Evidence mapPaperPMID 36917198Full record

ArticleJCI insight2023

GLUT1 is redundant in hypoxic and glycolytic nucleus pulposus cells of the intervertebral disc.

Shira N Johnston, Elizabeth S Silagi, Vedavathi Madhu, Duc H Nguyen, Irving M Shapiro, Makarand V Risbud

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Shira N JohnstonDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, and.
Elizabeth S SilagiDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, and.
Vedavathi MadhuDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, and.
Duc H NguyenDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, and.
Irving M ShapiroDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, and.
Makarand V RisbudDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, and.
Thomas Jefferson University · USBoston University · US

Funding

Pathogenesis of Inflammation-driven Intervertebral Disc Herniation: The Role of Syndecan 4R01AR074813 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI Makarand V Risbud · 2022 to 2023
$897k
Targeting cell senescence in a novel model of spontaneous disc degenerationR01AG073349 · THOMAS JEFFERSON UNIVERSITY · 2025 to 2025
$557k
NIAMS NIH HHS R01 AR055655NIAMS NIH HHS R01 AR074813NIAMS NIH HHS T32 AR052273NIA NIH HHS R01 AG073349
6 · The paper itself

Abstract

Glycolysis is central to homeostasis of nucleus pulposus (NP) cells in the avascular intervertebral disc. Since the glucose transporter, GLUT1, is a highly enriched phenotypic marker of NP cells, we hypothesized that it is vital for the development and postnatal maintenance of the disc. Surprisingly, primary NP cells treated with 2 well-characterized GLUT1 inhibitors maintained normal rates of glycolysis and ATP production, indicating intrinsic compensatory mechanisms. We showed in vitro that NP cells mitigated GLUT1 loss by rewiring glucose import through GLUT3. Of note, we demonstrated that substrates, such as glutamine and palmitate, did not compensate for glucose restriction resulting from dual inhibition of GLUT1/3, and inhibition compromised long-term cell viability. To investigate the redundancy of GLUT1 function in NP, we generated 2 NP-specific knockout mice: Krt19CreERT Glut1fl/fl and Foxa2Cre Glut1fl/fl. There were no apparent defects in postnatal disc health or development and maturation in mutant mice. Microarray analysis verified that GLUT1 loss did not cause transcriptomic alterations in the NP, supporting that cells are refractory to GLUT1 loss. These observations provide the first evidence to our knowledge of functional redundancy in GLUT transporters in the physiologically hypoxic intervertebral disc and underscore the importance of glucose as the indispensable substrate for NP cells.

Indexed as

Intervertebral DiscNucleus PulposusAnimalsGlucoseGlucose Transporter Type 1GlycolysisHypoxiaMiceMice, KnockoutGlucoseGlucose Transporter Type 1Bone BiologyCartilageGlucose metabolismHypoxiaMetabolism

Identifiers

PMID36917198
PMCPMC10243741
OpenAlexW4324128899

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.