UPTAKE OF GLUCOSE ANALOGUES BY RAT BRAIN CORTEX SLICES: MEMBRANE TRANSPORT VERSUS METABOLISM OF 2‐DEOXY‐<scp>d</scp>‐GLUCOSE

Lund‐Andersen, Henrik; Kjeldsen, Christel S.

doi:10.1111/j.1471-4159.1977.tb09610.x

Cited by 22 publications

(5 citation statements)

References 12 publications

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“…The directional change of LlCMICf. (i.e., 2.6 to 5.4) is in good agreement with prior studies of complete ischemia (Lowry et aI., 1964a,b ;Meyer et aI., 1970;Lund-Anderson and Kj eldsen, 1977). It should be noted that in the very early phase of acute ischemia, Lowry et aL (l964a) noted a decrease in the G-6-P/glucose ratio (i.e., tJ.. CJdC; < 1).…”

Section: Effects Of Rate Constants On Metabolic Rate Determinationssupporting

confidence: 92%

“…This metabolic trapping effe ct facilitates measurements of tissue radioactivity concentration of FDG and DG and allows near-steady-state conditions for the tracer to be reached without significant loss of the tracer through metabolic processes. Because re lease from the metabolic trapping (i.e., dephos phorylation) requires glucose-6-phosphatase, an enzyme of normally low activity in the brain (Hers, 1957;Raggi et aI., 1960;Prasannan and Subrahma nyan, 1968;Lund-Anderson and Kj eldsen, 1977), Sokoloff et al (1977) did not consider the influence of dephosphorylation in their fo rmulation of the model. With the longer times of in vivo scanning in humans (compared to animal autoradiography in which the animal is sacrifice d at 45 min), dephos phorylation of FDG-6-P becomes more significant .…”

mentioning

confidence: 99%

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Effect of Ischemia on Quantification of Local Cerebral Glucose Metabolic Rate in Man

Hawkins

Phelps

Huang

et al. 1981

J Cereb Blood Flow Metab

145

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Summary:The model for quantifying local cerebral glucose metabolic rates originally developed by Sokoloff et aL and modified by Phelps, Huang and co-workers was applied to humans with cerebral ischemia (i.e" stroke), Rate constants for fluorodeoxyglucose were measured in ischemic and nonischemic regions with positron computed tomography, Using measured rate constants for ischemia. the model generates more accurate estimates of local cerebral glucose metabolism as compared to the use of rate constants from normal young adults, because the local metabolic rate is significantly underestimated, and temporal instability of the model is observed when normal values are applied to ischemic regions. A method was also developed to test the stability of the local lumped constant. The estimates of the lumped constant showed no or only small variations between ischemic and nonischemic types. Thus, errors introduced in the calculated local cerebral glucose metabolism by inappropri ate rate constants appear to be more significant than those caused by any potential change in the lumped constant in ischemia.The method of tomographic measurement of the local ce rebral metabolic rate fo r glucose (LCMRGlc) provides, for the first time, a noninva sive method of evaluating local ce rebral metabolism in humans in vivo. The technique has been pre vi ou sly described (Phelps et aI., 1979; Re ivich et aI. , 1979;Huang et al. 1980) and is an extension of the deoxyglucose autoradiographic approach for the me asurement of LCMRGlc (Sokoloff et aI., 1977(Sokoloff et aI., , 1979.The model provides a measurement of LCMRGlc in animals, with [14C]deoxyglucose (DG), or in man, with [18F]fluorodeoxyglucose (FDG), if the fo llow ing parameters are known (parameters will be dis cu ssed only in terms of FDG): (i) the total local Address correspondence and reprint requests to Dr. Phelps at UCLA School of Medicine. Division of Nuclear Medicine: Los Angeles. California 90024.Ahhreviations used: DG, 2-Deoxyglucose: FOG. Fluorode oxyglucose; FDG-6-P, Fluorodeoxyglucose-6-phosphate; G-6-P. Glucose-6-phosphate; LC. Lumped constant; LCMRGlc, Local cerebral metabolic rate for glucose, 37tissue radioactivity co ncentration of IHF [FDG plus FDG-6-phosphate (FDG-6-P)] and the capillary plasma FDG concentration as a fu nction of time; (ii) rate constants for fo rward and reverse transport between plasma and tissue (k� and k�) and fo r phos phorylation of FDG and dephosphorylation of FDG-6-P (ktl and k�); and (iii) the "lumped co n stant" (LC), which is a ratio of arteriovenous ex traction fraction of FDG to that of gluco se under steady-state conditions when k� is small. LC is a term that accounts for the differences in transport and phosphorylation between glucose and FDG.Both DG and FDG are transported from blood to brain in a manner analogous to glucose (Bidder, 1968; Bachelard, 1971;Oldendorf, 1971; Horton et aI., 1973). Both compete for hexokinase for phos phorylation to DG-6-P and FDG-6-P, re spectively (Bessell et aI., 1972; Re ivich et aI., 1979) but...

