance (RI), insulin secretion (beta %) and insulin disposition (ID), were calculated using fasting blood glucose and insulin levels, using the homeostasis model assessment (HOMA I and II). RESULTS: Sixty percent of studied subjects had first grade relatives with diabetes mellitus and 1097 (78%) were categorized as normal (N), 45 (3%) as Diabetes Mellitus (DM), 161 (11%) as high fasting glucose levels (GAA) and 103 (7%) as glucose intolerant (ITG). Fifty three of the 106 subjects with GAA (50%), were also glucose intolerant. Subjects with GAA had similar insulin sensitivity and lower beta cell function than N (insulin disposition 58 +/- 12 and 111 +/- 32%, respectively p < 0.01). ITG had less insulin sensitivity than N (HOMA-IR 2.6 +/- 1.50 +/- and 2.0 +/- 1.30, respectively) and only a mild decrease in beta cell function (insulin disposition 96 +/- 26 and 111 +/- 32% respectively, p < 0.01). Patients GAA plus ITG had similar alterations than those with DM (HOMA-IR 3.8 +/- 2.2 and 4.4 +/- 3.7 respectively; insulin disposition 57 +/- 10 and 56.0 +/- 26% respectively. CONCLUSIONS: Patients with higher fasting glucose levels behave differently from those with glucose intolerance. High fasting glucose levels are highly prevalent in subjects with high risk of DM and must be considered as risk indicator in preventive programs for diabetes mellitus.

Arteaga Llona A; Pollak F; Robres L; Velasco N

2009-02-01

74

Expression of NLRP3 inflammasome and T cell population markers in adipose tissue are associated with insulin resistance and impaired glucose metabolism in humans.  

Science.gov (United States)

Recent studies in rodents indicate that the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome and a proinflammatory shift in the T cell population in adipose tissue (AT) contribute to AT inflammation and insulin resistance. We investigated: (1) the interplay between the NLRP3 inflammasome and T cell populations in abdominal subcutaneous AT in obese and lean humans in relation to AT inflammatory processes, and (2) involvement of the NLRP3 inflammasome and T cell populations in insulin resistance. Abdominal subcutaneous AT biopsies were collected in 10 obese men with impaired glucose tolerance and 9 lean normal glucose tolerant age-matched controls. AT gene expression of NLRP3 inflammasome-related genes and markers of T cell populations, chemoattraction, macrophage infiltration and other aspects of inflammation were examined. Furthermore, we examined systemic adaptive immune activation and insulin sensitivity (hyperinsulinemic-euglycemic clamp). CASPASE-1 mRNA and the proportion of T(h)1 transcripts (TBX21/CD3?) were significantly higher in AT from obese compared with lean subjects. CASPASE-1 expression and a relative increase in T(h)1 transcripts in AT were strongly associated with insulin resistance and impairments in glucose homeostasis. Gene expression of NLRP3, CASPASE-1, CD3? (pan T cells), TBX21 (T(h)1 cells) and RORC (T(h)17 cells) was positively, whereas GATA3 (T(h)2 cells) was inversely correlated with AT inflammation. Our data suggest that NLRP3 inflammasome activation and a T(h)1 shift in the T cell population in AT of obese subjects is related to insulin resistance and impaired glucose metabolism, which may be explained by AT inflammatory processes. PMID:22325453

Goossens, Gijs H; Blaak, Ellen E; Theunissen, Ruud; Duijvestijn, Adriaan M; Clément, Karine; Tervaert, Jan-Willem Cohen; Thewissen, Marielle M

2012-02-08

75

Expression of NLRP3 inflammasome and T cell population markers in adipose tissue are associated with insulin resistance and impaired glucose metabolism in humans.  

UK PubMed Central (United Kingdom)

Recent studies in rodents indicate that the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome and a proinflammatory shift in the T cell population in adipose tissue (AT) contribute to AT inflammation and insulin resistance. We investigated: (1) the interplay between the NLRP3 inflammasome and T cell populations in abdominal subcutaneous AT in obese and lean humans in relation to AT inflammatory processes, and (2) involvement of the NLRP3 inflammasome and T cell populations in insulin resistance. Abdominal subcutaneous AT biopsies were collected in 10 obese men with impaired glucose tolerance and 9 lean normal glucose tolerant age-matched controls. AT gene expression of NLRP3 inflammasome-related genes and markers of T cell populations, chemoattraction, macrophage infiltration and other aspects of inflammation were examined. Furthermore, we examined systemic adaptive immune activation and insulin sensitivity (hyperinsulinemic-euglycemic clamp). CASPASE-1 mRNA and the proportion of T(h)1 transcripts (TBX21/CD3?) were significantly higher in AT from obese compared with lean subjects. CASPASE-1 expression and a relative increase in T(h)1 transcripts in AT were strongly associated with insulin resistance and impairments in glucose homeostasis. Gene expression of NLRP3, CASPASE-1, CD3? (pan T cells), TBX21 (T(h)1 cells) and RORC (T(h)17 cells) was positively, whereas GATA3 (T(h)2 cells) was inversely correlated with AT inflammation. Our data suggest that NLRP3 inflammasome activation and a T(h)1 shift in the T cell population in AT of obese subjects is related to insulin resistance and impaired glucose metabolism, which may be explained by AT inflammatory processes.

Goossens GH; Blaak EE; Theunissen R; Duijvestijn AM; Clément K; Tervaert JW; Thewissen MM

2012-03-01

76

1-deoxynojirimycin inhibits glucose absorption and accelerates glucose metabolism in streptozotocin-induced diabetic mice.  

Science.gov (United States)

We investigated the role of 1-deoxynojirimycin (DNJ) on glucose absorption and metabolism in normal and diabetic mice. Oral and intravenous glucose tolerance tests and labeled (13)C6-glucose uptake assays suggested that DNJ inhibited intestinal glucose absorption in intestine. We also showed that DNJ down-regulated intestinal SGLT1, Na(+)/K(+)-ATP and GLUT2 mRNA and protein expression. Pretreatment with DNJ (50?mg/kg) increased the activity, mRNA and protein levels of hepatic glycolysis enzymes (GK, PFK, PK, PDE1) and decreased the expression of gluconeogenesis enzymes (PEPCK, G-6-Pase). Assays of protein expression in hepatic cells and in vitro tests with purified enzymes indicated that the increased activity of glucose glycolysis enzymes was resulted from the relative increase in protein expression, rather than from direct enzyme activation. These results suggest that DNJ inhibits intestinal glucose absorption and accelerates hepatic glucose metabolism by directly regulating the expression of proteins involved in glucose transport systems, glycolysis and gluconeogenesis enzymes. PMID:23536174

Li, You-Gui; Ji, Dong-Feng; Zhong, Shi; Lin, Tian-Bao; Lv, Zhi-Qiang; Hu, Gui-Yan; Wang, Xin

2013-01-01

77

1-deoxynojirimycin inhibits glucose absorption and accelerates glucose metabolism in streptozotocin-induced diabetic mice.  

UK PubMed Central (United Kingdom)

We investigated the role of 1-deoxynojirimycin (DNJ) on glucose absorption and metabolism in normal and diabetic mice. Oral and intravenous glucose tolerance tests and labeled (13)C6-glucose uptake assays suggested that DNJ inhibited intestinal glucose absorption in intestine. We also showed that DNJ down-regulated intestinal SGLT1, Na(+)/K(+)-ATP and GLUT2 mRNA and protein expression. Pretreatment with DNJ (50?mg/kg) increased the activity, mRNA and protein levels of hepatic glycolysis enzymes (GK, PFK, PK, PDE1) and decreased the expression of gluconeogenesis enzymes (PEPCK, G-6-Pase). Assays of protein expression in hepatic cells and in vitro tests with purified enzymes indicated that the increased activity of glucose glycolysis enzymes was resulted from the relative increase in protein expression, rather than from direct enzyme activation. These results suggest that DNJ inhibits intestinal glucose absorption and accelerates hepatic glucose metabolism by directly regulating the expression of proteins involved in glucose transport systems, glycolysis and gluconeogenesis enzymes.

Li YG; Ji DF; Zhong S; Lin TB; Lv ZQ; Hu GY; Wang X

2013-01-01

78

Direct Effects of Exendin-(9,39) and GLP-1-(9,36)amide on Insulin Action, ?-Cell Function, and Glucose Metabolism in Nondiabetic Subjects.  

UK PubMed Central (United Kingdom)

Exendin-(9,39) is a competitive antagonist of glucagon-like peptide-1 (GLP-1) at its receptor. However, it is unclear if it has direct and unique effects of its own. We tested the hypothesis that exendin-(9,39) and GLP-1-(9,36)amide have direct effects on hormone secretion and ?-cell function as well as glucose metabolism in healthy subjects. Glucose containing [3-(3)H]glucose was infused to mimic the systemic appearance of glucose after a meal. Saline, GLP-1-(9,36)amide, or exendin-(9,39) at 30 pmol/kg/min (Ex 30) or 300 pmol/kg/min (Ex 300) were infused in random order on separate days. Integrated glucose concentrations were slightly but significantly increased by exendin-(9,39) (365 ± 43 vs. 383 ± 35 vs. 492 ± 49 vs. 337 ± 50 mmol per 6 h, saline, Ex 30, Ex 300, and GLP-1-[9,36]amide, respectively; P = 0.05). Insulin secretion did not differ among groups. However, insulin action was lowered by exendin-(9,39) (25 ± 4 vs. 20 ± 4 vs. 18 ± 3 vs. 21 ± 4 10(-4) dL/kg[min per ?U/mL]; P = 0.02), resulting in a lower disposition index (DI) during exendin-(9,39) infusion (1,118 ± 118 vs. 816 ± 83 vs. 725 ± 127 vs. 955 ± 166 10(-14) dL/kg/min(2) per pmol/L; P = 0.003). Endogenous glucose production and glucose disappearance did not differ significantly among groups. We conclude that exendin-(9,39), but not GLP-1-(9,36)amide, decreases insulin action and DI in healthy humans.

Sathananthan M; Farrugia LP; Miles JM; Piccinini F; Dalla Man C; Zinsmeister AR; Cobelli C; Rizza RA; Vella A

2013-08-01

79

Catabolite repression mutants of Saccharomyces cerevisiae show altered fermentative metabolism as well as cell cycle behavior in glucose-limited chemostat cultures.  

Science.gov (United States)

In glucose-limited continuous cultures, a Crabtree positive yeast such as Saccharomyces cerevisiae displays respiratory metabolism at low dilution rates (D) and respiro-fermentative metabolism at high D. We have studied the onset of ethanol production and cell cycle behavior in glucose-limited chemostat cultures of the wild type S. cerevisiae strain CEN.PK122 (WT) and isogenic mutants, snf1 (cat1) and snf4 (cat3) defective in proteins involved in catabolite derepression and the mutant in glucose repression mig1 (cat4). The triggering of fermentative metabolism was dependent upon catabolite repression properties of yeast and was coincident with a significant decrease of G1 length. WT cells of the strain CEN.PK122 displayed respiratory metabolism up to a D of 0.2 h-1 and exhibited longer G1 lengths than the snf1 and snf4 mutants that started fermenting after a D of 0.1 and 0.15 h-1, respectively. The catabolite derepression mutant snf4 showed a significant decrease in the duration of G1 with respect to the WT. An increase of 300% to 400% in the expression of CDC28 (CDC28-lacZ) with a noticeable shortening in G1 to values lower than approximately 150 min, was detected in the transformed wild type CEN.SC13-9B in glucose-limited chemostat cultures. The expression of CDC28-lacZ was analyzed in the wild type and isogenic mutant strains growing at maximal rate on glucose or in the presence of ethanol or glycerol. Two- to three-fold lower expression of the CDC28-lacZ fusion gene was detected in the snf1 or snf4 disruptants with respect to the WT and mig1 strains in the presence of all carbon sources. This effect was further shown to be growth rate-dependent exhibiting apparently, a threshold effect in the expression of the fusion gene with respect to the length of G1, similar to that shown in chemostat cultures. At the onset of fermentation, the control of the glycolytic flux was highly distributed between the uptake, hexokinase, and phosphofructokinase steps. Particularly interesting was the fact that the snf1 mutant exhibited the lowest fluxes of ethanol production, the highest of respiration and correspondingly, the branch to the tricarboxylic acid cycle was significantly rate-controling of glycolysis. PMID:10099331

Aon, M A; Cortassa, S

1998-07-20

80

REGULATION OF GLUCOSE METABOLISM BY INSULIN IN CARDIOMYOCYTES  

Directory of Open Access Journals (Sweden)

Full Text Available Cardiac function is improved during ischemia by stimulating glucose metabolism and subsequent decreasing of fatty acid (FA) oxidation. The impairment of heart glucose metabolism may contribute to the heart dysfunction and cardiomyopathy. Glucose transport is one of the first steps in insulin stimulated glucose uptake. Glucose entry into cells is a process that requires the involvement of a carrier protein in order to facilitate the movement of glucose across the plasma membrane. In cardiomyocytes (CMY), insulin stimulated glucose disposal is mediated via translocation of glucose transporters (GLUTs): GLUT4 and GLUT1.The major mechanism by which insulin regulatesGLUT4translocation and stimulation of glycogen synthesis in CMY is through activation of the protein kinaseB(PKB via phosphoinositol 3 kinase (PI3-K). In addition, insulin stimulates GLUT4 translocation and increases glucose uptake in CMY via PI3- K independent pathway by Cbl proto-oncoprotein phosphorylation. Combined activity of both pathways is required forGLUT4translocation inCMY. Insulin independent pathways, likeAMP-activated protein kinase (AMPK) pathway, also contributes to increased glucose uptake in CMY and PKB, and AMPK activity are inversely correlated during myocardial ischemia, although the influence of insulin on AMPK cardiac signaling would contradict previous observations. It has been reported that via PKB, insulin has an ability to inactivate AMPK. Inhibition of AMPK by insulin may be a contributory mechanism to the observation that cardiac FAoxidation is inhibited by insulin. Understanding how these two kinases interact at the molecular level in response to insulin may provide insights into how insulin is cardioprotective against ischemia.

Emina Sudar; Jelena Velebit; Zoran Gluvic; Emilija Lazic; Esma R. Isenovic

2007-01-01

 
 
 
 
81

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

DEFF Research Database (Denmark)

The growth and product formation of Saccharomyces kluyveri was characterized in aerobic batch cultivation on glucose. At these conditions it was found that ethyl acetate was a major overflow metabolite in S. kluyveri. During the exponential-growth phase on glucose ethyl acetate was produced at a constant specific rate of 0.12 g ethyl acetate per g dry weight per hour. The aerobic glucose metabolism in S. kluyveri was found to be less fermentative than in S. cerevisiae, as illustrated by the comparably low yield of ethanol on glucose (0.08 +/- 0.02 g/g), and high yield of biomass on glucose (0.29 +/- 0.01 g/g). The glucose metabolism of S. kluyveri was further characterized by the new and powerful techniques of metabolic network analysis. Flux distributions in the central carbon metabolism were estimated for respiro-fermentative growth in aerobic batch cultivation on glucose and respiratory growth in aerobic glucose-limited continuous cultivation. It was found that in S. kluyveri the flux into the pentose phosphate pathway was 18.8 mmole per 100 mmole glucose consumed during respiratory growth in aerobic glucose-limited continuous cultivation. Such a low flux into the pentose phosphate pathway cannot provide the cell with enough NADPH for biomass formation which is why the remaining NADPH will have to be provided by another pathway. During batch cultivation of S. kluyveri the tricarboxylic acid cycle was working as a cycle with a considerable flux, that is in sharp contrast to what has previously been observed in S. cerevisiae at the same growth conditions, where the tricarboxylic acid cycle operates as two branches. This indicates that the respiratory system was not significantly repressed in S. kluyveri during batch cultivation on glucose.

MØller, Kasper; Christensen, B.

2002-01-01

82

Cerebral glucose metabolism in Parkinson's disease  

International Nuclear Information System (INIS)

[en] 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

1984-01-01

83

Adult glucose metabolism in extremely birthweight-discordant monozygotic twins  

DEFF Research Database (Denmark)

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

Nielsen, Morten Frost Munk; Petersen, I

2012-01-01

84

Biosynthesis of highly enriched 13C-lycopene for human metabolic studies using repeated batch tomato cell culturing with 13C-glucose.  

UK PubMed Central (United Kingdom)

While putative disease-preventing lycopene metabolites are found in both tomato (Solanum lycopersicum) products and in their consumers, mammalian lycopene metabolism is poorly understood. Advances in tomato cell culturing techniques offer an economical tool for generation of highly-enriched (13)C-lycopene for human bioavailability and metabolism studies. To enhance the (13)C-enrichment and yields of labelled lycopene from the hp-1 tomato cell line, cultures were first grown in (13)C-glucose media for three serial batches and produced increasing proportions of uniformly labelled lycopene (14.3±1.2%, 39.6±0.5%, and 48.9±1.5%) with consistent yields (from 5.8 to 9 mg/L). An optimised 9-day-long (13)C-loading and 18-day-long labelling strategy developed based on glucose utilisation and lycopene yields, yielded (13)C-lycopene with 93% (13)C isotopic purity, and 55% of isotopomers were uniformly labelled. Furthermore, an optimised acetone and hexane extraction led to a fourfold increase in lycopene recovery from cultures compared to a standard extraction.

Moran NE; Rogers RB; Lu CH; Conlon LE; Lila MA; Clinton SK; Erdman JW Jr

2013-08-01

85

Biosynthesis of highly enriched 13C-lycopene for human metabolic studies using repeated batch tomato cell culturing with 13C-glucose.  

Science.gov (United States)

While putative disease-preventing lycopene metabolites are found in both tomato (Solanum lycopersicum) products and in their consumers, mammalian lycopene metabolism is poorly understood. Advances in tomato cell culturing techniques offer an economical tool for generation of highly-enriched (13)C-lycopene for human bioavailability and metabolism studies. To enhance the (13)C-enrichment and yields of labelled lycopene from the hp-1 tomato cell line, cultures were first grown in (13)C-glucose media for three serial batches and produced increasing proportions of uniformly labelled lycopene (14.3±1.2%, 39.6±0.5%, and 48.9±1.5%) with consistent yields (from 5.8 to 9 mg/L). An optimised 9-day-long (13)C-loading and 18-day-long labelling strategy developed based on glucose utilisation and lycopene yields, yielded (13)C-lycopene with 93% (13)C isotopic purity, and 55% of isotopomers were uniformly labelled. Furthermore, an optimised acetone and hexane extraction led to a fourfold increase in lycopene recovery from cultures compared to a standard extraction. PMID:23561155

Moran, Nancy Engelmann; Rogers, Randy B; Lu, Chi-Hua; Conlon, Lauren E; Lila, Mary Ann; Clinton, Steven K; Erdman, John W

2013-01-23

86

Protons and glucose metabolism in shock  

Energy Technology Data Exchange (ETDEWEB)

When oxygen is limiting, animals can ferment glucose via several metabolic pathways varying in energetic efficiency and leading to various end products (such as lactate, succinate, or propionate). Because the pH dependence of H/sup +/ production by fermentation is opposite to that by hydrolysis of adenosine triphosphate formed in the fermentation, the total number of moles of protons generated is always two per mole of fermentable substrate. However, two and three times more adenosine triphosphate can be turned over per mole of protons produced in succinate and propionate fermentations, respectively, than in lactate fermentation. At its limit, this advantage would achieve the same balance between H/sup +/ production and H/sup +/ consumption during ATP cycling that is observed in aerobic metabolism, a situation observed in certain alcohol fermentations. Since proton balance during anaerobiosis is clearly adaptable, we consider possible impact and functions of net H/sup +/ accumulation during carbohydrate metabolism in endotoxin shock.

Hochachka, P.W.

1983-01-01

87

Telomerase deficiency impairs glucose metabolism and insulin secretion  

Science.gov (United States)

Reduced telomere length and impaired telomerase activity have been linked to several diseases associated with senescence and aging. However, a causal link to metabolic disorders and in particular diabetes mellitus is pending. We here show that young adult mice which are deficient for the Terc subunit of telomerase exhibit impaired glucose tolerance. This is caused by impaired glucose-stimulated insulin secretion (GSIS) from pancreatic islets, while body fat content, energy expenditure and insulin sensitivity were found to be unaltered. The impaired secretion capacity for insulin is due to reduced islet size which is linked to an impaired replication capacity of insulin-producing beta-cells in Terc-deficient mice. Taken together, telomerase deficiency and hence short telomeres impair replicative capacity of pancreatic beta-cells to cause impaired insulin secretion and glucose intolerance, mechanistically defining diabetes mellitus as an aging-associated disorder.

Kuhlow, Doreen; Florian, Simone; von Figura, Guido; Weimer, Sandra; Schulz, Nadja; Petzke, Klaus J.; Zarse, Kim; Pfeiffer, Andreas F.H; Rudolph, K. Lenhard; Ristow, Michael

2010-01-01

88

Quantification of serial tumor glucose metabolism  

Energy Technology Data Exchange (ETDEWEB)

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

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

1996-03-01

89

GLUCOSE METABOLISM OF TWO STRAINS OF MYCOPLASMA LAIDLAWII.  

UK PubMed Central (United Kingdom)

Castrejon-Diez, Jaime (Tulane University School of Medicine, New Orleans, La.), Thelma N. Fisher, and Earl Fisher, Jr. Glucose metabolism of two strains of Mycoplasma laidlawii. J. Bacteriol. 86:627-636. 1963.-Two strains of Mycoplasma laidlawii were incubated in systems containing d-glucose-C(14); carbon dioxide, acetate, pyruvate, and lactate were isolated from appropriate fluids after resting-cell and growth experiments. In resting-cell experiments, radioactivity recoveries were shown to be 95% for M. laidlawii A and 89% for M. laidlawii (Adler). By growth studies, the radioactivity recovery for M. laidlawii A was 83% and for M. laidlawii (Adler) was 90.5%. Low specific activities of the products as compared with the specific activity of glucose suggested cellular pools, or that the dissimilation of other substances present in the complex growth medium yielded products which contributed to the dilution factors. Enzyme studies added support to the hypothesis that glycolysis is operative in these organisms. Experiments with d-glucose-1-C(14) or d-glucose-6-C(14) as substrate suggested that the hexose monophosphate shunt may be functional in M. laidlawii (Adler), particularly since glucose-6-phosphate dehydrogenase, ribose-5-phosphate isomerase, and transketolase were demonstrated. This pathway is absent in M. laidlawii A.

CASTREJON-DIEZ J; FISHER TN; FISHER E Jr

1963-10-01

90

Longitudinal Association of Glucose Metabolism With Retinopathy  

Science.gov (United States)

OBJECTIVE—We determined the longitudinal association of glucose metabolism with retinopathy in a sample of the Australian population. RESEARCH DESIGN AND METHODS—The Australian Diabetes Obesity and Lifestyle (AusDiab) study is a national, longitudinal study of adults aged ?25 years from 42 randomly selected areas of Australia. Retinopathy was assessed at baseline in 1999–2000 and 5 years later in 2004–2005 in participants identified as having diabetes (based on self-report and oral glucose tolerance test) and impaired glucose metabolism and in a random sample with normal glucose tolerance. Complete retinal data were available for 1,192 participants. Photographs were graded at two time points according to a simplified version of the Wisconsin grading system. RESULTS—The 5-year incidences of retinopathy were 13.9 and 3.0% among those with known and newly diagnosed diabetes at baseline, respectively. Of those who developed incident newly diagnosed diabetes at follow-up, 11.9% had retinopathy at baseline compared with 5.6% of those who did not progress to incident newly diagnosed diabetes (P = 0.037). After adjustment for factors identified as risk factors for diabetes, individuals with retinopathy signs at baseline were twice as likely to develop incident newly diagnosed diabetes compared with those who did not have retinopathy signs at baseline. CONCLUSIONS—The 5-year incidence of retinopathy was 13.9% among individuals with known diabetes. Nondiabetic individuals with retinopathy signs at baseline had a twofold higher risk of developing incident newly diagnosed diabetes 5 years later. This result provides further evidence that mild retinopathy signs may be a preclinical marker of underlying microvascular disease and future diabetes risk.

Tapp, Robyn J.; Tikellis, Gabriella; Wong, Tien Y.; Harper, C. Alex; Zimmet, Paul Z.; Shaw, Jonathan E.

2008-01-01

91

Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance  

Science.gov (United States)

OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance.

Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

2011-01-01

92

Effects of insulin on brain glucose metabolism in impaired glucose tolerance.  

UK PubMed Central (United Kingdom)

OBJECTIVE: Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS: We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [(18)F]fluorodeoxyglucose (for brain glucose metabolism) and [(15)O]H(2)O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS: The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS: We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance.

Hirvonen J; Virtanen KA; Nummenmaa L; Hannukainen JC; Honka MJ; Bucci M; Nesterov SV; Parkkola R; Rinne J; Iozzo P; Nuutila P

2011-02-01

93

[Status of glucose metabolism in Chinese essential hypertensive patients].  

UK PubMed Central (United Kingdom)

OBJECTIVE: To investigate glucose metabolism status and its relationship with blood pressure, obesity, renal function and cardio-cerebral vascular events in Chinese essential hypertensive patients. METHODS: Essential hypertensive patients without diabetic history were enrolled in this cross-sectional survey. All patients filled in questionnaires and received physical examination and laboratory tests. Oral glucose tolerance test (OGTT, fasting and 2 hours glucose level after drinking the 75 g glucose solution) was performed in patients who signed the informed consent. RESULTS: (1) The control rate of systolic BP was lower in patients with dysglycaemia than in patients without dysglycaemia (41.0% vs. 46.4%, P = 0.000). (2) The albuminuria detection rate and the abnormal rate of estimated glumerular filtration rate (eGFR) increased significantly with the deterioration of glucose metabolism. (3) Multifactor-analysis showed that abnormal waist circumference, decreased eGFR and presence of albuminuria were independent risk factors for abnormal glucose metabolism. Cardiovascular events was significantly higher in patients with abnormal glucose metabolism than patients with normal glucose metabolism. CONCLUSION: Abnormal glucose metabolism is common in Chinese essential hypertensive patients. When complicated with abnormal glucose metabolism, essential hypertensive patients had poor blood pressure control rate and were related to higher cardiovascular risk.

Sun NL; Wang HY; Chen XP; Sun YM; Zhao LY; Wang H; Xiang MX; Wang JP; Zhu ZM; Hao YM

2013-04-01

94

The importance of glucose metabolism in the hypoxic cytotoxicity of Misonidazole  

International Nuclear Information System (INIS)

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

1985-01-01

95

Factors associated with glucose metabolism disorders after kidney transplantation.  

UK PubMed Central (United Kingdom)

INTRODUCTION: Post-transplant diabetes mellitus (PTDM), pre-diabetes-impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are frequent complications after organ transplantation. The aim of this study was to assess the frequency of PTDM, IFG and IGT in a group of renal transplant recipients, to compare the frequency of glucose metabolism disorders in subjects treated with tacrolimus and with cyclosporine, and to establish the influence of different risk factors on the development of glucose metabolism disorders. MATERIAL AND METHODS: We examined 206 non-diabetic kidney allograft recipients (age 46.4 ± 12.3 years, time since transplantation 45.5 ± ± 33.6 months, BMI 26.3 ± 4.5 kg/m2). Glucose metabolism disorders were diagnosed using an oral glucose tolerance test. Logistic regression was used to assess the influence of each risk factor (age, BMI, waist circumference, physical activity, the presence of cardiovascular disease, positive family history of diabetes, cholesterol and triglycerides concentration) on the development of glucose metabolism disorders. RESULTS: In 103 patients (50%), we diagnosed glucose metabolism disorders. 19% of patients had PTDM, 14% IFG, and 17% IGT. We did not find any differences in the frequency of glucose metabolism disorders between patients treated with tacrolimus and with cyclosporine. Multivariate analysis identified BMI and a family history of diabetes as independent risk factors of glucose metabolism disorders. CONCLUSIONS: We found a high prevalence of glucose metabolism disorders in the examined group. This suggests that kidney transplant recipients should be screened for these disturbances. Patients with higher BMI and with first-degree relatives with diabetes had an increased risk of glucose metabolism disorders after kidney transplantation.

Brzezi?ska B; Junik R; Kami?ska A; W?odarczyk Z; Adamowicz A

2013-01-01

96

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

UK PubMed Central (United Kingdom)

Altered carbohydrate metabolism in cancer cells was first noted by Otto Warburg more than 80 years ago. Upregulation of genes controlling the glycolytic pathway under normoxia, known as the Warburg effect, clearly differentiates malignant from non-malignant cells. The resurgence of interest in cancer metabolism aims at a better understanding of the metabolic differences between malignant and non-malignant cells and the creation of novel therapeutic and diagnostic agents exploiting these differences. Modified d-glucose and d-mannose analogs were shown to interfere with the metabolism of their respective monosaccharide parent molecules and are potentially clinically useful anticancer and diagnostic agents. One such agent, 2-deoxy-d-glucose (2-DG), has been extensively studied in vitro and in vivo and also clinically evaluated. Studies clearly indicate that 2-DG has a pleiotropic mechanism of action. In addition to effectively inhibiting glycolysis, 2-DG has also been shown to affect protein glycosylation. In order to better understand its molecular mechanism of action, we have designed and synthesized deuterated molecular probes to study 2-DG interference with d-glucose and d-mannose metabolism using mass spectrometry. We present here the synthesis of all desired probes: 2-deutero-d-glucose, 2-deutero-d-mannose, 6-deutero-d-glucose, 6-deutero-d-mannose, and 2-deutero-2-deoxy-d-glucose as well as their complete chemical characterization.

Fokt I; Skora S; Conrad C; Madden T; Emmett M; Priebe W

2013-03-01

97

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

Directory of Open Access Journals (Sweden)

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

Frank Diederichs

2010-01-01

98

[The relationship between bone and glucose/lipid metabolism].  

