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Akt2 modulates glucose availability and downstream apoptotic pathways during development.

Penny J Jensen1, Laura B Gunter, Mary O Carayannopoulos

  • 1Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA.

The Journal of Biological Chemistry
|April 2, 2010
PubMed
Summary
This summary is machine-generated.

The antiapoptotic kinase Akt2 regulates embryonic brain development by controlling glucose transporter Glut1 expression. Impaired Akt2 function leads to increased apoptosis and decreased glucose uptake, highlighting Akt2

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Developmental Biology

Background:

  • Glucose is essential for brain function and cellular viability.
  • The glucose transporter Glut1 is critical for embryonic brain development.
  • The role of Akt2 in glucose metabolism and its link to apoptosis is not fully understood.

Purpose of the Study:

  • To investigate the role of the antiapoptotic kinase Akt2 in regulating glucose transport and cellular viability.
  • To identify mediators in the Glut1-sensitive process of embryonic brain development.
  • To explore the relationship between Akt2, Glut1 expression, and apoptosis.

Main Methods:

  • Utilized zebrafish as a model system to study impaired glucose transport and metabolism.
  • Abrogated akt2 expression using morpholino knockdown.
  • Inhibited the expression of the proapoptotic protein bad.
  • Overexpressed glut1 in akt2 morphants.
  • Performed quantitative reverse transcription-PCR to analyze glut1 transcript expression.

Main Results:

  • Abrogating akt2 expression phenocopied glut1 inhibition, causing increased neuronal apoptosis, impaired glucose uptake, and embryonic death.
  • Inhibiting bad expression rescued akt2-deficient embryos.
  • Overexpressing glut1 also rescued akt2 morphants.
  • Quantitative reverse transcription-PCR revealed decreased glut1 transcript expression in akt2 morphant embryos.

Conclusions:

  • Akt2 modulates glucose availability by regulating Glut1 expression at the transcript level.
  • Akt2 plays a crucial role in an integrative pathway linking glucose, Glut1 expression, and apoptosis.
  • Akt2 is essential for maintaining cellular viability, particularly in the central nervous system, and its function is dependent on glucose availability.