Central versus peripheral impact of estradiol on the impaired glucose metabolism in ovariectomized mice on a high-fat diet

摘要

Estrogen has been thought to exert its biological functions through classical genomic actions initiated by direct binding to the estrogen receptors (ER) (19, 23). Previous studies utilizing ERalpha and ERbeta knockout mice showed a predominant role for ERa in the regulation of glucose metabolism (3, 20). In 3T3-L1 adipocytes, we have previously reported that a low dose of estrogen enhanced insulin signaling at insulin receptor substrate 1 through ERa (27). In addition, estrogen stimulated Akt and AMP kinase in rat soleus muscle, and enhanced glucose uptake via ER by facilitating glucose transporter 4 (GLUT4)'s translocation to the plasma membrane in C2C12 myotubes (12, 32). On the basis of these studies in vitro, the beneficial effects of estrogen on glucose and lipid metabolism appear to be exerted via a direct action in peripheral tissues.