UK PubMed Central (United Kingdom)

The fracture risks are increased in patients with lifestyle-related diseases such as diabetes mellitus and dyslipidemia. Bone has been recognized as an endocrine organ to regulate glucose and fat metabolism. Hyperglycemia, advanced glycation end products (AGEs) , and insulin signal are involved in diabetes-related bone disease. Previous studies suggest that hypercholesterolemia may increase the risk of fractures. Adipokines such as leptin and adiponectin derived from fat tissue, which are important regulators for glucose and lipid metabolism, regulate bone metabolism. On the other hand, it has been revealed that osteocalcin, which is secreted from bone tissue into the circulation, has a hormonal function in glucose and fat metabolism.

Kanazawa I; Sugimoto T

2013-02-01

99

Glucose Metabolism in Breast Cancer and its Implication in Cancer Therapy  

Directory of Open Access Journals (Sweden)

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

Ning Li; Wen Tan; Jing Li; Ping Li; Simon Lee; Yitao Wang; Yuewen Gong

2011-01-01

100

Metabolism of [U-13C]glucose in Human Brain Tumors In Vivo  

Science.gov (United States)

Glioblastomas (GBMs) and brain metastases demonstrate avid uptake of 18fluoro-2-deoxyglucose (FDG) by positron emission tomography (PET) and display perturbations of intracellular metabolite pools by 1H magnetic resonance spectroscopy (MRS). These observations suggest that metabolic reprogramming contributes to brain tumor growth in vivo. The Warburg effect, excess metabolism of glucose to lactate in the presence of oxygen, is a hallmark of cancer cells in culture. FDG-positive tumors are assumed to metabolize glucose in a similar manner, with high rates of lactate formation compared to mitochondrial glucose oxidation, but few studies have specifically examined the metabolic fates of glucose in vivo. In particular, the capacity of human brain malignancies to oxidize glucose in the tricarboxylic acid cycle is unknown. Here we studied the metabolism of human brain tumors in situ. [U-13C]glucose was infused during surgical resection, and tumor samples were subsequently subjected to 13C NMR spectroscopy. Analysis of tumor metabolites revealed lactate production, as expected. We also determined that pyruvate dehydrogenase, turnover of the TCA cycle, anaplerosis and de novo glutamine and glycine synthesis contributed significantly to the ultimate disposition of glucose carbon. Surprisingly, less than 50% of the acetyl-CoA pool was derived from blood-borne glucose, suggesting that additional substrates contribute to tumor bioenergetics. This study illustrates a convenient approach that capitalizes on the high information content of 13C NMR spectroscopy and enables the analysis of intermediary metabolism in diverse malignancies growing in their native microenvironment.

Maher, Elizabeth A.; Marin-Valencia, Isaac; Bachoo, Robert M.; Mashimo, Tomoyuki; Raisanen, Jack; Hatanpaa, Kimmo J.; Jindal, Ashish; Jeffrey, F. Mark; Choi, Changho; Madden, Christopher; Mathews, Dana; Pascual, Juan M.; Mickey, Bruce E.; Malloy, Craig R.; DeBerardinis, Ralph J.

2012-01-01

 
 
 
 
101

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

International Nuclear Information System (INIS)

[en] 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

102

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 activa...

Wu, Ai-Luen; Coulter, Sally; Liddle, Christopher; Wong, Anne; Eastham-Anderson, Jeffrey; French, Dorothy M.; Peterson, Andrew S.

103

Chemostat studies on the regulation of glucose metabolism in Pseudomonas aeruginosa by citrate.  

UK PubMed Central (United Kingdom)

The effect of the relative concentrations of citrate and glucose on the regulation of key enzymes of the direct oxidative, phosphorylative, Entner-Doudoroff and pentose-cycle pathways of glucose metabolism in Pseudomonas aeruginosa has been investigated in continuous culture under conditions of NH(4) (+)-limitation. For comparison isocitrate dehydrogenase and aconitase were also assayed. Measurements were made for steady-state and transient conditions and the effect of growth rate was also studied. When cells grew on 75mm-citrate the glucose concentration had to attain 6-8mm before significant induction of enzymes of glucose metabolism occurred; the specific activities increased further as the result of both raising the glucose concentration to 30mm and then subsequently lowering the citrate to 60mm and then to 45mm. The specific activities of the glucose enzymes increased immediately during the transient period between the steady states characteristic of growth on 6mm- and 8mm-glucose, the increase continuing for about two doubling times. The converse experiment of adding increasing citrate concentrations to 45mm-glucose medium revealed an immediate induction of the citrate-transport system, oxidation of citrate following the increase in citrate concentration up to 8mm. Between 8mm- and 16mm-citrate a marked repression of gluconate, glucose 6-phosphate and 6-phosphogluconate dehydrogenases and the Entner-Doudoroff enzymes occurred. Increased growth rate in citrate medium resulted in decreased specific activities of glucose 6-phosphate dehydrogenase and isocitrate dehydrogenase. Increased growth rate in citrate-glucose medium gave decreased specific activities of isocitrate dehydrogenase and aconitase whereas the activities of some of the glucose enzymes decreased initially but then increased at the highest growth rate (0.5h(-1)), at which a marked increase in glucose utilization occurred. These observations accord with the regulation of glucose enzymes by induction with glucose or its metabolites and repression by citrate or its metabolic products.

Ng FM; Dawes EA

1973-02-01

104

Chemostat studies on the regulation of glucose metabolism in Pseudomonas aeruginosa by citrate.  

Science.gov (United States)

The effect of the relative concentrations of citrate and glucose on the regulation of key enzymes of the direct oxidative, phosphorylative, Entner-Doudoroff and pentose-cycle pathways of glucose metabolism in Pseudomonas aeruginosa has been investigated in continuous culture under conditions of NH(4) (+)-limitation. For comparison isocitrate dehydrogenase and aconitase were also assayed. Measurements were made for steady-state and transient conditions and the effect of growth rate was also studied. When cells grew on 75mm-citrate the glucose concentration had to attain 6-8mm before significant induction of enzymes of glucose metabolism occurred; the specific activities increased further as the result of both raising the glucose concentration to 30mm and then subsequently lowering the citrate to 60mm and then to 45mm. The specific activities of the glucose enzymes increased immediately during the transient period between the steady states characteristic of growth on 6mm- and 8mm-glucose, the increase continuing for about two doubling times. The converse experiment of adding increasing citrate concentrations to 45mm-glucose medium revealed an immediate induction of the citrate-transport system, oxidation of citrate following the increase in citrate concentration up to 8mm. Between 8mm- and 16mm-citrate a marked repression of gluconate, glucose 6-phosphate and 6-phosphogluconate dehydrogenases and the Entner-Doudoroff enzymes occurred. Increased growth rate in citrate medium resulted in decreased specific activities of glucose 6-phosphate dehydrogenase and isocitrate dehydrogenase. Increased growth rate in citrate-glucose medium gave decreased specific activities of isocitrate dehydrogenase and aconitase whereas the activities of some of the glucose enzymes decreased initially but then increased at the highest growth rate (0.5h(-1)), at which a marked increase in glucose utilization occurred. These observations accord with the regulation of glucose enzymes by induction with glucose or its metabolites and repression by citrate or its metabolic products. PMID:4199011

Ng, F M; Dawes, E A

1973-02-01

105

Postprandial gut hormone responses and glucose metabolism in cholecystectomized patients.  

UK PubMed Central (United Kingdom)

Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat-rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum bile acids were measured. We found similar basal glucose concentrations in the two groups, whereas cholecystectomized subjects had elevated postprandial glucose excursions. Cholecystectomized subjects had reduced postprandial concentrations of duodenal bile acids, but preserved postprandial plasma GLP-1 responses, compared with control subjects. Also, cholecystectomized patients exhibited augmented fasting glucagon. Basal plasma CCK concentrations were lower and peak concentrations were higher in cholecystectomized patients. The concentrations of GIP, GLP-2, and gastrin were similar in the two groups. In conclusion, cholecystectomized subjects had preserved postprandial GLP-1 responses in spite of decreased duodenal bile delivery, suggesting that gallbladder emptying is not a prerequisite for GLP-1 release. Cholecystectomized patients demonstrated a slight deterioration of postprandial glycemic control, probably because of metabolic changes unrelated to incretin secretion.

Sonne DP; Hare KJ; Martens P; Rehfeld JF; Holst JJ; Vilsbøll T; Knop FK

2013-02-01

106

Postprandial gut hormone responses and glucose metabolism in cholecystectomized patients.  

Science.gov (United States)

Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat-rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum bile acids were measured. We found similar basal glucose concentrations in the two groups, whereas cholecystectomized subjects had elevated postprandial glucose excursions. Cholecystectomized subjects had reduced postprandial concentrations of duodenal bile acids, but preserved postprandial plasma GLP-1 responses, compared with control subjects. Also, cholecystectomized patients exhibited augmented fasting glucagon. Basal plasma CCK concentrations were lower and peak concentrations were higher in cholecystectomized patients. The concentrations of GIP, GLP-2, and gastrin were similar in the two groups. In conclusion, cholecystectomized subjects had preserved postprandial GLP-1 responses in spite of decreased duodenal bile delivery, suggesting that gallbladder emptying is not a prerequisite for GLP-1 release. Cholecystectomized patients demonstrated a slight deterioration of postprandial glycemic control, probably because of metabolic changes unrelated to incretin secretion. PMID:23275610

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

2012-12-28

107

Postprandial gut hormone responses and glucose metabolism in cholecystectomized patients  

DEFF Research Database (Denmark)

Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat-rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum bile acids were measured. We found similar basal glucose concentrations in the two groups, whereas cholecystectomized subjects had elevated postprandial glucose excursions. Cholecystectomized subjects had reduced postprandial concentrations of duodenal bile acids, but preserved postprandial plasma GLP-1 responses, compared with control subjects. Also, cholecystectomized patients exhibited augmented fasting glucagon. Basal plasma CCK concentrations were lower and peak concentrations were higher in cholecystectomized patients. The concentrations of GIP, GLP-2, and gastrin were similar in the two groups. In conclusion, cholecystectomized subjects had preserved postprandial GLP-1 responses in spite of decreased duodenal bile delivery, suggesting that gallbladder emptying is not a prerequisite for GLP-1 release. Cholecystectomized patients demonstrated a slight deterioration of postprandial glycemic control, probably because of metabolic changes unrelated to incretin secretion.

Sonne, David P; Hare, Kristine J

2013-01-01

108

Glucose metabolism in pregnant sheep when placental growth is restricted  

International Nuclear Information System (INIS)

[en] 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

109

Glucose metabolism in pregnant sheep when placental growth is restricted  

Energy Technology Data Exchange (ETDEWEB)

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

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

1989-08-01

110

Oxidative Metabolism in Pediococcus pentosaceus III. Glucose Dehydrogenase System1  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Lee, Chin K. (North Carolina State of the University of North Carolina, Raleigh), and Walter J. Dobrogosz. Oxidative metabolism in Pediococcus pentosaceus. III. Glucose dehydrogenase system. J. Bacteriol. 90:653–660. 1965.—A method was developed for the purification of glucose dehydrogenase from Ped...

Lee, Chin K.; Dobrogosz, Walter J.

111

GLUCOSE METABOLISM OF TWO STRAINS OF MYCOPLASMA LAIDLAWII  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Castrejon-Diez, Jaime (Tulane University School of Medicine, New Orleans, La.), Thelma N. Fisher, and Earl Fisher, Jr. Glucose metabolism of two strains of Mycoplasma laidlawii. J. Bacteriol. 86:627–636. 1963.—Two strains of Mycoplasma laidlawii were incubated in systems containing d-glucose-C14; ca...

Castrejon-Diez, Jaime; Fisher, Thelma N.; Fisher, Earl

112

Glutamine and glucose metabolism in bovine blood lymphocytes.  

UK PubMed Central (United Kingdom)

1. Glutamine and glucose metabolism was studied in bovine blood lymphocytes incubated at 37 degrees C in the presence of Krebs-Ringer bicarbonate buffer (pH 7.4) containing 1 mM [U-14C]glutamine and 5 mM [U-14C]glucose, respectively. 2. The major metabolic products from glutamine were ammonia, glutamate, and to a lesser extent, aspartate and CO2. Glucose was metabolized mainly to lactate and, to a lesser extent, pyruvate and CO2. These findings indicate incomplete oxidation of glutamine and glucose carbons in bovine blood lymphocytes. 3. Glucose provided three-fold greater amounts of energy to bovine blood lymphocytes than did glutamine on the basis of their measured end-products. Glycolysis accounted for 50% of glucose-derived ATP production. 4. Our findings suggest similar metabolic patterns of glutamine and glucose in lymphocytes between ruminants and non-ruminant species (e.g. rats). However, in contrast to rat peripheral lymphocytes, glucose, rather than glutamine, was a major energy substrate for bovine blood lymphocytes.

Wu G; Greene LW

1992-12-01

113

Effects of hypoglycaemia on neuronal metabolism in the adult brain: role of alternative substrates to glucose.  

Science.gov (United States)

Hypoglycaemia is characterized by decreased blood glucose levels and is associated with different pathologies (e.g. diabetes, inborn errors of metabolism). Depending on its severity, it might affect cognitive functions, including impaired judgment and decreased memory capacity, which have been linked to alterations of brain energy metabolism. Glucose is the major cerebral energy substrate in the adult brain and supports the complex metabolic interactions between neurons and astrocytes, which are essential for synaptic activity. Therefore, hypoglycaemia disturbs cerebral metabolism and, consequently, neuronal function. Despite the high vulnerability of neurons to hypoglycaemia, important neurochemical changes enabling these cells to prolong their resistance to hypoglycaemia have been described. This review aims at providing an overview over the main metabolic effects of hypoglycaemia on neurons, covering in vitro and in vivo findings. Recent studies provided evidence that non-glucose substrates including pyruvate, glycogen, ketone bodies, glutamate, glutamine, and aspartate, are metabolized by neurons in the absence of glucose and contribute to prolong neuronal function and delay ATP depletion during hypoglycaemia. One of the pathways likely implicated in the process is the pyruvate recycling pathway, which allows for the full oxidation of glutamate and glutamine. The operation of this pathway in neurons, particularly after hypoglycaemia, has been re-confirmed recently using metabolic modelling tools (i.e. Metabolic Flux Analysis), which allow for a detailed investigation of cellular metabolism in cultured cells. Overall, the knowledge summarized herein might be used for the development of potential therapies targeting neuronal protection in patients vulnerable to hypoglycaemic episodes. PMID:23109064

Amaral, Ana I

2012-10-30

114

Effects of hypoglycaemia on neuronal metabolism in the adult brain: role of alternative substrates to glucose.  

UK PubMed Central (United Kingdom)

Hypoglycaemia is characterized by decreased blood glucose levels and is associated with different pathologies (e.g. diabetes, inborn errors of metabolism). Depending on its severity, it might affect cognitive functions, including impaired judgment and decreased memory capacity, which have been linked to alterations of brain energy metabolism. Glucose is the major cerebral energy substrate in the adult brain and supports the complex metabolic interactions between neurons and astrocytes, which are essential for synaptic activity. Therefore, hypoglycaemia disturbs cerebral metabolism and, consequently, neuronal function. Despite the high vulnerability of neurons to hypoglycaemia, important neurochemical changes enabling these cells to prolong their resistance to hypoglycaemia have been described. This review aims at providing an overview over the main metabolic effects of hypoglycaemia on neurons, covering in vitro and in vivo findings. Recent studies provided evidence that non-glucose substrates including pyruvate, glycogen, ketone bodies, glutamate, glutamine, and aspartate, are metabolized by neurons in the absence of glucose and contribute to prolong neuronal function and delay ATP depletion during hypoglycaemia. One of the pathways likely implicated in the process is the pyruvate recycling pathway, which allows for the full oxidation of glutamate and glutamine. The operation of this pathway in neurons, particularly after hypoglycaemia, has been re-confirmed recently using metabolic modelling tools (i.e. Metabolic Flux Analysis), which allow for a detailed investigation of cellular metabolism in cultured cells. Overall, the knowledge summarized herein might be used for the development of potential therapies targeting neuronal protection in patients vulnerable to hypoglycaemic episodes.

Amaral AI

2013-07-01

115

The CX3CL1/CX3CR1 reprograms glucose metabolism through HIF-1 pathway in pancreatic adenocarcinoma.  

UK PubMed Central (United Kingdom)

One of the hallmarks of cancer is revised glucose metabolism that promotes cell survival and proliferation. In pancreatic cancer, the regulatory mechanism of glucose metabolism remains to be elucidated. In this study, we found that CX3CR1 is expressed in pancreatic cancer cells lines. Exogenous or transfected CX3CL1 increased glucose uptake and lactate secretion. CX3CL1 stimulated HIF-1 expression through PI3K/Akt and MAPK pathways. Furthermore, knockdown of HIF-1 blocked CX3CL1-modified glucose metabolism in pancreatic adenocarcinoma cells. In conclusion, the CX3CL1/CX3CR1 reprograms glucose metabolism through HIF-1 pathway in pancreatic cancer cells. J. Cell. Biochem. 114: 2603-2611, 2013. © 2013 Wiley Periodicals, Inc.

Ren H; Zhao T; Sun J; Wang X; Liu J; Gao S; Yu M; Hao J

2013-11-01

116

The CX3CL1/CX3CR1 reprograms glucose metabolism through HIF-1 pathway in pancreatic adenocarcinoma.  

Science.gov (United States)

One of the hallmarks of cancer is revised glucose metabolism that promotes cell survival and proliferation. In pancreatic cancer, the regulatory mechanism of glucose metabolism remains to be elucidated. In this study, we found that CX3CR1 is expressed in pancreatic cancer cells lines. Exogenous or transfected CX3CL1 increased glucose uptake and lactate secretion. CX3CL1 stimulated HIF-1 expression through PI3K/Akt and MAPK pathways. Furthermore, knockdown of HIF-1 blocked CX3CL1-modified glucose metabolism in pancreatic adenocarcinoma cells. In conclusion, the CX3CL1/CX3CR1 reprograms glucose metabolism through HIF-1 pathway in pancreatic cancer cells. J. Cell. Biochem. 114: 2603-2611, 2013. © 2013 Wiley Periodicals, Inc. PMID:23857671

Ren, He; Zhao, Tiansuo; Sun, Junwei; Wang, Xiuchao; Liu, Jingcheng; Gao, Song; Yu, Ming; Hao, Jihui

2013-11-01

117

Metabolism of [U-13 C]glucose in human brain tumors in vivo.  

UK PubMed Central (United Kingdom)

Glioblastomas and brain metastases demonstrate avid uptake of 2-[(18) F]fluoro-2-deoxyglucose by positron emission tomography and display perturbations of intracellular metabolite pools by (1) H MRS. These observations suggest that metabolic reprogramming contributes to brain tumor growth in vivo. The Warburg effect, excess metabolism of glucose to lactate in the presence of oxygen, is a hallmark of cancer cells in culture. 2-[(18) F]Fluoro-2-deoxyglucose-positive tumors are assumed to metabolize glucose in a similar manner, with high rates of lactate formation relative to mitochondrial glucose oxidation, but few studies have specifically examined the metabolic fates of glucose in vivo. In particular, the capacity of human brain cancers to oxidize glucose in the tricarboxylic acid cycle is unknown. Here, we studied the metabolism of human brain tumors in situ. [U-(13) C]Glucose (uniformly labeled glucose, i.e. d-glucose labeled with (13) C in all six carbons) was infused during surgical resection, and tumor samples were subsequently subjected to (13) C NMR spectroscopy. The analysis of tumor metabolites revealed lactate production, as expected. We also determined that pyruvate dehydrogenase, turnover of the tricarboxylic acid cycle, anaplerosis and de novo glutamine and glycine synthesis contributed significantly to the ultimate disposition of glucose carbon. Surprisingly, less than 50% of the acetyl-coenzyme A pool was derived from blood-borne glucose, suggesting that additional substrates contribute to tumor bioenergetics. This study illustrates a convenient approach that capitalizes on the high information content of (13) C NMR spectroscopy and enables the analysis of intermediary metabolism in diverse cancers growing in their native microenvironment.

Maher EA; Marin-Valencia I; Bachoo RM; Mashimo T; Raisanen J; Hatanpaa KJ; Jindal A; Jeffrey FM; Choi C; Madden C; Mathews D; Pascual JM; Mickey BE; Malloy CR; DeBerardinis RJ

2012-11-01

118

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.  

Science.gov (United States)

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 that the gene expression levels of apoptotic proteins death-associated protein kinase 2 and cell death-inducing DFFA-like effector b were upregulated, whereas that of oncoproteins DEK and MYCL1, cell migration-promoting proteins CD24 and integrin-alpha 9, and glycolytic enzyme aldolase A were downregulated. These findings suggest that YXQ-EQ may exert anticancer effect through modulating gene expression in a way that facilitates cancer cell apoptosis while represses proliferation, metastasis, and glucose metabolism. PMID:22160803

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

2011-12-10

119

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.  

UK PubMed Central (United Kingdom)

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 that the gene expression levels of apoptotic proteins death-associated protein kinase 2 and cell death-inducing DFFA-like effector b were upregulated, whereas that of oncoproteins DEK and MYCL1, cell migration-promoting proteins CD24 and integrin-alpha 9, and glycolytic enzyme aldolase A were downregulated. These findings suggest that YXQ-EQ may exert anticancer effect through modulating gene expression in a way that facilitates cancer cell apoptosis while represses proliferation, metastasis, and glucose metabolism.

Yan X; Li F; Dozmorov I; Frank MB; Dao M; Centola M; Cao W; Hu D

2012-04-01

120

Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo.  

UK PubMed Central (United Kingdom)

Many pathways regulating blood formation have been elucidated, yet how each coordinates with embryonic biophysiology to modulate the spatiotemporal production of hematopoietic stem cells (HSCs) is currently unresolved. Here, we report that glucose metabolism impacts the onset and magnitude of HSC induction in vivo. In zebrafish, transient elevations in physiological glucose levels elicited dose-dependent effects on HSC development, including enhanced runx1 expression and hematopoietic cluster formation in the aorta-gonad-mesonephros region; embryonic-to-adult transplantation studies confirmed glucose increased functional HSCs. Glucose uptake was required to mediate the enhancement in HSC development; likewise, metabolic inhibitors diminished nascent HSC production and reversed glucose-mediated effects on HSCs. Increased glucose metabolism preferentially impacted hematopoietic and vascular targets, as determined by gene expression analysis, through mitochondrial-derived reactive oxygen species (ROS)-mediated stimulation of hypoxia-inducible factor 1? (hif1?). Epistasis assays demonstrated that hif1? regulates HSC formation in vivo and mediates the dose-dependent effects of glucose metabolism on the timing and magnitude of HSC production. We propose that this fundamental metabolic-sensing mechanism enables the embryo to respond to changes in environmental energy input and adjust hematopoietic output to maintain embryonic growth and ensure viability.

Harris JM; Esain V; Frechette GM; Harris LJ; Cox AG; Cortes M; Garnaas MK; Carroll KJ; Cutting CC; Khan T; Elks PM; Renshaw SA; Dickinson BC; Chang CJ; Murphy MP; Paw BH; Vander Heiden MG; Goessling W; North TE

2013-03-01

 
 
 
 
121

Effects of MDMA on blood glucose levels and brain glucose metabolism  

International Nuclear Information System (INIS)

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

2007-01-01

122

Effects of MDMA on blood glucose levels and brain glucose metabolism  

Energy Technology Data Exchange (ETDEWEB)

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

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

2007-06-15

123

Autoradiographic studies on glucose metabolism in the salivary gland of Lygaeus SP. (Heteroptera, Lygalidae)  

International Nuclear Information System (INIS)

Autoradiographic studies using 3H-glucose in the salivary glands of Lygaeus sp.were carried out. It has been observed that the radioactivity appears in the cell cytoplasm and lumen within a short period of incubation and attains its peak after 30 min of incubation. Afterwards, the radioactivity is exhausted from the cell and lumen suggesting a very high rate of glucose metabolism in this species. (author)

1985-01-01

124

A comparative radiorespirometric study of glucose metabolism in yeasts.  

Science.gov (United States)

A comparative radiorespirometric study of glucose metabolism in glucose-limited chemostat cultures of Saccharomyces cerevisiae, Candida utilis and Rhodosporidium toruloides was performed in an attempt to estimate the contribution of the hexose monophosphate (HMP) pathway to glucose metabolism. Radioactively labelled glucose was administered directly to the cultures in a constant substrate feed, without disturbance of the steady state. The 14CO2 yields from [1-14C]- and [6-14C]-glucose demonstrated that the HMP pathway activities for the three yeasts were very similar. Furthermore, a quantitative analysis of results indicated that the HMP pathway activities were close to the theoretical minimum needed to cover the NADPH requirement for biomass formation. PMID:3333300

Bruinenberg, P M; Waslander, G W; van Dijken, J P; Scheffers, W A

1986-06-01

125

A comparative radiorespirometric study of glucose metabolism in yeasts.  

UK PubMed Central (United Kingdom)

A comparative radiorespirometric study of glucose metabolism in glucose-limited chemostat cultures of Saccharomyces cerevisiae, Candida utilis and Rhodosporidium toruloides was performed in an attempt to estimate the contribution of the hexose monophosphate (HMP) pathway to glucose metabolism. Radioactively labelled glucose was administered directly to the cultures in a constant substrate feed, without disturbance of the steady state. The 14CO2 yields from [1-14C]- and [6-14C]-glucose demonstrated that the HMP pathway activities for the three yeasts were very similar. Furthermore, a quantitative analysis of results indicated that the HMP pathway activities were close to the theoretical minimum needed to cover the NADPH requirement for biomass formation.

Bruinenberg PM; Waslander GW; van Dijken JP; Scheffers WA

1986-06-01

126

Contribution of brain glucose and ketone bodies to oxidative metabolism.  

Science.gov (United States)

Ketone bodies are an alternative energy substrate to glucose in brain. Under conditions of oxidative stress, we hypothesize that ketosis stabilizes glucose metabolism by partitioning glucose away from oxidative metabolism towards ketone body oxidation. In this study we assessed oxidative metabolism in ketotic rat brain using stable isotope mass spectrometry analysis. The contribution of glucose and ketone bodies to oxidative metabolism was studied in cortical brain homogenates isolated from anesthetized ketotic rats. To induce chronic ketosis, rats were fed either a ketogenic (high-fat, carbohydrate restricted) or standard rodent chow for 3 weeks and then infused intravenously with tracers of [U-(13)C] glucose or [U-(13)C] acetoacetate for 60 min. The measured percent contribution of glucose or ketone bodies to oxidative metabolism was analyzed by measuring the (13)C-label incorporation into acetyl-CoA. Using mass spectrometry (gas-chromatography; GC-MS, and liquid-chromatography; LCMS) and isotopomer analysis, the fractional amount of substrate oxidation was measured as the M + 2 enrichment (%) of acetyl-CoA relative to the achieved enrichment of the infused precursors, [U-(13)C]glucose or [U-(13)C] acetoacetate. Results: the percent contribution of glucose oxidation in cortical brain in rats fed the ketogenic diet was 71.2 ± 16.8 (mean% ± SD) compared to the standard chow, 89.0 ± 14.6. Acetoacetate oxidation was significantly higher with ketosis compared to standard chow, 41.7 ± 9.4 vs. 21.9 ± 10.6. These data confer the high oxidative capacity for glucose irrespective of ketotic or non-ketotic states. With ketosis induced by 3 weeks of diet, cortical brain utilizes twice as much acetoacetate compared to non-ketosis. PMID:22879057

Zhang, Yifan; Kuang, Youzhi; LaManna, Joseph C; Puchowicz, Michelle A

2013-01-01

127

Contribution of brain glucose and ketone bodies to oxidative metabolism.  

UK PubMed Central (United Kingdom)

Ketone bodies are an alternative energy substrate to glucose in brain. Under conditions of oxidative stress, we hypothesize that ketosis stabilizes glucose metabolism by partitioning glucose away from oxidative metabolism towards ketone body oxidation. In this study we assessed oxidative metabolism in ketotic rat brain using stable isotope mass spectrometry analysis. The contribution of glucose and ketone bodies to oxidative metabolism was studied in cortical brain homogenates isolated from anesthetized ketotic rats. To induce chronic ketosis, rats were fed either a ketogenic (high-fat, carbohydrate restricted) or standard rodent chow for 3 weeks and then infused intravenously with tracers of [U-(13)C] glucose or [U-(13)C] acetoacetate for 60 min. The measured percent contribution of glucose or ketone bodies to oxidative metabolism was analyzed by measuring the (13)C-label incorporation into acetyl-CoA. Using mass spectrometry (gas-chromatography; GC-MS, and liquid-chromatography; LCMS) and isotopomer analysis, the fractional amount of substrate oxidation was measured as the M + 2 enrichment (%) of acetyl-CoA relative to the achieved enrichment of the infused precursors, [U-(13)C]glucose or [U-(13)C] acetoacetate. Results: the percent contribution of glucose oxidation in cortical brain in rats fed the ketogenic diet was 71.2 ± 16.8 (mean% ± SD) compared to the standard chow, 89.0 ± 14.6. Acetoacetate oxidation was significantly higher with ketosis compared to standard chow, 41.7 ± 9.4 vs. 21.9 ± 10.6. These data confer the high oxidative capacity for glucose irrespective of ketotic or non-ketotic states. With ketosis induced by 3 weeks of diet, cortical brain utilizes twice as much acetoacetate compared to non-ketosis.

Zhang Y; Kuang Y; LaManna JC; Puchowicz MA

2013-01-01

128

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

International Nuclear Information System (INIS)

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

1989-01-01

129

A link between sleep loss, glucose metabolism and adipokines  

Scientific Electronic Library Online (English)

Full Text Available 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 literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems (more) 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

2011-10-01

130

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

2011-01-01

131

Metabolism of tritiated D-glucose in rat erythrocytes  

Energy Technology Data Exchange (ETDEWEB)

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.

