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Glucose metabolism down-regulates the uptake of 6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (6-NBDG) mediated by glucose transporter 1 isoform (GLUT1): theory and simulations using the symmetric four-state carrier model.
MedLine Citation:
PMID:  23336592     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The non-metabolizable fluorescent glucose analogue 6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (6-NBDG) is increasingly used to study cellular transport of glucose. Intracellular accumulation of exogenously applied 6-NBDG is assumed to reflect concurrent gradient-driven glucose uptake by glucose transporters (GLUTs). Here theoretical considerations are provided that put this assumption into question. In particular, depending on the microscopic parameters of the carrier proteins, theory proves that changes in glucose transport can be accompanied by opposite changes in flow of 6-NBDG. Simulations were carried out applying the symmetric four-state carrier model on the GLUT1 isoform, which is the only isoform whose kinetic parameters are presently available. Results show that cellular 6-NBDG uptake decreases with increasing rate of glucose utilization under core-model conditions supported by literature, namely where the transporter is assumed to work in regime of slow reorientation of the free-carrier compared to the ligand-carrier complex. In order to observe an increase of 6-NBDG uptake with increasing rate of glucose utilization, and thus interpret 6-NBDG increase as surrogate of glucose uptake, the transporter must be assumed to operate in regime of slow ligand-carrier binding, a condition that is currently not supported by literature. Our findings suggest that the interpretation of data obtained with NBDG derivatives is presently ambiguous and should be cautious because the underlying transport kinetics are not adequately established. © 2013 International Society for Neurochemistry, J. Neurochem. (2013) 10.1111/jnc.12164.
Authors:
Mauro Dinuzzo; Federico Giove; Bruno Maraviglia; Silvia Mangia
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-22
Journal Detail:
Title:  Journal of neurochemistry     Volume:  -     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 International Society for Neurochemistry, J. Neurochem. (2013) 10.1111/jnc.12164.
Affiliation:
MARBILab, Museo storico della fisica e Centro di studi e ricerche "Enrico Fermi", Rome, Italy.
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