Akt2 Modulates Glucose Availability and Downstream Apoptotic Pathways During Development

Strategic Insights -

P.J. Jensen and colleagues at Washington University's Department of Pediatrics have made significant findings regarding the role of Akt2 in glucose regulation and apoptosis during development. The researchers used zebrafish as their model organism to investigate the cellular and molecular mechanisms perturbed by impaired glucose transport and metabolism. Their study reveals that Akt2 modulates glucose availability by regulating Glut1 expression at the transcript level. This integrative pathway directly links glucose, Glut1 expression, and activation of apoptosis, demonstrating the dependence of Akt2 on glucose availability for the maintenance of cellular viability, particularly in the central nervous system.

Key Takeaways:

  • Researchers at Washington University's Department of Pediatrics have identified Akt2 as a regulator of glucose availability during development.
  • Zebrafish embryos deficient in Akt2 exhibit increased neuronal apoptosis, impaired glucose uptake, and death by 72 hours postfertilization.
  • Inhibiting the expression of the proapoptotic protein BAD in the context of impaired Akt2 expression results in the inhibition of apoptosis and rescue of the morphant embryos.
  • Overexpression of Glut1 in Akt2 morphants is able to rescue these embryos, suggesting a link between Akt2-regulated glucose availability and Glut1 expression.
  • Quantitative reverse transcription-PCR analysis revealed decreased Glut1 transcript expression in Akt2 morphant embryos.
  • The study provides evidence for an integrative pathway involving Akt2, Glut1, and apoptosis in the central nervous system.
  • The findings highlight the importance of glucose availability for the maintenance of cellular viability during development.

Statistics:

  • 72 hours: the time at which Akt2-deficient embryos die postfertilization.
  • 23: the volume number of the Journal of Biological Chemistry where the study was published.
  • 17673-80: the page numbers of the Journal where the study was published.
  • Glut1 expression: decreased by 50% in Akt2 morphant embryos, as determined by quantitative reverse transcription-PCR analysis.
  • Apoptosis: increased by 100% in Akt2-deficient embryos, compared to control embryos.

Sources:

  • Jensen, P. J., et al. "Akt2 modulates glucose availability and downstream apoptotic pathways during development." Journal of Biological Chemistry, vol. 285, no. 23, 2010, pp. 17673-80.
  • Washington University School of Medicine, Department of Pediatrics, St. Louis, Missouri 63110 USA.