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Characterization of cerebral glucose dynamics in vivo with a four-state conformational model of transport at the blood-brain barrier

Duarte, João M N LU and Gruetter, Rolf (2012) In Journal of Neurochemistry 121(3). p.396-406
Abstract

Determination of brain glucose transport kinetics in vivo at steady-state typically does not allow distinguishing apparent maximum transport rate (T(max)) from cerebral consumption rate. Using a four-state conformational model of glucose transport, we show that simultaneous dynamic measurement of brain and plasma glucose concentrations provide enough information for independent and reliable determination of the two rates. In addition, although dynamic glucose homeostasis can be described with a reversible Michaelis-Menten model, which is implicit to the large iso-inhibition constant (K(ii)) relative to physiological brain glucose content, we found that the apparent affinity constant (K(t)) was better determined with the four-state... (More)

Determination of brain glucose transport kinetics in vivo at steady-state typically does not allow distinguishing apparent maximum transport rate (T(max)) from cerebral consumption rate. Using a four-state conformational model of glucose transport, we show that simultaneous dynamic measurement of brain and plasma glucose concentrations provide enough information for independent and reliable determination of the two rates. In addition, although dynamic glucose homeostasis can be described with a reversible Michaelis-Menten model, which is implicit to the large iso-inhibition constant (K(ii)) relative to physiological brain glucose content, we found that the apparent affinity constant (K(t)) was better determined with the four-state conformational model of glucose transport than with any of the other models tested. Furthermore, we confirmed the utility of the present method to determine glucose transport and consumption by analysing the modulation of both glucose transport and consumption by anaesthesia conditions that modify cerebral activity. In particular, deep thiopental anaesthesia caused a significant reduction of both T(max) and cerebral metabolic rate for glucose consumption. In conclusion, dynamic measurement of brain glucose in vivo in function of plasma glucose allows robust determination of both glucose uptake and consumption kinetics.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Algorithms, Anesthesia, Anesthetics, Animals, Biological Transport, Active, Blood Glucose, Blood-Brain Barrier, Brain Chemistry, Glucose, Homeostasis, Kinetics, Magnetic Resonance Spectroscopy, Male, Models, Biological, Rats, Rats, Sprague-Dawley
in
Journal of Neurochemistry
volume
121
issue
3
pages
11 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:84859592535
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2012.07688.x
language
English
LU publication?
no
id
ca56cb15-34cf-4f42-ba43-e5499449a175
date added to LUP
2017-10-19 15:14:20
date last changed
2017-11-12 04:36:03
@article{ca56cb15-34cf-4f42-ba43-e5499449a175,
  abstract     = {<p>Determination of brain glucose transport kinetics in vivo at steady-state typically does not allow distinguishing apparent maximum transport rate (T(max)) from cerebral consumption rate. Using a four-state conformational model of glucose transport, we show that simultaneous dynamic measurement of brain and plasma glucose concentrations provide enough information for independent and reliable determination of the two rates. In addition, although dynamic glucose homeostasis can be described with a reversible Michaelis-Menten model, which is implicit to the large iso-inhibition constant (K(ii)) relative to physiological brain glucose content, we found that the apparent affinity constant (K(t)) was better determined with the four-state conformational model of glucose transport than with any of the other models tested. Furthermore, we confirmed the utility of the present method to determine glucose transport and consumption by analysing the modulation of both glucose transport and consumption by anaesthesia conditions that modify cerebral activity. In particular, deep thiopental anaesthesia caused a significant reduction of both T(max) and cerebral metabolic rate for glucose consumption. In conclusion, dynamic measurement of brain glucose in vivo in function of plasma glucose allows robust determination of both glucose uptake and consumption kinetics.</p>},
  author       = {Duarte, João M N and Gruetter, Rolf},
  issn         = {1471-4159},
  keyword      = {Algorithms,Anesthesia,Anesthetics,Animals,Biological Transport, Active,Blood Glucose,Blood-Brain Barrier,Brain Chemistry,Glucose,Homeostasis,Kinetics,Magnetic Resonance Spectroscopy,Male,Models, Biological,Rats,Rats, Sprague-Dawley},
  language     = {eng},
  number       = {3},
  pages        = {396--406},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Characterization of cerebral glucose dynamics in vivo with a four-state conformational model of transport at the blood-brain barrier},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2012.07688.x},
  volume       = {121},
  year         = {2012},
}