Manuel y Keenoy, B.; Malaisse-Lagae, F.; Malaisse, W.J. (Laboratory of Experimental Medicine, Brussels Free University (Belgium))

1991-09-01

132

Metabolism of tritiated D-glucose in rat erythrocytes  

International Nuclear Information System (INIS)

[en] 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

133

Glucose metabolism during embryogenesis of the hard tick Boophilus microplus.  

Science.gov (United States)

Glucose metabolism plays an essential role in the physiology and development of almost all living organisms. In the present study we investigated glucose metabolism during the embryogenesis of the hard tick Boophilus microplus. An increase in glucose and glycogen content during the embryonic development of B. microplus was detected and shown to be due to the high enzyme activity of both gluconeogenesis and glycolytic pathways. Glucose 6-phosphate (G-6P), formed by hexokinase, is driven mainly to pentose-phosphate pathway, producing fundamental substrates for cellular biosynthesis. We detected an increase in glucose 6-phosphate dehydrogenase and pyruvate kinase activities after embryo cellularization. Accumulation of key metabolites such as glycogen and glucose was monitored and revealed that glycogen content decreases from day 1 up to day 6, as the early events of embryogenesis take place, and increases after the formation of embryo cellular blastoderm on day 6. Glucose and guanine (a sub-product of amino acids degradation in arachnids) accumulate almost concomitantly. The activity of phosphoenolpyruvate carboxykinase was increased after embryo cellularization. Taken together these data indicate that glycogen and glucose, formed during B. microplus embryogenesis after blastoderm formation, are produced by intense gluconeogenesis. PMID:16904922

Moraes, Jorge; Galina, Antônio; Alvarenga, Patrícia H; Rezende, Gustavo Lazzaro; Masuda, Aoi; da Silva Vaz, Itabajara; Logullo, Carlos

2006-05-23

134

Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism.  

UK PubMed Central (United Kingdom)

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.

Murai H; Suzuki Y; Kiyosawa M; Wakakura M; Mochizuki M; Ishiwata K; Ishii K

2011-01-01

135

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

2011-02-05

136

Does rimonabant independently affect free fatty acid and glucose metabolism?  

UK PubMed Central (United Kingdom)

CONTEXT: Endocannabinoid receptor 1 blockade is proposed to improve metabolic complications of obesity via central and peripheral effects. OBJECTIVE: Our objective was to test whether rimonabant improves insulin regulation of free fatty acid and glucose metabolism after controlling for fat loss. DESIGN: This was a double-blind, placebo-controlled substudy of the visceral fat reduction assessed by computed tomography scan on rimonabant (VICTORIA) trial. PARTICIPANTS AND SETTING: Sixty-seven abdominally obese, metabolic syndrome volunteers age 35-70 yr participated at academic medical center general clinical research centers. INTERVENTION: Intervention included a 12-month lifestyle weight management program plus rimonabant 20 mg/d or placebo. MAIN OUTCOME MEASURES: Body composition and two-step euglycemic, hyperinsulinemic clamp before and after intervention were performed. Insulin sensitivity was assessed as insulin concentration needed to suppress by 50% palmitate concentration [IC50(palmitate)], flux [IC50(palmitate)f], and hepatic glucose output [IC50(HGO)] and as insulin-stimulated glucose disposal (? glucose disappearance per ? insulin concentration--glucose slope). RESULTS: Body fat decreased by 4.5±2.9% (SD) in the rimonabant and 1.9±4.5% in the placebo group (P<0.005). The primary [improvement in IC50(palmitate) and IC50(palmitate)f] and secondary [improvement in IC50(HGO) and glucose slope] outcomes were not significantly different between the rimonabant and placebo groups. Post hoc analyses revealed that 1) changes in body mass index (BMI) and IC50(palmitate) were correlated (P=0.005) in the rimonabant group; this relationship was not significantly different from placebo when controlling for greater BMI loss (P=0.5); 2) insulin-regulated glucose disposal improved in both groups (P=0.002) and correlated with changes in BMI. CONCLUSIONS: Improvements observed in insulin regulation of free fatty acid and glucose metabolism with rimonabant treatment in humans was not greater than that predicted by weight loss alone.

Triay J; Mundi M; Klein S; Toledo FG; Smith SR; Abu-Lebdeh H; Jensen M

2012-03-01

137

Does Rimonabant Independently Affect Free Fatty Acid and Glucose Metabolism?  

Science.gov (United States)

Context: Endocannabinoid receptor 1 blockade is proposed to improve metabolic complications of obesity via central and peripheral effects. Objective: Our objective was to test whether rimonabant improves insulin regulation of free fatty acid and glucose metabolism after controlling for fat loss. Design: This was a double-blind, placebo-controlled substudy of the visceral fat reduction assessed by computed tomography scan on rimonabant (VICTORIA) trial. Participants and Setting: Sixty-seven abdominally obese, metabolic syndrome volunteers age 35–70 yr participated at academic medical center general clinical research centers. Intervention: Intervention included a 12-month lifestyle weight management program plus rimonabant 20 mg/d or placebo. Main Outcome Measures: Body composition and two-step euglycemic, hyperinsulinemic clamp before and after intervention were performed. Insulin sensitivity was assessed as insulin concentration needed to suppress by 50% palmitate concentration [IC50(palmitate)], flux [IC50(palmitatef], and hepatic glucose output [IC50(HGO)] and as insulin-stimulated glucose disposal (? glucose disappearance per ? insulin concentration ? glucose slope). Results: Body fat decreased by 4.5 ± 2.9% (SD) in the rimonabant and 1.9 ± 4.5% in the placebo group (P < 0.005). The primary [improvement in IC50(palmitate) and IC50(palmitate)f] and secondary [improvement in IC50(HGO) and glucose slope] outcomes were not significantly different between the rimonabant and placebo groups. Post hoc analyses revealed that 1) changes in body mass index (BMI) and IC50(palmitate) were correlated (P = 0.005) in the rimonabant group; this relationship was not significantly different from placebo when controlling for greater BMI loss (P = 0.5); 2) insulin-regulated glucose disposal improved in both groups (P = 0.002) and correlated with changes in BMI. Conclusions: Improvements observed in insulin regulation of free fatty acid and glucose metabolism with rimonabant treatment in humans was not greater than that predicted by weight loss alone.

Triay, Jessica; Mundi, Manpreet; Klein, Samuel; Toledo, Frederico G.; Smith, Steven R.; Abu-Lebdeh, Haitham

2012-01-01

138

Ghrelin function in insulin release and glucose metabolism.  

UK PubMed Central (United Kingdom)

Given its wide spectrum of biological activities such as growth hormone (GH) release, feeding stimulation, adiposity and cardiovascular actions, the discovery of ghrelin opened many new perspectives within neuroendocrine, metabolic and cardiovascular research, thus suggesting its possible clinical application. Circulating ghrelin is produced predominantly in the stomach, and its receptor GH secretagogue receptor (GHS-R) is expressed in a variety of central and peripheral tissues. Ghrelin, GHS-R and ghrelin O-acyltransferase (GOAT), the enzyme that promotes the acylation of the third serine residue of ghrelin, are all expressed in pancreatic islets, and this peptide is released into pancreatic microcirculations. Ghrelin inhibits insulin release in mice, rats and humans. The signal transduction mechanisms of ghrelin receptor in islet ?-cells are very unique, being distinct from those utilized for GH release. Pharmacological and genetic blockade of islet-derived ghrelin markedly augments glucose-induced insulin release in vitro. Ablation of ghrelin, GHS-R or GOAT enhances insulin release and prevents impaired glucose tolerance in high-fat, diet-induced and leptin-deficient obese models. Thus, manipulation of the insulinostatic function of the ghrelin-GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand. Ghrelin antagonism provides a novel strategy to treat type 2 diabetes with dysregulated insulin release.

Dezaki K

2013-01-01

139

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.

140

Glutamine and glucose metabolism in intraepithelial lymphocytes from pre- and post-weaning pigs.  

UK PubMed Central (United Kingdom)

The metabolism of glutamine (Gln) and glucose was studied in intraepithelial lymphocytes (IEL) from 21-, 29- and 56-day-old pigs. Pigs were weaned at 21 days of age. Cells were incubated at 37 degrees C in the presence of Krebs-Ringer bicarbonate buffer (pH 7.4) containing 1 mM [U-14C]glutamine plus 5 mM glucose, or 5 mM [U-14C]glucose plus 1 mM glutamine. Glucose was converted to lactate, pyruvate and CO2, which accounted for 81, 11 and 8% of measured glucose carbon, respectively. Glutamine was metabolized mainly to glutamate (92% of Gln C) and ammonia, and to a lesser extent, to aspartate (4% of Gln C) and CO2 (4% of Gln C). In the presence of both glucose and glutamine, glucose provided 2-3-fold more ATP to IELs than glutamine in 21-56-day-old pigs, on the basis of their measured end products. The rates of ammonia and glutamate production from glutamine in IELs from 29-day-old pigs were 112 and 90% greater than those in cells from 56-day-old pigs, respectively. The rates of glucose oxidation to CO2 in IELs from 29-day-old pigs were elevated 56 and 64% respectively, compared with 21- and 56-day-old pigs. Elevated rates of substrate metabolism in IELs from 29-day-old post-weaning pigs indicated a metabolic alteration of these cells possibly due to changes in diet and intestinal bacterial population.

Dugan ME; Knabe DA; Wu G

1994-12-01

 
 
 
 
141

EFFECTS OF GROWTH RATE AND LIMITING SUBSTRATE ON GLUCOSE METABOLISM IN ESCHERICHIA COLI.  

UK PubMed Central (United Kingdom)

Wright, D. N. (Iowa State University, Ames), and W. R. Lockhart. Effects of growth rate and limiting substrate on glucose metabolism in Escherichia coli. J. Bacteriol. 89:1082-1085. 1965.-Escherichia coli was grown in continuous culture at various rates in a defined medium with either glucose of (NH(4))(2)SO(4) as the rate-limiting substrate. Cellular content of polysaccharide ("glycogen") is greater in cells grown under nitrogen limitation with glucose available in excess, and is greater in rapidly grown than in slowly grown cells. The ability of cells to carry on endogenous respiration, as measured by tetrazolium reduction, can be correlated with their glycogen content. In carbon-limited cultures, the proportion of substrate glucose diverted to glycogen production is least for cells grown slowly, which may reflect greater energy requirements for cell maintenance in such cultures. The activity of glucose-6-phosphate dehydrogenase (indicating function of a C-1 preferential pathway for glucose degradation) is greater in rapidly grown cells, confirming earlier observations in batch cultures. Activity of this enzyme is also greater in nitrogen-limited than in carbon-limited cells, suggesting that there may be catabolic repression of the Embden-Meyerhoff pathway when glucose is available in excess.

WRIGHT DN; LOCKHART WR

1965-04-01

142

A distinct metabolic signature predicts development of fasting plasma glucose  

Directory of Open Access Journals (Sweden)

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

Hische Manuela; Larhlimi Abdelhalim; Schwarz Franziska; Fischer-Rosinský Antje; Bobbert Thomas; Assmann Anke; Catchpole Gareth S; Pfeiffer Andreas FH; Willmitzer Lothar; Selbig Joachim; Spranger Joachim

2012-01-01

143

Snail modulates cell metabolism in MDCK cells.  

UK PubMed Central (United Kingdom)

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.

Haraguchi M; Indo HP; Iwasaki Y; Iwashita Y; Fukushige T; Majima HJ; Izumo K; Horiuchi M; Kanekura T; Furukawa T; Ozawa M

2013-03-01

144

Tff3, as a Novel Peptide, Regulates Hepatic Glucose Metabolism  

Science.gov (United States)

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder strongly associated with hepatic glucose intolerance and insulin resistance. The trefoil peptides are a family of small regulatory proteins and Tff3 is widely expressed in multiple tissues including liver. But the roles of Tff3 in regulation of glucose metabolism and insulin sensitivity in liver remain unclear. Here we show that the hepatic Tff3 expression levels were decreased in ob/ob and high-fat diet-induced obese mice. Overexpression of Tff3 in primary mouse hepatocytes inhibited the expression of gluconeogenic genes, including G6pc, PEPCK and PGC-1?, subsequently decreasing cellular glucose output. GTT and ITT experiments revealed that adenovirus-mediated overexpression of Tff3 in diabetic or obese mice improved glucose tolerance and insulin sensitivity. Collectively, our results indicated that Tff3 peptides are involved in glucose homeostasis and insulin sensitivity, providing a promising peptide on new therapies against the metabolic disorders associated with T2DM.

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

2013-01-01

145

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1989-12-01

146

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

International Nuclear Information System (INIS)

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

1989-01-01

147

Disorders of glucose metabolism among HIV-infected women.  

UK PubMed Central (United Kingdom)

BACKGROUND: Abnormal glucose metabolism in HIV-infected patients has largely been attributed to the use of protease inhibitors. However, most studies of glucose metabolism in HIV-infected patients have focused on men or have lacked appropriate control groups. METHODS: We assessed the factors associated with previously diagnosed diabetes among 620 middle-aged women with or at risk for HIV infection. For a subset of 221 women without previously diagnosed diabetes, we performed an oral glucose tolerance test (OGTT) to measure glucose and insulin levels, and we assessed factors associated with abnormal glucose tolerance, insulin resistance, and insulin secretion. RESULTS: Thirteen percent of the women in the present study had previously diagnosed diabetes. Among women without previously diagnosed diabetes who underwent an OGTT, 6% had previously undiagnosed diabetes, and 12% had impaired glucose tolerance (IGT). According to multivariate analysis, factors that were associated with previously diagnosed diabetes included current methadone treatment, body mass index of > or =25, family history of diabetes, and physical inactivity. Factors that were independently associated with an abnormal result of an OGTT (i.e., a result consistent with IGT or diabetes) included age > or =50 years, family history of diabetes, physical inactivity, and a high number of pack-years of smoking. Factors independently associated with insulin resistance included waist circumference, Hispanic ethnicity, physical inactivity, and, among HIV-infected women, use of HAART that did not include protease inhibitors. Factors associated with lower levels of insulin secretion included current opiate use (i.e., methadone or heroin) and older age. CONCLUSIONS: Abnormal glucose metabolism is highly prevalent among middle-aged women with or at risk for HIV infection, particularly women who use opiates. Screening for diabetes in the HIV primary care setting should occur for women who have classic risk factors for diabetes, rather than solely for women who are taking PIs. Interventions that target modifiable risk factors, including obesity and physical inactivity, are also warranted.

Howard AA; Floris-Moore M; Arnsten JH; Santoro N; Fleischer N; Lo Y; Schoenbaum EE

2005-05-01

148

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

UK PubMed Central (United Kingdom)

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.

de Boer IH; Sachs M; Hoofnagle AN; Utzschneider KM; Kahn SE; Kestenbaum B; Himmelfarb J

2013-02-01

149

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

2012-08-22

150

UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets  

DEFF Research Database (Denmark)

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

Dalgaard, Louise Torp

2012-01-01

151

The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism.  

UK PubMed Central (United Kingdom)

Immune cells are somewhat unique in that activation responses can alter quantitative phenotypes upwards of 100,000-fold. To date little is known about the metabolic adaptations necessary to mount such dramatic phenotypic shifts. Screening for novel regulators of macrophage activation, we found nonprotein kinases of glucose metabolism among the most enriched classes of candidate immune modulators. We find that one of these, the carbohydrate kinase-like protein CARKL, is rapidly downregulated in vitro and in vivo upon LPS stimulation in both mice and humans. Interestingly, CARKL catalyzes an orphan reaction in the pentose phosphate pathway, refocusing cellular metabolism to a high-redox state upon physiological or artificial downregulation. We find that CARKL-dependent metabolic reprogramming is required for proper M1- and M2-like macrophage polarization and uncover a rate-limiting requirement for appropriate glucose flux in macrophage polarization.

Haschemi A; Kosma P; Gille L; Evans CR; Burant CF; Starkl P; Knapp B; Haas R; Schmid JA; Jandl C; Amir S; Lubec G; Park J; Esterbauer H; Bilban M; Brizuela L; Pospisilik JA; Otterbein LE; Wagner O

2012-06-01

152

The Sedoheptulose Kinase CARKL Directs Macrophage Polarization through Control of Glucose Metabolism  

Science.gov (United States)

Summary Immune cells are somewhat unique in that activation responses can alter quantitative phenotypes upwards of 100,000-fold. To date little is known about the metabolic adaptations necessary to mount such dramatic phenotypic shifts. Screening for novel regulators of macrophage activation, we found nonprotein kinases of glucose metabolism among the most enriched classes of candidate immune modulators. We find that one of these, the carbohydrate kinase-like protein CARKL, is rapidly downregulated in vitro and in vivo upon LPS stimulation in both mice and humans. Interestingly, CARKL catalyzes an orphan reaction in the pentose phosphate pathway, refocusing cellular metabolism to a high-redox state upon physiological or artificial downregulation. We find that CARKL-dependent metabolic reprogramming is required for proper M1- and M2-like macrophage polarization and uncover a rate-limiting requirement for appropriate glucose flux in macrophage polarization.

Haschemi, Arvand; Kosma, Paul; Gille, Lars; Evans, Charles R.; Burant, Charles F.; Starkl, Philipp; Knapp, Bernhard; Haas, Robert; Schmid, Johannes A.; Jandl, Christoph; Amir, Shahzada; Lubec, Gert; Park, Jaehong; Esterbauer, Harald; Bilban, Martin; Brizuela, Leonardo; Pospisilik, J. Andrew; Otterbein, Leo E.; Wagner, Oswald

2012-01-01

153

Measurement of glucose and lipid metabolism in avian liver explants.  

Science.gov (United States)

1. A mechanical tissue chopper was used to obtain 35-75 mg explants from 21- to 28-day-old chick liver to determine assay conditions (substrates, buffers, time), regulators (metals and hormones) and points of endogenous regulation of de novo lipogenesis (ATPase, reductive potential and protein phosphorylation). High- and low-bicarbonate-based buffers (Earl's balance salts, EBSS and Hanks' balanced salts, HBSS; respectively) were used in conjunction with sources and types of bovine serum albumin (BSA), divalent cations (Mg2+ or Ca2+), substrate (glucose or acetate) and hormones (insulin and catecholamines). 2. Neither EBSS nor HBSS changed in vitro lipogenesis, CO2 or glucose production when 20 mM HEPES was added to these salts. 3. Neither the presence nor the source of BSA (Sigma or Armour) affected metabolism. In contrast, reducing the vessel reaction surface area (5.1 vs 10.5 cm2) decreased metabolic rates. 4. Acetate was more readily utilized than glucose as an in vitro fatty acid precursor. Use of glucose was complicated by production of glucose from endogenous precursors and by label recycling. Divalent cations (Mg2+ or Ca2+) had little affect upon lipogenesis. 5. Chicken insulin (50 ng/ml) did not affect lipogenesis; however, incorporation of acetate into fatty acids was decreased by dibutyryl cyclic AMP. A catecholamine-induced decrease in vitro lipogenesis indicates that major points of regulation are under control of phosphorylation-dephosphorylation steps. PMID:3427927

Rosebrough, R W; Steele, N C

1987-01-01

154

Measurement of glucose and lipid metabolism in avian liver explants.  

UK PubMed Central (United Kingdom)

1. A mechanical tissue chopper was used to obtain 35-75 mg explants from 21- to 28-day-old chick liver to determine assay conditions (substrates, buffers, time), regulators (metals and hormones) and points of endogenous regulation of de novo lipogenesis (ATPase, reductive potential and protein phosphorylation). High- and low-bicarbonate-based buffers (Earl's balance salts, EBSS and Hanks' balanced salts, HBSS; respectively) were used in conjunction with sources and types of bovine serum albumin (BSA), divalent cations (Mg2+ or Ca2+), substrate (glucose or acetate) and hormones (insulin and catecholamines). 2. Neither EBSS nor HBSS changed in vitro lipogenesis, CO2 or glucose production when 20 mM HEPES was added to these salts. 3. Neither the presence nor the source of BSA (Sigma or Armour) affected metabolism. In contrast, reducing the vessel reaction surface area (5.1 vs 10.5 cm2) decreased metabolic rates. 4. Acetate was more readily utilized than glucose as an in vitro fatty acid precursor. Use of glucose was complicated by production of glucose from endogenous precursors and by label recycling. Divalent cations (Mg2+ or Ca2+) had little affect upon lipogenesis. 5. Chicken insulin (50 ng/ml) did not affect lipogenesis; however, incorporation of acetate into fatty acids was decreased by dibutyryl cyclic AMP. A catecholamine-induced decrease in vitro lipogenesis indicates that major points of regulation are under control of phosphorylation-dephosphorylation steps.

Rosebrough RW; Steele NC

1987-01-01

155

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

UK PubMed Central (United Kingdom)

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 phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (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.

Shoji I; Deng L; Hotta H

2011-01-01

156

Linking neuronal brain activity to the glucose metabolism.  

UK PubMed Central (United Kingdom)

BACKGROUND: Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. METHODS: First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. RESULTS: Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. CONCLUSIONS: The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

Göbel B; Oltmanns KM; Chung M

2013-08-01

157

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

158

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

159

PHGDH amplification and altered glucose metabolism in human melanoma.  

Science.gov (United States)

The metabolic requirements of cancer cells differ from that of their normal counterparts. To support their proliferation, cancer cells switch to a fermentative metabolism that is thought to support biomass production. Instances where metabolic enzymes promote tumorigenesis remain rare. However, an enzyme involved in the de novo synthesis of serine, 3-phosphoglycerate dehydrogenase (PHGDH), was recently identified as a putative oncogene. The potential mechanisms by which PHGDH promotes cancer are discussed. PMID:21981974

Mullarky, Edouard; Mattaini, Katherine R; Vander Heiden, Matthew G; Cantley, Lewis C; Locasale, Jason W

2011-10-28

160

PHGDH amplification and altered glucose metabolism in human melanoma.  

UK PubMed Central (United Kingdom)

The metabolic requirements of cancer cells differ from that of their normal counterparts. To support their proliferation, cancer cells switch to a fermentative metabolism that is thought to support biomass production. Instances where metabolic enzymes promote tumorigenesis remain rare. However, an enzyme involved in the de novo synthesis of serine, 3-phosphoglycerate dehydrogenase (PHGDH), was recently identified as a putative oncogene. The potential mechanisms by which PHGDH promotes cancer are discussed.

Mullarky E; Mattaini KR; Vander Heiden MG; Cantley LC; Locasale JW

2011-12-01

 
 
 
 
161

Glucose metabolism during the early "flow phase" after burn injury.  

UK PubMed Central (United Kingdom)

BACKGROUND: Burn injury (BI) is associated with insulin resistance (IR) and hyperglycemia which complicate clinical management. We investigated the impact of BI on glucose metabolism in a rabbit model of BI using a combination of positron emission tomography (PET) and stable isotope studies under euglycemic insulin clamp (EIC) conditions. MATERIALS AND METHODS: Twelve male rabbits were subjected to either full-thickness BI (B) or sham burn. An EIC condition was established by constant infusion of insulin, concomitantly with a variable rate of dextrose infusion 3 d after treatment. PET imaging of the hind limbs was conducted to determine the rates of peripheral O(2) and glucose utilization. Each animal also received a primed constant infusion of [6,6-(2)H(2)] glucose to determine endogenous glucose production. RESULTS: The fasting blood glucose in the burned rabbits was higher than that in the sham group. Under EIC conditions, the sham burn group required more exogenous dextrose than the B group to maintain blood glucose at physiological levels (22.2 ± 2.6 versus 13.3 ± 2.9 mg/min, P < 0.05), indicating a state of IR. PET imaging demonstrated that the rates of O(2) consumption and (18)F 2-fluoro-2-deoxy-D-glucose utilization by skeletal muscle remained at similar levels in both groups. Hepatic gluconeogenesis determined by the stable isotope tracer study was found significantly increased in the B group. CONCLUSIONS: These findings demonstrated that hyperglycemia and IR develop during the early "flow phase" after BI. Unsuppressed hepatic gluconeogenesis, but not peripheral skeletal muscular utilization of glucose, contributes to hyperglycemia at this stage.

Xu H; Yu YM; Ma H; Carter EA; Fagan S; Tompkins RG; Fischman AJ

2013-01-01

162

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

163

[The role of glucose transporters in human metabolic regulation].  

UK PubMed Central (United Kingdom)

Glucose is one of the most important sources of energy in human metabolizm. Cells absorb it by active transport (with SGLT transporters) or by facilitated diffusion (with GLUT transporters). GLUT family consists of 14 proteins grouped in 3 subclasses based on similarities in their architecture. They differ from one another in affinity to glucose, tissue distribution and type of signals that cause their translocaton to the cell membrane what results in different levels of sugar transport into the tissues. SGLT proteins cotransport glucose with Na+ ions. Energy required to this transport is acquired from gradient of Na+ ions that is maintained by Na+/K(+)-ATPase. SGLT family consists of 12 proteins which include sugar cotransporters of anions, vitamins and short-chain fatty acids. Some of them also have a function of glucose sensors as well as water and urea channels.

Magier Z; Jarzyna R

2013-01-01

164

Glucose metabolism in rats submitted to skeletal muscle denervation  

Directory of Open Access Journals (Sweden)

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

Wilton Marlindo Santana Nunes; Maria Alice Rostom de Mello

2005-01-01

165

Metabolic glucose status and pituitary pathology portend therapeutic outcomes in acromegaly.  

UK PubMed Central (United Kingdom)

INTRODUCTION: Acromegaly is frequently associated with impaired glucose tolerance and/or diabetes. To evaluate the relationship between glucose metabolism and acromegaly disease, we evaluated 269 consecutive patients from two referral centres. METHODS: Clinical presentation, pituitary tumor size and invasiveness, and pituitary pathology were captured in a dedicated database. RESULTS: 131 women and 138 men with a mean age of 53.8 years were included. Of these, 201 (74.7%) presented with a macroadenoma and 18 (6.7%) with a microadenoma. Radiographic invasion was present in 91 cases (33.8%). Mean tumor diameter was 1.86 cm (0.2-4.6). Pituitary histopathologic findings revealed pure GH-producing somatotroph adenomas (SA) in 147 patients, prolactin-production by mixed lactotroph (LA) and SA or mammosomatotroph adenoma (MSA) in 46 [22.4%], acidophil stem cell adenoma in 6 [2.9%], and other diagnoses in 6 [2.9%]. Medical treatment included octreotide in 96 [36.9%] and in combination with pegvisomant or dopamine agonists in 63 [24.2%]. Nearly 80% of patients achieved IGF-1 normalization. Importantly, patients with pure somatotroph adenomas were significantly more likely to present with abnormal glucose metabolism [48.7%] than those with mixed adenomas [9.7%] [p<0.001] independent of GH/IGF-1 levels or tumor invasiveness. Abnormal glucose metabolism and pituitary pathology also remained linked following IGF-1 normalization. Moreover patients with pure SA and abnormal glucose metabolism were significantly (p<0.001) less likely to achieve disease remission despite the same therapeutic strategies. Conversely, patients with mixed adenomas were more likely (OR: 2.766 (95% CI: 1.490-5.136) to achieve disease remission. CONCLUSIONS: Patients with pure somatotroph adenomas are more likely than those with mixed adenomas to exhibit abnormal glucose metabolism.

Cheng S; Al-Agha R; Araujo PB; Serri O; L Asa S; Ezzat S

2013-01-01

166

The Lin28/let-7 axis regulates glucose metabolism.  

UK PubMed Central (United Kingdom)

The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promote an insulin-sensitized state that resists high-fat-diet induced diabetes. Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in insulin resistance and impaired glucose tolerance. These phenomena occur, in part, through the let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. In addition, the mTOR inhibitor, rapamycin, abrogates Lin28a-mediated insulin sensitivity and enhanced glucose uptake. Moreover, let-7 targets are enriched for genes containing SNPs associated with type 2 diabetes and control of fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism.

Zhu H; Shyh-Chang N; Segrè AV; Shinoda G; Shah SP; Einhorn WS; Takeuchi A; Engreitz JM; Hagan JP; Kharas MG; Urbach A; Thornton JE; Triboulet R; Gregory RI; Altshuler D; Daley GQ

2011-09-01

167

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

Science.gov (United States)

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

Nehlig, Astrid; Coles, Jonathan A

2007-09-01

168

Energetic aspects of glucose metabolism in a pyruvate-dehydrogenase-negative mutant of Saccharomyces cerevisiae.  

Science.gov (United States)

Saccharomyces cerevisiae T23C (pda1::Tn5ble) is an isogenic gene replacement mutant of the wild-type strain S. cerevisiae T23D. The mutation causes a complete loss of pyruvate dehydrogenase activity. Pyruvate metabolism in this pyruvate-dehydrogenase-negative (Pdh-) strain was investigated in aerobic glucose-limited chemostat cultures, grown at a dilution rate of 0.10 h-1, and compared with the metabolism in the isogenic wild-type strain. Under these conditions, growth of the Pdh- strain was fully respiratory. Enzyme activities in cell-free extracts indicated that the enzymes pyruvate decarboxylase, acetaldehyde dehydrogenase and acetyl-coenzyme A (acetyl-CoA) synthetase could provide a functional bypass of the pyruvate dehydrogenase complex. Since this metabolic sequence involves ATP hydrolysis in the acetyl-CoA synthetase reaction, a negative effect of the pda1::Tn5ble mutation on the growth efficiency was anticipated. Indeed, the biomass yield of the Pdh- strain [0.44 g biomass (g glucose)-1] was significantly lower than that of wild-type S. cerevisiae [0.52 g biomass (g glucose)-1]. The effect of the mutation on biomass yield could be quantitatively explained in terms of a lower ATP yield from glucose catabolism and an increased ATP requirement for the synthesis of acetyl-CoA used in anabolism. Control experiments showed that the pda1::Tn5ble mutation did not affect biomass yield in ethanol-limited chemostat cultures. The results support the view that, during aerobic glucose-limited growth of S. cerevisiae at low growth rates, the pyruvate dehydrogenase complex accounts for the major part of the pyruvate flux. Moreover, it is concluded that hydrolysis of pyrophosphate formed in the acetyl-CoA synthetase reaction does not contribute significantly to energy transduction in this yeast. Respiratory-deficient cells did not contribute to glucose metabolism in the chemostat cultures and were probably formed upon plating. PMID:8012582

Pronk, J T; Wenzel, T J; Luttik, M A; Klaassen, C C; Scheffers, W A; Steensma, H Y; van Dijken, J P

1994-03-01

169

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

170

Metabolic flux rewiring in mammalian cell cultures.  

