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

First Author  Shiojima I Year  2002
Journal  J Biol Chem Volume  277
Issue  40 Pages  37670-7
PubMed ID  12163490 Mgi Jnum  J:79359
Mgi Id  MGI:2387905 Doi  10.1074/jbc.M204572200
Citation  Shiojima I, et al. (2002) Akt signaling mediates postnatal heart growth in response to insulin and nutritional status. J Biol Chem 277(40):37670-7
abstractText  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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