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Elaine Cristina Lima de Souza Laboratório de Fisiologia Endócrina Doris Rosenthal, Serviço de Endocrinologia, Laboratório de Interações Celulares do Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Biofísica Carlos Chagas Filho

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Álvaro Souto Padrón Laboratório de Fisiologia Endócrina Doris Rosenthal, Serviço de Endocrinologia, Laboratório de Interações Celulares do Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Biofísica Carlos Chagas Filho

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William Miranda Oliveira Braga Laboratório de Fisiologia Endócrina Doris Rosenthal, Serviço de Endocrinologia, Laboratório de Interações Celulares do Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Biofísica Carlos Chagas Filho

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Bruno Moulin de Andrade Laboratório de Fisiologia Endócrina Doris Rosenthal, Serviço de Endocrinologia, Laboratório de Interações Celulares do Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Biofísica Carlos Chagas Filho

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Mário Vaisman Laboratório de Fisiologia Endócrina Doris Rosenthal, Serviço de Endocrinologia, Laboratório de Interações Celulares do Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Biofísica Carlos Chagas Filho

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Luiz Eurico Nasciutti Laboratório de Fisiologia Endócrina Doris Rosenthal, Serviço de Endocrinologia, Laboratório de Interações Celulares do Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Biofísica Carlos Chagas Filho

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Andrea Claudia Freitas Ferreira Laboratório de Fisiologia Endócrina Doris Rosenthal, Serviço de Endocrinologia, Laboratório de Interações Celulares do Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Biofísica Carlos Chagas Filho

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Denise Pires de Carvalho Laboratório de Fisiologia Endócrina Doris Rosenthal, Serviço de Endocrinologia, Laboratório de Interações Celulares do Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Biofísica Carlos Chagas Filho

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). Concerning the differentiation of thyroid cells, the activation of PI3K by IGF1 inhibits the expression of NIS that is stimulated by TSH and cAMP ( Garcia & Santisteban 2002 ). Moreover, TSH stimulates AKT phosphorylation in a PI3K-dependent and cAMP

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Donato A Rivas
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Ben B Yaspelkis III Exercise Metabolism Group, Exercise Biochemistry Lab, School of Medical Sciences, RMIT University, Bundoora, Victoria 3083, Australia

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John A Hawley
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Sarah J Lessard
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; Tremblay & Marette 2001 ). In contrast, mTORC2 is a positive regulator of insulin signal transduction through its phosphorylation of protein kinase B/Akt on its serine 473 activation site ( Hresko & Mueckler 2005 , Sarbassov et al . 2005 ). Its ability to

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Liza Margareth Medeiros de Carvalho Sousa Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

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Renata dos Santos Silva Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

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Vanessa Uemura da Fonseca Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

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Rafael Magdanelo Leandro Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

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Thiago Senna Di Vincenzo Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

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Ana Bárbara Alves-Wagner Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

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Ubiratan Fabres Machado Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

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Paula de Carvalho Papa Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

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.05). Additionally, we verified that despite unchanged total AKT content, insulin increased ( P  < 0.001) the AKT phosphorylation ( Fig. 1A and B ). GLUT4 and GLUT1 staining revealed that both were present in luteal cells; however, only GLUT4 showed a qualitative

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Lin Xia
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Zhongqiu Wang Center for Molecular Metabolism, Department of Radiology, Department of Biochemistry and Molecular Biology, Nanjing University of Science and Technology, B508, #364, 200 Xiaolingwei Street, Nanjing 210094, China

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Ying Zhang Center for Molecular Metabolism, Department of Radiology, Department of Biochemistry and Molecular Biology, Nanjing University of Science and Technology, B508, #364, 200 Xiaolingwei Street, Nanjing 210094, China

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Xiao Yang
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Yibei Zhan
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Rui Cheng
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Shiming Wang
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Jianfa Zhang
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PI3K/AKT pathway is a key regulator of insulin signaling ( Whiteman et al . 2002 ). In adipose and muscle cells, AKT (AKT1) overexpression results in an increased insulin-sensitive glucose transporter GLUT4 translocation and glucose uptake ( Kohn et

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Li Li Department of Psychiatry and Behavioral Neurobiology, St Vincent Health System, Department of Animal Sciences, Division of Molecular and Cellular Pathology, Veterans Affairs Medical Center, The University of Alabama at Birmingham, 1720 University Boulevard, Birmingham, Alabama 35294, USA