UK PubMed Central (United Kingdom)

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

Young JD

2013-05-01

171

[A new flavanol glycoside from Phymatopteris hastata with effect on glucose metabolism].  

UK PubMed Central (United Kingdom)

By repeated column chromatography, including silica gel, macroporous resin, and preparative HPLC, a new compound (1) was isolated and purified. On the basis of spectroscopic methods, the structure of 1 was elucidated as ( - ) -epiafzelechin-3, 5-di-O-beta-D-apiofuranoside (1). In the bioassay screening experiments, glucose consumption assays in IR HepG2 cells and colorimetric assay of surface GLUT4myc translocation were used to assess the effects on glucose metabolism of compound 1. Both compound 1 and its derivatives--naringin could improve glucose consumption in IR HepG2 cells and enhance GLUT4 translocation in skeletal muscle cell L6myc in a dose-dependent manner, indicating that these two compouds showed potential anti-diabetic activities in vitro.

Ma SN; Duan SL; Jin MN; Duan HQ

2013-03-01

172

Anterior cingulate gyrus volume and glucose metabolism in autistic disorder.  

UK PubMed Central (United Kingdom)

OBJECTIVE: This study reports the first paired measurements of glucose metabolism and volume of the anterior cingulate gyrus in autism. METHOD: Magnetic resonance imaging (MRI) and positron emission tomography (PET) scans of seven high-functioning autistic patients and seven sex- and age-matched normal volunteers were coregistered. After the anterior cingulate gyri were outlined on the MRI images, the volumes of the structures were measured and corrected for brain volume. The volumes were then applied to the PET images and metabolic maps were obtained. RESULTS: Right anterior cingulate area 24' was significantly smaller in relative volume, and both area 24 and area 24' were metabolically less active, in the autistic patients than in the normal subjects. CONCLUSIONS: Autism may be characterized by structural and functional alterations in the anterior cingulate gyrus.

Haznedar MM; Buchsbaum MS; Metzger M; Solimando A; Spiegel-Cohen J; Hollander E

1997-08-01

173

Metabolic pathway alterations that support cell proliferation.  

Science.gov (United States)

Proliferating cells adapt metabolism to support the conversion of available nutrients into biomass. How cell metabolism is regulated to balance the production of ATP, metabolite building blocks, and reducing equivalents remains uncertain. Proliferative metabolism often involves an increased rate of glycolysis. A key regulated step in glycolysis is catalyzed by pyruvate kinase to convert phosphoenolpyruvate (PEP) to pyruvate. Surprisingly, there is strong selection for expression of the less active M2 isoform of pyruvate kinase (PKM2) in tumors and other proliferative tissues. Cell growth signals further decrease PKM2 activity, and cells with less active PKM2 use another pathway with separate regulatory properties to convert PEP to pyruvate. One consequence of using this alternative pathway is an accumulation of 3-phosphoglycerate (3PG) that leads to the diversion of 3PG into the serine biosynthesis pathway. In fact, in some cancers a substantial portion of the total glucose flux is directed toward serine synthesis, and genetic evidence suggests that glucose flux into this pathway can promote cell transformation. Environmental conditions can also influence the pathways that cells use to generate biomass with the source of carbon for lipid synthesis changing based on oxygen availability. Together, these findings argue that distinct metabolic phenotypes exist among proliferating cells, and both genetic and environmental factors influence how metabolism is regulated to support cell growth. PMID:22262476

Vander Heiden, M G; Lunt, S Y; Dayton, T L; Fiske, B P; Israelsen, W J; Mattaini, K R; Vokes, N I; Stephanopoulos, G; Cantley, L C; Metallo, C M; Locasale, J W

2012-01-19

174

Metabolic pathway alterations that support cell proliferation.  

UK PubMed Central (United Kingdom)

Proliferating cells adapt metabolism to support the conversion of available nutrients into biomass. How cell metabolism is regulated to balance the production of ATP, metabolite building blocks, and reducing equivalents remains uncertain. Proliferative metabolism often involves an increased rate of glycolysis. A key regulated step in glycolysis is catalyzed by pyruvate kinase to convert phosphoenolpyruvate (PEP) to pyruvate. Surprisingly, there is strong selection for expression of the less active M2 isoform of pyruvate kinase (PKM2) in tumors and other proliferative tissues. Cell growth signals further decrease PKM2 activity, and cells with less active PKM2 use another pathway with separate regulatory properties to convert PEP to pyruvate. One consequence of using this alternative pathway is an accumulation of 3-phosphoglycerate (3PG) that leads to the diversion of 3PG into the serine biosynthesis pathway. In fact, in some cancers a substantial portion of the total glucose flux is directed toward serine synthesis, and genetic evidence suggests that glucose flux into this pathway can promote cell transformation. Environmental conditions can also influence the pathways that cells use to generate biomass with the source of carbon for lipid synthesis changing based on oxygen availability. Together, these findings argue that distinct metabolic phenotypes exist among proliferating cells, and both genetic and environmental factors influence how metabolism is regulated to support cell growth.

Vander Heiden MG; Lunt SY; Dayton TL; Fiske BP; Israelsen WJ; Mattaini KR; Vokes NI; Stephanopoulos G; Cantley LC; Metallo CM; Locasale JW

2011-01-01

175

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).

1992-01-01

176

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

DEFF Research Database (Denmark)

Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways. As the proliferative potential of myoblasts decreased dramatically with passage number, a number of cellular functions were altered: the capacity of myoblasts to fuse and differentiate into myotubes was reduced, and metabolic processes in myotubes such as glucose uptake, glycogen synthesis, glucose oxidation and fatty acid ?-oxidation became gradually impaired. Upon insulin stimulation, glucose uptake and glycogen synthesis increased but as the cellular proliferative capacity became gradually exhausted, the response dropped concomitantly. Palmitic acid incorporation into lipids in myotubes decreased with passage number and could be explained by reduced incorporation into diacyl- and triacylglycerols. The levels of long-chain acyl-CoA esters decreased with increased passage number. Late-passage, non-proliferating, myoblast cultures showed strong senescence-associated ?-galactosidase activity indicating that the observed metabolic defects accompany the induction of a senescent state. The main function of SCs is regeneration and skeletal muscle-build up. Thus, the metabolic defects observed during aging of SC-derived myotubes could have a role in sarcopenia, the gradual age-related loss of muscle mass and strength.

Nehlin, Jan O; Just, Marlene

2011-01-01

177

Association of traits of metabolic syndrome with glucose abnormalities.  

Science.gov (United States)

The association of glucose abnormalities (GAs) with the early appearance of traits of the metabolic syndrome (MS) was studied in an unselected sample of apparently healthy Urban Hispanics. GAs were defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and newly diagnosed diabetes mellitus (DM). Overall, GAs were associated with older age, abdominal obesity, low high-density lipoprotein cholesterol levels, hypertriglyceridemia, hyperinsulinemia, hypertension, and MS. Prevalence of MS defined as per NCPE-ATPIII was the greatest in subjects with DM (54.3%) and with combined abnormalities (IFG + IGT) (54.1%; P > 0.5). Similar prevalence of MS was found in subjects with isolated IFG (34.3%) and isolated IGT (36.8%) but higher than in normal fasting-glucose tolerant individuals (23.3%) (P type 2 DM had not only an increased prevalence of MS, but also the MS was characterized by the presence of more than 3 traits, and by a greater severity of each of the coexisting traits. PMID:23591026

Hoffmann, Irene S; Cubeddu, Luigi X

178

Zinc deficiency aggravates abnormal glucose metabolism in thalassemia major patients.  

UK PubMed Central (United Kingdom)

BACKGROUND: The aim was to determine whether reduced serum zinc level has a contributory effect on impairment of insulin secretion in beta-thalassemic patients with transfusion-induced iron overload. MATERIAL/METHODS: Seventy thalassemia patients who received deferoxamine chelation therapy and 69 healthy individuals as the control group were evaluated. A standard oral glucose tolerance test (OGTT) was performed and blood samples for measurement of serum ferritin, zinc, and insulin concentrations were obtained. RESULTS: Although the fasting serum insulin concentrations were quite similar between the patient and the control groups, serum insulin levels were significantly lower in the thalassemia patients one hour and two hours after oral glucose load ingestion compared with the healthy controls. Among the thalassemic adults, zinc deficiency (present in 37% of patients) resulted in significantly lower fasting and 1-hour post-OGTT serum insulin concentrations. The serum zinc level in patients with impaired OGTT was also considerably lower than in patients with normal OGTT. CONCLUSIONS: These data support the assumption that zinc deficiency might lead to an exacerbation of the inability of the pancreas to secrete sufficient amounts of insulin in response to glucose stimulation in beta-thalassemia patients. We suggest that serum zinc levels be routinely monitored in these patients as it might provide useful complementaly information regarding glucose metabolism.

Dehshal MH; Hooghooghi AH; Kebryaeezadeh A; Kheirabadi M; Kazemi S; Nasseh A; Shariftabrizi A; Pasalar P

2007-05-01

179

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

180

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

UK PubMed Central (United Kingdom)

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.

Rathmell JC; Fox CJ; Plas DR; Hammerman PS; Cinalli RM; Thompson CB

2003-10-01

 
 
 
 
181

Glucose transporters are expressed in taste receptor cells.  

Science.gov (United States)

In the intestine, changes of sugar concentration generated in the lumen during digestion induce adaptive responses of glucose transporters in the epithelium. A close matching between the intestinal expression of glucose transporters and the composition and amount of the diet has been provided by several experiments. Functional evidence has demonstrated that the regulation of glucose transporters into enterocytes is induced by the sensing of sugar of the enteroendocrine cells through activation of sweet taste receptors (T1R2 and T1R3) and their associated elements of G-protein-linked signaling pathways (e.g. ?-gustducin, phospholipase C ? type 2 and transient receptor potential channel M5), which are signaling molecules also involved in the perception of sweet substances in the taste receptor cells (TRCs) of the tongue. Considering this phenotypical similarity between the intestinal cells and TRCs, we evaluated whether the TRCs themselves possess proteins of the glucose transport mechanism. Therefore, we investigated the expression of the typical intestinal glucose transporters (i.e. GLUT2, GLUT5 and SGLT1) in rat circumvallate papillae, using immunohistochemistry, double-labeling immunofluorescence, immunoelectron microscopy and reverse transcriptase-polymerase chain reaction analysis. The results showed that GLUT2, GLUT5 and SGLT1 are expressed in TRCs; their immunoreactivity was also observed in cells that displayed staining for ?-gustducin and T1R3 receptor. The immunoelectron microscopic results confirmed that GLUT2, GLUT5 and SGLT1 were predominantly expressed in cells with ultrastructural characteristics of chemoreceptor cells. The presence of glucose transporters in TRCs adds a further link between chemosensory information and cellular responses to sweet stimuli that may have important roles in glucose homeostasis, contributing to a better understanding of the pathways implicated in glucose metabolism. PMID:21592100

Merigo, Flavia; Benati, Donatella; Cristofoletti, Mirko; Osculati, Francesco; Sbarbati, Andrea

2011-05-17

182

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

183

Regional cerebral glucose metabolism in frontotemporal lobar degeneration  

International Nuclear Information System (INIS)

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

2002-10-02

184

Glucose metabolism disorders in cancer patients in a Chinese population.  

UK PubMed Central (United Kingdom)

BACKGROUND: Characteristics of glucose metabolism disorders (GMDs) in different cancers and the contributory role of GMDs in developing cancers are still not so clear. METHODS: Two thousand four hundred and five patients with malignancy who had been hospitalized in the First Affiliated Hospital of Jinan University were pooled as case group. Two thousand and sixteen non-cancer people who finished health examinations in the Affiliated Yangcheng Hospital of Guangzhou Medical College were enrolled as control group. We compared glucose metabolism among patients with different kinds of malignancy. Based on logistic regression models, we analyzed factors that affect the development of carcinoma. RESULTS: (1) Among 2,408 malignancy patients, the total prevalence of diabetes mellitus (DM) and impaired fasting glucose (IFG) reached 28.0%. Pancreatic cancer, lymphoma, liver cancer, leukemia, and colorectal cancer showed most striking hyperglycemia. (2) Leukemia and esophageal cancer accounting for 12.5% and 12.1%, respectively, were the most likely to suffer from hypoglycemia. (3) Older cancer patients seem to be more vulnerable to hyperglycemia, while the younger tend to be more likely to develop hypoglycemia. (4) High level of fasting plasma glucose (FPG) was associated with lung cancer, breast cancer, leukemia, lymphoma, thyroid cancer, bladder cancer, and pancreatic cancer. Patients with DM increased risks for developing colorectal cancer, liver cancer, esophageal cancer, thyroid cancer, cervical cancer, and pancreatic cancer. CONCLUSIONS: GMDs are frequent events in malignancy patients. Hyperglycemia and hypoglycemia are found in the same kinds or different kinds of cancers, and the incidence of hyperglycemia is higher than that of hypoglycemia. Characteristics of GMDs were dissimilar in different cancers and different ages. Hyperglycemia was a risk factor for many cancers.

Zhan YS; Feng L; Tang SH; Li WG; Xu M; Liu TF; Zhou YF; Ma YL; Zhang Y; Pu XM

2010-06-01

185

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

UK PubMed Central (United Kingdom)

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.

Wu J; Du G; Zhou J; Chen J

2013-03-01

186

Posterior cingulate glucose metabolism, hippocampal glucose metabolism, and hippocampal volume in cognitively normal, late-middle-aged persons at 3 levels of genetic risk for Alzheimer disease.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ?4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease. DESIGN: Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxyglucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ?4 homozygotes, ?4 heterozygotes, and noncarriers. SETTING: Academic medical center. PARTICIPANTS: A total of 31 ?4 homozygotes, 42 ?4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. MAIN OUTCOME MEASURES: The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume. RESULTS: Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P = .60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P = .001). The APOE ?4 gene dose was significantly associated with posterior cingulate glucose metabolism (r = 0.29, P = .0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P < .05, determined by use of pairwise Fisher z tests). CONCLUSIONS: Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for Alzheimer disease.

Protas HD; Chen K; Langbaum JB; Fleisher AS; Alexander GE; Lee W; Bandy D; de Leon MJ; Mosconi L; Buckley S; Truran-Sacrey D; Schuff N; Weiner MW; Caselli RJ; Reiman EM

2013-03-01

187

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

UK PubMed Central (United Kingdom)

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

Jacobsen SH; Bojsen-Møller KN; Dirksen C; Jørgensen NB; Clausen TR; Wulff BS; Kristiansen VB; Worm D; Hansen DL; Holst JJ; van Hall G; Madsbad S

2013-10-01

188

Carbon balance studies of glucose metabolism in rat cerebral cortical synaptosomes  

Energy Technology Data Exchange (ETDEWEB)

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

Bauer, U.; Brand, K.

1982-07-01

189

[Effect of smoking on diabetes mellitus and dyslipidemia (effect of smoking on glucose and lipid metabolism)].  

UK PubMed Central (United Kingdom)

Smoking is one of the important risk factors of cardiovascular disease. Its effects on arteriosclerotic diseases act not only directly but indirectly, by worsening control of blood pressure, lipid metabolism and glucose metabolism. And in patients with diabetes, it affects both macroangiopathy and diabetic microangiopathy(especially diabetic nephronpathy) adversely. Unfortunately, all effects and mechanisms of smoking on metabolic diseases are not yet unclear. But smoking cessation improves lipid metabolism and may improve glucose metabolism and may decrease risk of impaired glucose tolerance, type 2 diabetes, and diabetic microangiopathy. All patients with metabolic diseases must quit smoking for control of diseases and prevention of arteriosclerotic disease as soon as possible.

Saito K; Sone H

2013-03-01

190

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

Energy Technology Data Exchange (ETDEWEB)

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 {sup 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.).

Meguro, K. (Tohoku Univ. School of Medicine (Japan). Dept. of Geriatric Medicine Miyama Hospital (Japan)); Doi, C. (Tohoku Univ. School of Literature (Japan). Dept. of Psychology); Yamaguchi, T.; Sasaki, H. (Tohoku Univ. School of Medicine (Japan). Dept. of Geriatric Medicine); Matsui, H.; Yamada, K. (Tohoku Univ. (Japan). Research Inst. for Tuberculosis and Cancer); Kinomura, S. (Miyama Hospital (Japan) Tohoku Univ. (Japan). Research Inst. for Tuberculosis and Cancer); Itoh, M. (Tohoku Univ. School of Medicine (Japan). Cyclotron Radioisotope Center)

1991-08-01

191

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

International Nuclear Information System (INIS)

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

2007-01-01

192

Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health.  

Science.gov (United States)

Alterations of cell volume induced by changes of extracellular osmolality have been reported to regulate intracellular metabolic pathways. Hypo-osmotic cell swelling counteracts proteolysis and glycogen breakdown in the liver, whereas hyperosmotic cell shrinkage promotes protein breakdown, glycolysis and glycogenolysis. To investigate the effect of acute changes of extracellular osmolality on whole-body protein, glucose and lipid metabolism in vivo, we studied 10 male subjects during three conditions: (i) hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl (2-5%, wt/vol) during 17 h; (ii) hypo-osmolality was produced by intravenous administration of desmopressin, liberal water drinking and infusion of hypotonic saline (0.4%); and (iii) the iso-osmolality study comprised oral water intake ad libitum. Plasma osmolality increased from 285+/-1 to 296+/-1 mosm/kg (P<0.001 during hyperosmolality, and decreased from 286+/-1 to 265+/-1 mosm/kg during hypo-osmolality (P<0.001). Total body leucine flux ([1-(13)C]leucine infusion technique), reflecting whole-body protein breakdown, as well as whole-body leucine oxidation rate (irreversible loss of amino acids) decreased significantly during hypo-osmolality. The glucose metabolic clearance rate during hyperinsulinaemic-euglycemic clamping increased significantly less during hypo-osmolality than iso-osmolality, indicating diminished peripheral insulin sensitivity. Glycerol turnover (2-[(13)C]glycerol infusion technique), reflecting whole-body lipolysis, increased significantly during hypo-osmolar conditions. The results demonstrate that the metabolic adaptation to acute hypo-osmolality resembles that of acute fasting, that is, it results in protein sparing associated with increased lipolysis, ketogenesis and lipid oxidation and impaired insulin sensitivity of glucose metabolism. PMID:14681716

Keller, U; Szinnai, G; Bilz, S; Berneis, K

2003-12-01

193

Regulation of ?-cell glucose transporter gene expression  

International Nuclear Information System (INIS)

[en] 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

194

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

Directory of Open Access Journals (Sweden)

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

Rudolf Tito Pillich; Gianfranco Scarsella; Gianfranco Risuleo

2008-01-01

195

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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...

Carbó Roxana; Guarner Verónica

196

Effect of oxygen on glucose metabolism: utilization of lactate in Staphylococcus aureus as revealed by in vivo NMR studies.  

UK PubMed Central (United Kingdom)

The ability to successfully adapt to changing host conditions is crucial for full virulence of bacterial pathogens. Staphylococcus aureus has to cope with fluctuating oxygen concentrations during the course of infection. Hence, we studied the effect of oxygen on glucose metabolism in non-growing S. aureus COL-S cells by in vivo(13)C-NMR. Glucose catabolism was probed at different oxygen concentrations in suspensions of cells grown aerobically (direct effects on metabolism) or anaerobically (transcriptional adjustment to oxygen deprivation). In aerobically-grown cells, the rate of glucose consumption diminished progressively with decreasing oxygen concentrations. Additionally, oxygen deprivation resulted in biphasic glucose consumption, with the second phase presenting a higher rate. The fructose-1,6-bisphosphate pool peaked while glucose was still abundant, but the transient maximum varied with the oxygen concentration. As oxygen became limiting mannitol/mannitol-1-phosphate were detected as products of glucose catabolism. Under anoxic conditions, accumulation of mannitol-1-phosphate ceased with the switch to higher glucose consumption rates, which implies the activation of a more efficient means by which NAD(+) can be regenerated. The distribution of end-products deriving from glucose catabolism was dramatically affected by oxygen: acetate increased and lactate decreased with the oxygen concentration; ethanol was formed only anaerobically. Moreover, oxygen promoted the energetically favourable conversion of lactate into acetate, which was particularly noticeable under fully oxygenated conditions. Interestingly, under aerobiosis growing S. aureus cells also converted lactate to acetate, used simultaneously glucose and lactate as substrates for growth, and grew considerably well on lactate-medium. We propose that the efficient lactate catabolism may endow S. aureus with a metabolic advantage in its ecological niche.

Ferreira MT; Manso AS; Gaspar P; Pinho MG; Neves AR

2013-01-01

197

The "metabolic syndrome" is less useful than random plasma glucose to screen for glucose intolerance.  

UK PubMed Central (United Kingdom)

AIMS: To compare the utility of metabolic syndrome (MetS) to random plasma glucose (RPG) in identifying people with diabetes or prediabetes. METHODS: RPG was measured and an OGTT was performed in 1155 adults. Test performance was measured by area under the receiver-operating-characteristic curve (AROC). RESULTS: Diabetes was found in 5.1% and prediabetes in 20.0%. AROC for MetS with fasting plasma glucose (FPG) was 0.80 to detect diabetes, and 0.76 for diabetes or prediabetes--similar to RPG alone (0.82 and 0.72). However, the AROC for MetS excluding fasting plasma glucose was lower: 0.69 for diabetes (p<0.01 vs. both RPG and MetS with FPG), and 0.69 for diabetes or prediabetes. AROCs for MetS with FPG and RPG were comparable and higher for recognizing diabetes in blacks vs. whites, and females vs. males. MetS with FPG was superior to RPG for identifying diabetes only in subjects with age <40 or BMI <25. CONCLUSIONS: MetS features can be used to identify risk of diabetes, but predictive usefulness is driven largely by FPG. Overall, to identify diabetes or prediabetes in blacks and whites with varying age and BMI, MetS is no better than RPG--a more convenient and less expensive test.

El Bassuoni EA; Ziemer DC; Kolm P; Rhee MK; Vaccarino V; Tsui CW; Kaufman JM; Osinski GE; Koch DD; Narayan KM; Weintraub WS; Phillips LS

2008-09-01

198

Determination of metabolic fluxes during glucose catabolism in Propionibacterium freudenreichii subsp. shermanii.  

UK PubMed Central (United Kingdom)

In vivo 13C Nuclear Magnetic Resonance (NMR) spectroscopy was used to investigate the pathways of glucose metabolism, non-invasively, in living cell suspensions of Propionibacterium freudenreichii subsp. shermanii. This species is the main ripening flora of the Swiss-type cheeses and is widely used as propionic acid and vitamin B12 industrial producer. The flow of labelled [1-13C]glucose was monitored in living cell suspensions and enrichment was detected in main products like [1-13C]glycogen, [6-13C]lycogen, [1-13C]trehalose, [6-13C]trehalose, [1-13C]propionate, [2-13C]propionate, [3-13C]propionate, [1-13C]acetate, [2-13C]acetate, [1-13C]succinate, [2-13C]succinate and [1-13C]CO2. alpha and beta glucose consumption could be examined separately and were catabolized at the same rate. Three intermediates were also found out, namely [1-13C]glucose-6-phosphate, [6-13C]glucose-6-phosphate and [1-13C]glucose-1-phosphate. From the formation of intermediates such as [6-3C]glucose-6-phosphate and products like [6-13C]glycogen from [1-13C]glucose we concluded the bidirectionality of reactions in the first part of glycolysis and the isomerization at the triose-phosphate level. Comparison of spectra obtained after addition of [1-13C]glucose or [U-12C]glucose revealed production of [1-13C]CO2 which means that pentose phosphates pathway is active under our experimental conditions. From the isotopic pattern of trehalose, it could be postulated that trehalose biosynthesis occurred either by direct condensation of two glucose molecules or by gluconeogenesis. A chemically defined medium was elaborated for the study and trehalose was the main osmolyte found in the intracellular fraction of P. shermanii grown in this medium.

Meurice G; Bondon A; Deborde C; Boyaval P

2001-01-01

199

Hypothalamic Actions of Apelin on Energy Metabolism: New Insight on Glucose Homeostasis and Metabolic Disorders.  

UK PubMed Central (United Kingdom)

Hypothalamus is key area implicated in control of glucose homeostasis. This structure integrates nervous and peripheral informations to adapt a response modifying peripheral glucose utilization and maintaining energetic balance. Among peripheral signals, adipokines such as adiponectin and leptin are of special importance since deregulations of their actions are closely associated to metabolic disorders such as obesity and type 2 diabetes. During the past ten years, we have identified a new adipokine named apelin which has emerging role in the control of metabolism. The originality of the apelinergic system is to be largely represented in peripheral tissues (adipose tissue, intestine, etc.) and in the brain. Then, apelin is released by adipose tissue as all adipokines, but also present another crucial role as neurotransmitter in hypothalamic neurons. By acting in the whole body, apelin exerts pleiotropic actions and is now considered as a major determinant of physiological functions. Besides its general beneficial effects on peripheral targets, central action of apelin remains still a matter of debate. In this review, we have made a parallel between peripheral vs. central actions of apelin in term of signalization and effects. Then, we have focused our attention on hypothalamic apelin and its potential role in glucose metabolism and associated pathologies.

Knauf C; Drougard A; Fournel A; Duparc T; Valet P

2013-08-01

200

Adenosine, adenosine receptors and their role in glucose homeostasis and lipid metabolism.  

UK PubMed Central (United Kingdom)

Adenosine is an endogenous metabolite that is released from all tissues and cells including liver, pancreas, muscle and fat, particularly under stress, intense exercise, or during cell damage. The role of adenosine in glucose homeostasis has been attributed to its ability to regulate, through its membrane receptors, processes such as insulin secretion, glucose release and clearance, glycogenolysis, and glycogenesis. Additionally, adenosine and its multiple receptors have been connected to lipid metabolism by augmenting insulin-mediated inhibition of lipolysis, and the subsequent increase in free fatty acids and glycerol levels. Furthermore, adenosine was reported to control liver cholesterol synthesis, consequently affecting plasma levels of cholesterol and triglycerides, and the amount of fat tissue. Alterations in the balance of glucose and lipid homeostasis have implications in both cardiovascular disease and diabetes. The ability of different adenosine receptors to activate and inhibit the same signaling cascades has made it challenging to study the influence of adenosine, adenosine analogs and their receptors in health and disease. This review focuses on the role and significance of different adenosine receptors in mediating the effect of adenosine on glucose and lipid homeostasis. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.

Koupenova M; Ravid K

2013-03-01

 
 
 
 
201

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.

Fraga, Amanda; Ribeiro, Lupis; Lobato, Mariana; Santos, Vitoria; Silva, Jose Roberto; Gomes, Helga; da Cunha Moraes, Jorge Luiz; de Souza Menezes, Jackson

2013-01-01

202

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

Directory of Open Access Journals (Sweden)

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

Yan-Ming HE; Wen-Jian WANG

2006-01-01

203

Enzyme relationships in a sorbitol pathway that bypasses glycolysis and pentose phosphates in glucose metabolism.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A pathway from glucose via sorbitol bypasses the control points of hexokinase and phosphofructokinase in glucose metabolism. It also may produce glycerol, linking the bypass to lipid synthesis. Utilization of this bypass is favored by a plentiful supply of glucose--hence, conditions under which glyc...

Jeffery, J; Jörnvall, H

204

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

205

Effects of novel neuroprotective and neurorestorative multifunctional drugs on iron chelation and glucose metabolism.  

UK PubMed Central (United Kingdom)

Iron accumulation and iron-related oxidative stress are involved in several pathological conditions and provide a rationale for the development of iron chelators as novel promising therapeutic strategies. Thus, we have recently synthesized multifunctional non-toxic, brain permeable iron chelating compounds, M30 and HLA20, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase (MAO)-B inhibitor, rasagiline and the antioxidant-iron chelating moiety of an 8-hydroxyquinoline derivative of the iron chelator, VK28. Here, we examined the hepatic regulatory effects of these novel compounds using two experimental approaches: chelation activity and glucose metabolism parameters. The present study demonstrated that M30 and HLA20 significantly decreased intracellular iron content and reduced ferritin expression levels in iron-loaded hepatoma Hep3B cells. In electron microscopy analysis, M30 was shown to reduce the electron-dense deposits of siderosomes by ~30 %, as well as down-regulate cytosolic ferritin particles observed in iron-overloaded cells. In vivo studies demonstrated that M30 administration (1 mg/kg, P.O. three times a week) reduced hepatic ferritin levels; increased hepatic insulin receptor and glucose transporter-1 levels and improved glucose tolerance in C57BL/6 mice and in a mouse model of type-2 diabetes, the ob/ob (leptin(-/-)). The results clearly indicate that the novel multifunctional drugs, especially M30, display significant capacity of chelating intracellular iron and regulating glucose metabolism parameters. Such effects can have therapeutic significance in conditions with abnormal local or systemic iron metabolism, including neurological diseases.

