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Marcella Salzano Department of Medicine and Surgery, Clinical and Molecular Endocrinology and Oncology, University of Salerno, Via Allende, 84081 Baronissi, Salerno, Italy Departments of

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Eleonora Russo Department of Medicine and Surgery, Clinical and Molecular Endocrinology and Oncology, University of Salerno, Via Allende, 84081 Baronissi, Salerno, Italy Departments of

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Loredana Postiglione Department of Medicine and Surgery, Clinical and Molecular Endocrinology and Oncology, University of Salerno, Via Allende, 84081 Baronissi, Salerno, Italy Departments of

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Anna Guerra
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Vincenzo Marotta Department of Medicine and Surgery, Clinical and Molecular Endocrinology and Oncology, University of Salerno, Via Allende, 84081 Baronissi, Salerno, Italy Departments of

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Silvano Esposito
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Mario Vitale
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4 °C with a HRP-conjugated anti-mouse secondary antibody. After a final wash, protein bands were detected by an ECL system (Amersham Pharmacia Biotech). Mouse MABs to ERK and phosphorylated ERK, Akt and phospho-threonine-308-Akt, caspase-3, and PARP

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Yun-Ju Chen Institute of Physiology, School of Medicine, National Yang-Ming University, 155 Linong Street, Section 2, Taipei 112, Taiwan, Republic of China
Agricultural Biotechnology Research Center,
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Republic of China
Division of Reproductive and Developmental Science, Queen’s Medical Research Institute, Edinburgh University, Edinburgh EH16 4TJ, UK
Institute of Molecular and Cellular Biology, School of Life Science, National Taiwan University, Taipei 106, Taiwan, ROC

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Pei-Wen Hsiao Institute of Physiology, School of Medicine, National Yang-Ming University, 155 Linong Street, Section 2, Taipei 112, Taiwan, Republic of China
Agricultural Biotechnology Research Center,
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Republic of China
Division of Reproductive and Developmental Science, Queen’s Medical Research Institute, Edinburgh University, Edinburgh EH16 4TJ, UK
Institute of Molecular and Cellular Biology, School of Life Science, National Taiwan University, Taipei 106, Taiwan, ROC

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Ming-Ting Lee Institute of Physiology, School of Medicine, National Yang-Ming University, 155 Linong Street, Section 2, Taipei 112, Taiwan, Republic of China
Agricultural Biotechnology Research Center,
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Republic of China
Division of Reproductive and Developmental Science, Queen’s Medical Research Institute, Edinburgh University, Edinburgh EH16 4TJ, UK
Institute of Molecular and Cellular Biology, School of Life Science, National Taiwan University, Taipei 106, Taiwan, ROC

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J Ian Mason Institute of Physiology, School of Medicine, National Yang-Ming University, 155 Linong Street, Section 2, Taipei 112, Taiwan, Republic of China
Agricultural Biotechnology Research Center,
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Republic of China
Division of Reproductive and Developmental Science, Queen’s Medical Research Institute, Edinburgh University, Edinburgh EH16 4TJ, UK
Institute of Molecular and Cellular Biology, School of Life Science, National Taiwan University, Taipei 106, Taiwan, ROC

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Ferng-Chun Ke Institute of Physiology, School of Medicine, National Yang-Ming University, 155 Linong Street, Section 2, Taipei 112, Taiwan, Republic of China
Agricultural Biotechnology Research Center,
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Republic of China
Division of Reproductive and Developmental Science, Queen’s Medical Research Institute, Edinburgh University, Edinburgh EH16 4TJ, UK
Institute of Molecular and Cellular Biology, School of Life Science, National Taiwan University, Taipei 106, Taiwan, ROC

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Jiuan-Jiuan Hwang Institute of Physiology, School of Medicine, National Yang-Ming University, 155 Linong Street, Section 2, Taipei 112, Taiwan, Republic of China
Agricultural Biotechnology Research Center,
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, Republic of China
Division of Reproductive and Developmental Science, Queen’s Medical Research Institute, Edinburgh University, Edinburgh EH16 4TJ, UK
Institute of Molecular and Cellular Biology, School of Life Science, National Taiwan University, Taipei 106, Taiwan, ROC

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also activate the phosphatidylinositol-3-OH kinase (PI3K) pathway. FSH activates PI3K in rat granulosa cells leading to phosphorylation of Akt and serum and glucocorticoid-induced kinase (Sgk; Gonzalez-Robayna et al. 2000 , Richards et al. 2002

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Junhong Chen Institute of Comparative Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China

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Jing Sun Institute of Comparative Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China

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Michelle E Doscas Department of Cell and Molecular Medicine, Rush University Medical Center, Chicago, Illinois, USA

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Jin Ye Department of Cell and Molecular Medicine, Rush University Medical Center, Chicago, Illinois, USA

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Ashley J Williamson Rush Medical College, Rush University Medical Center, Chicago, Illinois, USA

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Yanchun Li Section of Endocrinology, Department of Medicine, University of Chicago, Chicago, Illinois, USA

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Yi Li Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas, USA

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Richard A Prinz Department of Surgery, NorthShore University Health System, Evanston, Illinois, USA

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Xiulong Xu Institute of Comparative Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China
Department of Cell and Molecular Medicine, Rush University Medical Center, Chicago, Illinois, USA
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, China

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protein kinase B (AKT) ( Guo 2013 , 2014 ). AKT activation plays a critical role in glucose metabolism ( Dann et al. 2007 , Copps & White 2012 ). AKT activation stimulates glucose uptake by inducing translocation of the glucose transporter type 4 (GLUT

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Kelly D McCall Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center

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Dawn Holliday Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center

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Eric Dickerson Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center

