Indeed, physiological cardiac hypertrophy induced by swimming exercise (a model producing mild growth of the ventricle with no evidence of interstitial fibrosis and no elevation of ANP and BNP [43]) was impaired in cardiomyocyte-specific IGF1R knockout mice [44], in mice expressing a dominant negative form of the p110α isoform of PI3K (dnPI3K) specifically in the heart [45] or in AKT mutant animals [46]. This evidence concerns the gene AKT1 and cardiac hypertrophy.