Pollak Y; Mechlovich D; Amit T; Bar-Am O; Manov I; Mandel SA; Weinreb O; Meyron-Holtz EG; Iancu TC; Youdim MB

2013-01-01

206

Effects of novel neuroprotective and neurorestorative multifunctional drugs on iron chelation and glucose metabolism.  

Science.gov (United States)

Iron accumulation and iron-related oxidative stress are involved in several pathological conditions and provide a rationale for the development of iron chelators as novel promising therapeutic strategies. Thus, we have recently synthesized multifunctional non-toxic, brain permeable iron chelating compounds, M30 and HLA20, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase (MAO)-B inhibitor, rasagiline and the antioxidant-iron chelating moiety of an 8-hydroxyquinoline derivative of the iron chelator, VK28. Here, we examined the hepatic regulatory effects of these novel compounds using two experimental approaches: chelation activity and glucose metabolism parameters. The present study demonstrated that M30 and HLA20 significantly decreased intracellular iron content and reduced ferritin expression levels in iron-loaded hepatoma Hep3B cells. In electron microscopy analysis, M30 was shown to reduce the electron-dense deposits of siderosomes by ~30 %, as well as down-regulate cytosolic ferritin particles observed in iron-overloaded cells. In vivo studies demonstrated that M30 administration (1 mg/kg, P.O. three times a week) reduced hepatic ferritin levels; increased hepatic insulin receptor and glucose transporter-1 levels and improved glucose tolerance in C57BL/6 mice and in a mouse model of type-2 diabetes, the ob/ob (leptin(-/-)). The results clearly indicate that the novel multifunctional drugs, especially M30, display significant capacity of chelating intracellular iron and regulating glucose metabolism parameters. Such effects can have therapeutic significance in conditions with abnormal local or systemic iron metabolism, including neurological diseases. PMID:22446839

Pollak, Yulia; Mechlovich, Danit; Amit, Tamar; Bar-Am, Orit; Manov, Irena; Mandel, Silvia A; Weinreb, Orly; Meyron-Holtz, Esther G; Iancu, Theodore C; Youdim, Moussa B H

2012-03-25

207

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

International Nuclear Information System (INIS)

[en] 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)

1992-01-01

208

Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy.  

UK PubMed Central (United Kingdom)

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by bilateral renal cyst formation. Recent identification of signaling cascades deregulated in ADPKD has led to the initiation of several clinical trials, but an approved therapy is still lacking. Using a metabolomic approach, we identify a pathogenic pathway in this disease that can be safely targeted for therapy. We show that mutation of PKD1 results in enhanced glycolysis in cells in a mouse model of PKD and in kidneys from humans with ADPKD. Glucose deprivation resulted in lower proliferation and higher apoptotic rates in PKD1-mutant cells than in nondeprived cells. Notably, two distinct PKD mouse models treated with 2-deoxyglucose (2DG), to inhibit glycolysis, had lower kidney weight, volume, cystic index and proliferation rates as compared to nontreated mice. These metabolic alterations depend on the extracellular signal-related kinase (ERK) pathway acting in a dual manner by inhibiting the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) axis on the one hand while activating the mTOR complex 1 (mTORC1)-glycolytic cascade on the other. Enhanced metabolic rates further inhibit AMPK. Forced activation of AMPK acts in a negative feedback loop, restoring normal ERK activity. Taken together, these data indicate that defective glucose metabolism is intimately involved in the pathobiology of ADPKD. Our findings provide a strong rationale for a new therapeutic strategy using existing drugs, either individually or in combination.

Rowe I; Chiaravalli M; Mannella V; Ulisse V; Quilici G; Pema M; Song XW; Xu H; Mari S; Qian F; Pei Y; Musco G; Boletta A

2013-04-01

209

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

International Nuclear Information System (INIS)

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

2008-01-01

210

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

211

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

212

Cytotoxicity,radiosensitization, and chemosensitization of tumor cells by 2-deoxy-D-glucose In vitro  

Directory of Open Access Journals (Sweden)

Full Text Available The glucose analog 2-deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolytic ATP production, is the most widely investigated metabolic inhibitor for targeting glucose metabolism. Besides depleting energy in cells, 2-DG has also been found to alter N-linked glycosylation leading to unfolded protein responses and induce changes in gene expression and phosphorylation status of proteins involved in signaling, cell cycle control, DNA repair, calcium influx, and apoptosis. Inhibition of cell proliferation and induction of apoptosis have been observed as cytotoxic effects in a wide variety of tumor cells in vitro, while sensitization of tumor cells to ionizing radiation and certain chemotherapeutic drugs is associated with enhanced mitotic as well as apoptotic cell death induced by the primary therapeutic agent. Therefore, there has been a considerable amount of interest in developing 2-DG as a therapeutic agent or adjuvant in the radiotherapy and chemotherapy of tumors.

Dwarakanath B

2009-01-01

213

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

2002-01-01

214

Weight loss after bariatric surgery reverses insulin-induced increases in brain glucose metabolism of the morbidly obese.  

UK PubMed Central (United Kingdom)

Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not different between groups. However, the hyperinsulinemic clamp increased brain glucose metabolism in a widespread manner in the obese but not control subjects, and brain glucose metabolism was significantly higher during clamp in obese than in control subjects. After follow-up, 6 months postoperatively, the increase in glucose metabolism was no longer observed, and this attenuation was coupled with improved peripheral insulin sensitivity after weight loss. We conclude that obesity is associated with increased insulin-stimulated glucose metabolism in the brain and that this abnormality can be reversed by bariatric surgery.

Tuulari JJ; Karlsson HK; Hirvonen J; Hannukainen JC; Bucci M; Helmiö M; Ovaska J; Soinio M; Salminen P; Savisto N; Nummenmaa L; Nuutila P

2013-08-01

215

Metabolome response to glucose in the ?-cell line INS-1 832/13.  

Science.gov (United States)

Glucose-stimulated insulin secretion (GSIS) from pancreatic ?-cells is triggered by metabolism of the sugar to increase ATP/ADP ratio that blocks the KATP channel leading to membrane depolarization and insulin exocytosis. Other metabolic pathways believed to augment insulin secretion have yet to be fully elucidated. To study metabolic changes during GSIS, liquid chromatography with mass spectrometry was used to determine levels of 87 metabolites temporally following a change in glucose from 3 to 10 mM glucose and in response to increasing concentrations of glucose in the INS-1 832/13 ?-cell line. U-[(13)C]Glucose was used to probe flux in specific metabolic pathways. Results include a rapid increase in ATP/ADP, anaplerotic tricarboxylic acid cycle flux, and increases in the malonyl CoA pathway, support prevailing theories of GSIS. Novel findings include that aspartate used for anaplerosis does not derive from the glucose fuel added to stimulate insulin secretion, glucose flux into glycerol-3-phosphate, and esterification of long chain CoAs resulting in rapid consumption of long chain CoAs and de novo generation of phosphatidic acid and diacylglycerol. Further, novel metabolites with potential roles in GSIS such as 5-aminoimidazole-4-carboxamide ribotide (ZMP), GDP-mannose, and farnesyl pyrophosphate were found to be rapidly altered following glucose exposure. PMID:23426361

Lorenz, Matthew A; El Azzouny, Mahmoud A; Kennedy, Robert T; Burant, Charles F

2013-02-20

216

Metabolome Response to Glucose in the ?-Cell Line INS-1 832/13*  

Science.gov (United States)

Glucose-stimulated insulin secretion (GSIS) from pancreatic ?-cells is triggered by metabolism of the sugar to increase ATP/ADP ratio that blocks the KATP channel leading to membrane depolarization and insulin exocytosis. Other metabolic pathways believed to augment insulin secretion have yet to be fully elucidated. To study metabolic changes during GSIS, liquid chromatography with mass spectrometry was used to determine levels of 87 metabolites temporally following a change in glucose from 3 to 10 mm glucose and in response to increasing concentrations of glucose in the INS-1 832/13 ?-cell line. U-[13C]Glucose was used to probe flux in specific metabolic pathways. Results include a rapid increase in ATP/ADP, anaplerotic tricarboxylic acid cycle flux, and increases in the malonyl CoA pathway, support prevailing theories of GSIS. Novel findings include that aspartate used for anaplerosis does not derive from the glucose fuel added to stimulate insulin secretion, glucose flux into glycerol-3-phosphate, and esterification of long chain CoAs resulting in rapid consumption of long chain CoAs and de novo generation of phosphatidic acid and diacylglycerol. Further, novel metabolites with potential roles in GSIS such as 5-aminoimidazole-4-carboxamide ribotide (ZMP), GDP-mannose, and farnesyl pyrophosphate were found to be rapidly altered following glucose exposure.

Lorenz, Matthew A.; El Azzouny, Mahmoud A.; Kennedy, Robert T.; Burant, Charles F.

2013-01-01

217

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

Science.gov (United States)

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

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

2013-02-13

218

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

UK PubMed Central (United Kingdom)

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

Chin YW; Park JB; Park YC; Kim KH; Seo JH

2013-06-01

219

Zonation of Nitrogen and Glucose Metabolism Gene Expression upon Acute Liver Damage in Mouse  

Science.gov (United States)

Zonation of metabolic activities within specific structures and cell types is a phenomenon of liver organization and ensures complementarity of variant liver functions like protein production, glucose homeostasis and detoxification. To analyze damage and regeneration of liver tissue in response to a toxic agent, expression of liver specific enzymes was analyzed by in situ hybridization in mouse over a 6 days time course following carbon tetrachloride (CCl4) injection. CCl4 mixed with mineral oil was administered to BALB/c mice by intraperitoneal injection, and mice were sacrificed at different time points post injection. Changes in the expression of albumin (Alb), arginase (Arg1), glutaminase 2 (Gls2), Glutamine synthetase (Gs), glucose-6-phosphatase (G6pc), glycogen synthase 2 (Gys2), Glycerinaldehyd-3-phosphat-Dehydrogenase (Gapdh), Cytochrom p450 2E1 (Cyp2e1) and glucagon receptor (Gcgr) genes in the liver were studied by in situ hybridization and qPCR. We observed significant changes in gene expression of enzymes involved in nitrogen and glucose metabolism and their local distribution following CCl4 injury. We also found that Cyp2e1, the primary metabolizing enzyme for CCl4, was strongly expressed in the pericentral zone during recovery. Furthermore, cells in the damaged area displayed distinct gene expression profiles during the analyzed time course and showed complete recovery with strong albumin production 6 days after CCl4 injection. Our results indicate that despite severe damage, liver cells in the damaged area do not simply die but instead display locally adjusted gene expression supporting damage response and recovery.

Ghafoory, Shahrouz; Breitkopf-Heinlein, Katja; Li, Qi; Scholl, Catharina; Dooley, Steven; Wolfl, Stefan

2013-01-01

220

Zonation of Nitrogen and Glucose Metabolism Gene Expression upon Acute Liver Damage in Mouse.  

Science.gov (United States)

Zonation of metabolic activities within specific structures and cell types is a phenomenon of liver organization and ensures complementarity of variant liver functions like protein production, glucose homeostasis and detoxification. To analyze damage and regeneration of liver tissue in response to a toxic agent, expression of liver specific enzymes was analyzed by in situ hybridization in mouse over a 6 days time course following carbon tetrachloride (CCl4) injection. CCl4 mixed with mineral oil was administered to BALB/c mice by intraperitoneal injection, and mice were sacrificed at different time points post injection. Changes in the expression of albumin (Alb), arginase (Arg1), glutaminase 2 (Gls2), Glutamine synthetase (Gs), glucose-6-phosphatase (G6pc), glycogen synthase 2 (Gys2), Glycerinaldehyd-3-phosphat-Dehydrogenase (Gapdh), Cytochrom p450 2E1 (Cyp2e1) and glucagon receptor (Gcgr) genes in the liver were studied by in situ hybridization and qPCR. We observed significant changes in gene expression of enzymes involved in nitrogen and glucose metabolism and their local distribution following CCl4 injury. We also found that Cyp2e1, the primary metabolizing enzyme for CCl4, was strongly expressed in the pericentral zone during recovery. Furthermore, cells in the damaged area displayed distinct gene expression profiles during the analyzed time course and showed complete recovery with strong albumin production 6 days after CCl4 injection. Our results indicate that despite severe damage, liver cells in the damaged area do not simply die but instead display locally adjusted gene expression supporting damage response and recovery. PMID:24147127

Ghafoory, Shahrouz; Breitkopf-Heinlein, Katja; Li, Qi; Scholl, Catharina; Dooley, Steven; Wölfl, Stefan

2013-10-17

 
 
 
 
221

Statins impair glucose uptake in tumor cells.  

UK PubMed Central (United Kingdom)

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

Malenda A; Skrobanska A; Issat T; Winiarska M; Bil J; Oleszczak B; Sinski M; Firczuk M; Bujnicki JM; Chlebowska J; Staruch AD; Glodkowska-Mrowka E; Kunikowska J; Krolicki L; Szablewski L; Gaciong Z; Koziak K; Jakobisiak M; Golab J; Nowis DA

2012-04-01

222

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

International Nuclear Information System (INIS)

[en] 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

223

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

International Nuclear Information System (INIS)

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

2008-08-01

224

Wnt/Snail signaling regulates cytochrome C oxidase and glucose metabolism.  

UK PubMed Central (United Kingdom)

Wnt signaling plays a critical role in embryonic development, and its deregulation is closely linked to the occurrence of a number of malignant tumors, including breast and colon cancer. The pathway also induces Snail-dependent epithelial-to-mesenchymal transition (EMT), which is responsible for tumor invasion and metastasis. In this study, we show that Wnt suppresses mitochondrial respiration and cytochrome C oxidase (COX) activity by inhibiting the expression of 3 COX subunits, namely, COXVIc, COXVIIa, and COXVIIc. We found that Wnt induced a glycolytic switch via increased glucose consumption and lactate production, with induction of pyruvate carboxylase (PC), a key enzyme of anaplerosis. In addition, Wnt-induced mitochondrial repression and glycolytic switching occurred through the canonical ?-catenin/T-cell factor 4/Snail pathway. Short hairpin RNA-mediated knockdown of E-cadherin, a regulator of EMT, repressed mitochondrial respiration and induced a glycolytic switch via Snail activation, indicating that EMT may contribute to Wnt/Snail regulation of mitochondrial respiration and glucose metabolism. Together, our findings provide a new function for Wnt/Snail signaling in the regulation of mitochondrial respiration (via COX gene expression) and glucose metabolism (via PC gene expression) in tumor growth and progression.

Lee SY; Jeon HM; Ju MK; Kim CH; Yoon G; Han SI; Park HG; Kang HS

2012-07-01

225

Wnt/Snail signaling regulates cytochrome C oxidase and glucose metabolism.  

Science.gov (United States)

Wnt signaling plays a critical role in embryonic development, and its deregulation is closely linked to the occurrence of a number of malignant tumors, including breast and colon cancer. The pathway also induces Snail-dependent epithelial-to-mesenchymal transition (EMT), which is responsible for tumor invasion and metastasis. In this study, we show that Wnt suppresses mitochondrial respiration and cytochrome C oxidase (COX) activity by inhibiting the expression of 3 COX subunits, namely, COXVIc, COXVIIa, and COXVIIc. We found that Wnt induced a glycolytic switch via increased glucose consumption and lactate production, with induction of pyruvate carboxylase (PC), a key enzyme of anaplerosis. In addition, Wnt-induced mitochondrial repression and glycolytic switching occurred through the canonical ?-catenin/T-cell factor 4/Snail pathway. Short hairpin RNA-mediated knockdown of E-cadherin, a regulator of EMT, repressed mitochondrial respiration and induced a glycolytic switch via Snail activation, indicating that EMT may contribute to Wnt/Snail regulation of mitochondrial respiration and glucose metabolism. Together, our findings provide a new function for Wnt/Snail signaling in the regulation of mitochondrial respiration (via COX gene expression) and glucose metabolism (via PC gene expression) in tumor growth and progression. PMID:22637725

Lee, Su Yeon; Jeon, Hyun Min; Ju, Min Kyung; Kim, Cho Hee; Yoon, Gyesoon; Han, Song Iy; Park, Hye Gyeong; Kang, Ho Sung

2012-05-25

226

Modulation of sporulation and metabolic fluxes in Saccharomyces cerevisiae by 2 deoxy glucose.  

Science.gov (United States)

Quantitative studies of metabolic fluxes during Saccharomyces cerevisiae sporulation on acetate in the presence of the glucose analog, 2-deoxy glucose (2dG) are reported. We have studied the inhibition of sporulation and associated catabolic or anabolic fluxes by 2dG. Sporulation frequencies decreased from 50% to 2% asci per cell at 2dG concentrations in the range of 0.03 to 0.30 g l-1, respectively. Under the same conditions, the acetate consumption flux was inhibited up to 60% and the glyoxylate cycle and gluconeogenic fluxes decreased from 0.7 and 0.3 mmol h-1 g-1 dw, respectively, to negligible values. We observed a linear correlation of the acetate consumption rate with the sporulation frequency by varying the 2dG concentration. The linear correlation was also verified between the frequency of sporulation and the fluxes through glyoxylate cycle and gluconeogenic pathways. In addition, the same association of inhibition of sporulation and metabolic fluxes was found in other S. cerevisiae strains displaying different potentials of sporulation. The results presented suggest that inhibition of sporulation in the presence of the glucose analog may be attributed, at least in part, to the inhibition of anabolic fluxes and might be associated with catabolite repression. PMID:9442269

Aon, J C; Aon, M A; Spencer, J F; Cortassa, S

1997-11-01

227

Glucose metabolism in mice during and after whole-body hyperthermia  

Energy Technology Data Exchange (ETDEWEB)

Researchers studied glucose turnover in male inbred mice during and after whole-body hyperthermia for 1 hour at 40 degrees or 41 degrees C by giving them injections of (/sup 14/C)glucose with and without a glucose load and measuring the expired /sup 14/Co/sub 2/. Expiration of /sup 14/CO/sub 2/ was increased during hyperthermia but decreased considerably afterward. The latter effect was enhanced by a glucose load. This inhibition depended on the glucose concentration. Metabolic studies showed a depletion of several glycolytic metabolites, especially glycogen and lactate, after whole-body hyperthermia. Combined treatment of hyperthermia and a glucose injection 1 hour later led to an increased level of glucose 6-phosphate, which indicated a block in glycolysis between glucose 6-phosphate and fructose 1,6-diphosphate. This inhibition did not occur when glucose was given before the hyperthermia treatment. Lactate accumulation was not observed under any conditions.

Schubert, B.; Streffer, C.; Tamulevicius, P.

1982-06-01

228

Glucose metabolism in mice during and after whole-body hyperthermia  

International Nuclear Information System (INIS)

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

1982-01-01

229

Glucose metabolism in Legionella pneumophila: dependence on the Entner-Doudoroff pathway and connection with intracellular bacterial growth.  

UK PubMed Central (United Kingdom)

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-phosphogluconate aldolase, presumed to be encoded by the glk, edd, and eda genes, respectively. Gene-disrupted mutants for the three genes and the ywtG gene encoding a putative sugar transporter were devoid of the ability to metabolize exogenous glucose, indicating that the pathway is almost exclusively responsible for glucose metabolism and that the ywtG gene product is the glucose transporter. It was also established that these four genes formed part of an operon in which the gene order was edd-glk-eda-ywtG, as predicted by genomic information. Intriguingly, while the mutants exhibited no appreciable change in growth characteristics in vitro, they were defective in multiplication within eukaryotic cells, strongly indicating that the ED pathway must be functional for the intracellular growth of the bacterium to occur. Curiously, while the deficient glucose metabolism of the ywtG mutant was successfully complemented by the ywtG(+) gene supplied in trans via plasmid, its defect in intracellular growth was not. However, the latter defect was also manifested in wild-type cells when a plasmid carrying the mutant ywtG gene was introduced. This phenomenon, resembling so-called dominant negativity, awaits further investigation.

Harada E; Iida K; Shiota S; Nakayama H; Yoshida S

2010-06-01

230

Glucose metabolism in Legionella pneumophila: dependence on the Entner-Doudoroff pathway and connection with intracellular bacterial growth.  

Science.gov (United States)

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-phosphogluconate aldolase, presumed to be encoded by the glk, edd, and eda genes, respectively. Gene-disrupted mutants for the three genes and the ywtG gene encoding a putative sugar transporter were devoid of the ability to metabolize exogenous glucose, indicating that the pathway is almost exclusively responsible for glucose metabolism and that the ywtG gene product is the glucose transporter. It was also established that these four genes formed part of an operon in which the gene order was edd-glk-eda-ywtG, as predicted by genomic information. Intriguingly, while the mutants exhibited no appreciable change in growth characteristics in vitro, they were defective in multiplication within eukaryotic cells, strongly indicating that the ED pathway must be functional for the intracellular growth of the bacterium to occur. Curiously, while the deficient glucose metabolism of the ywtG mutant was successfully complemented by the ywtG(+) gene supplied in trans via plasmid, its defect in intracellular growth was not. However, the latter defect was also manifested in wild-type cells when a plasmid carrying the mutant ywtG gene was introduced. This phenomenon, resembling so-called dominant negativity, awaits further investigation. PMID:20363943

Harada, Eiji; Iida, Ken-Ichiro; Shiota, Susumu; Nakayama, Hiroaki; Yoshida, Shin-Ichi

2010-04-02

231

Longitudinal multicenter analysis on the course of glucose metabolism in obese children.  

UK PubMed Central (United Kingdom)

OBJECTIVE: Although there is evidence of increasing prevalence of impaired glucose metabolism in obese children from smaller single cohorts, data are lacking on the progression of glucose metabolism in this patient group.We aimed to assess the prevalence and the longitudinal course of impaired glucose metabolism assessed by oral glucose tolerance test (oGTT) in a large multi-center pediatric obesity registry. SUBJECTS: We performed an observational multicenter (n=84) cross-sectional (n=11?156) and longitudinal analysis (n=1008) on the course of glucose metabolism evaluated by oGTT in obese children documented in the Adiposity Patients Verlaufsbeobachtung (APV) registry. Patients were stratified with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and Type 2 diabetes (T2D), according to American Diabetes Association criteria. RESULTS: A total of 12.6% of the children presented with abnormal glucose metabolism (5.99% IFG, 5.51% IGT, 1.07% T2D). Body mass index (BMI) correlated modestly with 2-h blood glucose (r=0.04, P<0.001).In the 1008 patients with follow-up oGTT, metabolic parameters improved and the percentage of abnormal glucose metabolism decreased from 18.7 to 14.2%. Of the children with initial IGT, 70.6% converted to normal glucose tolerance. The improvement in oGTT results was associated with, but not dependent on, a reduction of BMI s.d. score. CONCLUSION: In summary, we provide evidence for significant improvement of oGTT parameters in obese children treated in specialized treatment centers, even though reduction in BMI was modest.

Körner A; Wiegand S; Hungele A; Tuschy S; Otto KP; l'Allemand-Jander D; Widhalm K; Kiess W; Holl RW

2013-07-01

232

Relationship between regional brain glucose metabolism and temperament factor of personality  

Energy Technology Data Exchange (ETDEWEB)

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

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

2005-07-01

233

Change in glucose metabolism after long-term treatment with deflazacort and betamethasone.  

UK PubMed Central (United Kingdom)

We have compared the long-term effects of different corticosteroids on glucose metabolism by carrying out a 75 g oral glucose tolerance test in 27 subjects before and after the administration of deflazacort or betamethasone for two months in random balanced sequence. Fasting plasma glucose and insulin concentrations were significantly higher after betamethasone, whereas deflazacort increased only fasting plasma insulin. After oral glucose there were significant increases in blood glucose and insulin after betamethasone compared with deflazacort. These results suggest that the degree of glucose intolerance and insulin resistance depends on the steroid used and on the dose given, although long-term treatment with deflazacort has a smaller effect on glucose metabolism than betamethasone.

Bruno A; Pagano G; Benzi L; Di Ciani G; Spallone V; Calabrese G; Passeri A

1992-01-01

234

Developmental role for endocannabinoid signaling in regulating glucose metabolism and growth.  

UK PubMed Central (United Kingdom)

Treatment of ob/ob (obese) mice with a cannabinoid receptor 1 (Cnr1) antagonist reduces food intake, suggesting a role for endocannabinoid signaling in leptin action. We further evaluated the role of endocannabinoid signaling by analyzing the phenotype of Cnr1 knockout ob/ob mice. Double mutant animals show a more severe growth retardation than ob/ob mice with similar levels of adiposity and reduced IGF-I levels without alterations of growth hormone (GH) levels. The double mutant mice are also significantly more glucose intolerant than ob/ob mice. This is in contrast to treatment of ob/ob mice with a Cnr1 antagonist that had no effect on glucose metabolism, suggesting a possible requirement for endocannabinoid signaling during development for normal glucose homeostasis. Double mutant animals also showed similar leptin sensitivity as ob/ob mice, suggesting that there are developmental changes that compensate for the loss of Cnr1 signaling. These data establish a role for Cnr1 during development and suggest that compensatory changes during development may mitigate the requirement for Cnr1 in mediating the effects of leptin. The data also suggest a developmental role for Cnr1 to promote growth, regulate the GH/IGF-I axis, and improve ?-cell function and glucose homeostasis in the setting of leptin deficiency.

Li Z; Schmidt SF; Friedman JM

2013-07-01

235

The relationship between glucose metabolism, metabolic syndrome, and bone-specific alkaline phosphatase: a structural equation modeling approach.  

Science.gov (United States)

Context: Serum alkaline phosphatase plays a role in vascular calcification. It is found in various tissues, whereas bone-specific alkaline phosphatase (BAP) more specifically reflects mineral metabolism. The relationship of serum alkaline phosphatase (total and bone-specific) with diabetes and metabolic syndrome (MetS), 2 major risk factors of vascular calcification, is largely unknown. Objective: We aimed to investigate the relationships between glucose metabolism, components of the MetS, and alkaline phosphatase. Design and Setting: This was a cross-sectional study of a nationally representative sample of the U.S. population in 1999 through 2004. Participants: Participants were 3773 nondiabetic participants of the National Health and Nutrition Examination Survey 1999-2004. Main Outcome Measures: We measured serum BAP and total alkaline phosphatase. Results: In multivariable linear regression, updated homeostasis model assessment (HOMA2) for insulin resistance (? = 0.068), HOMA2 for ?-cell function (? = 0.081), insulin (? = 0.065), mean arterial pressure (? = 0.15), and high-density lipoprotein (HDL)-cholesterol (? = 0.209) were positively associated with BAP, whereas HOMA2 for insulin sensitivity (? = -0.065) was negatively associated with BAP. On the other hand, only mean arterial pressure and HDL-cholesterol were significantly associated with total alkaline phosphatase. Moreover, a structural equation model revealed that hypertension, low HDL, and insulin resistance had significant direct effects on serum BAP levels, whereas obesity and inflammation might have indirect effects on serum BAP levels. The overall model showed very good fit to the data (comparative fit index = 0.995, root mean square error of approximation = 0.037, and standardized root mean square residual = 0.006). Conclusion: Glucose metabolism and MetS are significantly related to serum BAP levels. How BAP mediates vascular calcification in diabetes and MetS warrants further studies. PMID:23796564

Cheung, Ching-Lung; Tan, Kathryn C B; Lam, Karen S L; Cheung, Bernard M Y

2013-06-24

236

The prevalence of impaired glucose metabolism in patients referred to cardiac rehabilitation.  

UK PubMed Central (United Kingdom)

PURPOSE: The aim of this study was to assess the prevalence of impaired glucose metabolism in patients who attended hospital-based cardiac rehabilitation. METHODS: We performed a single-group cross-sectional study. In a 7-month period, from September 2010. The study was conducted in a cardiac rehabilitation setting at a university hospital. Overall, 273 patients, with an established diagnosis of ischemic heart disease, who were referred to the cardiac rehabilitation center, were included. The primary outcome measure was the prevalence of impaired glucose metabolism. We also compared cardiovascular disease risk profile among participants. RESULTS: One hundred twenty-one participants (44%) had diabetes mellitus, of which, for 80 patients, the diagnosis was previously established. Of the 193 patients without a previous diagnosis of diabetes, 52 patients (27%) had normal glucose levels, 41 (21.2%) had diabetes, 51 (26.4%) showed impaired glucose tolerance, and 49 (25.4%) had isolated impaired fasting glucose according to the American Diabetic Association criteria. Consistent with the World Health Organization criteria, 27 patients (14%) would have had isolated impaired fasting glucose and using fasting criteria alone, 22 patients would have had undiagnosed diabetes. CONCLUSION: Impaired fasting glucose and impaired glucose tolerance did not identify the same patients. It seems that both fasting plasma glucose and oral glucose tolerance test are necessary in the diagnosis of impaired glucose metabolism in patients with coronary artery disease.

Ettefagh L; Maleki M; Panahi A; Abdi M; Oskuie ME; Kermanshahi TZ; Jamaloo M; Bakhshandeh H

2013-01-01

237

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

Directory of Open Access Journals (Sweden)

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

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

2009-01-01

238

Association between dopamine D4 receptor polymorphism and age related changes in brain glucose metabolism.  

