D‐Glucose Transport in Cultured Cells of Neural Origin: The Membrane as Possible Control Point of Glucose Utilization

Keller, Konrad; Lange, Klaus; Noske, W

doi:10.1111/j.1471-4159.1981.tb01694.x

Cited by 36 publications

(23 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study on C6 cells, no glycogen was detected in extracts of control cells when using I3C-NMR, suggesting a rather low glycogen store in the cells, as already reported for C6 cells at confluency (Keller et al, 1981). The comparison of the "C-NMR signals of glucose C1 from control and stimulated cells indicated, however, a higher glucose content in stimulated cells.…”

Section: Cellssupporting

confidence: 83%

β‐Adrenergic stimulation of C6 glioma cells: effects of cAMP overproduction on cellular metabolites

Pianet

Canioni

Labouesse

et al. 1992

European Journal of Biochemistry

View full text Add to dashboard Cite

We used 31P-NMR spectroscopy to investigate the response of living C6 glioma cells to stimulation by a /I-adrenergic agonist, isoproterenol. In the presence of 3-isobutyl-l-methylxanthine, stimulation induced an accumulation of CAMP, making possible the NMR detection of the second messenger in living cells grown on microcarrier beads and perfused in the NMR tube. The cAMP signal rose to a maximum level within 20 -25 min of stimulation; thereafter it decreased to the detection threshold within 60 min. At the same time, 40% increases of phosphomonoester and diphosphodiester signals were observed, whereas no significant change in phosphocreatine and nucleotide signals was detected. The kinetics of changes of the cellular content in phosphorylated metabolites were analyzed after recording 31P-NMR spectra of cell perchloric acid extracts as a function of time of stimulation. CAMP accumulation in stimulated cells was evidenced by a near linear increase of its NMR signal as a function of incubation time (from 0 to 60 rnin). Concomitantly with the production of CAMP, the data showed 30% decreases ofphosphocrcatine and ATP levels within 60 min of stimulation, and an unexpected redistribution of pyrimidine and purine nucleoside triphosphates. At the same time, levels of phosphomonoesters (phosphorylcholine and phosphorylethanolamine) and phosphodiesters (glycerophosphorylcholine and glycerophosphorylethanolamine) rose (50% increase).3C-NMR spectra of cell perchloric acid extracts prepared after isoproterenol stimulation of cells incubated in the presence of [I-' 3C]glucose indicated a higher glucose content in stimulated cells, whereas the resonance of ribose C1 was diminished. Moreover, the resonances of C1 of ethanolamine and choline (and their derivatives) were increased in spectra of stimulated cells, whereas that of C3 of serine was decreased. In addition, the 13C-NMR data indicated that neither the pattern of glutamale carbon enrichment nor the glutamate/glutamine ratio was modified in stimulated cells. On the other hand, the heteronuclear coupling pattern of the lactate (methyl group) resonance in 'H-NMR spectra of cell incubation media indicated that no change occurred in the carbon flux through the pentosephosphate shunt under stimulation. The results of this multinuclear NMR approach are discussed in terms of metabolic responses of C6 cells to P-adrenergic stimulation and cAMP overproduction.In hormone and neurotransmitter action on metabolic pathways, short-and long-term effects are to be differentiated, both of which are nowadays explorcd at the molecular level. The latter arc recognized to occur a few hours after stimulation and generally correspond to the modification of the gene transcription of key enzymes of the considered pathway (Nimmo and Cohen, 1987); they are studied at both the mRNA and the protein level. Thc former imply metabolic modifications induced by changes occurring, firstly, at the plasma membrane level or in its close vicinity (changes in intracellular second messenger or critical cation c...

show abstract

Section: Cellssupporting

confidence: 83%

β‐Adrenergic stimulation of C6 glioma cells: effects of cAMP overproduction on cellular metabolites

Pianet

Canioni

Labouesse

et al. 1992

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…Alternatively, or in addition to controlled hexokinase activation or synthesis, glucose permeability across the tumor cell membrane could be involved in the regulation of tumor glycolysis, in particular, tumor age dependent changes in the magnitude of glucose transfer across the tumor cell membrane. As indicated by the results of Keller et al [36], in vitro glucose transport to glial tumor cells indeed was much lower than to glial cells; this supports the notion of membrane permeability as a possible control point of glucose utilization of tumor cells. Furthermore, as indicated by the difference in the glycolytic activity of the periphery and the center of the F98 tumor mass, a subsequent age-dependent decrease of the tumor cell membrane permeability could have contributed to a lower glucose metabolism in the older central part of tumors.…”

supporting

confidence: 67%

Measurement of in vivo glucose transport from blood to tissue of experimentally-induced glioma in rat brain

