17β-estradiol induces an interaction between adenosine monophosphate-activated protein kinase and the insulin signaling pathway in 3T3-L1 adipocytes

Kim,Ju-Young; Jo,Kyung-Jin; Kim,Byung-Joon; Baik,Haing-Woon; Lee,Seong-Kyu

doi:10.3892/ijmm.2012.1070

17β-estradiol induces an interaction between adenosine monophosphate-activated protein kinase and the insulin signaling pathway in 3T3-L1 adipocytes

Authors:
- Ju-Young Kim
- Kyung-Jin Jo
- Byung-Joon Kim
- Haing-Woon Baik
- Seong-Kyu Lee
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Affiliations: Soonchunhyang Medical Research Institute, College of Medicine, Soonchunhyang University, Chunan 330-721, Republic of Korea , Department of Safety Pharmacology, Korea Institute of Toxicology, Daejeon 305-323, Republic of Korea, Division of Endocrinology, Department of Internal Medicine, Konyang University School of Medicine, Daejeon 371-718, Republic of Korea, Department of Biochemistry and Molecular Biology, School of Medicine, Eulji University, Daejeon 301‑746, Republic of Korea, Department of Biochemistry and Molecular Biology, School of Medicine, Eulji University, Daejeon 301‑746, Republic of Korea
Published online on: July 18, 2012 https://doi.org/10.3892/ijmm.2012.1070
Pages: 979-985

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Abstract

Estrogen (17β-estradiol) has been implicated in maintaining insulin sensitivity. It is thought to act predominantly through genomic pathways and regulate the expression of various genes via binding to estrogen receptors (ERs)-α and -β. 17β-estradiol has been reported to simultaneously stimulate protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK) in ex vivo skeletal muscle. Since data regarding the interaction between AMPK and the insulin receptor substrate-1 (IRS-1)/Akt pathway are controversial, the correlation between AMPK activation and insulin signaling remains unclear. In this study, we examined whether 17β-estradiol simultaneously stimulates the activation of AMPK and IRS-1/Akt in 3T3-L1 adipocytes as well as the 17β-estradiol-ER-induced interaction between the AMPK and IRS-1/Akt pathway in 3T3-L1 adipocytes not exposed to insulin. 17β-estradiol (10-7 M) rapidly activated AMPK and IRS-1/Akt in 3T3-L1 adipocytes, while the ER-α/β non-specific antagonist, ICI 182.780 (10 µM), and the AMPK antagonist compound C (20 µM) reversed the estrogen-induced activation of AMPK and tyrosine (Tyr)-IRS-1/Akt in these cells. Moreover, 17β-estradiol increased the expression of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), adiponectin, uncoupling protein 2 (UCP2) and glucose transporter 4 (GLUT4) genes 24 h after treatment, whereas the ER-α/β non-specific antagonist, ICI 182.780 (10 µM), and the AMPK antagonist compound C (20 µM) reversed the estrogen-induced increase in the expression of these genes. These results indicate that 17β-estradiol activates AMPK through an ER and activates Akt through AMPK activation in 3T3-L1 adipocytes, despite the absence of insulin. Furthermore, 17β-estradiol regulates the expression of genes related to glucose metabolism through ER-AMPK activation in these cells.

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