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Brian Wallace Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center

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Anthony L Schwartz Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center

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Christopher Schwartz Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center

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Christopher J Lewis Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center

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Leonard D Kohn Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center

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Frank L Schwartz Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center

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IRS-1 when phosphorylated at serine 307 from Cell Signaling Technology (Danvers, MA, USA). For the detection of phosphorylated AKT, 10 μg of total protein was subjected to western blot analysis and identified using an anti-phospho-AKT serine 473

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M Schütt
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J Zhou
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M Meier
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H H Klein
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308 / Ser 473 -Akt phosphorylation ( Schütt et al. 2000 , Rudich et al. 2001 , Ben-Romano et al. 2003 ) in HepG2 hepatoma cells ( Schütt et al. 2000 ) or 3T3-L1 cells ( Rudich et al. 2001 , Ben-Romano et al. 2003 , 2004 ) respectively

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Mahsa Hamzeh Department of Pharmacology and Therapeutics, Department of Obstetrics and Gynecology, McGill University, McIntyre Medical Sciences Building, 3655 Promenade Sir-William-Osler, Room 104, Montréal, Québec, Canada H3G 1Y6

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Bernard Robaire Department of Pharmacology and Therapeutics, Department of Obstetrics and Gynecology, McGill University, McIntyre Medical Sciences Building, 3655 Promenade Sir-William-Osler, Room 104, Montréal, Québec, Canada H3G 1Y6
Department of Pharmacology and Therapeutics, Department of Obstetrics and Gynecology, McGill University, McIntyre Medical Sciences Building, 3655 Promenade Sir-William-Osler, Room 104, Montréal, Québec, Canada H3G 1Y6

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et al . 2005 , Gatson et al . 2006 ). Androgens can also activate the phosphatidylinositol-3 kinase (PI-3K) and AKT pathway rapidly in a ligand binding-independent manner ( Lutz et al . 2003 , Sun et al . 2003 , Kang et al . 2004

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Gen Chen School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Xiangjuan Chen Department of Obstetrics and Gynecology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Chao Niu The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China

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Xiaozhong Huang The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China

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Ning An School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Jia Sun School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Shuai Huang School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Weijian Ye The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China

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Santie Li School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Yingjie Shen School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Jiaojiao Liang School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Weitao Cong School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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Litai Jin School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China

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. (Nanjing, China). The primary antibodies used to probe the membranes included Nrf2 (1:1000), Fyn (1:2000) and GAPDH (1:5000) were purchased from Santa Cruz Biotechnology, Santa Cruz; Akt and p-Akt (Ser473; 1:2000), GSK3B and p-GSK3B (Ser9; 1:2000), c

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M E Cleasby Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK
Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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Q Lau Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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E Polkinghorne Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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S A Patel Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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S J Leslie Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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N Turner Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK
Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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G J Cooney Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK
Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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A Xu Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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E W Kraegen Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK
Department of Veterinary Basic Sciences, Diabetes and Obesity Research Program, Faculty of Medicine, Department of Medicine, Faculty of Medicine, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK

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act as a dynamic scaffold for endosomal signalling proteins ( Miaczynska et al . 2004 , Chial et al . 2008 ) and was first identified as an interacting partner for the serine/threonine kinase AKT2 ( Mitsuuchi et al . 1999 ). AKT2 is required for

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Min Kyong Moon Department of Internal Medicine, Department of Internal Medicine, Department of Internal Medicine, Clinical Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea
Department of Internal Medicine, Department of Internal Medicine, Department of Internal Medicine, Clinical Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea

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In-Kyong Jeong Department of Internal Medicine, Department of Internal Medicine, Department of Internal Medicine, Clinical Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea

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Tae Jung Oh Department of Internal Medicine, Department of Internal Medicine, Department of Internal Medicine, Clinical Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea

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Hwa Young Ahn Department of Internal Medicine, Department of Internal Medicine, Department of Internal Medicine, Clinical Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea
Department of Internal Medicine, Department of Internal Medicine, Department of Internal Medicine, Clinical Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea

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Hwan Hee Kim Department of Internal Medicine, Department of Internal Medicine, Department of Internal Medicine, Clinical Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea

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Young Joo Park Department of Internal Medicine, Department of Internal Medicine, Department of Internal Medicine, Clinical Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea

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Hak Chul Jang Department of Internal Medicine, Department of Internal Medicine, Department of Internal Medicine, Clinical Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea
Department of Internal Medicine, Department of Internal Medicine, Department of Internal Medicine, Clinical Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea

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Kyong Soo Park Department of Internal Medicine, Department of Internal Medicine, Department of Internal Medicine, Clinical Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea

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membrane was reincubated with secondary antibody for 1 h. The primary antibodies were pAkt (Ser473 and Thr308), Akt (Cell Signaling Technology), pGSK3β (Ser9) (Cell Signaling Technology), GSK3β (BD Transduction Laboratories, San Jose, CA, USA), and γ

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Karen Kar-Loen Chan Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, 6/F Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong

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Thomas Ho-Yin Leung Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, 6/F Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong

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David Wai Chan Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, 6/F Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong

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Na Wei Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, 6/F Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong

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Grace Tak-Yi Lau Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, 6/F Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong

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Stephanie Si Liu Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, 6/F Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong

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Michelle K-Y Siu Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, 6/F Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong

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Hextan Yuen-Sheung Ngan Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, 6/F Professorial Block, Queen Mary Hospital, Pokfulam, Hong Kong

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Institute's guidance on animal experiments. Western blotting For the examination of AKT activity, ovarian cancer cells (SKOV3) treated with vehicle solution DMSO, MPP (100 pM), DPN (10 nM), or a combination of MPP and DPN at different time points (0, 4, and

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