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Related Experiment Videos

Localization of exercise- and denervation-responsive elements in the mouse GLUT4 gene.

N Tsunoda1, K Maruyama, D W Cooke

  • 1Division of Clinical Nutrition, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8636, Japan.

Biochemical and Biophysical Research Communications
|February 16, 2000
PubMed
Summary

Exercise upregulates glucose transporter type 4 (GLUT4) in muscle. Regulatory elements for exercise response and brown fat expression are between -551 and -442 bp of the GLUT4 gene.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Physiology

Background:

  • Exercise training enhances glucose uptake in skeletal muscle, largely mediated by increased expression of glucose transporter type 4 (GLUT4).
  • Previous research localized exercise-responsive elements of the murine GLUT4 gene to a region between -1001 and -442 bp relative to the transcription start site.

Purpose of the Study:

  • To further delineate the specific regulatory elements within the GLUT4 gene responsible for exercise-induced expression and tissue-specific regulation.
  • To investigate the role of the myocyte enhancer factor 2 (MEF2) binding site in GLUT4 gene regulation in response to exercise and denervation.

Main Methods:

  • Generation and analysis of transgenic mice harboring GLUT4 minigenes with varying lengths of the 5'-flanking region (-701, -551, -442, and -423 bp).

Related Experiment Videos

  • Assessment of minigene expression in skeletal muscle, heart, and brown adipose tissue.
  • Evaluation of the impact of exercise training (swimming, treadmill running) and denervation on minigene mRNA levels.

    • Main Results:

    • All minigenes, including the -423 construct lacking the MEF2-binding domain, showed expression in skeletal muscle and heart.
    • Expression in brown adipose tissue was observed for -701 and -551 constructs but not for -442 or -423 constructs.
    • Exercise training up-regulated GLUT4 minigene mRNA in -701 and -551 transgenic mice, but not in -442 or -423 mice. Denervation down-regulated expression in all constructs.

    Conclusions:

    • Exercise-responsive elements and brown adipocyte-specific elements are located within the -551 to -442 bp region of the GLUT4 gene.
    • The MEF2 binding site (-437 to -428 bp) is not essential for GLUT4 expression in skeletal muscle and heart.
    • The cis-element mediating denervation-induced down-regulation of GLUT4 is located downstream of -423 bp.