UK PubMed Central (United Kingdom)

Aging is associated with reductions in brain glucose metabolism in some cortical and subcortical regions, but the rate of decrease varies significantly between individuals, likely reflecting genetic and environmental factors and their interactions. Here we test the hypothesis that the variant of the dopamine receptor D4 (DRD4) gene (VNTR in exon 3), which has been associated with novelty seeking and sensitivity to environmental stimuli (negative and positive) including the beneficial effects of physical activity on longevity, influence the effects of aging on the human brain. We used positron emission tomography (PET) and [(18)F]fluoro-D-glucose ((18)FDG) to measure brain glucose metabolism (marker of brain function) under baseline conditions (no stimulation) in 82 healthy individuals (age range 22-55 years). We determined their DRD4 genotype and found an interaction with age: individuals who did not carry the 7-repeat allele (7R-, n?=?53) had a significant (p<0.0001) negative association between age and relative glucose metabolism (normalized to whole brain glucose metabolism) in frontal (r?=?-0.52), temporal (r?=?-0.51) and striatal regions (r?=?-0.47, p<0.001); such that older individuals had lower metabolism than younger ones. In contrast, for carriers of the 7R allele (7R+ n?=?29), these correlations with age were not significant and they only showed a positive association with cerebellar glucose metabolism (r?=?+0.55; p?=?0.002). Regression slopes of regional brain glucose metabolism with age differed significantly between the 7R+ and 7R- groups in cerebellum, inferior temporal cortex and striatum. These results provide evidence that the DRD4 genotype might modulate the associations between regional brain glucose metabolism and age and that the carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism.

Volkow ND; Tomasi D; Wang GJ; Telang F; Fowler JS; Goldstein RZ; Klein N; Wong C; Swanson JM; Shumay E

2013-01-01

239

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

240

UCP2, a metabolic sensor coupling glucose oxidation to mitochondrial metabolism?  

UK PubMed Central (United Kingdom)

Mitochondrial uncoupling of oxidative phosphorylation may serve a variety of purposes such as the regulation of substrate oxidation, free radical production (a major by-product of mitochondrial respiration) and ATP production and turnover. As regulators of energy expenditure and antioxidant defenses, uncoupling proteins would seem to offer an attractive mechanism by which to explain the control of body weight, resting metabolic rate and aging. As a result, the discovery of UCP1 homologues has led to an impressive number of publications. However, 10 years after their identification, no consensus has been found concerning the function of UCP homologues, and there are controversies as to whether or not they even have physiologically significant uncoupling activity. Here, we discuss a potential new function for UCP2, as a carrier involved in the coupling between glucose oxidation and mitochondrial metabolism.

Pecqueur C; Alves-Guerra C; Ricquier D; Bouillaud F

2009-07-01

 
 
 
 
241

MYC, Metabolism, Cell Growth, and Tumorigenesis.  

UK PubMed Central (United Kingdom)

The MYC proto-oncogene is frequently activated in human cancers through a variety of mechanisms. Its deregulated expression, unconstrained by inactivation of key checkpoints, such as p53, contributes to tumorigenesis. Unlike its normal counterpart, which is restrained by negative regulators, the unleashed MYC oncogene produces a transcription factor that alters global gene expression through transcriptional regulation, resulting in tumorigenesis. Key genes involved in ribosomal and mitochondrial biogenesis, glucose and glutamine metabolism, lipid synthesis, and cell-cycle progression are robustly activated by MYC, contributing to the acquisition of bioenergetics substrates for the cancer cell to grow and proliferate.

Dang CV

2013-01-01

242

Splanchnic bed metabolism of glucose in preterm neonates  

Digital Repository Infrastructure Vision for European Research (DRIVER)

BACKGROUND: Glucose is a major oxidative substrate for intestinal energy generation in neonatal animals; however, few data in preterm infants are available. Early administration of enteral nutrition, including glucose, may be an effective strategy to support intestinal adaptation t...

Schoor, S.R. van der; Stoll, B.; Wattimena, D.L.; Büller, H.A.; Tibboel, D.; Burrin, D.G.; Goudoever, J.B. van

243

Molecular regulators of glucose and lipid metabolism in skeletal muscle  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Skeletal muscle is a primary site of insulin action and insulin-stimulated glucose transport and occupies a center stage in maintaining whole body glucose and lipid homeostasis. Another key feature of a healthy skeletal muscle is its ability to switch between utilization of lipids and glucose as fue...

Kulkarni, Sameer S

244

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

UK PubMed Central (United Kingdom)

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.

Poomthavorn P; Chaya W; Mahachoklertwattana P; Sukprasert M; Weerakiet S

2013-01-01

245

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

246

EDIM-TKTL1 blood test: a noninvasive method to detect upregulated glucose metabolism in patients with malignancies.  

UK PubMed Central (United Kingdom)

AIM: To determine whether the TKTL1 protein epitope detection in monocytes (EDIM) test allows detection of upregulated glucose metabolism in malignancies. MATERIALS & METHODS: The EDIM-TKTL1 blood test was conducted in 240 patients with 17 different confirmed or suspected malignancies. Test scores were compared with (18)F-fluoro-2-deoxy-D-glucose (FDG)-PET/computed tomography (CT) results. RESULTS: EDIM-TKTL1 score and FDG-PET results showed a concordance of 90% with a sensitivity of 94% and specificity of 81%. Including CT data, all values were enhanced. A subgroup analysis of non-small-cell lung cancer patients showed a significant correlation between the EDIM-TKTL1 score and the primary tumor size determined by FDG-PET/CT. CONCLUSION: EDIM-TKTL1 blood test revealed good concordance with FDG-PET/CT results in patients with malignancies demonstrating its efficacy to detect upregulation of glucose metabolism in primary tumors or metastases.

Feyen O; Coy JF; Prasad V; Schierl R; Saenger J; Baum RP

2012-10-01

247

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

UK PubMed Central (United Kingdom)

Increasing evidence supports an association between the skeleton and energy metabolism. These interactions are mediated by a variety of hormones, cytokines and nutrients. Here, the evidence for a role of osteocalcin in the regulation of glucose metabolism in humans is reviewed. Osteocalcin is a bone matrix protein that regulates hydroxyapatite size and shape through its vitamin-K-dependent, ?-carboxylated form. The concentration of osteocalcin in the circulation is a measure of bone formation. The undercarboxylated form of osteocalcin is active in glucose metabolism in mice. Total serum osteocalcin concentrations in humans are inversely associated with measures of glucose metabolism; however, human data are inconclusive with regard to the role of uncarboxylated osteocalcin in glucose metabolism because most studies do not account for the influence of vitamin K on the proportion of undercarboxylated osteocalcin or differentiate between the total and uncarboxylated forms of osteocalcin. Furthermore, most human studies do not concomitantly measure other bone turnover markers to isolate the role of osteocalcin as a measure of bone formation from its effect on glucose metabolism. Carefully designed studies are required to define the role of osteocalcin and its carboxylated or undercarboxylated forms in the regulation of glucose metabolism in humans.

Booth SL; Centi A; Smith SR; Gundberg C

2013-01-01

248

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

1989-10-01

249

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

250

Hypothalamic ATF3 is involved in regulating glucose and energy metabolism in mice.  

UK PubMed Central (United Kingdom)

AIMS/HYPOTHESIS: The pancreas and hypothalamus are critical for maintaining nutrient and energy homeostasis, and combined disorders in these organs account for the onset of the metabolic syndrome. Activating transcription factor 3 (ATF3) is an adaptive response transcription factor. The physiological role of ATF3 in the pancreas has been controversial, and its role in the hypothalamus remains unknown. To elucidate the roles of ATF3 in these organs, we generated pancreas- and hypothalamus-specific Atf3 knockout (PHT-Atf3-KO) mice in this study. METHODS: We crossed mice bearing floxed Atf3 alleles with Pdx1-cre mice, in which cre is specifically expressed in the pancreas and hypothalamus, and analysed metabolic variables, pancreatic morphology, food intake, energy expenditure and sympathetic activity in adipose tissue. We also used a hypothalamic cell line to investigate the molecular mechanism by which ATF3 regulates transcription of the gene encoding agouti-related protein (Agrp). RESULTS: Although PHT-Atf3-KO mice displayed better glucose tolerance, neither plasma glucagon nor insulin level was altered in these mice. However, these mice exhibited higher insulin sensitivity, which was accompanied by a leaner phenotype due to decreased food intake and increased energy expenditure. We also observed decreased hypothalamic Agrp expression in PHT-Atf3-KO mice. Importantly, an increase in ATF3 levels is induced by fasting or low glucose in the hypothalamus. We also showed that ATF3 interacts with forkhead box-containing protein, O subfamily 1 (FoxO1) on the Agrp promoter and activates Agrp transcription. CONCLUSIONS/INTERPRETATION: Our results suggest that ATF3 plays an important role in the control of glucose and energy metabolism by regulating Agrp.

Lee YS; Sasaki T; Kobayashi M; Kikuchi O; Kim HJ; Yokota-Hashimoto H; Shimpuku M; Susanti VY; Ido-Kitamura Y; Kimura K; Inoue H; Tanaka-Okamoto M; Ishizaki H; Miyoshi J; Ohya S; Tanaka Y; Kitajima S; Kitamura T

2013-06-01

251

Cerebral glucose metabolism in neurofibromatosis type 1 assessed with [18F]-2-fluoro-2-deoxy-D-glucose and PET.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Cerebral PET with [18F]-2-fluoro-2-deoxy-D-glucose has been performed in four patients with neurofibromatosis type 1 (NF1) to assess the relation between cerebral metabolic activity, MRI, and the presence of neurological symptoms, including seizures, as well as mental and language retardation. Wides...

Balestri, P; Lucignani, G; Fois, A; Magliani, L; Calistri, L; Grana, C; Di Bartolo, R M; Perani, D; Fazio, F

252

Alloxan reversibly impairs glucagon release and glucose oxidation by pancreatic A2-cells.  

Science.gov (United States)

Alloxan is known as a selective B-cell cytotoxic substance, and there is so far little evidence for a direct toxic effect on the other islet cell types. To elucidate further whether such effects occur, the actions of alloxan on glucagon release and glucose oxidation were studied in isolated normal or A(2)-cell-rich pancreatic islets of the guinea pig. The A(2)-cell-rich islets were obtained from animals injected with streptozotocin 1-2 weeks before islet isolation. After exposure to alloxan (2 or 5mm) in vitro for 30min at 4 degrees C, the islets were incubated in media containing either 1.7mm-glucose or 16.7mm-glucose plus 30m-i.u. of bovine insulin/ml. In both types of islet, alloxan abolished the ability of glucose and insulin both to decrease glucagon release and to increase the rate of glucose oxidation. A high concentration of glucose (28mm) during exposure to alloxan protected against these injurious effects. Tissue culture of alloxan-treated islets for 24h in 5.5mm-glucose restored neither the suppressive effect of glucose on glucagon release nor the inhibition of glucose oxidation of the A(2)-cells. However, culture for 1 week completely normalized both the glucagon-secretory response and glucose oxidation by both kinds of islets. It is therefore concluded that alloxan affects the secretory mechanism of not only the B-cell but also of the islet A(2)-cell, although this latter cell type is not primarily destroyed by the drug. The data furthermore support the concept of a relationship between glucose metabolism and the glucose-mediated glucagon release of the A(2)-cell. PMID:6996677

Ostenson, C G

1980-04-15

253

Alloxan reversibly impairs glucagon release and glucose oxidation by pancreatic A2-cells.  

UK PubMed Central (United Kingdom)

Alloxan is known as a selective B-cell cytotoxic substance, and there is so far little evidence for a direct toxic effect on the other islet cell types. To elucidate further whether such effects occur, the actions of alloxan on glucagon release and glucose oxidation were studied in isolated normal or A(2)-cell-rich pancreatic islets of the guinea pig. The A(2)-cell-rich islets were obtained from animals injected with streptozotocin 1-2 weeks before islet isolation. After exposure to alloxan (2 or 5mm) in vitro for 30min at 4 degrees C, the islets were incubated in media containing either 1.7mm-glucose or 16.7mm-glucose plus 30m-i.u. of bovine insulin/ml. In both types of islet, alloxan abolished the ability of glucose and insulin both to decrease glucagon release and to increase the rate of glucose oxidation. A high concentration of glucose (28mm) during exposure to alloxan protected against these injurious effects. Tissue culture of alloxan-treated islets for 24h in 5.5mm-glucose restored neither the suppressive effect of glucose on glucagon release nor the inhibition of glucose oxidation of the A(2)-cells. However, culture for 1 week completely normalized both the glucagon-secretory response and glucose oxidation by both kinds of islets. It is therefore concluded that alloxan affects the secretory mechanism of not only the B-cell but also of the islet A(2)-cell, although this latter cell type is not primarily destroyed by the drug. The data furthermore support the concept of a relationship between glucose metabolism and the glucose-mediated glucagon release of the A(2)-cell.

Ostenson CG

1980-04-01

254

Relationship of ethnicity and CD4 Count with glucose metabolism among HIV patients on Highly-Active Antiretroviral Therapy (HAART).  

UK PubMed Central (United Kingdom)

BACKGROUND: HIV patients on HAART are prone to metabolic abnormalities, including insulin resistance, lipodystrophy and diabetes. This study purports to investigate the relationship of ethnicity and CD4+ T cell count attained after stable highly-active antiretroviral treatment (HAART) with glucose metabolism in hyperrtriglyceridemic HIV patients without a history of diabetes. METHODS: Demographic, anthropometric, clinical, endocrinologic, energy expenditure and metabolic measures were obtained in 199 multiethnic, healthy but hypertriglyceridemic HIV-infected patients [46% Hispanic, 17% African-American, 37% Non-Hispanic White (NHW)] on stable HAART without a history of diabetes. The relationship of glucose and insulin responses to ethnicity, CD4 strata (low (<300/cc) or moderate-to-high (? 300/cc)), and their interaction was determined. RESULTS: African-Americans had significantly greater impairment of glucose tolerance (P?glucose, insulin and lipids), African-Americans and Hispanics had significantly higher HbA1c and 2-hour glucose levels than NHW's. Demonstrating a significant interaction between ethnicity and CD4 count (P?=?0.023), African Americans with CD4 <300/cc and Hispanics with CD4 ?300/cc had the most impaired glucose response following oral glucose challenge. CONCLUSIONS: Among hypertriglyceridemic HIV patients on HAART, African-Americans and Hispanics are at increased risk of developing diabetes. Ethnicity also interacts with CD4+ T cell count attained on stable HAART to affect post-challenge glycemic response.

Misra R; Chandra P; Riechman SE; Long DM; Shinde S; Pownall HJ; Coraza I; Lewis DE; Sekhar RV; Balasubramanyam A

2013-01-01

255

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

256

Anomeric specificity of D-glucose metabolism study in rat and human erythrocytes  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The anomeric specificity of D-glucose metabolism in erythrocytes has been since 1985 the matter of extensive investigations reported in about ten publications. The present report aims at providing an integrated review of the major findings on this issue.

Willy J. Malaisse

257

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

UK PubMed Central (United Kingdom)

The Entner-Doudoroff pathway was shown to be induced for oxidative glucose metabolism when Escherichia coli was provided with the periplasmic glucose dehydrogenase cofactor pyrroloquinoline quinone (PQQ). Induction of the Entner-Doudoroff pathway by glucose plus PQQ was established both genetically and biochemically and was shown to occur in glucose transport mutants, as well as in wild-type E. coli. These data complete the body of evidence that proves the existence of a pathway for oxidative glucose metabolism in E. coli. PQQ-dependent oxidative glucose metabolism provides a metabolic branch point in the periplasm; the choices are either oxidation to gluconate followed by induction of the Entner-Doudoroff pathway or phosphotransferase-mediated transport. The oxidative glucose pathway might be important for survival of enteric bacteria in aerobic, low-phosphate, aquatic environments.

Fliege R; Tong S; Shibata A; Nickerson KW; Conway T

1992-12-01

258

Metabolic pathway promiscuity in the archaeon Sulfolobus solfataricus revealed by studies on glucose dehydrogenase and 2-keto-3-deoxygluconate aldolase.  

Science.gov (United States)

The hyperthermophilic Archaeon Sulfolobus solfataricus metabolizes glucose by a non-phosphorylative variant of the Entner-Doudoroff pathway. In this pathway glucose dehydrogenase and gluconate dehydratase catalyze the oxidation of glucose to gluconate and the subsequent dehydration of gluconate to 2-keto-3-deoxygluconate. 2-Keto-3-deoxygluconate (KDG) aldolase then catalyzes the cleavage of 2-keto-3-deoxygluconate to glyceraldehyde and pyruvate. The gene encoding glucose dehydrogenase has been cloned and expressed in Escherichia coli to give a fully active enzyme, with properties indistinguishable from the enzyme purified from S. solfataricus cells. Kinetic analysis revealed the enzyme to have a high catalytic efficiency for both glucose and galactose. KDG aldolase from S. solfataricus has previously been cloned and expressed in E. coli. In the current work its stereoselectivity was investigated by aldol condensation reactions between D-glyceraldehyde and pyruvate; this revealed the enzyme to have an unexpected lack of facial selectivity, yielding approximately equal quantities of 2-keto-3-deoxygluconate and 2-keto-3-deoxygalactonate. The KDG aldolase-catalyzed cleavage reaction was also investigated, and a comparable catalytic efficiency was observed with both compounds. Our evidence suggests that the same enzymes are responsible for the catabolism of both glucose and galactose in this Archaeon. The physiological and evolutionary implications of this observation are discussed in terms of catalytic and metabolic promiscuity. PMID:12824170

Lamble, Henry J; Heyer, Narinder I; Bull, Steven D; Hough, David W; Danson, Michael J

2003-06-24

259

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

UK PubMed Central (United Kingdom)

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 Y; Solomon TP; Haus JM; Saidel GM; Cabrera ME; Kirwan JP

2010-06-01

260

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

 
 
 
 
261

Modulation of glucose metabolism in isolated rat hepatocytes by 1,1,1,2-tetrafluoroethane.  

Science.gov (United States)

The thermodynamic behavior and lack of ozone-depleting potential of 1,1,1,2-tetrafluoroethane (R-134a) suggest it as a likely replacement for dichlorodifluoromethane (R-12), now used as the refrigerant in many air-conditioning systems. To further the presently incomplete toxicological analysis of R-134a, the effects of R-134a on cell viability and functional competence of glucose metabolism were evaluated in suspension cultures of hepatocytes derived from fed or fasted rats. R-134a concentrations up to and including 75% (750,000 ppm) in the gas phase of sealed culture flasks did not produce evidence of cytolethality (LDH leakage) following 2 hr of exposure; in contrast, halothane (1,1,1-trifluoro-2-bromo-2-chloroethane) caused cell death at a gas phase concentration of only 1250 ppm. In hepatocytes isolated from fed rats. R-134a at concentrations of 12.5 to 75% increased glycolysis (production of lactate + pyruvate) in a concentration-dependent manner; no effect was observed at 5%. At 25%, R-12 and 1,1,2,2-tetrafluoro-1,2-dichloroethane (R-114) were of equal potency to R-134a in stimulating glycolysis: 1,1,1,2,2-pentafluoro-2-chloroethane (R-115) depressed glycolysis slightly. Halothane, at concentrations as low as 300 ppm, markedly increased rates of glycolysis. Glucose production by hepatocytes of fed rats was decreased by R-134, R-12, and R-114 only at concentrations of 25% or more. On the other hand, halothane (greater than or equal to 300 ppm) potently decreased glucose production by hepatocytes. In cells isolated from livers of fasted rats, R-134a exposure inhibited gluconeogenesis in a concentration-dependent manner although this effect was not significant until R-134a concentrations reached 12.5%. Comparative potency studies showed that R-134a, R-12, or R-114 (25% gas phase) inhibited gluconeogenesis about equally while as little as 300 ppm halothane was effective and R-115 (25%) was without effect. Considering that the threshold for alteration of the rate of glucose metabolism in this in vitro paradigm is about 12.5% R-134a, we conclude that toxicologically significant alteration of glucose-linked bioenergetics is unlikely at the levels of R-134a exposure anticipated in workplace or environment. PMID:2227155

Olson, M J; Reidy, C A; Johnson, J T

1990-08-01

262

Characterization of a glucose polymer from PC12 cells and neuronal cells of rat embryo.  

UK PubMed Central (United Kingdom)

A large-sized glucose polymer was isolated by pronase digestion from line PC12 pheochromocytoma cells metabolically labeled with [1-3H]galactose. The polymer was included on a column of concanavalin A-Sepharose and could be eluted with 10 mM methyl-alpha-mannoside. Its slight retention in a column of Bio-Gel A-5m suggested that its molecular weight was in the several millions. Glucose was the component monosaccharide and there were two minor lipophilic components present. The polymer was digested with alpha-amylase into a series of oligosaccharides and was cleaved by glucoamylase into glucose residues. The disaccharide obtained by digestion with alpha-amylase was identified as maltose in several HPLC systems and by NMR spectroscopy. NMR measurement revealed the trisaccharide to be maltotriose. Susceptibility of the polymer molecule to alpha-amylase, and the digestion products obtained, indicated a resemblance to glycogen. An analysis for saccharide compositions before and after reduction of the polymer suggested the presence of an aglycon part. Contrary to expectations based on the presence of this moiety, the polymer displayed good solubility in neutral organic solvents. Two-thirds of the glucose polymer was also soluble in 10% TCA. A similar glucose polymer was isolated from neuronal cells of rat embryos metabolically labeled with [1-3H]galactose. Mouse neuroblastoma cells did not synthesize the polymer.

Rasilo ML; Yamagata T

1988-11-01

263

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

264

Small is fast: astrocytic glucose and lactate metabolism at cellular resolution.  

UK PubMed Central (United Kingdom)

Brain tissue is highly dynamic in terms of electrical activity and energy demand. Relevant energy metabolites have turnover times ranging from milliseconds to seconds and are rapidly exchanged between cells and within cells. Until recently these fast metabolic events were inaccessible, because standard isotopic techniques require use of populations of cells and/or involve integration times of tens of minutes. Thanks to fluorescent probes and recently available genetically-encoded optical nanosensors, this Technology Report shows how it is now possible to monitor the concentration of metabolites in real-time and in single cells. In combination with ad hoc inhibitor-stop protocols, these probes have revealed a key role for K(+) in the acute stimulation of astrocytic glycolysis by synaptic activity. They have also permitted detection of the Warburg effect in single cancer cells. Genetically-encoded nanosensors currently exist for glucose, lactate, NADH and ATP, and it is envisaged that other metabolite nanosensors will soon be available. These optical tools together with improved expression systems and in vivo imaging, herald an exciting era of single-cell metabolic analysis.

Barros LF; San Martín A; Sotelo-Hitschfeld T; Lerchundi R; Fernández-Moncada I; Ruminot I; Gutiérrez R; Valdebenito R; Ceballo S; Alegría K; Baeza-Lehnert F; Espinoza D

2013-01-01

265

High concentrations of glucose reduce the oxidative metabolism of dog neutrophils in vitro.  

UK PubMed Central (United Kingdom)

BACKGROUND: Dogs are commonly affected by hyperglycemic conditions. Hyperglycemia compromises the immune response and favors bacterial infections; however, reports on the effects of glucose on neutrophil oxidative metabolism and apoptosis are conflicting in humans and rare in dogs. Considering the many complex factors that affect neutrophil oxidative metabolism in vivo, we investigated in vitro the specific effect of high concentrations of glucose on superoxide production and apoptosis rate in neutrophils from healthy dogs. RESULTS: The capacity of the neutrophils to reduce tetrazolium nitroblue decreased significantly in the higher concentration of glucose (15.13 ± 9.73% (8 mmol/L) versus 8.93 ± 5.71% (16 mmol/L)). However, there were no changes in tetrazolium nitroblue reduction at different glucose concentrations when the neutrophils were first activated with phorbol myristate acetate. High concentrations of glucose did not affect the viability and apoptosis rate of canine neutrophils either with or without prior camptothecin stimulation. This study provides the first evidence that high concentrations of glucose inhibit the oxidative metabolism of canine neutrophils in vitro in a manner similar to that which occurs in humans, and that the decrease in superoxide production did not increase the apoptosis rate. CONCLUSIONS: A high concentration of glucose reduces the oxidative metabolism of canine neutrophils in vitro. It is likely that glucose at high concentrations rapidly affects membrane receptors responsible for the activation of NADPH oxidase in neutrophils; therefore, the nonspecific immune response can be compromised in dogs with acute and chronic hyperglycemic conditions.

Bosco AM; de Almeida BF; Pereira PP; Narciso LG; Lima VM; Ciarlini PC

2013-01-01

266

NADPH oxidase activation by hyperglycaemia in cardiomyocytes is independent of glucose metabolism but requires SGLT1.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

AIMS: Exposure to high glucose (HG) stimulates reactive oxygen species (ROS) production by NADPH oxidase in cardiomyocytes, but the underlying mechanism remains elusive. In this study, we have dissected the link between glucose transport and metabolism and NADPH oxidase activation under hyperglycaem...

Balteau, Magali; Tajeddine, Nicolas; De Meester, Carole; Ginion, Audrey; Des Rosiers, Christine; Brady, Nathan R

267

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

268

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

International Nuclear Information System (INIS)

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

1986-03-05

269

High concentrations of glucose reduce the oxidative metabolism of dog neutrophils in vitro  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Dogs are commonly affected by hyperglycemic conditions. Hyperglycemia compromises the immune response and favors bacterial infections; however, reports on the effects of glucose on neutrophil oxidative metabolism and apoptosis are conflicting in humans and rare in dogs. Considering the many complex factors that affect neutrophil oxidative metabolism in vivo, we investigated in vitro the specific effect of high concentrations of glucose on superoxide production and apoptosis rate in neutrophils from healthy dogs. Results The capacity of the neutrophils to reduce tetrazolium nitroblue decreased significantly in the higher concentration of glucose (15.13 ± 9.73% (8 mmol/L) versus 8.93 ± 5.71% (16 mmol/L)). However, there were no changes in tetrazolium nitroblue reduction at different glucose concentrations when the neutrophils were first activated with phorbol myristate acetate. High concentrations of glucose did not affect the viability and apoptosis rate of canine neutrophils either with or without prior camptothecin stimulation. This study provides the first evidence that high concentrations of glucose inhibit the oxidative metabolism of canine neutrophils in vitro in a manner similar to that which occurs in humans, and that the decrease in superoxide production did not increase the apoptosis rate. Conclusions A high concentration of glucose reduces the oxidative metabolism of canine neutrophils in vitro. It is likely that glucose at high concentrations rapidly affects membrane receptors responsible for the activation of NADPH oxidase in neutrophils; therefore, the nonspecific immune response can be compromised in dogs with acute and chronic hyperglycemic conditions.

Bosco Anelise M; de Almeida Breno FM; Pereira Priscila P; Narciso Luis G; Lima Valéria MF; Ciarlini Paulo C

2013-01-01

270

Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.  

UK PubMed Central (United Kingdom)

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

Tirado-Vélez JM; Joumady I; Sáez-Benito A; Cózar-Castellano I; Perdomo G

2012-01-01

271

Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.  

Science.gov (United States)

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

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

2012-09-28

272

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

International Nuclear Information System (INIS)

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

1991-01-01

273

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; Li Hongbin; Zeng Xiao; Yang Pengbo; Liu Xinyu; Zhao Xia; Liang Shufang

2012-01-01

274

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder  

Energy Technology Data Exchange (ETDEWEB)

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

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

1989-06-01

275

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

UK PubMed Central (United Kingdom)

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

Swedo SE; Schapiro MB; Grady CL; Cheslow DL; Leonard HL; Kumar A; Friedland R; Rapoport SI; Rapoport JL

1989-06-01

276

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder  

International Nuclear Information System (INIS)

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

1989-01-01

277

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; Bo ZHOU; Ya-qian DUAN; Chao DU

2013-01-01

278

Longitudinal studies of cerebral glucose metabolism in late-life depression and normal aging.  

UK PubMed Central (United Kingdom)

OBJECTIVE: Late-life depression (LLD) has a substantial public health impact and is both a risk factor for and a prodrome of dementia. Positron emission tomography (PET) studies of cerebral glucose metabolism have demonstrated sensitivity in evaluating neural circuitry involved in depression, aging, incipient cognitive decline, and dementia. The present study evaluated the long term effects of a course of antidepressant treatment on glucose metabolism in LLD patients. METHODS: Nine LLD patients and seven non-depressed control subjects underwent clinical and cognitive evaluations as well as brain magnetic resonance imaging and PET studies of cerebral glucose metabolism at baseline, after 8 weeks of treatment with citalopram for a major depressive episode (patients only), and at an approximately 2-year follow-up. RESULTS: The majority of LLD patients were remitted at follow-up (7/9). Neither patients nor controls showed significant cognitive decline. The patients showed greater increases in glucose metabolism than the controls in regions associated with mood symptoms (anterior cingulate and insula). Both groups showed decreases in metabolism in posterior association cortices implicated in dementia. CONCLUSIONS: Longitudinal changes in cerebral glucose metabolism are observed in controls and in LLD patients without significant cognitive decline that are more extensive than the decreases in brain volume. Longer duration follow-up studies and the integration of other molecular imaging methods will have implications for understanding the clinical and neurobiological significance of these metabolic changes.

Marano CM; Workman CI; Kramer E; Hermann CR; Ma Y; Dhawan V; Chaly T; Eidelberg D; Smith GS

2013-04-01

279

MYC-induced cancer cell energy metabolism and therapeutic opportunities.  

UK PubMed Central (United Kingdom)

Although cancers have altered glucose metabolism, termed the Warburg effect, which describes the increased uptake and conversion of glucose to lactate by cancer cells under adequate oxygen tension, changes in the metabolism of glutamine and fatty acid have also been documented. The MYC oncogene, which contributes to the genesis of many human cancers, encodes a transcription factor c-Myc, which links altered cellular metabolism to tumorigenesis. c-Myc regulates genes involved in the biogenesis of ribosomes and mitochondria, and regulation of glucose and glutamine metabolism. With E2F1, c-Myc induces genes involved in nucleotide metabolism and DNA replication, and microRNAs that homeostatically attenuate E2F1 expression. With the hypoxia inducible transcription factor HIF-1, ectopic c-Myc cooperatively induces a transcriptional program for hypoxic adaptation. Myc regulates gene expression either directly, such as glycolytic genes including lactate dehydrogenase A (LDHA), or indirectly, such as repression of microRNAs miR-23a/b to increase glutaminase (GLS) protein expression and glutamine metabolism. Ectopic MYC expression in cancers, therefore, could concurrently drive aerobic glycolysis and/or oxidative phosphorylation to provide sufficient energy and anabolic substrates for cell growth and proliferation in the context of the tumor microenvironment. Collectively, these studies indicate that Myc-mediated altered cancer cell energy metabolism could be translated for the development of new anticancer therapies.

