Impaired PI3 K Akt expression in liver and skeletal muscle of ovariectomized rats.

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.