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Yi Luan Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

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Maxwell E Edmonds Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

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Teresa K Woodruff Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

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So-Youn Kim Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
Olson Center for Women’s Health, Department of Obstetrics and Gynecology, and Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, 985860 Nebraska Medical Center, Omaha, Nebraska, USA

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as follows: Ki67 (ab833-500, 1:100) from Abcam; p-H3 (3377S, 1:50), γH2AX (9718s, 1:100), phospho-p63 (4981s, 1:50), cleaved PARP (9548s, 1;100), phospho-ATR (2853T, 1:50), phospho-CHK1 (12302T, 1:50), phospho-CHK2 (2197S, 1:50) and phospho-AKT (9271s

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Mirian A Kurauti Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Brazil

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José M Costa-Júnior Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Brazil

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Sandra M Ferreira Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Brazil

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Gustavo J dos Santos Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Brazil

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André O P Protzek Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Brazil

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Tarlliza R Nardelli Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Brazil

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Luiz F de Rezende Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Brazil

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Antonio C Boschero Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Brazil

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/mL aprotinin). Akt phosphorylation assay An i.p. administration of 100μL (10U) of insulin (Humulin, Eli Lilly) was performed in all groups (CTL, DIO, and DIO+EXE). Some of the CTL mice received 100μL of saline solution, instead of insulin, as described

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Michael P Walker Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Mail Drop D4-01, PO Box 12233, Research Triangle Park, North Carolina 27709, USA

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Richard P DiAugustine Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Mail Drop D4-01, PO Box 12233, Research Triangle Park, North Carolina 27709, USA

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Ernest Zeringue Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Mail Drop D4-01, PO Box 12233, Research Triangle Park, North Carolina 27709, USA

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Maureen K Bunger Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Mail Drop D4-01, PO Box 12233, Research Triangle Park, North Carolina 27709, USA

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Martina Schmitt Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Mail Drop D4-01, PO Box 12233, Research Triangle Park, North Carolina 27709, USA

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Trevor K Archer Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Mail Drop D4-01, PO Box 12233, Research Triangle Park, North Carolina 27709, USA

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R Gregg Richards Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Mail Drop D4-01, PO Box 12233, Research Triangle Park, North Carolina 27709, USA

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-195), cdk1 (06-141), and cdk2 (05-596) were purchased from Upstate (Temecula, CA, USA); antibodies to cyclin A (sc-596), cyclin B1 (sc-595), and cytokeratin 18 (sc-28264) were from Santa Cruz Biotechnology (Santa Cruz, CA, USA); antibodies to AKT (9272) and

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Helena C Barbosa
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Silvana Bordin Departamento de Fisiologia e Biofísica, Departamento de Fisiologia e Biofísica, Beta Cell Development and Function Group, CENEXA, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970 Campinas-SP, São Paulo-SP, Brazil

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Gabriel Anhê Departamento de Fisiologia e Biofísica, Departamento de Fisiologia e Biofísica, Beta Cell Development and Function Group, CENEXA, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970 Campinas-SP, São Paulo-SP, Brazil

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Shanta J Persaud Departamento de Fisiologia e Biofísica, Departamento de Fisiologia e Biofísica, Beta Cell Development and Function Group, CENEXA, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970 Campinas-SP, São Paulo-SP, Brazil

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James Bowe Departamento de Fisiologia e Biofísica, Departamento de Fisiologia e Biofísica, Beta Cell Development and Function Group, CENEXA, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970 Campinas-SP, São Paulo-SP, Brazil

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Maria I Borelli Departamento de Fisiologia e Biofísica, Departamento de Fisiologia e Biofísica, Beta Cell Development and Function Group, CENEXA, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970 Campinas-SP, São Paulo-SP, Brazil

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Juan J Gagliardino Departamento de Fisiologia e Biofísica, Departamento de Fisiologia e Biofísica, Beta Cell Development and Function Group, CENEXA, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970 Campinas-SP, São Paulo-SP, Brazil

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Antonio C Boschero
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), anti-PLC-β2 (rabbit polyclonal, sc-9018), anti-Akt1 (rabbit polyclonal, sc-8312), anti P70S6K (mouse monoclonal sc-8418) anti-phospho Akt1 -Ser473 (rabbit polyclonal, sc-7985), anti-MAPK3 (rabbit polyclonal, sc-94), anti-MAPK 2 (rabbit polyclonal, sc

