Campbell Carmen S G, Caperuto Luciana C, Hirata A Emiko, Araujo Eliana P, Velloso Licio A, Saad Mario J, Carvalho Carla R O
Departamento de Fisiologia e Biofísica, ICB1, USP, São Paulo, SP, Brasil, Caixa Postal, CEP05389-970, Brazil.
Life Sci. 2004 Nov 19;76(1):57-70. doi: 10.1016/j.lfs.2004.06.017.
DHEA improves insulin sensitivity and has anti-obesity effect in animal models and men. However, the molecular mechanisms by which DHEA improves insulin action have not been clearly understood. In the present study, we examined the protein levels and phosphorylation state of insulin receptor (IR), IRS-1 and IRS-2, the association between IRSs and PI3K and SHP2, the insulin-induced IRSs associated PI 3-kinase activities, and the phosphorylation status of AKT and atypical PKCzeta/lambda in the liver and the muscle of 6 month-old Wistar rats treated with DHEA. There was no change in IR, IRS-1 and IRS-2 protein levels in both tissues of treated rats analysed by immunoblotting. On the other hand, insulin-induced IRS-1 tyrosine phosphorylation was increased in both tissues while IRS-2 tyrosyl phosphorylation was increased in liver of DHEA treated group. The PI3-kinase/AKT pathway was increased in the liver and the PI3K/atypical PKCzeta/lambda pathway was increased in the muscle of DHEA treated rats. These data indicate that these regulations of early steps of insulin action may play a role in the intracellular mechanism for the improved insulin sensitivity observed in this animal model.
脱氢表雄酮（DHEA）在动物模型和男性中可改善胰岛素敏感性并具有抗肥胖作用。然而，DHEA改善胰岛素作用的分子机制尚未完全明确。在本研究中，我们检测了6月龄经DHEA处理的Wistar大鼠肝脏和肌肉中胰岛素受体（IR）、胰岛素受体底物-1（IRS-1）和胰岛素受体底物-2（IRS-2）的蛋白水平及磷酸化状态、IRS与磷脂酰肌醇-3激酶（PI3K）和含Src同源2结构域蛋白酪氨酸磷酸酶2（SHP2）的关联、胰岛素诱导的与IRS相关的PI 3-激酶活性，以及蛋白激酶B（AKT）和非典型蛋白激酶Cζ/λ的磷酸化状态。通过免疫印迹分析，处理组大鼠两个组织中的IR、IRS-1和IRS-2蛋白水平均无变化。另一方面，胰岛素诱导的IRS-1酪氨酸磷酸化在两个组织中均增加，而DHEA处理组大鼠肝脏中的IRS-2酪氨酸磷酸化增加。DHEA处理组大鼠肝脏中PI3-激酶/AKT信号通路增强，肌肉中PI3K/非典型蛋白激酶Cζ/λ信号通路增强。这些数据表明，胰岛素作用早期步骤的这些调节可能在该动物模型中观察到的胰岛素敏感性改善的细胞内机制中发挥作用。
