Accelerative exchange diffusion kinetics of glucose between blood and brain and its relation to transport during anoxia

Betz, A. Lorris; Gilboe, David D.; Drewes, Lester R.

doi:10.1016/0005-2736(75)90240-0

Cited by 22 publications

(16 citation statements)

References 33 publications

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“…there is counter-transport for GLUT1 at the blood–brain barrier just as in red blood cells. Further evidence that GLUT1 behaves in a similar manner in the two environments was obtained by Betz et al [ 327 ] who found that the rate of glucose influx was increased by increasing the concentration of glucose within the brain, i.e. there is trans-stimulation (see Appendix D ).…”

Section: Clearance Of Specific Substancessupporting

confidence: 64%

“…Secondly once across the blood–brain barrier, glucose is metabolized at a rate comparable to the rates of influx and efflux across the barrier while in red blood cells transport is much faster than metabolism. Thirdly there is also the technical difficulty that, with the important exception of the study in 1975 by Betz et al [ 327 ], it has not proved possible to manipulate interstitial fluid glucose concentrations during the experiments. In most studies all that has been done is either to measure the extraction of glucose (total or labelled) from blood as described above or to measure the variation in the total amount of glucose present in the parenchyma with time as a function of glucose concentration in plasma.…”

Section: Clearance Of Specific Substancesmentioning

confidence: 99%

“…Buschiazzo et al [ 319 ] and Betz et al [ 327 ] determined the total glucose in the parenchyma for different glucose concentrations in plasma (see Fig. 14 ).…”

Section: Clearance Of Specific Substancesmentioning

confidence: 99%

“…14 Four studies of brain glucose content versus glucose concentration in blood. In two studies glucose content was measured by chemical assay, a in anaesthetized rats by Buschiazzo et al [ 319 ] and b in isolated perfused brains from dogs by Betz et al [ 327 ]. In the latter it was assumed that brain water was 0.75 mL g −1 .…”

Section: Clearance Of Specific Substancesmentioning

confidence: 99%

“…Furthermore if it can be assumed that the fluxes are described by the expressions of the form derived from the carrier model, the rate of efflux can be calculated from the measured rates of influx versus the concentrations in plasma and ISF. An example of this using the data from Betz et al [ 327 ] for the isolated perfused dog brain is given in Appendix D and Additional file 1 . These data remain the only measurements of glucose influx versus plasma concentration for a range of known concentrations within the brain.…”

Section: Clearance Of Specific Substancesmentioning

confidence: 99%

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Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier

Hladky

Barrand

2018

Fluids Barriers CNS

165

156

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This review considers efflux of substances from brain parenchyma quantified as values of clearances (CL, stated in µL g−1 min−1). Total clearance of a substance is the sum of clearance values for all available routes including perivascular pathways and the blood–brain barrier. Perivascular efflux contributes to the clearance of all water-soluble substances. Substances leaving via the perivascular routes may enter cerebrospinal fluid (CSF) or lymph. These routes are also involved in entry to the parenchyma from CSF. However, evidence demonstrating net fluid flow inwards along arteries and then outwards along veins (the glymphatic hypothesis) is still lacking. CLperivascular, that via perivascular routes, has been measured by following the fate of exogenously applied labelled tracer amounts of sucrose, inulin or serum albumin, which are not metabolized or eliminated across the blood–brain barrier. With these substances values of total CL ≅ 1 have been measured. Substances that are eliminated at least partly by other routes, i.e. across the blood–brain barrier, have higher total CL values. Substances crossing the blood–brain barrier may do so by passive, non-specific means with CLblood-brain barrier values ranging from < 0.01 for inulin to > 1000 for water and CO2. CLblood-brain barrier values for many small solutes are predictable from their oil/water partition and molecular weight. Transporters specific for glucose, lactate and many polar substrates facilitate efflux across the blood–brain barrier producing CLblood-brain barrier values > 50. The principal route for movement of Na+ and Cl− ions across the blood–brain barrier is probably paracellular through tight junctions between the brain endothelial cells producing CLblood-brain barrier values ~ 1. There are large fluxes of amino acids into and out of the brain across the blood–brain barrier but only small net fluxes have been observed suggesting substantial reuse of essential amino acids and α-ketoacids within the brain. Amyloid-β efflux, which is measurably faster than efflux of inulin, is primarily across the blood–brain barrier. Amyloid-β also leaves the brain parenchyma via perivascular efflux and this may be important as the route by which amyloid-β reaches arterial walls resulting in cerebral amyloid angiopathy.Electronic supplementary materialThe online version of this article (10.1186/s12987-018-0113-6) contains supplementary material, which is available to authorized users.

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Section: Clearance Of Specific Substancessupporting

confidence: 64%

Section: Clearance Of Specific Substancesmentioning

confidence: 99%

“…Buschiazzo et al [ 319 ] and Betz et al [ 327 ] determined the total glucose in the parenchyma for different glucose concentrations in plasma (see Fig. 14 ).…”

Section: Clearance Of Specific Substancesmentioning

confidence: 99%

Section: Clearance Of Specific Substancesmentioning

confidence: 99%

Section: Clearance Of Specific Substancesmentioning

confidence: 99%

See 3 more Smart Citations

Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier

Hladky

Barrand

2018

Fluids Barriers CNS

165

156

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A quantitative overview of glucose dynamics in the gliovascular unit

Barros

Bittner

Loaiza

et al. 2007

Glia

116

152

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While glucose is constantly being "pulled" into the brain by hexokinase, its flux across the blood brain barrier (BBB) is allowed by facilitative carriers of the GLUT family. Starting from the microscopic properties of GLUT carriers, and within the constraints imposed by the available experimental data, chiefly NMR spectroscopy, we have generated a numerical model that reveals several hidden features of glucose transport and metabolism in the brain. The half-saturation constant of glucose uptake into the brain (K(t)) is close to 8 mM. GLUT carriers at the BBB are symmetric, show accelerated-exchange, and a K(m) of zero-trans flux (K(zt)) close to 5 mM, determining a ratio of 3.6 between maximum transport rate and net glucose flux (T(max)/CMR(glc)). In spite of the low transporter occupancy, the model shows that for a stimulated hexokinase to pull more glucose into the brain, the number or activity of GLUT carriers must also increase, particularly at the BBB. The endothelium is therefore predicted to be a key modulated element for the fast control of energy metabolism. In addition, the simulations help to explain why mild hypoglycemia may be asymptomatic and reveal that [glucose](brain) (as measured by NMR) should be much more sensitive than glucose flux (as measured by PET) as an indicator of GLUT1 deficiency. In summary, available data from various sources has been integrated in a predictive model based on the microscopic properties of GLUT carriers.

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Cerebral Microvascular Transport and Metabolism: Implications for Diabetes

McCall¹

1992

Hyperglycemia, Diabetes, and Vascular Disease

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Accelerative exchange diffusion kinetics of glucose between blood and brain and its relation to transport during anoxia

Cited by 22 publications

References 33 publications

Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier

Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood–brain barrier

A quantitative overview of glucose dynamics in the gliovascular unit

Cerebral Microvascular Transport and Metabolism: Implications for Diabetes

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