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Akt Signaling Mediates Postnatal Heart Growth in Response to Insulin and Nutritional Status
Journal article   Open access   Peer reviewed

Akt Signaling Mediates Postnatal Heart Growth in Response to Insulin and Nutritional Status

Ichiro Shiojima, Mikkael Yefremashvili, Zhengyu Luo, Yasuko Kureishi, Akihiro Takahashi, Jingzang Tao, Anthony Rosenzweig, C. Ronald Kahn, E. Dale Abel and Kenneth Walsh
The Journal of biological chemistry, Vol.277(40), pp.37670-37677
10/04/2002
DOI: 10.1074/jbc.M204572200
PMID: 12163490
url
https://doi.org/10.1074/jbc.M204572200View
Published (Version of record) Open Access

Abstract

Akt is a serine-threonine kinase that mediates a variety of cellular responses to external stimuli. During postnatal development, Akt signaling in the heart was up-regulated when the heart was rapidly growing and was down-regulated by caloric restriction, suggesting a role of Akt in nutrient-dependent regulation of cardiac growth. Consistent with this notion, reductions in Akt, 70-kDa S6 kinase 1, and eukaryotic initiation factor 4E-binding protein 1 phosphorylation were observed in mice with cardiac-specific deletion of insulin receptor gene, which exhibit a small heart phenotype. In contrast to wild type animals, caloric restriction in these mice had little effect on Akt phosphorylation in the heart. Furthermore, forced expression of Akt1 in these hearts restored 70-kDa S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1 phosphorylation to normal levels and rescued the small heart phenotype. Collectively, these results indicate that Akt signaling mediates insulin-dependent physiological heart growth during postnatal development and suggest a mechanism by which heart size is coordinated with overall body size as the nutritional status of the organism is varied.

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