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Lorena González
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Ma. Eugenia Díaz
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Johanna G Miquet
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Ana I Sotelo
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Diego Fernández Departamento de Química Biológica, Cátedra de Bioquímica Humana, Geriatrics Research, Facultad de Farmacia y Bioquímica, Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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Fernando P Dominici
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Andrzej Bartke Departamento de Química Biológica, Cátedra de Bioquímica Humana, Geriatrics Research, Facultad de Farmacia y Bioquímica, Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina

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Daniel Turyn
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42 MAPK), p38 MAPK, the PKC, the PI3K/AKT, and the STAT pathways, involved in cell proliferation, survival, and motility ( Jorissen et al . 2003 , Henson & Gibson 2006 , Normanno et al . 2006 ). ErbB receptors are activated not only by direct

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Jitendra Vishwakarma Developmental Toxicology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

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Keerti Gupta Developmental Toxicology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

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Juhi Mishra Developmental Toxicology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India

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Asmita Garg Developmental Toxicology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

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Rafat Malik Developmental Toxicology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India

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Amit Kashyap Developmental Toxicology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India

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Manoj Shukla Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow-226014, Uttar Pradesh, India

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Dhirendra Singh Central Pathology Laboratory, Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR–IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India

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Sanghamitra Bandyopadhyay Developmental Toxicology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

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). Moreover, mTOR regulates autophagy involving ULK1 phosphorylation and phosphoinositide 3-kinase (PI3K)-AKT activation, which associates with apoptosis as well ( Zhang & Wang 2018 , Pandey et al. 2020 ). We reported that dysregulated autophagy mechanism

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Kok Lim Kua Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Shanming Hu Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Chunlin Wang Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Jianrong Yao Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Diana Dang Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Alexander B Sawatzke Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Jeffrey L Segar Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

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Kai Wang Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA

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Andrew W Norris Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, USA

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fat tissues were collected and snap frozen 15 min after injection. Immunodetection Tissues were homogenized on ice and centrifuged at 10,000  g at 4°C for 4 min. Supernatant content of AKT/phospho-AKT, PDK1/phosphor-PDK1, MTOR

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Ernane Torres Uchoa Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
Department of Physiological Sciences, State University of Londrina, Londrina, Brazil

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Paula Beatriz Marangon Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil

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Rodrigo Rorato Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
Biotechnology Unit, University of Ribeirao Preto, Ribeirao Preto, Brazil

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Silvia Graciela Ruginsk Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
Department of Physiological Sciences, Biomedical Sciences Institute, Federal University of Alfenas, Alfenas, Brazil

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Lucas Kniess Debarba Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil

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Jose Antunes-Rodrigues Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil

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Lucila L K Elias Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil

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tyr1222 (1:1500, Cell Signaling # 3066), rabbit anti β-actin (1:1000, Cell Signaling # 8457), rabbit anti-AKT (1:10000, Cell Signaling # 4691); rabbit anti-phospho AKT S473 (1:1500, Cell signaling # 9271), rabbit anti-JNK (1:5000, Cell Signaling # 9252

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Binbin Guan Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China
Department of Endocrinology, FuJian Union hospital, Fuzhou, P R China

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Wenyi Li Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China

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Fengying Li Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China

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Yun Xie Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China

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Qicheng Ni Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China

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Yanyun Gu Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China

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Xiaoying Li Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China

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Qidi Wang Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China

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Hongli Zhang Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China

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Guang Ning Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P R China

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has been proposed to upregulate the expression of insulin receptor substrate 2 (IRS2) through increased cytosolic calcium levels and then activate the PI3K/AKT pathway to induce β-cell proliferation ( Jhala et al . 2003 , Heit et al . 2006 , Porat

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Whasun Lim Department of Biotechnology, Department of Animal Resources Science, College of Life Sciences and Biotechnology, Korea University, Seoul 136‐713, Republic of Korea

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Wooyoung Jeong Department of Biotechnology, Department of Animal Resources Science, College of Life Sciences and Biotechnology, Korea University, Seoul 136‐713, Republic of Korea

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Gwonhwa Song Department of Biotechnology, Department of Animal Resources Science, College of Life Sciences and Biotechnology, Korea University, Seoul 136‐713, Republic of Korea

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. 2007 ). For example genistein, one of the phytoestrogens, affects transcriptional activity of ESR1 and ESR2 by modulating their binding affinity to estrogen-response elements (ERE) and inhibiting activity of both the PI3K/AKT and MAPK cell signaling

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