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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1020-1028
Number of pages9
JournalEndocrinology
Volume147
Issue number2
DOIs
Publication statusPublished - 2006 Feb 1
Externally publishedYes

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Adipocytes
Estrogen Receptors
Estradiol
Insulin Receptor Substrate Proteins
Insulin
Phosphorylation
JNK Mitogen-Activated Protein Kinases
Tyrosine
Insulin Receptor
Deoxyglucose
Estrogens
Cell Membrane
Membranes

ASJC Scopus subject areas

  • Endocrinology

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Altered subcellular distribution of estrogen receptor α is implicated in estradiol-induced dual regulation of insulin signaling in 3T3-L1 adipocytes. / Nagira, Kiyofumi; Sasaoka, Toshiyasu; Wada, Tsutomu; Fukui, Kazuhito; Ikubo, Mariko; Hori, Satoko; Tsuneki, Hiroshi; Saito, Shigeru; Kobayashi, Masashi.

In: Endocrinology, Vol. 147, No. 2, 01.02.2006, p. 1020-1028.

Research output: Contribution to journalArticle

Nagira, K, Sasaoka, T, Wada, T, Fukui, K, Ikubo, M, Hori, S, Tsuneki, H, Saito, S & Kobayashi, M 2006, 'Altered subcellular distribution of estrogen receptor α is implicated in estradiol-induced dual regulation of insulin signaling in 3T3-L1 adipocytes', Endocrinology, vol. 147, no. 2, pp. 1020-1028. https://doi.org/10.1210/en.2005-0825
Nagira, Kiyofumi ; Sasaoka, Toshiyasu ; Wada, Tsutomu ; Fukui, Kazuhito ; Ikubo, Mariko ; Hori, Satoko ; Tsuneki, Hiroshi ; Saito, Shigeru ; Kobayashi, Masashi. / Altered subcellular distribution of estrogen receptor α is implicated in estradiol-induced dual regulation of insulin signaling in 3T3-L1 adipocytes. In: Endocrinology. 2006 ; Vol. 147, No. 2. pp. 1020-1028.
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