Dang CV; Le A; Gao P

2009-11-01

280

Analysis of CHO cells metabolic redistribution in a glutamate-based defined medium in continuous culture.  

UK PubMed Central (United Kingdom)

The effect of glutamine replacement by glutamate and the balance between glutamate and glucose metabolism on the redistribution of t-PA-producing recombinant CHO cells metabolism is studied in a series of glucose shift down and shift up experiments in continuous culture. These experiments reveal the existence of multiple steady states, and experimental data are used to perform metabolic flux analysis to gain a better insight into cellular metabolism and its redistribution. Regulation of glucose feed rate promotes a higher efficiency of glucose and nitrogen source utilization, with lower production of metabolic byproducts, but this reduces t-PA specific production rate. This reduction under glucose limitation can be attributed to the fact that the cells are forced to efficiently utilize the carbon and energy source for growth, impairing the production of dispensable metabolites. It is, therefore, the combination of growth rate and carbon and energy source availability that determines the level of t-PA production in continuous culture.

Altamirano C; Illanes A; Casablancas A; Gámez X; Cairó JJ; Gòdia C

2001-11-01

 
 
 
 
281

Analysis of CHO cells metabolic redistribution in a glutamate-based defined medium in continuous culture.  

Science.gov (United States)

The effect of glutamine replacement by glutamate and the balance between glutamate and glucose metabolism on the redistribution of t-PA-producing recombinant CHO cells metabolism is studied in a series of glucose shift down and shift up experiments in continuous culture. These experiments reveal the existence of multiple steady states, and experimental data are used to perform metabolic flux analysis to gain a better insight into cellular metabolism and its redistribution. Regulation of glucose feed rate promotes a higher efficiency of glucose and nitrogen source utilization, with lower production of metabolic byproducts, but this reduces t-PA specific production rate. This reduction under glucose limitation can be attributed to the fact that the cells are forced to efficiently utilize the carbon and energy source for growth, impairing the production of dispensable metabolites. It is, therefore, the combination of growth rate and carbon and energy source availability that determines the level of t-PA production in continuous culture. PMID:11735437

Altamirano, C; Illanes, A; Casablancas, A; Gámez, X; Cairó, J J; Gòdia, C

282

[Research progress of effect of anti-diabetic traditional Chinese medicines based on regulation of glucose metabolic enzyme].  

Science.gov (United States)

Diabetes is a global threat threatening human health in the world, with an increasing incidence rate in recent years. The disorder of glucose metabolism is one of the major factors. As relevant glucose metabolic enzymes such as alpha-glucosidase, glucose-6-phosphatase (G-6-P), glycogen phosphorylase (GP) and glycogen synthase kinase-3 (GSK-3) get involved in and control the process of glucose metabolism, the regulation of the activity of glucose metabolic enzymes is of significance to the treatment of diabetes. Traditional Chinese medicines (TCMs) have been widely researched because of their low toxicology and high efficiency, and many extracts and components from TCMs have been proven to be regulators of glucose metabolic enzymes. Compared with anti-diabetic western medicines, anti-diabetic TCMs feature safety, reliability and low price. This essay summarizes the anti-diabetic effect of TCMs on regulating glucose metabolic enzymes. PMID:23477131

Ji, Liu; Tang, Xin-Qiang; Peng, Jin-Yong

2012-12-01

283

[Research progress of effect of anti-diabetic traditional Chinese medicines based on regulation of glucose metabolic enzyme].  

UK PubMed Central (United Kingdom)

Diabetes is a global threat threatening human health in the world, with an increasing incidence rate in recent years. The disorder of glucose metabolism is one of the major factors. As relevant glucose metabolic enzymes such as alpha-glucosidase, glucose-6-phosphatase (G-6-P), glycogen phosphorylase (GP) and glycogen synthase kinase-3 (GSK-3) get involved in and control the process of glucose metabolism, the regulation of the activity of glucose metabolic enzymes is of significance to the treatment of diabetes. Traditional Chinese medicines (TCMs) have been widely researched because of their low toxicology and high efficiency, and many extracts and components from TCMs have been proven to be regulators of glucose metabolic enzymes. Compared with anti-diabetic western medicines, anti-diabetic TCMs feature safety, reliability and low price. This essay summarizes the anti-diabetic effect of TCMs on regulating glucose metabolic enzymes.

Ji L; Tang XQ; Peng JY

2012-12-01

284

Regulation of Glucose Transport and Metabolism in Thiobacillus novellus  

Digital Repository Infrastructure Vision for European Research (DRIVER)

To investigate the physiological basis of decreased rate of glucose utilization by Thiobacillus novellus in a mixotrophic environment (R. C. Perez and A. Matin, J. Bacteriol. 142:633–638, 1980), its glucose transport system was characterized and the modulation of this system as well as enzymes of gl...

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

285

Abnormal glucose metabolism and insulin sensitivity in chinese patients with Gitelman syndrome.  

UK PubMed Central (United Kingdom)

BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive disease of renal tubulopathy, primarily characterized by hypokalemic metabolic alkalosis with significant hypomagnesemia, low urinary calcium, secondary aldosteronism and normal blood pressure. Both hypokalemia and hypomagnesemia were reported to cause impaired glucose tolerance and/or insulin resistance, but it is unclear whether impaired glucose tolerance and/or insulin resistance are common in GS patients. METHODS: An oral glucose tolerance test was performed among 16 GS patients and 12 healthy adults as control subjects. Fasting glucose and serum insulin levels were measured and the values of glucose and serum insulin after 30, 60, 120 and 180 min were also measured after an oral glucose load. The area under curve (AUC) of glucose and insulin was calculated. RESULTS: One patient had isolated impaired fasting glucose, 2 had isolated impaired glucose tolerance, and 1 had combined impaired fasting glucose and glucose tolerance. Six patients were diagnosed with type 2 diabetes mellitus. Compared with a healthy normal control group, GS patients showed a higher AUC glucose level [16.1 (IQR 12.5-25.4 mEq · h/l) vs. 13.0 (IQR 11.9-13.7 mEq · h/l); p < 0.05] and AUC insulin level [81.0 (IQR 58.9-138 µU · h/ml) vs. 46.4 (IQR 35.6-63.3 µU · h/ml); p < 0.01]. GS patients showed a delay of insulin secretion peak which was observed 120 min after a glucose load. Homeostasis model assessment of insulin resistance in GS patients was significantly higher than in control volunteers. Quantitative insulin sensitivity check index and insulin sensitivity index composite in the GS group were significantly lower than in the control group. CONCLUSION: Abnormal glucose metabolism and insulin secretion is common in GS patients. It is speculated that hypokalemia and hypomagnesemia may be the main cause.

Ren H; Qin L; Wang W; Ma J; Zhang W; Shen PY; Shi H; Li X; Chen N

2013-01-01

286

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

DEFF Research Database (Denmark)

OBJECTIVE: We have recently shown that the level of soluble urokinase plasminogen activator receptor (suPAR), which is associated with the immune status of HIV-infected patients undergoing highly active antiretroviral therapy (HAART), correlates with the insulin action of such patients. Here we extend these findings by investigating the association of suPAR to glucose metabolic insufficiency during an oral glucose challenge (OGTT). METHODS: In 16 HIV-infected patients with lipodystrophy and 15 HIV-infected patients without lipodystrophy, glucose tolerance, insulin sensitivity (ISI(composite)), prehepatic insulin secretion, proinsulin level and suppression of free fatty acids (FFA) were determined during an OGTT. Stability of suPAR was tested in 6 HIV-infected patients during a 3h OGTT. RESULTS: Lipodystrophy was associated with a 70% increase in plasma suPAR (P<0.05). During the OGTT, plasma suPAR correlated inversely with ISI(composite) and positively with 2h plasma glucose, fasting insulin secretion, fasting intact proinsulin and FFA level during the OGTT (all P<0.05). In multiple regression analyses, in which anthropometric measures (BMI, limbadiposity and fat mass), immune markers (CD4, HIV-RNA, duration of HIV infection), and dyslipidemia (plasma total cholesterol, triglyceride and free fatty acid level during the OGTT) were included, suPAR remained a significant marker of glucose tolerance and insulin sensitivity. Plasma suPAR exhibited a small CV (11%) during the 3h OGTT. CONCLUSIONS: suPAR associated to important glucose metabolic aberrations in HIV-infected patients on HAART. Moreover, suPAR was stable after a glucose challenge. Future research is required to confirm these findings and explore the potential of suPAR as marker of dysmetabolism in HIV-infected patients Udgivelsesdato: 2008/7

Andersen, Ove; Eugen-Olsen, Jesper

2008-01-01

287

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

The Entner-Doudoroff pathway was shown to be induced for oxidative glucose metabolism when Escherichia coli was provided with the periplasmic glucose dehydrogenase cofactor pyrroloquinoline quinone (PQQ). Induction of the Entner-Doudoroff pathway by glucose plus PQQ was established both genetically ...

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

288

Optimized [1-13C]glucose infusion protocol for 13C magnetic resonance spectroscopy at 3 Tesla of human brain glucose metabolism under euglycemic and hypoglycemic conditions  

Science.gov (United States)

The effect of insulin-induced hypoglycemia on cerebral glucose metabolism is largely unknown. 13C MRS is a unique tool to study cerebral glucose metabolism, but the concurrent requirement for [1-13C]glucose administration limits its use under hypoglycemic conditions. To facilitate 13C MRS data analysis we designed separate [1-13C]glucose infusion protocols for hyperinsulinemic euglycemic and hypoglycemic clamps in such a way that plasma isotopic enrichment of glucose was stable and comparable under both glycemic conditions. 13C MR spectra were acquired with optimized 13C MRS measurement techniques to obtain high quality 13C MR spectra with these protocols.

van de Ven, Kim C.C.; van der Graaf, Marinette; Tack, Cees J.J.; Klomp, Dennis W.J.; Heerschap, Arend; de Galan, Bastiaan E.

2009-01-01

289

Studies on citrate metabolism in liver injuries. 2. Response of liver citrate to glucose load.  

Directory of Open Access Journals (Sweden)

Full Text Available The effect of glucose load on the levels of blood glucose, serum non-esterified fatty acids (NEFA) and liver citrate was investigated in carbontetrachloride-intoxicated (injured) rats and compared with non-intoxicated controls. The citrate level in the liver from injured animals showed 15-fold of the value of the control. Glucose load on these animals caused gradual decrease in the citrate level, whereas similar administration to the control caused inverse results. The serum NEFA levels were lowered by glucose load in both of injured and control animals. The pattern of changes in the citrate level after glucose load in the liver from injured animals was similar to that in the muscle from the control, suggesting a similarity on citrate metabolism between the injured liver and the muscle.The possible mechanisms for these results were discussed in relation to the difference in citrate metabolism between the liver and the muscle.

Kaneshige,Junji

1975-01-01

290

Metabolism Of C(14)-Glucose By Eurytrema Pancreaticum.  

Science.gov (United States)

1. The glucose uptake rate by Eurytrema pancreaticum was a mean value of 16.44 +/- 2.42 micro moles/hr/g, and total CO2 production rate by the fluke averaged 5.82 +/- 0.97 micro moles/hr/g. The relative specific activity of respiratory CO2 showed a mean value of 5.75 +/- 0.84 per cent. The rate of CO2 production derived from medium C(14)-glucose was a mean of 0.33 +/- 0.10 micor-mole/hr/g. Therefore, the average value of 0.32 +/- 0.04 per cent of glucose utilized by the flukes from the medium C(14)-glucose was oxidized to respiratory CO2. 2. The tissue concentration of glycogen in E. pancreaticum was a mean of 45.50 +/- 2.18 mg/g or 4.55 +/- 0.22 %/g. But the turnover rate of glycogen pool was a mean of 0.027 +/- 0.003 %/hr or 0.009 +/- 0.002 mg/hr/g. The average value of 0.64 +/- 0.23 percent of glucose utilized by the flukes from the medium C(14)-glucose was incorporated into the glycogen. 3. These data account for that only 1 per cent of the utilized glucose by the flukes participated in furnishing the oxidation into respiratory CO2 and the synthetic process into glycogen. PMID:12913599

Seo, Byong Seol; Rim, Han Jong; Kim, Kwang Soo; Lee, Myung Sang; Kim, Yeong Uhn; Song, Hi Yong

1964-12-01

291

Metabolism Of C(14)-Glucose By Eurytrema Pancreaticum.  

UK PubMed Central (United Kingdom)

1. The glucose uptake rate by Eurytrema pancreaticum was a mean value of 16.44 +/- 2.42 micro moles/hr/g, and total CO2 production rate by the fluke averaged 5.82 +/- 0.97 micro moles/hr/g. The relative specific activity of respiratory CO2 showed a mean value of 5.75 +/- 0.84 per cent. The rate of CO2 production derived from medium C(14)-glucose was a mean of 0.33 +/- 0.10 micor-mole/hr/g. Therefore, the average value of 0.32 +/- 0.04 per cent of glucose utilized by the flukes from the medium C(14)-glucose was oxidized to respiratory CO2. 2. The tissue concentration of glycogen in E. pancreaticum was a mean of 45.50 +/- 2.18 mg/g or 4.55 +/- 0.22 %/g. But the turnover rate of glycogen pool was a mean of 0.027 +/- 0.003 %/hr or 0.009 +/- 0.002 mg/hr/g. The average value of 0.64 +/- 0.23 percent of glucose utilized by the flukes from the medium C(14)-glucose was incorporated into the glycogen. 3. These data account for that only 1 per cent of the utilized glucose by the flukes participated in furnishing the oxidation into respiratory CO2 and the synthetic process into glycogen.

Seo BS; Rim HJ; Kim KS; Lee MS; Kim YU; Song HY

1964-12-01

292

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

293

Photoelectrochemical oxidation of glucose for sensing and fuel cell applications.  

UK PubMed Central (United Kingdom)

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.

Yan Y; Fang J; Yang Z; Qiao J; Wang Z; Yu Q; Sun K

2013-10-01

294

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

295

A glucose biofuel cell implanted in rats.  

Science.gov (United States)

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

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

2010-05-04

296

A glucose biofuel cell implanted in rats.  

UK PubMed Central (United Kingdom)

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

Cinquin P; Gondran C; Giroud F; Mazabrard S; Pellissier A; Boucher F; Alcaraz JP; Gorgy K; Lenouvel F; Mathé S; Porcu P; Cosnier S

2010-01-01

297

Regulation of glucose and glycogen metabolism during and after exercise.  

UK PubMed Central (United Kingdom)

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 TE; Richter EA

2012-03-01

298

Age differences in intercorrelations between regional cerebral metabolic rates for glucose  

Energy Technology Data Exchange (ETDEWEB)

Patterns of cerebral metabolic intercorrelations were compared in the resting state in 15 healthy young men (ages 20 to 32 years) and 15 healthy elderly men (ages 64 to 83 years). Controlling for whole-brain glucose metabolism, partial correlation coefficients were determined between pairs of regional cerebral metabolic rates for glucose determined by positron emission tomography using (18F)fluorodeoxyglucose and obtained in 59 brain regions. Compared with the young men, the elderly men had fewer statistically significant correlations, with the most notable reductions observed between the parietal lobe regions, and between the parietal and frontal lobe regions. These results suggest that cerebral functional interactions are reduced in healthy elderly men.

Horwitz, B.; Duara, R.; Rapoport, S.I.

1986-01-01

299

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1989-01-01

300

Cardiac stem cell regeneration in metabolic syndrome.  

UK PubMed Central (United Kingdom)

The metabolic syndrome (MetS) is a constellation of multiple metabolic risk factors including obesity, glucose intolerance, insulin resistance, dyslipidemia and hypertension. Individuals with MetS are found to be afflicted with an increased risk of type 2 diabetes mellitus and overall cardiovascular diseases. One of the common comorbidities of MetS is the impairment of heart function en route to loss of cardiomyocytes and ultimately heart failure. Although it is accepted that cardiomyocytes are terminally differentiated, recent evidence has challenged this concept to indicate the ability of cardiomyocytes to regenerate from progenitor cells of the heart and other organs. Moreover, it has been suggested that pathological conditions such as MetS may play a role in the regulation of cardiomyocyte regeneration. This mini-review will discuss the role of MetS in the regulatory machineries of cardiomyocyte regeneration.

Xu X; Ren J

2013-01-01

 
 
 
 
301

Cardiac stem cell regeneration in metabolic syndrome.  

Science.gov (United States)

The metabolic syndrome (MetS) is a constellation of multiple metabolic risk factors including obesity, glucose intolerance, insulin resistance, dyslipidemia and hypertension. Individuals with MetS are found to be afflicted with an increased risk of type 2 diabetes mellitus and overall cardiovascular diseases. One of the common comorbidities of MetS is the impairment of heart function en route to loss of cardiomyocytes and ultimately heart failure. Although it is accepted that cardiomyocytes are terminally differentiated, recent evidence has challenged this concept to indicate the ability of cardiomyocytes to regenerate from progenitor cells of the heart and other organs. Moreover, it has been suggested that pathological conditions such as MetS may play a role in the regulation of cardiomyocyte regeneration. This mini-review will discuss the role of MetS in the regulatory machineries of cardiomyocyte regeneration. PMID:23323616

Xu, Xihui; Ren, Jun

2013-01-01

302

Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study.  

UK PubMed Central (United Kingdom)

AIMS: Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic control in relation to human leukocyte antigen (HLA) genetic risk and islet autoantibodies in prepubertal children. METHODS: In 47 healthy children with GADA and at least one additional islet autoantibody, intravenous glucose tolerance test (IvGTT) and oral glucose tolerance test (OGTT) were performed 8-65 d apart. Hemoglobin A1c, plasma glucose as well as serum insulin and C-peptide were determined at fasting and during IvGTT and OGTT. RESULTS: All children aged median 5.1 (4.0-9.2) yr had autoantibodies to two to six of the beta-cell antigens GAD65, insulin, IA-2, and the three amino acid position 325 variants of the ZnT8 transporter. In total, 20/47 children showed impaired glucose metabolism. Decreased (? 30 ?U/mL insulin) first-phase insulin response (FPIR) was found in 14/20 children while 11/20 had impaired glucose tolerance in the OGTT. Five children had both impaired glucose tolerance and FPIR ? 30 ?U/mL insulin. Number and levels of autoantibodies were not associated with glucose metabolism, except for an increased frequency (p = 0.03) and level (p = 0.01) of ZnT8QA in children with impaired glucose metabolism. Among the children with impaired glucose metabolism, 13/20 had HLA-DQ2/8, compared to 9/27 of the children with normal glucose metabolism (p = 0.03). CONCLUSION: Secondary prevention studies in children with islet autoantibodies are complicated by variability in baseline glucose metabolism. Evaluation of metabolic control with both IvGTT and OGTT is critical and should be taken into account before randomization. All currently available autoantibody tests should be analyzed, including ZnT8QA.

Andersson C; Carlsson A; Cilio C; Cedervall E; Ivarsson SA; Jonsdottir B; Jönsson B; Larsson K; Neiderud J; Lernmark A; Elding Larsson H

2013-08-01

303

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

International Nuclear Information System (INIS)

[en] The metabolism of 14C-1 labelled glucose was studied in the rat during 620 d. The results concerning (1) elimination by the exhalated air, urine and feces, (2) activity uptakes in 25 tissues or organes, (3) cumulated activity from the 4th to the 627 d are presented and discussed. About 50% of the activity is eliminated as CO2 in the 24 first hours, the remaining is eliminated more slowly. Some tissues such as bone and spinal cord have especially long retention half-lives. Consequently the dose delivered to these tissues is higher by a factor 10. In man, the dose should be generally around 10-4 rem per ?Ci of C-1 glucose administered[fr] Le metabolisme du glucose marque 14C-1 a ete etudie pendant 620 jours chez le rat. Le rapport contient la presentation et la discussion des resultats: - d'elimination par l'air exhale, les urines et les selles, - de retention de l'activite dans 25 tissus ou organes, - d'activite cumulee du 4eme au 627eme jour. Environ 50% de l'activite est eliminee sous forme de CO2 dans les premieres 24 heures. Le reste est elimine plus lentement. Certains tissus comme l'os et la moelle epiniere ont des periodes de retention particulierement longues. En consequence la dose recue par ces tissus est d'un ordre de grandeur superieur a celle des autres. Chez l'homme la dose serait en general d'environ 10-4 rem par ?Ci de glucose C-1 administre

1979-01-01

304

Measurements of glucose metabolism in single equine embryos during early development.  

UK PubMed Central (United Kingdom)

The contributions of 2 biochemical pathways to the total metabolism of glucose (the Embden-Meyerhof pathway [EMP] and the pentose phosphate pathway [PPP]), were assessed for equine embryos recovered on Day 4.5, 7.5 and 11.5 post ovulation. At all developmental stages studied, glucose was metabolized through both pathways. Through the EMP, the amounts of glucose metabolized per nl embryo volume per hour were 4.0, 9.9 and 3.1 pmol, whereas via the PPP, amounts were 0.9, 1.7 and 0.07 pmol for Day-4.5, -7.5 and -11.5 embryos, respectively. The ratio of EMP:PPP with age was 9.7 for Day -4.5 embryos, 7.6 for Day-7.5 embryos and 90.2 for Day -11.5 embryos. Two of the 6 unfertilized ova (UFO) exhibited metabolism through both pathways.

Brück I; Hyland JH

1991-01-01

305

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1985-05-01

306

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

International Nuclear Information System (INIS)

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

1985-01-01

307

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

UK PubMed Central (United Kingdom)

Effects of increasing extracellular K+ or intracellular Na+ concentrations on glucose metabolism in cultures of rat astroglia and neurons were examined. Cells were incubated in bicarbonate buffer, pH 7.2, containing 2 mM glucose, tracer amounts of [14C]deoxyglucose ([14C]dGlc), and 5.4, 28, or 56 mM KCl for 10, 15, or 30 min, and then for 5 min in [14C]dGlc-free buffer to allow efflux of unmetabolized [14C]dGlc. Cells were then digested and assayed for labeled products, which were shown to consist of 96-98% [14C]deoxyglucose 6-phosphate. Increased K+ concentrations significantly raised [14C]deoxyglucose 6-phosphate accumulation in both neuronal and mixed neuronal-astroglial cultures at 15 and 30 min but did not raise it in astroglial cultures. Veratridine (75 microM), which opens voltage-dependent Na+ channels, significantly raised rates of [14C]dGlc phosphorylation in astroglial cultures (+20%), and these elevations were blocked by either 1 mM ouabain, a specific inhibitor of Na+,K(+)-ATPase (EC 3.6.1.37), or 10 microM tetrodotoxin, which blocks Na+ channels. The carboxylic sodium ionophore, monensin (10 microM), more than doubled [14C]dGlc phosphorylation; this effect was only partially blocked by ouabain and unaffected by tetrodotoxin. L-Glutamate (500 microM) also stimulated [14C]dGlc phosphorylation in astroglia--not through N-methyl-D-aspartate or non-N-methyl-D-aspartate receptor mechanisms but via a Na(+)-dependent glutamate-uptake system. These results indicate that increased uptake of Na+ can stimulate energy metabolism in astroglial cells.

Takahashi S; Driscoll BF; Law MJ; Sokoloff L

1995-05-01

308

Compartmentalized glucose metabolism in Pseudomonas putida is controlled by the PtxS repressor.  

UK PubMed Central (United Kingdom)

Metabolic flux analysis revealed that in Pseudomonas putida KT2440 about 50% of glucose taken up by the cells is channeled through the 2-ketogluconate peripheral pathway. This pathway is characterized by being compartmentalized in the cells. In fact, initial metabolism of glucose to 2-ketogluconate takes place in the periplasm through a set of reactions catalyzed by glucose dehydrogenase and gluconate dehydrogenase to yield 2-ketogluconate. This metabolite is subsequently transported to the cytoplasm, where two reactions are carried out, giving rise to 6-phosphogluconate, which enters the Entner-Doudoroff pathway. The genes for the periplasmic and cytoplasmic set of reactions are clustered in the host chromosome and grouped within two independent operons that are under the control of the PtxS regulator, which also modulates its own synthesis. Here, we show that although the two catabolic operons are induced in vivo by glucose, ketogluconate, and 2-ketogluconate, in vitro we found that only 2-ketogluconate binds to the regulator with an apparent K(D) (equilibrium dissociation constant) of 15 muM, as determined using isothermal titration calorimetry assays. PtxS is made of two domains, a helix-turn-helix DNA-binding domain located at the N terminus and a C-terminal domain that binds the effector. Differential scanning calorimetry assays revealed that PtxS unfolds via two events characterized by melting points of 48.1 degrees C and 57.6 degrees C and that, in the presence of 2-ketogluconate, the unfolding of the effector binding domain occurs at a higher temperature, providing further evidence for 2-ketogluconate-PtxS interactions. Purified PtxS is a dimer that binds to the target promoters with affinities in the range of 1 to 3 muM. Footprint analysis revealed that PtxS binds to an almost perfect palindrome that is present within the three promoters and whose consensus sequence is 5'-TGAAACCGGTTTCA-3'. This palindrome overlaps with the RNA polymerase binding site.

Daddaoua A; Krell T; Alfonso C; Morel B; Ramos JL

2010-09-01

309

Compartmentalized glucose metabolism in Pseudomonas putida is controlled by the PtxS repressor.  

Science.gov (United States)

Metabolic flux analysis revealed that in Pseudomonas putida KT2440 about 50% of glucose taken up by the cells is channeled through the 2-ketogluconate peripheral pathway. This pathway is characterized by being compartmentalized in the cells. In fact, initial metabolism of glucose to 2-ketogluconate takes place in the periplasm through a set of reactions catalyzed by glucose dehydrogenase and gluconate dehydrogenase to yield 2-ketogluconate. This metabolite is subsequently transported to the cytoplasm, where two reactions are carried out, giving rise to 6-phosphogluconate, which enters the Entner-Doudoroff pathway. The genes for the periplasmic and cytoplasmic set of reactions are clustered in the host chromosome and grouped within two independent operons that are under the control of the PtxS regulator, which also modulates its own synthesis. Here, we show that although the two catabolic operons are induced in vivo by glucose, ketogluconate, and 2-ketogluconate, in vitro we found that only 2-ketogluconate binds to the regulator with an apparent K(D) (equilibrium dissociation constant) of 15 muM, as determined using isothermal titration calorimetry assays. PtxS is made of two domains, a helix-turn-helix DNA-binding domain located at the N terminus and a C-terminal domain that binds the effector. Differential scanning calorimetry assays revealed that PtxS unfolds via two events characterized by melting points of 48.1 degrees C and 57.6 degrees C and that, in the presence of 2-ketogluconate, the unfolding of the effector binding domain occurs at a higher temperature, providing further evidence for 2-ketogluconate-PtxS interactions. Purified PtxS is a dimer that binds to the target promoters with affinities in the range of 1 to 3 muM. Footprint analysis revealed that PtxS binds to an almost perfect palindrome that is present within the three promoters and whose consensus sequence is 5'-TGAAACCGGTTTCA-3'. This palindrome overlaps with the RNA polymerase binding site. PMID:20581202

Daddaoua, Abdelali; Krell, Tino; Alfonso, Carlos; Morel, Bertrand; Ramos, Juan-Luis

2010-06-25

310

Intermittent High Glucose Enhances Apoptosis in INS-1 Cells  

Science.gov (United States)

To investigate the effect of intermittent high glucose (IHG) and sustained high glucose (SHG) on inducing ?-cell apoptosis and the potential involved mechanisms, INS-1 beta cells were incubated for 72?h in the medium containing different glucose concentrations: control (5.5?mmol/L), SHG (33.3?mmol/L), and IHG (5.5?mmol/L and 33.3?mmol/L glucose alternating every 12?h). Cell viability, apoptosis rate, and oxidative-stress markers were determined. The results showed that the apoptosis induced by IHG was more obvious than that by SHG. Simultaneously, the intracellular level of oxidative stress was more significantly increased in INS-1 cells exposed to IHG. These findings suggest that intermittent high glucose could be more deleterious to ?-cell than a constant high concentration of glucose, this may be due to the aggravation of oxidative stress triggered by intermittent high glucose.

