title: 17β-estradiol induces an interaction between adenosine monophosphate-activated             protein kinase and the insulin signaling pathway in 3T3-L1 adipocytes.
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.
authors: Soonchunhyang Medical Research Institute, College of Medicine,                     Soonchunhyang University, Chunan 330-721, Republic of Korea.
authors: Ju-Young
authors: JY
authors: Kim
authors: Kyung-Jin
authors: KJ
authors: Jo
authors: Byung-Joon
authors: BJ
authors: Kim
authors: Haing-Woon
authors: HW
authors: Baik
authors: Seong-Kyu
authors: SK
authors: Lee
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation; D004958:Estradiol / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D005947:Glucose