Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China,
Endocrine. 2013 Dec;44(3):659-65. doi: 10.1007/s12020-013-9894-1. Epub 2013 Feb 2.
It is well established that estrogen deficiency is strongly linked to the development of insulin resistance (IR), but the mechanism is still unclear. Since IR is characterized by a marked reduction in insulin-stimulated PI3 K-mediated activation of Akt in liver and skeletal muscle, we hypothesized that ovariectomized rats (OVX) would exhibit reductions in the expression of proteins in PI3 K signaling pathway, including PI3 K and Akt. As hypothesized, after observing for 12 weeks, compared with the SHAM rats, ovariectomy led to decreased plasma estrogen level and increased HOMA-IR index; in addition, ovariectomy also caused decreased PI3 K and Akt expression levels in the liver and skeletal muscle. Interestingly, the expression patterns differed in tissue-dependent fashion: Akt1 was only found reduction in liver, whereas Akt2 decreased in muscle; these changes can be reversed by estrogen supplement (OVXE). In conclusion, data demonstrate that estrogen withdrawals may cause IR at least in part by impaired PI3 K/Akt signaling proteins in liver and skeletal muscle, and Akt1 and Akt2 might be tissue-specific expressions.
已经证实，雌激素缺乏与胰岛素抵抗（IR）的发展密切相关，但具体机制尚不清楚。由于 IR 的特征是胰岛素刺激 PI3K 介导的 Akt 激活明显减少，我们假设去卵巢大鼠（OVX）会表现出 PI3K 信号通路中蛋白质表达的减少，包括 PI3K 和 Akt。正如假设的那样，经过 12 周的观察，与 SHAM 大鼠相比，卵巢切除术导致血浆雌激素水平降低和 HOMA-IR 指数升高；此外，卵巢切除术还导致肝脏和骨骼肌中 PI3K 和 Akt 表达水平降低。有趣的是，表达模式在组织依赖性方面存在差异：仅在肝脏中发现 Akt1 减少，而 Akt2 在肌肉中减少；这些变化可以通过雌激素补充（OVXE）逆转。总之，数据表明，雌激素缺乏可能至少部分通过肝脏和骨骼肌中 PI3K/Akt 信号蛋白的损伤引起 IR，Akt1 和 Akt2 可能是组织特异性表达。
