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ludc web

Joao Duarte

Principal investigator

ludc web

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

Author

  • Malte F Alf
  • João M N Duarte
  • Roger Schibli
  • Rolf Gruetter
  • Stefanie D Krämer

Summary, in English

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.

Publishing year

2013-12

Language

English

Pages

60-2153

Publication/Series

Journal of Nuclear Medicine

Volume

54

Issue

12

Document type

Journal article

Publisher

Society of Nuclear Medicine

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

Status

Published

ISBN/ISSN/Other

  • ISSN: 0161-5505