Mies

1992

J Neuro-Oncol

View full text Add to dashboard Cite

In experimentally-induced F98 glioma of rat brain, regional blood flow and glucose transfer were assessed by means of double tracer autoradiography to measure Michaelis-Menten constants for the determination of unidirectional glucose transport across the blood-tumor and blood-brain barrier. In brain regions opposite the tumor hemisphere, the maximal glucose transport rate constant, Tm, ranged from 1.41 +/- 0.12 to 3.22 +/- 0.29 mumol/g/min and the half saturation transport constant of glucose, Kt, varied from 2.78 +/- 0.83 to 5.6 +/- 1.94 mumol/ml (estimate +/- standard error of the estimate) yielding a normoglycemic unidirectional glucose inward transport which ranged from 1.24 +/- 0.24 to 1.97 +/- 0.13 mumol/g/min (mean +/- standard deviation). In the tumor periphery, the Tm and the Kt values were 3.64 +/- 0.56 mumol/g/ml and 7.32 +/- 2.12 mumol/min, and in the tumor center, 1.77 +/- 0.25 mumol/ml and 2.76 +/- 1.13 mumol/g/min, respectively. The unidirectional glucose influx of tumor periphery and center in normoglycemia was 1.98 +/- 0.22 and 1.34 +/- 0.16 mumol/g/min, respectively. Despite comparable unidirectional glucose influxes, however, glucose metabolism of tumor tissue located in the periphery (0.83 +/- 0.12 mumol/g/min) and the center (0.41 +/- 0.10 mumol/g/min) of the tumor mass exceeded that of normal gray matter by about 68% and 100% which indicates uncoupling between glucose transport and phosphorylation in experimentally-induced F98 glioma of rat brain.

show abstract

“…However, it is conceivable that the permeability of tumor cell membranes is lower than in the normal brain. Keller et al (1981) [46] proposed that the cell membrane could be a possible control point of glucose utilization in cultured cells of neuronal origin. If tumor cells exercised a more severe membrane restriction of glucose metabolism than normal brain, this difference might be exploited therapeutically by reducing glucose availability in order to induce selective metabolic disturbances of the tumor cell (see also below).…”

Section: Discussionmentioning

confidence: 99%

Relationship between of blood flow, glucose metabolism, protein synthesis, glucose and ATP content in experimentally-induced glioma (RG12.2) of rat brain

Mies¹,

Paschen²,

Ebhardt³

et al. 1990

J Neuro-Oncol

View full text Add to dashboard Cite

In experimental RG1 2.2 glioma of rat brain, local blood flow, glucose utilization, protein synthesis, glucose and ATP content were measured by means of triple tracer autoradiography and bioluminescence technique, respectively, to determine hemodynamic and metabolic thresholds for local tumor energy failure. Perfusion thresholds were estimated at tumor blood flow values of 69.0 +/- 0.1 ml/100 g/min (estimate +/- standard error) and of 69 +/- 7.1 ml/100 g/min for the beginning of the decline in regional ATP and glucose content, respectively. Metabolic thresholds were derived at tumor glucose utilization values of 70.6 +/- 8.3 mumol/100 g/min for reduced protein synthesis, of 55.0 +/- 0.2 mumol/100 g/min for the decrease in glucose content, and 34.7 +/- 4.7 mumol/100 g/min for decline in ATP content. Our results suggest that blood flow limits glucose supply to tumor tissue at much higher flow rates than in normal brain which, in turn, is associated with a decrease in tumor glucose utilization. A reduction and not an increase in tumor glucose availability could be a more appropriate strategy for the induction of energy failure in tumors.

show abstract

D‐Glucose Transport in Cultured Cells of Neural Origin: The Membrane as Possible Control Point of Glucose Utilization

Cited by 36 publications

References 19 publications

β‐Adrenergic stimulation of C6 glioma cells: effects of cAMP overproduction on cellular metabolites

β‐Adrenergic stimulation of C6 glioma cells: effects of cAMP overproduction on cellular metabolites

Measurement of in vivo glucose transport from blood to tissue of experimentally-induced glioma in rat brain

Relationship between of blood flow, glucose metabolism, protein synthesis, glucose and ATP content in experimentally-induced glioma (RG12.2) of rat brain

Contact Info

Product

Resources

About