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Xiaohua Li Department of Psychiatry and Behavioral Neurobiology, St Vincent Health System, Department of Animal Sciences, Division of Molecular and Cellular Pathology, Veterans Affairs Medical Center, The University of Alabama at Birmingham, 1720 University Boulevard, Birmingham, Alabama 35294, USA
Department of Psychiatry and Behavioral Neurobiology, St Vincent Health System, Department of Animal Sciences, Division of Molecular and Cellular Pathology, Veterans Affairs Medical Center, The University of Alabama at Birmingham, 1720 University Boulevard, Birmingham, Alabama 35294, USA

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Wenjun Zhou Department of Psychiatry and Behavioral Neurobiology, St Vincent Health System, Department of Animal Sciences, Division of Molecular and Cellular Pathology, Veterans Affairs Medical Center, The University of Alabama at Birmingham, 1720 University Boulevard, Birmingham, Alabama 35294, USA
Department of Psychiatry and Behavioral Neurobiology, St Vincent Health System, Department of Animal Sciences, Division of Molecular and Cellular Pathology, Veterans Affairs Medical Center, The University of Alabama at Birmingham, 1720 University Boulevard, Birmingham, Alabama 35294, USA

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Joseph L Messina Department of Psychiatry and Behavioral Neurobiology, St Vincent Health System, Department of Animal Sciences, Division of Molecular and Cellular Pathology, Veterans Affairs Medical Center, The University of Alabama at Birmingham, 1720 University Boulevard, Birmingham, Alabama 35294, USA
Department of Psychiatry and Behavioral Neurobiology, St Vincent Health System, Department of Animal Sciences, Division of Molecular and Cellular Pathology, Veterans Affairs Medical Center, The University of Alabama at Birmingham, 1720 University Boulevard, Birmingham, Alabama 35294, USA

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). The protein concentrations of tissue lysates were determined by the BCA method (Pierce, Rockford, IL, USA). For immunoblotting, protein was separated by SDS–PAGE and analyzed by specific antibodies including anti-phosphothreonine 308-AKT, anti

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Márcio Pereira-da-Silva Department of Internal Medicine, State University of Campinas, Brazil

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Cláudio T De Souza Department of Internal Medicine, State University of Campinas, Brazil

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Alessandra L Gasparetti Department of Internal Medicine, State University of Campinas, Brazil

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Mário J A Saad Department of Internal Medicine, State University of Campinas, Brazil

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Lício A Velloso Department of Internal Medicine, State University of Campinas, Brazil

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-pERK (αpERK/Tyr 204, detecting pERK42 and pERK44), anti-Akt1, and anti-phospho [Ser 473 ]Akt1 were from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Rabbit anti-p85/phosphatidylinositol-3 kinase (PI3-kinase) antiserum was from UBI (Lake Placid, NY, USA

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Te Du Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China

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Liu Yang Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China

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Xu Xu School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, China

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Xiaofan Shi Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China

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Xin Xu Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China

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Jian Lu School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, China

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Jianlu Lv School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, China

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Xi Huang School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, China

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Jing Chen Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China

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Heyao Wang Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China

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Jiming Ye School of Health and Biomedical Sciences, RMIT University, Victoria, Australia

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Lihong Hu School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, China

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Xu Shen Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China
School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, China

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-coupled receptors, Akt, IRS2, PTEN, Fas/FasL, NF-κb, Bcl2 family, caspase family, ion channels and so on are tightly associated with β-cell apoptosis ( Anuradha et al . 2014 , Reimann & Gribble 2016 ), and some of the β-cell apoptosis-related proteins have been

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Patrícia Oliveira Prada Departamento de Clínica Médica da Universidade Estadual de Campinas, Campinas, Brazil
Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
Departamento de Clínica Médica, Divisão de Nefrologia, Laboratório de Hipertensão Experimental da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

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Michella Soares Coelho Departamento de Clínica Médica da Universidade Estadual de Campinas, Campinas, Brazil
Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
Departamento de Clínica Médica, Divisão de Nefrologia, Laboratório de Hipertensão Experimental da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

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Henrique Gottardello Zecchin Departamento de Clínica Médica da Universidade Estadual de Campinas, Campinas, Brazil
Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
Departamento de Clínica Médica, Divisão de Nefrologia, Laboratório de Hipertensão Experimental da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

