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Cited by 12Metabolism, Diabetes, and CancerIon Transport and Channel RegulationCancer, Hypoxia, and Metabolism

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 ( GLUT 1): theory and simulations using the symmetric four‐state carrier model

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DiNuzzo, Mauro, Giove, Federico, Maraviglia, Bruno, Mangia, Silvia·2013·Journal of Neurochemistry
DOI 10.1111/jnc.12164PMC PMC3655083
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Abstract

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 with the ligand-carrier complex. 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.

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  • 6-NBDG has been shown in some cases to correlate negatively with glucose utilization.

    “The first study (Chuquet et al., 2010) used the fluorescent glucose analogue 6-NBDG; because it cannot be phosphorylated by hexokinase (given that the 6 position was already occupied by the fluorophore), this analogue’s accumulation may not correspond with the actual rate of glucose utilization, and it has been shown in some cases to correlate negatively with glucose utilization (DiNuzzo et al., 2”

    From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as DiNuzzo et al., 2013

  • 6-NBDG accumulation may not correspond with the actual rate of glucose utilization.

    “The first study (Chuquet et al., 2010) used the fluorescent glucose analogue 6-NBDG; because it cannot be phosphorylated by hexokinase (given that the 6 position was already occupied by the fluorophore), this analogue’s accumulation may not correspond with the actual rate of glucose utilization, and it has been shown in some cases to correlate negatively with glucose utilization (DiNuzzo et al., 2”

    From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as DiNuzzo et al., 2013

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Authors
DiNuzzo, M., Giove, F., Maraviglia, B., & Mangia, S.
Affiliations
  • Centro Ricerche Enrico Fermi (IT)
  • University of Minnesota (US)
Corresponding author
DiNuzzo, Mauro
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2013-02-27
Volume
125
Issue
2
Pages
236-246
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/jnc.12164
PMC
PMC3655083
OpenAlex
W2000568232
Cited by
12
References
36
Citations by year
2025: 2 · 2024: 1 · 2023: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 3
FWCI
0.75
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Funders
  • American Diabetes Association (07-07-DC2)
  • the National Center for Research Resources (P41 RR008079)
  • National Institute of Biomedical Imaging and Bioengineering (P41 EB015894)
  • Minnesota Medical Foundation (P30 NS057091, P30 NS076408)
  • NIH (UL1RR033183, KL2 RR033182)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords
glucose transporter 1, GLUT1, glucose uptake, glucose metabolism, transporter kinetics, glucose utilization, glucose transport
MeSH terms
Animals, Astrocytes, Glucosamine, Glucose, Humans, Models, Theoretical, 4-Chloro-7-nitrobenzofurazan, Down-Regulation, Glucose Transporter Type 1

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