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Section: Effects Of Rate Constants On Metabolic Rate Determinationssupporting

confidence: 92%

mentioning

confidence: 99%

Effect of Ischemia on Quantification of Local Cerebral Glucose Metabolic Rate in Man

Hawkins

Phelps

Huang

et al. 1981

J Cereb Blood Flow Metab

145

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“…The absences of blood flow and blood-brain barrier have been mentioned. In the absence of hexose transport across the blood-brain barrier in slices, Kj and ki cannot be due to capil lary transport and probably reflect primarily dif fu sion (Lund-Andersen and Kj eldsen, 1977). A second difference is that regional afferents are dis rupted during isolation.…”

Section: Time Of Incubation (Min)mentioning

confidence: 99%

Kinetic Model of 2-Deoxyglucose Metabolism Using Brain Slices

Newman

Hospod

Patlak

1990

J Cereb Blood Flow Metab

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Summary: A six-compartment, nine-parameter kinetic model of 2-deoxyglucose (2DG) metabolism, which in cludes bidirectional tissue transport, phosphorylation, two-step dephosphorylation, phosphoisomerization, and conjugation to UDP and macromolecules, has been de rived. Data for analysis were obtained from 540-and 1,000-j.Lm-thick hippocampal and hypothalamic brain slices, which were incubated in buffer containing [14C]2DG, frozen, extracted with perchlorate, and sepa rated on anion-exchange columns. Solutions of the equa tions of the model were fit to the data by means of non linear least-squares analysis. These studies suggest that dephosphorylation is adequately described by a single re action so that the model reduces to eight parameters. The in vitro rate constants for transport, phosphorylation, and Regional mapping of brain metabolism permits correlation of behavior and physiology with ana tomically localized glucose or O2 consumption. Measurements of glucose and O2 metabolism, by autoradiography or with positron emission tomog raphy, have provided important insights into a wide variety of normal and pathological conditions in hu mans and experimental models.Radiolabeled 2-deoxyglucose (2DG) has an ad vantage over glucose as a radio tracer because 2DG is not metabolized by the Embden-Meyerhof path way, so loss of radiolabel as CO2 does not occur. Calculation of in vivo glucose utilization based upon measurement of tissue radioactivity after in jection of 2DG is possible with the kinetic theory and procedures described by Sokoloff et ai . (1977). Received September 27, 1989; revised December 21, 1989; ac cepted December 27, 1989. Address correspondence and reprint requests to Dr. G. C. Newman at Department of Neurology, HSC TI2-020, SUNY at Stony Brook, Stony Brook, NY 11794, U.S.A.Abbreviations used: 2DG, 2-deoxyglucose; ER, endoplasmic reticulum. 510dephosphorylation are very similar to prior in vivo re sults. The phosphoisomerization rate constant is similar to dephosphorylation, so glycosylated macromolecules slowly accumulate and gradually assume larger relative importance as other compounds disappear more rapidly. Rate constants for 540-j.Lm slices from hypothalamus and hippocampus are similar, while 1,000-j.Lm slices have smaller tissue transport constants and larger phosphory lation constants. The rate equation for glucose utilization of this model is relatively insensitive to uncertainties re garding the rate constants. Including later metabolic com ponents in kinetic models improves the calculations of glucose utilization with long isotope exposures.

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“…Perhaps the two most fruitful approaches have been to measure sugar fluxes in cultured cells (Edstrom, Kanje & Walum, 1975) or synaptosomes prepared from cerebral cortex (Diamond & Fishman, 1973). Even here the results are controversial since it is not clear whether sugar uptake is rate limiting for sugar metabolism (Bachelard, 1975) or whether the rate of sugar uptake is so rapid that sugar metabolism becomes rate limiting for sugar uptake (Lund-Andersen & Kjeldsen, 1977). If uptake is rate limiting measurements of glucose uptake ought to be reliable but if metabolism is limiting uptake will be underestimated.…”

Section: Comparison With Other Nervesmentioning

confidence: 99%

3‐O‐methylglucose transport in internally dialysed giant axons of Loligo.

Baker¹,

Carruthers²

1981

The Journal of Physiology

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SUMMARY1. The transport of the non-metabolized sugar, 3-0-methylglucose, has been studied in the squid axon under conditions where the intracellular environment of the axon is controlled by internal dialysis.2. Sugar transport is passive, shows saturation kinetics and is asymmetric. At 15 'C, the Michaelis and velocity constants for exit are approximately four times those for uptake. The asymmetry of transport is increased by raising the temperature.3. Sugar uptake is not affected by intracellular sugar levels as high as 100 mM. Sugar exit is, however, reduced by external sugars although the apparent Km for exit is unaffected.4. The kinetics of sugar exit under exchange conditions are determined by the kinetics of sugar uptake. These results can be accounted for by the asymmetric mobile-carrier and simultaneous-carrier models for transport.5. Both sugar uptake and exit are reduced in the absence of ATP1. Kinetic analysis oftransport under these conditions shows that the capacity of the system to transport sugar is unchanged but that the affinity of the system for sugar is reduced. Internal cyclic AMP, AMP, ADP or GTP (2 mM) do not mimic this action of ATP. The hydrolysable analogue of ATP, a, fl-methylene-5-ATP (2 mM), (but not the nonhydrolysable analogue fi, y-methylene-5-ATP, 2 mM) has an ATP-like action on sugar transport.6. Transport is unaffected by internal Ca2+ concentrations in the range 4 x 10 8-9x 10-7 M.

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UPTAKE OF GLUCOSE ANALOGUES BY RAT BRAIN CORTEX SLICES: MEMBRANE TRANSPORT VERSUS METABOLISM OF 2‐DEOXY‐d‐GLUCOSE

Cited by 22 publications

References 12 publications

Effect of Ischemia on Quantification of Local Cerebral Glucose Metabolic Rate in Man

Effect of Ischemia on Quantification of Local Cerebral Glucose Metabolic Rate in Man

Kinetic Model of 2-Deoxyglucose Metabolism Using Brain Slices

3‐O‐methylglucose transport in internally dialysed giant axons of Loligo.

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