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November 18, 2016
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Factors involved in GLUT-1 glucose transporter gene transcription in cardiac muscle

Publicated to: Journal Of Biological Chemistry. 274 (25): 17626-17634 - 1999-01-01 274(25), DOI: 10.1074/jbc.274.25.17626

Authors:

Santalucía T., Boheler K.R., Brand N.J., Sahye U., Fandos C., Viñals F., Ferré J., Testar X., Palacín M., Zorzano A.
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Affiliations

Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St., London SW3 6LY, United Kingdom - Author
Dept. de Bioquim. i Biol. Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, Barcelona 08028, Spain - Author
Molecular Cardiology Unit, Laboratory of Cardiovascular Science, National Institutes of Health, Baltimore, MD 21224, United States - Author
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Abstract

Glucose constitutes a major fuel for the heart, and high glucose uptake during fetal development is coincident with the highest level of expression of the glucose transporter GLUT-1 during life. We have previously reported that GLUT-1 is repressed perinatally in rat heart, and GLUT-4, which shows a low level of expression in the fetal stage, becomes the main glucose transporter in the adult. Here, we show that the perinatal expression of GLUT-1 and GLUT-4 glucose transporters in heart is controlled directly at the level of gene transcription. Transient transfection assays show that the -99/-33 fragment of the GLUT-1 gene is sufficient to drive transcriptional activity in rat neonatal cardiomyocytes. Electrophoretic mobility shift assays demonstrate that the transcription factor Sp1, a trans-activator of GLUT-1 promoter, binds to the -102/-82 region of GLUT-1 promoter during the fetal state but not during adulthood. Mutation of the Sp1 site in this region demonstrates that Sp1 is essential for maintaining a high transcriptional activity in cardiac myocytes. Sp1 is markedly down-regulated both in heart and in skeletal muscle during neonatal life, suggesting an active role for Sp1 in the regulation of GLUT-1 transcription. In all, these results indicate that the expression of GLUT-1 and GLUT-4 in heart during perinatal development is largely controlled at a transcriptional level by mechanisms that might be related to hyperplasia and that are independent from the signals that trigger cell hypertrophy in the developing heart. Furthermore, our results provide the first functional insight into the mechanisms regulating muscle GLUT-1 gene expression in a live animal.
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Keywords

Age factorsAnimal cellAnimalsAnimals, newbornArticleCells, culturedControlled studyDna-binding proteinsElectrophoretic mobilityFetusGeneGene expressionGene expression regulation, developmentalGenetic transcriptionGlucoseGlucose transporterGlucose transporter type 1Glucose transporter type 4HeartHeart muscleImmunoblottingMonosaccharide transport proteinsMuscle proteinsMutationMyocardiumNewbornNonhumanNuclear proteinsPolyacrylamide gel electrophoresisPriority journalPromoter regions (genetics)RatRatsRegulatory sequences, nucleic acidRna, messengerSkeletal muscleSp1 transcription factorTranscription factor sp1Transcription, genetic

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal JOURNAL OF BIOLOGICAL CHEMISTRY due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 1999, it was in position 22/295, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-04-04:

  • WoS: 42
  • Scopus: 44
  • Europe PMC: 27
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-04:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 28.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 28 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 6.

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Timor-Leste; United Kingdom; United States of America.

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