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Akt signaling mediates postnatal heart growth in response to insulin and nutritional status

Ichiro Shiojima1, Mikkael Yefremashvili, Zhengyu Luo

  • 1Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

The Journal of Biological Chemistry
|August 7, 2002
PubMed

Insights

Akt signaling regulates heart growth based on nutrient availability. Enhancing Akt1 in mice with insulin receptor defects rescued small heart size, indicating its crucial role in physiological cardiac development.

Area of Science:

  • Cardiovascular Biology
  • Molecular Signaling
  • Developmental Biology

Background:

  • Akt is a key kinase regulating cellular responses.
  • Akt signaling in the heart is linked to nutrient availability and cardiac growth during development.

Purpose of the Study:

  • To investigate the role of Akt signaling in nutrient-dependent regulation of physiological heart growth.
  • To elucidate the mechanism by which Akt mediates insulin-dependent cardiac development.

Main Methods:

  • Studied Akt signaling and phosphorylation in mice with cardiac-specific insulin receptor deletion.
  • Assessed the impact of caloric restriction on Akt phosphorylation in wild-type and mutant mice.
  • Utilized forced expression of Akt1 to rescue cardiac phenotypes.

Main Results:

  • Cardiac-specific insulin receptor deletion led to reduced Akt, S6K1, and 4E-BP1 phosphorylation and a small heart phenotype.
  • Caloric restriction had minimal effect on Akt phosphorylation in mutant mice compared to wild-type.
  • Forced Akt1 expression restored S6K1 and 4E-BP1 phosphorylation and rescued the small heart phenotype.

Conclusions:

  • Akt signaling is essential for insulin-dependent physiological heart growth during postnatal development.
  • Akt acts as a crucial mediator coordinating heart size with organismal nutritional status.

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