Shi, Xiao-li; Ren, Yue-zhong; Wu, Jing

2011-01-01

311

Temporal analysis of myocardial glucose metabolism by 2-[18F]fluoro-2-deoxy-D-glucose  

International Nuclear Information System (INIS)

[en] To assess kinetic changes of myocardial glucose metabolism after physiological interventions, we perfused isolated working rat hearts with glucose and 2-[18F]fluoro-2-deoxy-D-glucose (2-FDG). Tissue uptake of 2-FDG and the input function were measured on-line by external detection. The fractional rate of 2-FDG phosphorylation was determined by graphical analysis of time-activity curves. The steady-state uptake of 2-FDG was linear with time, and the tracer was retained predominantly in its phosphorylated form. Tissue accumulation of 2-FDG decreased with a reduction in work load and with the addition of competing substrates. Insulin caused a significant increase in 2-FDG accumulation in hearts from fasted but not from fed animals. We conclude that in the isolated working rat heart there is rapid adjustment of exogenous substrate utilization and that most interventions known to alter glucose metabolism induce parallel changes in 2-FDG uptake. Qualitative differences in the in vitro response to insulin may be affected by the presence of either endogenous insulin or glycogen

1990-01-01

312

Características clínicas y metabólicas de los estados de intolerancia a la glucosa y glicemia de ayuno alteradas Clinical and metabolic features of subjects with glucose intolerance and high fasting glucose levels  

Directory of Open Access Journals (Sweden)

Full Text Available Background: Subjects with glucose intolerance or high fasting glucose levels have a higher cardiovascular rísk and frequently become diabetic. Aim: To assess clinical and metabolic characteristics of patients with glucose intolerance or high fasting glucose levels. Material and methods: Fasting and post glucose load serum glucose and insulin levels were measured in 1404 people, aged 42,0 ± 14,2 years (81% women) with high diabetic rísk. We categorízed subjects in different alterations of blood glucose, according to 2006 Amerícan Diabetes Association categoríes. Insulin resistance (RI), insulin secretion (B %) and insulin disposition (ID), were calculated using fasting blood glucose and insulin levels, using the homeostasis model assessment (HOMA I and II). Results: Sixty percent of studied subjects had first grade relatives with diabetes mellitus and 1097 (78%) were categorízed as normal (N), 45 (3%) as Diabetes Mellitus (DM), 161 (11%) as high fasting glucose levels (GAA) and 103 (7%) as glucose intolerant (ITG). Fifty three of the 106 subjects with GAA (50%), were also glucose intolerant. Subjects with GAA had similar insulin sensitivity and lower B cell function than N (insulin disposition 58 ± 12 and 111 ± 32%, respectively p <0.01). ITG had less insulin sensitivity than N (HOMA-IR 2.6 ± 1.50 ± and 2.0 ± 1.30, respectively) and only a mild decrease in B cell function (insulin disposition 96 ± 26 and 111 ± 32% respectively, p < 0.01). Patients GAA plus ITG had similar alterations than those with DM (HOMA-IR 3.8 ± 2.2 and 4.4 ± 3.7respectively; insulin disposition 57 ± 10 and 56.0 ± 26% respectively. Conclusions: Patients with higher fasting glucose levels behave differently from those with glucose intolerance. High fasting glucose levels are highly prevalent in subjects with high rísk of DM and must be considered as rísk indicator in preventive programs for diabetes mellitus.

Antonio Arteaga; Felipe Pollak; Leonor Robres; Nicolás Velasco

2009-01-01

313

Serum hepcidin is associated with parameters of glucose metabolism in women with gestational diabetes mellitus.  

UK PubMed Central (United Kingdom)

OBJECTIVES: Hepcidin is considered a major regulator of iron metabolism. Despite previous studies showing elevated ferritin and hepcidin levels in type 2 diabetes mellitus (DM), no study has investigated hepcidin levels in pregnant women with gestational DM (GDM). METHODS: A case-control study was conducted in 30 cases of GDM, 47 pregnant women with impaired glucose tolerance (IGT) and 72 pregnant women with normal glucose tolerance (control) between April 2009 and July 2011. Serum hepcidin and other iron metabolism parameters were analyzed in all groups. RESULTS: Serum ferritin and serum iron were significantly elevated in the GDM group compared to controls (p = 0.014, p = 0.018, respectively) and to the IGT group (p = 0.021, p = 0.008, respectively). Hepcidin levels were elevated significantly in the diabetic patients compared to the IGT group (p = 0.011) and controls (p = 0.002). We found no correlation between hepcidin and other iron metabolism parameters (Hb, serum iron and ferritin), whereas positive correlations were found between hepcidin and parameters of glucose metabolism (fasting blood glucose, fasting insulin level and glucose value response to glucose challenge test). CONCLUSIONS: Serum hepcidin concentrations were increased in pregnant women with IGT and GDM and this was not related to inflammation parameters.

Derbent AU; Simavli SA; Kaygusuz I; Gumus II; Y?lmaz S; Yildirim M; Uysal S

2013-07-01

314

Alterations of glucose metabolism during perfusion of rat lung with paraquat.  

UK PubMed Central (United Kingdom)

Isolated perfused rat lungs were used to investigate effects of paraquat on lung glucose metabolism. Lungs were ventilated with 5% CO2 in air and perfused with Krebs-Ringer bicarbonate buffer, pH 7.4, containing albumin and 5.5 mM radiolabeled D-glucose. Control lung glucose utilization, estimated from rate of 3H2O production from [5-3H]glucose, was 44 mumol/h-g dry wt. Pentose cycle activity, based on 14CO2 specific yields at the end of perfusions with [1-14C]- and [6-14C]glucose, was 14% of glucose utilization. During perfusion with 1.5 mM paraquat, glucose utilization increased 28%, 14CO2 production via the pentose cycle increased 182% (P less than 0.005), CO2 production via mitochondrial metabolism increased 39% (P less than 0.02), and the rate of lactate production increased 28% (P less than 0.05). Pyruvate production and the lactate-to-pyruvate ratio were not significantly altered. The data indicate that interaction of paraquat with the lung results in increased turnover of cytoplasmic NADPH and increased mitochondrial metabolism, but no significant change in cytoplasmic redox state. The findings are compatible with intracellular enzymatic reduction of paraquat by an NADPH-requiring reductase.

Bassett DJ; Fisher AB

1978-06-01

315

In situ coexpression of glucose and monocarboxylate transporter mRNAs in metabolic-sensitive caudal dorsal vagal complex catecholaminergic neurons: transcriptional reactivity to insulin-induced hypoglycemia and caudal hindbrain glucose or lactate repletion during insulin-induced hypoglycemia.  

UK PubMed Central (United Kingdom)

The neurochemical phenotype(s) of metabolic sensing neurons in the dorsal vagal complex (DVC) remains unclear. These studies utilized single-cell quantitative real-time RT-PCR, in conjunction with laser-catapult microdissection, to address the hypothesis that DVC A2 neurons express genes that encode the characterized metabolic transducers, e.g. glucokinase (GCK) and the energy-dependent potassium channel, K(ATP). Studies show that either glucose or lactate alters synaptic firing of DVC chemosensory neurons, and that delivery of the latter fuel into the caudal hindbrain amplifies insulin-induced hypoglycemia (IIH) and elevates neuronal glucose and monocarboxylate transporter, GCK, and sulfonylurea-1 mRNA in the DVC. We thus examined the additional premise that IIH modifies A2 substrate transporter and metabolic transducer gene profiles, and that such transcriptional responses may be reversed by exogenous lactate and/or glucose. Individual tyrosine hydroxylase (TH)-immunoreactive (-ir) A2 neurons were microdissected from the caudal DVC 2 h after injection of insulin or saline, and continuous caudal fourth ventricular (CV4) infusion of lactate, glucose, or artificial cerebrospinal fluid. The data show that IIH decreased MCT2, but elevated GLUT3, GLUT4, GCK, and SUR-1 transcripts in A2 neurons. Blood glucose levels in insulin-injected rats were further reduced by CV4 infusion of either lactate or glucose. Lactate plus insulin reversed hypoglycemic reductions in MCT2 mRNA and further augmented GLUT3 transcripts in A2 neurons, whereas glucose infusion in insulin-injected rats further increased GLUT3 and GCK gene profiles. The present results demonstrate that caudal DVC A2 neurons express molecular markers for metabolic sensing, and genes that encode glucose and monocarboxylate transporters. Evidence that IIH reduces A2 MCT2, but elevates GLUT3 and GLUT4 gene profiles suggests that glucose may be a primary energy source to these cells during hypoglycemia, while decreased lactate uptake, alone or relative to glucose uptake, may be a critical manifestation of systemic glucose deficiency at the cellular level. Findings that singular fuel repletion does not normalize hypoglycemic patterns of glucose transporter, GCK, or SUR-1 mRNA expression in A2 neurons imply that sufficient supply of both energy substrates is required for metabolic balance, and that cellular adaptation to the prevalence of either fuel may increase cellular dependence on glucose-specific metabolites or other products.

Briski KP; Cherian AK; Genabai NK; Vavaiya KV

2009-12-01

316

In situ coexpression of glucose and monocarboxylate transporter mRNAs in metabolic-sensitive caudal dorsal vagal complex catecholaminergic neurons: transcriptional reactivity to insulin-induced hypoglycemia and caudal hindbrain glucose or lactate repletion during insulin-induced hypoglycemia.  

Science.gov (United States)

The neurochemical phenotype(s) of metabolic sensing neurons in the dorsal vagal complex (DVC) remains unclear. These studies utilized single-cell quantitative real-time RT-PCR, in conjunction with laser-catapult microdissection, to address the hypothesis that DVC A2 neurons express genes that encode the characterized metabolic transducers, e.g. glucokinase (GCK) and the energy-dependent potassium channel, K(ATP). Studies show that either glucose or lactate alters synaptic firing of DVC chemosensory neurons, and that delivery of the latter fuel into the caudal hindbrain amplifies insulin-induced hypoglycemia (IIH) and elevates neuronal glucose and monocarboxylate transporter, GCK, and sulfonylurea-1 mRNA in the DVC. We thus examined the additional premise that IIH modifies A2 substrate transporter and metabolic transducer gene profiles, and that such transcriptional responses may be reversed by exogenous lactate and/or glucose. Individual tyrosine hydroxylase (TH)-immunoreactive (-ir) A2 neurons were microdissected from the caudal DVC 2 h after injection of insulin or saline, and continuous caudal fourth ventricular (CV4) infusion of lactate, glucose, or artificial cerebrospinal fluid. The data show that IIH decreased MCT2, but elevated GLUT3, GLUT4, GCK, and SUR-1 transcripts in A2 neurons. Blood glucose levels in insulin-injected rats were further reduced by CV4 infusion of either lactate or glucose. Lactate plus insulin reversed hypoglycemic reductions in MCT2 mRNA and further augmented GLUT3 transcripts in A2 neurons, whereas glucose infusion in insulin-injected rats further increased GLUT3 and GCK gene profiles. The present results demonstrate that caudal DVC A2 neurons express molecular markers for metabolic sensing, and genes that encode glucose and monocarboxylate transporters. Evidence that IIH reduces A2 MCT2, but elevates GLUT3 and GLUT4 gene profiles suggests that glucose may be a primary energy source to these cells during hypoglycemia, while decreased lactate uptake, alone or relative to glucose uptake, may be a critical manifestation of systemic glucose deficiency at the cellular level. Findings that singular fuel repletion does not normalize hypoglycemic patterns of glucose transporter, GCK, or SUR-1 mRNA expression in A2 neurons imply that sufficient supply of both energy substrates is required for metabolic balance, and that cellular adaptation to the prevalence of either fuel may increase cellular dependence on glucose-specific metabolites or other products. PMID:19744543

Briski, K P; Cherian, A K; Genabai, N K; Vavaiya, K V

2009-09-08

317

Effects of acute intermittent hypoxia on glucose metabolism in awake healthy volunteers.  

UK PubMed Central (United Kingdom)

Accumulating evidence suggests that obstructive sleep apnea is associated with alterations in glucose metabolism. Although the pathophysiology of metabolic dysfunction in obstructive sleep apnea is not well understood, studies of murine models indicate that intermittent hypoxemia has an important contribution. However, corroborating data on the metabolic effects of intermittent hypoxia on glucose metabolism in humans are not available. Thus the primary aim of this study was to characterize the acute effects of intermittent hypoxia on glucose metabolism. Thirteen healthy volunteers were subjected to 5 h of intermittent hypoxia or normoxia during wakefulness in a randomized order on two separate days. The intravenous glucose tolerance test (IVGTT) was used to assess insulin-dependent and insulin-independent measures of glucose disposal. The IVGTT data were analyzed using the minimal model to determine insulin sensitivity (S(I)) and glucose effectiveness (S(G)). Drops in oxyhemoglobin saturation were induced during wakefulness at an average rate of 24.3 events/h. Compared with the normoxia condition, intermittent hypoxia was associated with a decrease in S(I) [4.1 vs. 3.4 (mU/l)(-1).min(-1); P = 0.0179] and S(G) (1.9 vs. 1.3 min(-1)x10(-2), P = 0.0065). Despite worsening insulin sensitivity with intermittent hypoxia, pancreatic insulin secretion was comparable between the two conditions. Heart rate variability analysis showed the intermittent hypoxia was associated with a shift in sympathovagal balance toward an increase in sympathetic nervous system activity. The average R-R interval on the electrocardiogram was 919.0 ms during the normoxia condition and 874.4 ms during the intermittent hypoxia condition (P < 0.04). Serum cortisol levels after intermittent hypoxia and normoxia were similar. Hypoxic stress in obstructive sleep apnea may increase the predisposition for metabolic dysfunction by impairing insulin sensitivity, glucose effectiveness, and insulin secretion.

Louis M; Punjabi NM

2009-05-01

318

Effects of acute intermittent hypoxia on glucose metabolism in awake healthy volunteers.  

Science.gov (United States)

Accumulating evidence suggests that obstructive sleep apnea is associated with alterations in glucose metabolism. Although the pathophysiology of metabolic dysfunction in obstructive sleep apnea is not well understood, studies of murine models indicate that intermittent hypoxemia has an important contribution. However, corroborating data on the metabolic effects of intermittent hypoxia on glucose metabolism in humans are not available. Thus the primary aim of this study was to characterize the acute effects of intermittent hypoxia on glucose metabolism. Thirteen healthy volunteers were subjected to 5 h of intermittent hypoxia or normoxia during wakefulness in a randomized order on two separate days. The intravenous glucose tolerance test (IVGTT) was used to assess insulin-dependent and insulin-independent measures of glucose disposal. The IVGTT data were analyzed using the minimal model to determine insulin sensitivity (S(I)) and glucose effectiveness (S(G)). Drops in oxyhemoglobin saturation were induced during wakefulness at an average rate of 24.3 events/h. Compared with the normoxia condition, intermittent hypoxia was associated with a decrease in S(I) [4.1 vs. 3.4 (mU/l)(-1).min(-1); P = 0.0179] and S(G) (1.9 vs. 1.3 min(-1)x10(-2), P = 0.0065). Despite worsening insulin sensitivity with intermittent hypoxia, pancreatic insulin secretion was comparable between the two conditions. Heart rate variability analysis showed the intermittent hypoxia was associated with a shift in sympathovagal balance toward an increase in sympathetic nervous system activity. The average R-R interval on the electrocardiogram was 919.0 ms during the normoxia condition and 874.4 ms during the intermittent hypoxia condition (P < 0.04). Serum cortisol levels after intermittent hypoxia and normoxia were similar. Hypoxic stress in obstructive sleep apnea may increase the predisposition for metabolic dysfunction by impairing insulin sensitivity, glucose effectiveness, and insulin secretion. PMID:19265062

Louis, Mariam; Punjabi, Naresh M

2009-03-05

319

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

Science.gov (United States)

Fatty acid has been suggested to be involved in development of diabetes. However, its association is unclear among Japanese populations, which consume large amounts of fish rich in n-3 polyunsaturated fatty acids. The present cross-sectional study examined the association of individual dietary fatty acids and dietary fatty acid patterns with abnormal glucose metabolism among 1065 Japanese employees, aged 18-69 years. Impaired glucose metabolism is defined if a person has a history of diabetes, current use of anti-diabetic drug, fasting plasma glucose of 110 mg/dl (?6.1 mmol/L) or greater, or hemoglobin A1C of 6.0% (?42 mmol/mol) or greater. Dietary intake was assessed with a self-administered diet history questionnaire. Dietary fatty acid patterns were extracted by principal component analysis. Odds ratios of impaired glucose metabolism according to tertile categories of each fatty acids and dietary fatty acid patterns were estimated using logistic regression with adjustment for potential confounding variables. A higher intake of polyunsaturated fatty acid, n-6 fatty acid, linoleic acid, and oleic acid were significantly associated with a decreased prevalence of impaired glucose metabolism (P for trend?=?0.03, 0.01, 0.02, and 0.04, respectively). Alpha-linolenic acid was marginally significantly associated with a decreased prevalence of impaired glucose metabolism (P for trend?=?0.12). Of three fatty acid patterns identified, a higher plant oil pattern score, which characterized by high intake of alpha-linolenic acid, linoleic acid, and oleic acid, was associated with a decreased prevalence of impaired glucose metabolism (P for trend?=?0.03). No association was observed for other patterns. In conclusion, plant source fatty acids might be protectively associated with development of diabetes in Japanese adults. PMID:23741386

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

2013-05-31

320

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

UK PubMed Central (United Kingdom)

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

Kurotani K; Kochi T; Nanri A; Tsuruoka H; Kuwahara K; Pham NM; Kabe I; Mizoue T

2013-01-01

 
 
 
 
321

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

322

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

Directory of Open Access Journals (Sweden)

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

Carbó Roxana; Guarner Verónica

2010-01-01

323

Depletion of extremely radiosensitive subpopulation in crypt cells by 2-deoxy-D-glucose  

International Nuclear Information System (INIS)

Apoptosis is a mode of cell death that shows unique morphological appearance. At the time of death, apoptosis can be distinguished from necrosis: nuclear condensation and fragmentation due to DNA degradation. This type of cell death is observed at embryonic development, immune system, tumor and normal cells with or without cytotoxic injuries. Another feature of apoptosis is energy requirement; i.e., energy depletion inhibits apoptosis. The inhibition of protein synthesis or glucose metabolism inhibits apoptosis. Following irradiation, many apoptosis are found in the small intestinal crypt. This study observed apoptosis showed in two subpopulations: one has extreme radiosensitivity and the other has ordinary radiosensitivity. With pretreatment of 2-deoxy-D-glucose (2-DG) that inhibits glucose metabolism, extremely radiosensitive subpopulation was depleted. (author). 15 refs., 2 figs., 1 tab.

1992-01-01

324

Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.  

UK PubMed Central (United Kingdom)

Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

Flavahan WA; Wu Q; Hitomi M; Rahim N; Kim Y; Sloan AE; Weil RJ; Nakano I; Sarkaria JN; Stringer BW; Day BW; Li M; Lathia JD; Rich JN; Hjelmeland AB

2013-09-01

325

Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.  

Science.gov (United States)

Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis. PMID:23995067

Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

2013-09-01

326

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

UK PubMed Central (United Kingdom)

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?.

Jagust WJ; Landau SM

2012-12-01

327

Simultaneous utilization of glucose and gluconate in Penicillium chrysogenum during overflow metabolism.  

UK PubMed Central (United Kingdom)

The filamentous fungus P. chrysogenum is one of the most important production organism for ß-lactam antibiotics, especially penicillin. A specific feature of P. chrysogenum is the formation of gluconate as the primary overflow metabolite under non-limiting growth on glucose. Gluconate can be formed extracellularly by the enzyme glucose oxidase (GOD) that shows high activities under glucose excess conditions. Currently, it is assumed that under these conditions glucose is the preferred carbon substrate for P. chrysogenum and gluconate consumption first starts after glucose becomes limiting. Here, we specifically address this hypothesis by combining batch cultivation experiments on defined glucose media, time-dependent GOD activity measurements and (13) C-tracer studies. Our data prove that both substrates are metabolized simultaneously independent from the actual glucose concentration and therefore suggest that no distinct mechanism of carbon catabolite repression exists for gluconate in P. chrysogenum. Moreover, gluconate consumption does not interfere with penicillin V production, i.e. does not lead to repression of the penicillin genes. Finally, by following a model-driven approach the specific uptake rates for glucose and gluconate were quantified and found to be significantly higher for gluconate. In summary, our results show that P. chrysogenum metabolizes gluconate directly and at high rates making it an interesting alternative carbon source for production purposes. Biotechnol. Bioeng. © 2013 Wiley Periodicals, Inc.

Schmitz K; Peter V; Meinert S; Kornfeld G; Hardiman T; Wiechert W; Noack S

2013-06-01

328

Evaluation of EZSCAN as a screening tool for impaired glucose metabolism.  

UK PubMed Central (United Kingdom)

AIMS: To evaluate the performance of EZSCAN as a screening tool for impaired glucose metabolism (IGM), including impaired glucose tolerance, impaired fasting glucose and undiagnosed diabetes in a Chinese population. METHODS: 876 subjects participated in the study. All subjects underwent tests of EZSCAN, glycated hemoglobin, fasting plasma glucose (FPG), and oral glucose tolerance test (OGTT). Correlation of electrical skin conductance (ESC) with glucose level was evaluated by Pearson correlation coefficient. EZSCAN performance was assessed by receiver operating characteristic curve. RESULTS: Among the 876 subjects, 53% had normal glucose tolerance (NGT), and 47% had IGM. The ESC for the hands and feet was 72 ± 10 ?S and 75 ± 7 ?S, respectively, in NGT group; and 64 ± 13 ?S and 67 ± 11 ?S, respectively, in IGM group. The ESC at hands and feet was significantly correlated with both 2h-OGTT and FPG (p<0.001). NGT group demonstrated a EZSCAN score of 33 ± 11%, which is significantly lower than that of IGM group (44 ± 12%, p<0.001). The cut-off point of EZSCAN for IGM detection was 40% with a sensitivity of 80% and a specificity of 72%. CONCLUSIONS: EZSCAN is a useful screening tool for identifying subjects at increased risk for impaired glucose metabolism in prediabetes and diabetes. Diagnostic laboratory test should be performed in subjects with EZSCAN scores greater than 40%.

Chen L; Chen X; Ding R; Shi Q Jr; Hu D

2013-05-01

329

Simultaneous utilization of glucose and gluconate in Penicillium chrysogenum during overflow metabolism.  

Science.gov (United States)

The filamentous fungus Penicillium chrysogenum is one of the most important production organism for ?-lactam antibiotics, especially penicillin. A specific feature of P. chrysogenum is the formation of gluconate as the primary overflow metabolite under non-limiting growth on glucose. Gluconate can be formed extracellularly by the enzyme glucose oxidase (GOD) that shows high activities under glucose excess conditions. Currently, it is assumed that under these conditions glucose is the preferred carbon substrate for P. chrysogenum and gluconate consumption first starts after glucose becomes limiting. Here, we specifically address this hypothesis by combining batch cultivation experiments on defined glucose media, time-dependent GOD activity measurements, and (13) C-tracer studies. Our data prove that both substrates are metabolized simultaneously independent from the actual glucose concentration and therefore suggest that no distinct mechanism of carbon catabolite repression exists for gluconate in P. chrysogenum. Moreover, gluconate consumption does not interfere with penicillin V production by repression of the penicillin genes. Finally, by following a model-driven approach the specific uptake rates for glucose and gluconate were quantified and found to be significantly higher for gluconate. In summary, our results show that P. chrysogenum metabolizes gluconate directly and at high rates making it an interesting alternative carbon source for production purposes. Biotechnol. Bioeng. 2013;110: 3235-3243. © 2013 Wiley Periodicals, Inc. PMID:23775209

Schmitz, Katja; Peter, Vivien; Meinert, Sabine; Kornfeld, Georg; Hardiman, Timo; Wiechert, Wolfgang; Noack, Stephan

2013-07-05

330

Metabolic flux analysis in Synechocystis using isotope distribution from 13C-labeled glucose.  

UK PubMed Central (United Kingdom)

Using the carbon isotope labeling technique, the response of cyanobacterial central carbon metabolism to the change in environmental conditions was investigated. Synechocystis was grown in the heterotrophic and mixotrophic cultures fed with 13C-labeled glucose. The labeling patterns of the amino acids in biomass hydrolysates for both cultures were detected by the two-dimensional 1H-13C correlation nuclear magnetic resonance (2D 1H-13C COSY NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) technique. The in vivo intracellular flux distributions were then quantitated from the labeling measurements and metabolite balances using a parameters fitting approach. From the estimated flux distributions, it was found that the pentose phosphate pathway was the major pathway of glucose catabolism in the heterotrophic culture, while in the mixotrophic culture, the flux of CO2 fixation through the Calvin cycle was about two-fold of the glucose input flux. The relative flux through the phosphoenolpyruvate carboxylase was very high in both cultures, and this reaction represented about 25% of the assimilated CO2 in the mixotrophic culture. More importantly, we found a substantial outflow from the tricarboxylic acid cycle to glycolysis pathway carried by the malic enzyme, demonstrating the operation of a C4 pathway in cyanobacterial cells through the PEP carboxylase and malic enzyme. The estimated flux distributions also revealed that the NADPH synthesis was in excess relative to its requirement, and the excess NADPH might be reoxidized in cyanobacterial respiration to provide the energy for cellular requirement. Moreover, the analyzed result also suggested that the activity of the respiratory electron transport chain in cyanobacterial cells was not inhibited by light.

Yang C; Hua Q; Shimizu K

2002-07-01

331

Metabolic flux analysis in Synechocystis using isotope distribution from 13C-labeled glucose.  

Science.gov (United States)

Using the carbon isotope labeling technique, the response of cyanobacterial central carbon metabolism to the change in environmental conditions was investigated. Synechocystis was grown in the heterotrophic and mixotrophic cultures fed with 13C-labeled glucose. The labeling patterns of the amino acids in biomass hydrolysates for both cultures were detected by the two-dimensional 1H-13C correlation nuclear magnetic resonance (2D 1H-13C COSY NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) technique. The in vivo intracellular flux distributions were then quantitated from the labeling measurements and metabolite balances using a parameters fitting approach. From the estimated flux distributions, it was found that the pentose phosphate pathway was the major pathway of glucose catabolism in the heterotrophic culture, while in the mixotrophic culture, the flux of CO2 fixation through the Calvin cycle was about two-fold of the glucose input flux. The relative flux through the phosphoenolpyruvate carboxylase was very high in both cultures, and this reaction represented about 25% of the assimilated CO2 in the mixotrophic culture. More importantly, we found a substantial outflow from the tricarboxylic acid cycle to glycolysis pathway carried by the malic enzyme, demonstrating the operation of a C4 pathway in cyanobacterial cells through the PEP carboxylase and malic enzyme. The estimated flux distributions also revealed that the NADPH synthesis was in excess relative to its requirement, and the excess NADPH might be reoxidized in cyanobacterial respiration to provide the energy for cellular requirement. Moreover, the analyzed result also suggested that the activity of the respiratory electron transport chain in cyanobacterial cells was not inhibited by light. PMID:12616690

Yang, Chen; Hua, Qiang; Shimizu, Kazuyuki

2002-07-01

332

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

Science.gov (United States)

The structurally conserved and ubiquitous pathways of central carbon metabolism provide building blocks and cofactors for the biosynthesis of cellular macromolecules. The relative uses of pathways and reactions, however, vary widely among species and depend upon conditions, and some are not used at all. Here we identify the network topology of glucose metabolism and its in vivo operation by quantification of intracellular carbon fluxes from 13C tracer experiments. Specifically, we investigated Agrobacterium tumefaciens, two pseudomonads, Sinorhizobium meliloti, Rhodobacter sphaeroides, Zymomonas mobilis, and Paracoccus versutus, which grow on glucose as the sole carbon source, represent fundamentally different metabolic lifestyles (aerobic, anaerobic, photoheterotrophic, and chemoheterotrophic), and are phylogenetically distinct (firmicutes, gamma-proteobacteria, and alpha-proteobacteria). Compared to those of the model bacteria Escherichia coli and Bacillus subtilis, metabolisms of the investigated species differed significantly in several respects: (i) the Entner-Doudoroff pathway was the almost exclusive catabolic route; (ii) the pentose phosphate pathway exhibited exclusively biosynthetic functions, in many cases also requiring flux through the nonoxidative branch; (iii) all aerobes exhibited fully respiratory metabolism without significant overflow metabolism; and (iv) all aerobes used the pyruvate bypass of the malate dehydrogenase reaction to a significant extent. Exclusively, Pseudomonas fluorescens converted most glucose extracellularly to gluconate and 2-ketogluconate. Overall, the results suggest that metabolic data from model species with extensive industrial and laboratory history are not representative of microbial metabolism, at least not quantitatively. PMID:15716428

Fuhrer, Tobias; Fischer, Eliane; Sauer, Uwe

2005-03-01

333

[The insulin regulation of metabolism of fat acids and glucose next in the realization of biologic function of locomotion].  

UK PubMed Central (United Kingdom)

The becoming at the late stages of phylogeny of the biologic function of locomotion, insulin system and the earliest formed function of mitochondria make it possible to align all oxidized substrates in the following sequence: a) fatty acid metabolites C4 - ketone bodies; b) butyric fatty acid short-chained metabolites C6-C10; c) palmitic fatty acid with specific carrier; d) glucose. The mitochondria will begin to oxidize glucose if there will be no ketone bodies in cytosol and no remains of short-chained fatty acids and palmitic fatty acid. According to "the biologic subordination principle" philogenically late insulin can't change the functional characteristics of the phylogeny earliest mitochondria. To "force" the mitochondria starting to oxidize glucose first of all the insulin is to inhibit the biochemical reactions in all cells where releasing of polar non-etherified fatty acids and formation of their polar metabolites occurs. As in case of insulin, the same marked and prolonged hypoglycemia is induced by DL-aminocarnitine. This substance specifically inhibits both activity of carnitine-palmitoilacylaminotrsansferase and flux of acyl-KoA in mitochondria. The pronounced decrease of fatty acids content and their metabolites in matrix force mitochondria to oxidize glucose. It is possible to be validly of opinion that the same philogenically ancient principles as inhibition of activity of carnitine-palmitoilacylaminotrsansferase, decrease of formation of fatty acid metabolites C4 (ketone bodies), short-chained metabolites of palmitic fatty acid and olein mono fatty acid are applied in realization of philogenically late insulin effect. The first insulin effect in the hypoglycemia and biologic exotrophy reaction conditions is targeted to the regulation of fatty acids metabolism. Only second insulin effect is targeted to the glucose metabolic transformation. Therefore, there is a background to consider the diabetes mellitus primarily as a disorder of metabolism of unsaturated and mono fatty acids and only secondary and only then as a disorder of glucose metabolism. If insulin will not be able to decrease in cytosol the content of lipid substances of oxidation of insulin the mitochondria will not oxidize glucose. At that, a pathogenesis uniform syndrome of resistance to insulin is formed independently of etiologic factors. Under these conditions the mitochondria physiologically "don't want" to oxidize glucose a possibility exists to oxidize fatty acids and their polar metabolites.