Advanced

Brain glucose transport and phosphorylation under acute insulin-induced hypoglycemia in mice : an 18F-FDG PET study

Alf, Malte F; Duarte, João M N LU ; Schibli, Roger; Gruetter, Rolf and Krämer, Stefanie D (2013) In Journal of Nuclear Medicine 54(12). p.60-2153
Abstract

UNLABELLED: We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are.

METHODS: Quantitative (18)F-FDG PET combined with the acquisition of real-time arterial input function was performed on mice. Hypoglycemia was induced and maintained by insulin infusion. PET data were analyzed with the 2-tissue-compartment model for (18)F-FDG, and the results were evaluated with Michaelis-Menten saturation kinetics.

RESULTS: Glucose clearance from plasma to brain (K1,glc) and the phosphorylation rate constant increased with decreasing plasma glucose (Gp), in particular at a Gp of less than 2.5 mmol/L. Estimated cerebral glucose... (More)

UNLABELLED: We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are.

METHODS: Quantitative (18)F-FDG PET combined with the acquisition of real-time arterial input function was performed on mice. Hypoglycemia was induced and maintained by insulin infusion. PET data were analyzed with the 2-tissue-compartment model for (18)F-FDG, and the results were evaluated with Michaelis-Menten saturation kinetics.

RESULTS: Glucose clearance from plasma to brain (K1,glc) and the phosphorylation rate constant increased with decreasing plasma glucose (Gp), in particular at a Gp of less than 2.5 mmol/L. Estimated cerebral glucose extraction ratios taking into account an increased cerebral blood flow (CBF) at a Gp of less than 2 mmol/L were between 0.14 and 0.79. CBF-normalized K1,glc values were in agreement with saturation kinetics. Phosphorylation rate constants indicated intracellular glucose depletion at a Gp of less than 2-3 mmol/L. When brain regions were compared, glucose transport under hypoglycemia was lowest in the hypothalamus.

CONCLUSION: Alterations in glucose transport and phosphorylation, as well as intracellular glucose depletion, under acute hypoglycemia can be modeled by saturation kinetics taking into account an increase in CBF. Distinct transport kinetics in the hypothalamus may be involved in its glucose-sensing function.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Biological Transport, Blood-Brain Barrier, Brain, Cerebrovascular Circulation, Fluorodeoxyglucose F18, Glucose, Hypoglycemia, Insulin, Kinetics, Male, Mice, Organ Specificity, Permeability, Phosphorylation, Positron-Emission Tomography, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Nuclear Medicine
volume
54
issue
12
pages
8 pages
publisher
Society of Nuclear Medicine
external identifiers
  • scopus:84893359052
ISSN
0161-5505
DOI
10.2967/jnumed.113.122812
language
English
LU publication?
no
id
0b17378b-60a1-409d-b61b-079bff642570
date added to LUP
2017-10-19 15:16:23
date last changed
2018-05-29 12:04:29
@article{0b17378b-60a1-409d-b61b-079bff642570,
  abstract     = {<p>UNLABELLED: We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are.</p><p>METHODS: Quantitative (18)F-FDG PET combined with the acquisition of real-time arterial input function was performed on mice. Hypoglycemia was induced and maintained by insulin infusion. PET data were analyzed with the 2-tissue-compartment model for (18)F-FDG, and the results were evaluated with Michaelis-Menten saturation kinetics.</p><p>RESULTS: Glucose clearance from plasma to brain (K1,glc) and the phosphorylation rate constant increased with decreasing plasma glucose (Gp), in particular at a Gp of less than 2.5 mmol/L. Estimated cerebral glucose extraction ratios taking into account an increased cerebral blood flow (CBF) at a Gp of less than 2 mmol/L were between 0.14 and 0.79. CBF-normalized K1,glc values were in agreement with saturation kinetics. Phosphorylation rate constants indicated intracellular glucose depletion at a Gp of less than 2-3 mmol/L. When brain regions were compared, glucose transport under hypoglycemia was lowest in the hypothalamus.</p><p>CONCLUSION: Alterations in glucose transport and phosphorylation, as well as intracellular glucose depletion, under acute hypoglycemia can be modeled by saturation kinetics taking into account an increase in CBF. Distinct transport kinetics in the hypothalamus may be involved in its glucose-sensing function.</p>},
  author       = {Alf, Malte F and Duarte, João M N and Schibli, Roger and Gruetter, Rolf and Krämer, Stefanie D},
  issn         = {0161-5505},
  keyword      = {Animals,Biological Transport,Blood-Brain Barrier,Brain,Cerebrovascular Circulation,Fluorodeoxyglucose F18,Glucose,Hypoglycemia,Insulin,Kinetics,Male,Mice,Organ Specificity,Permeability,Phosphorylation,Positron-Emission Tomography,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {12},
  pages        = {60--2153},
  publisher    = {Society of Nuclear Medicine},
  series       = {Journal of Nuclear Medicine},
  title        = {Brain glucose transport and phosphorylation under acute insulin-induced hypoglycemia in mice : an 18F-FDG PET study},
  url          = {http://dx.doi.org/10.2967/jnumed.113.122812},
  volume       = {54},
  year         = {2013},
}