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Miriam Sterman Dolnikoff Departamento de Clínica Médica da Universidade Estadual de Campinas, Campinas, Brazil
Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
Departamento de Clínica Médica, Divisão de Nefrologia, Laboratório de Hipertensão Experimental da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

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Alessandra Lia Gasparetti Departamento de Clínica Médica da Universidade Estadual de Campinas, Campinas, Brazil
Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
Departamento de Clínica Médica, Divisão de Nefrologia, Laboratório de Hipertensão Experimental da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

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Luzia Naôko Shinohara Furukawa Departamento de Clínica Médica da Universidade Estadual de Campinas, Campinas, Brazil
Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
Departamento de Clínica Médica, Divisão de Nefrologia, Laboratório de Hipertensão Experimental da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

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Mario José Abdalla Saad Departamento de Clínica Médica da Universidade Estadual de Campinas, Campinas, Brazil
Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
Departamento de Clínica Médica, Divisão de Nefrologia, Laboratório de Hipertensão Experimental da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

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Joel Claudio Heimann Departamento de Clínica Médica da Universidade Estadual de Campinas, Campinas, Brazil
Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
Departamento de Clínica Médica, Divisão de Nefrologia, Laboratório de Hipertensão Experimental da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

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2002 ). Following tyrosine phosphorylation, IRS-1 and IRS-2 bind and activate the enzyme phosphatidylinositol 3-kinase (PI3-K) ( Folli et al. 1992 , Saltiel & Pessin 2002 ). The activation of PI3-K increases serine phosphorylation of Akt (protein

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Ida Alenkvist Department of Medical Cell Biology, Department of Neuroscience, Uppsala University, Box 571, Husargatan 3, 75123 Uppsala, Sweden

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Oleg Dyachok Department of Medical Cell Biology, Department of Neuroscience, Uppsala University, Box 571, Husargatan 3, 75123 Uppsala, Sweden

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Geng Tian Department of Medical Cell Biology, Department of Neuroscience, Uppsala University, Box 571, Husargatan 3, 75123 Uppsala, Sweden

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Jia Li Department of Medical Cell Biology, Department of Neuroscience, Uppsala University, Box 571, Husargatan 3, 75123 Uppsala, Sweden

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Saba Mehrabanfar Department of Medical Cell Biology, Department of Neuroscience, Uppsala University, Box 571, Husargatan 3, 75123 Uppsala, Sweden

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Yang Jin Department of Medical Cell Biology, Department of Neuroscience, Uppsala University, Box 571, Husargatan 3, 75123 Uppsala, Sweden

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Bryndis Birnir Department of Medical Cell Biology, Department of Neuroscience, Uppsala University, Box 571, Husargatan 3, 75123 Uppsala, Sweden

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Anders Tengholm Department of Medical Cell Biology, Department of Neuroscience, Uppsala University, Box 571, Husargatan 3, 75123 Uppsala, Sweden

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Michael Welsh Department of Medical Cell Biology, Department of Neuroscience, Uppsala University, Box 571, Husargatan 3, 75123 Uppsala, Sweden

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FAK activity, which in turn acts as a scaffold in focal adhesions and activates various downstream signaling pathways, such as AKT and ERK ( Parsons 2003 ). In β-cells, FAK has been shown to convey signals from the extracellular matrix ( Hammar et al

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Sattar Gorgani-Firuzjaee Department of Biochemistry, Department of Clinical Biochemistry, Endocrinology and Metabolism Research Centre, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran

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Salar Bakhtiyari Department of Biochemistry, Department of Clinical Biochemistry, Endocrinology and Metabolism Research Centre, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran

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Abolfazl Golestani Department of Biochemistry, Department of Clinical Biochemistry, Endocrinology and Metabolism Research Centre, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran

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Reza Meshkani Department of Biochemistry, Department of Clinical Biochemistry, Endocrinology and Metabolism Research Centre, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
Department of Biochemistry, Department of Clinical Biochemistry, Endocrinology and Metabolism Research Centre, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran

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carried out through overnight incubation at 4 °C with 5% nonfat dry milk in TBS with 0.5% Tween 20. Blots were incubated with antibodies against LAR, p-IRS1 (Tyr632), and IRS1 (Santa Cruz Biotechnology); Akt and phospho-Akt (Ser473) (Cell Signaling

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