Role of Akt1 and Akt2 in Cardiac and Skeletal Muscle

在这项研究中，为了深入了解Akt在心脏和SKM中的作用，我们通过将Akt1和Akt2系小鼠分别与MCK-Cre或MLC1-Cre转基因小鼠杂交，获得心脏和SKM特异性Akt1/Akt2基因敲除(M-Akt1/2DKO)小鼠或SKM特异性Akt1/Akt2基因敲除小鼠(MLC1-Akt1/2DKO)。M-Akt1/2DKO小鼠出生后5周内因心力衰竭死亡。定量RT-PCR分析显示，M-Akt1/2DKO小鼠心脏氧化磷酸化调控基因显著减少。在MLC1-Akt1/2DKO小鼠中，出生后6周体重和骨骼肌体积下降，32周时糖耐量和胰岛素抵抗受损，提示Akt1和Akt2通过调节线粒体能量代谢，控制参与全身葡萄糖代谢的骨骼肌的数量和质量，在维持心脏和SKM的生长和功能方面发挥重要作用。

In this study, to gain insight into the role of Akt in heart and SKM, we ablated Akt1 and Akt2 by crossing Akt1 and Akt2 floxed mice with MCK-Cre or MLC1-Cre transgenic mice, respectively, resulting in both heart and SKM specific Akt1/Akt2 knockout (M-Akt1/2DKO)mice or SKM specific Akt1/Akt2 knockout (MLC1-Akt1/2DKO) mice. M-Akt1/2DKO mice died within 5 weeks after birth due to heart failure. Quantitative RT-PCR analysis revealed genes regulating oxidative phosphorylation were decreased significantly in the heart of M-Akt1/2DKO mice. In MLC1-Akt1/2DKO mice, the body weight and skeletal muscle volume were decreased at 6 weeks after birth, and showed impaired glucose tolerance and insulin resistance at 32 weeks.These data suggest that Akt1 and Akt2 play an important role for maintaining heart and SKM growth and function by regulating mitochondrial energy metabolism and controlling quantity and quality of skeletal muscle which are involved in glucose metabolism in whole body.