The phosphatidylinositol/AKT/atypical PKC pathway is involved in the improved insulin sensitivity by DHEA in muscle and liver of rats in vivo
The phosphatidylinositol/AKT/atypical PKC pathway is involved in the improved insulin sensitivity by DHEA in muscle and liver of rats in vivo
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DOI：
10.1016/j.lfs.2004.06.017
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发表时间：
2004-11-19
期刊：
影响因子：
6.1
通讯作者：
Carvalho, CRO
中科院分区：
文献类型：
--
作者：
Campbell, CSG;Caperuto, LC;Carvalho, CRO
脱氢表雄酮在动物模型和男性中具有改善胰岛素敏感性和抗肥胖作用。然而，脱氢表雄酮改善胰岛素作用的分子机制尚不清楚。在本研究中，我们检测了6月龄Wistar大鼠DHEA处理后肝脏和肌肉中胰岛素受体（IR）、IRS-1和IRS-2的蛋白水平和磷酸化状态，irs与PI3K和SHP2的关系，胰岛素诱导的irs相关的PI3激酶活性，AKT和非典型PKCzeta/lambda的磷酸化状态。免疫印迹分析各组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酪氨酸磷酸化在两组织中升高，DHEA处理组肝脏中IRS-2酪氨酸磷酸化升高。DHEA处理大鼠肝脏中pi3 -激酶/AKT通路升高，肌肉中PI3K/非典型PKCzeta/lambda通路升高。这些数据表明，这些胰岛素作用早期步骤的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。(C) 2004爱思唯尔公司版权所有。
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. (C) 2004 Elsevier Inc. All rights reserved.