Altered subcellular distribution of estrogen receptor α is implicated in estradiol-induced dual regulation of insulin signaling in 3T3-L1 adipocytes

Kiyofumi Nagira, Toshiyasu Sasaoka, Tsutomu Wada, Kazuhito Fukui, Mariko Ikubo, Satoko Hori, Hiroshi Tsuneki, Shigeru Saito, Masashi Kobayashi

研究成果: Article査読

46 被引用数 (Scopus)

抄録

We investigated the mechanisms by which estrogen alters insulin signaling in 3T3-L1 adipocytes. Treatment with 17β-estradiol (E2) did not affect insulin-induced tyrosine phosphorylation of insulin receptor. E2 enhanced insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), IRS-1/p85 association, phosphorylation of Akt, and 2-deoxyglucose uptake at 10-8 M, but inhibited these effects at 10-5 M. A concentration of 10-5 M E2 enhanced insulin-induced phosphorylation of IRS-1 at Ser307, which was abolished by treatment with a c-Jun NH2-terminal kinase inhibitor. In addition, the effect of E2 was abrogated by pretreatment with a specific estrogen receptor antagonist, ICI182,780. Membrane-impermeable E2, E2-BSA, did not affect the insulin-induced phosphorylation of Akt at 10-8 M, but inhibited it at 10-5 M. Furthermore, E2 decreased the amount of estrogen receptor α at the plasma membrane at 10-8 M, but increased it at 10-5 M. In contrast, the subcellular distribution of estrogen receptor β was not altered by the treatment. These results indicate that E2 affects the metabolic action of insulin in a concentration-specific manner, that high concentrations of E2 inhibit insulin signaling by modulating phosphorylation of IRS-1 at Ser307 via a c-Jun NH2-terminal kinase-dependent pathway, and that the subcellular redistribution of estrogen receptor α in response to E2 may explain the dual effect of E2.

本文言語English
ページ(範囲)1020-1028
ページ数9
ジャーナルEndocrinology
147
2
DOI
出版ステータスPublished - 2006 2月
外部発表はい

ASJC Scopus subject areas

  • 内分泌学

フィンガープリント

「Altered subcellular distribution of estrogen receptor α is implicated in estradiol-induced dual regulation of insulin signaling in 3T3-L1 adipocytes」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル