Estrogen Receptor α Regulates Insulin Sensitivity through IRS-1 Tyrosine Phosphorylation in Mature 3T3-L1 Adipocytes

Endocrine Journal

Shigeru OKUYA¹  Yukio TANIZAWA¹  Kazuhiko MURAKI¹ 

[1] Division of Endocrinology, Metabolism, Hematological Sciences and Therapeutics, Department of Bio-Signal Analysis, Yamaguchi University Graduate School of Medicine

关键词: ER-α;    Estradiol;    IRS-1;    Tyrosine phosphorylation;    Adipocyte;   

DOI  :  10.1507/endocrj.K06-005

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(31)Cited-By(19)There are many clinical and experimental reports demonstrating that estrogens and insulin interact when affecting their target organs. Estrogen receptors consist of two isoforms, estrogen receptors-alpha (ER-α) and -beta (ER-β), but their roles in insulin-induced glucose uptake in mature adipose tissue have yet to be clarified. To evaluate the roles of ER-α, expressed predominantly in adipocytes, we have investigated the effects of estradiol (E2), an ER-α selective agonist (PPT), and its selective antagonist (MPP) on glucose uptake and insulin action in 3T3-L1 adipocytes. 3T3-L1 adipocytes were exposed to E2 or PPT and/or MPP at different concentrations. The cells were then subjected to 2-deoxy-D-glucose transport assay, western blot analysis, or RT-PCR analysis. Treatment of these cells with E2 or PPT resulted in biphasic effects on glucose transport, that is high (10-5 M or 3 × 10-6 M each) and low (10-8 M) doses produced inhibition and stimulation, respectively. The favorable effect observed at 10-8 M of E2 was diminished by treatment with MPP. Western bolt analysis revealed that these effects of E2, PPT and MPP paralleled the level of IRS-1 tyrosine phosphorylation. However, IRS-1 serine phosphorylation, suppressor of cytokine signaling (SOCS)-1,-2,-3 and protein tyrosine phosphatase 1B (PTP1B) expression did not change compaired to control subjects. Our data clearly show that ER-α contributes to insulin stimulated glucose uptake through regulation of the tyrosine phosphorylation of IRS-1 protein.

【 授权许可】

Unknown