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Mahendra Prasad Bhatt Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Yeon-Ju Lee Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Se-Hui Jung Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Yong Ho Kim SKKU Advanced Institute of Nanotechnology and Department of Chemistry, Sungkyunkwan University, Suwon, Gyeonggi-do, Korea

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Jong Yun Hwang Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Eun-Taek Han Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Won Sun Park Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Seok-Ho Hong Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Young-Myeong Kim Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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Kwon-Soo Ha Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, Korea

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-supplemented diabetic (DM+ins, n  = 11) and both insulin- and C-peptide-supplemented diabetic (DM+ins+CP, n  = 14) mice were dissected and cut longitudinally to expose the endothelium for immediate staining. To measure the intracellular levels, aortic segments were

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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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, immunofluorescence staining for CD31 (an endothelial cell marker) revealed the presence of de-endothelialized region in aortal endothelium of diabetic mice induced by STZ (100 mg/kg body weight, i.p.) compared with its corresponding control littermates. Systemic

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Alpha Dian-Yu Lin Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Anita Mannikarottu Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Barry A Kogan Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Catherine Whitbeck Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Paul Chichester Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Robert E Leggett Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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Robert M Levin Albany College of Pharmacy,
Albany Medical College,
Stratton VA Medical Center, 106 New Scotland Ave, Albany, New York 12208, USA
Taichung Poah-Ai Hospital, Taipei, Taiwan

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. The tissue blocks were sectioned at 5 μm and were used for the immunostaining studies. Immunostaining for vascular endothelium using CD31 Tissue sections were stained with the mouse monoclonal antibody anti-CD31

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Kenichi Serizawa Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Kenji Yogo Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Yoshihito Tashiro Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Satoshi Takeda Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Ryohei Kawasaki Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Ken Aizawa Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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Koichi Endo Product Research Department, Product Research Department, Medical Science Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan

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diameter changes after transient ischemia. Transient ischemia leads to reactive hyperemia with increase in flow velocity and vascular wall shear stress. Increased shear stress can induce nitric oxide (NO) production from endothelium, leading to vasodilation

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Svetlana I Sofronova Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia
Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia

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Dina K Gaynullina Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia
Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia
Department of Physiology, Russian National Research Medical University, Moscow, Russia

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Anastasia A Shvetsova Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia
Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia

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Anna A Borzykh Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia

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Ekaterina K Selivanova Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia
Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia

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Daria S Kostyunina Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia
Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia

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Anna P Sharova Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia

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Andrey A Martyanov Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia
Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia

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Olga S Tarasova Institute for Biomedical Problems, Russian Academy of Sciences, Moscow, Russia
Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia

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the developing vasculature is NO-mediated anticontractile effect of the endothelium that is prominent in early postnatal period and gradually decreases with maturation ( Gaynullina et al. 2013 , Sofronova et al. 2016 ). These two mechanisms are

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Daniel M Kelly Department of Human Metabolism, Robert Hague Centre for Diabetes and Endocrinology, Medical School, The University of Sheffield, Sheffield S10 2RX, UK

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T Hugh Jones Department of Human Metabolism, Robert Hague Centre for Diabetes and Endocrinology, Medical School, The University of Sheffield, Sheffield S10 2RX, UK
Department of Human Metabolism, Robert Hague Centre for Diabetes and Endocrinology, Medical School, The University of Sheffield, Sheffield S10 2RX, UK

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vascular reactivity is the monitoring of changes in brachial artery diameter by a non-invasive ultrasound assessment as it is considered an accurate and reproducible measurement of endothelium-dependent response to shear stress ( Celermajer et al . 1992

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Kumiko Taguchi Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, Japan

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Haruka Narimatsu Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, Japan

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Takayuki Matsumoto Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, Japan

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Tsuneo Kobayashi Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, Japan

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. 2014 , 2016 , Taguchi et al. 2017 a , b , 2018 ). Furthermore, impairment of endothelium-derived NO is a common feature of endothelial dysfunction in diabetic individuals ( Steinberg et al. 1996 , Montagnani et al. 2002 , Taguchi et al

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Jordan M Willcox Departments of Biomedical Sciences, Human Health and Nutritional Sciences, University of Guelph, ANNU Bldg, Room 350, Guelph, Ontario, Canada N1G 2W1

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Alastair J S Summerlee Departments of Biomedical Sciences, Human Health and Nutritional Sciences, University of Guelph, ANNU Bldg, Room 350, Guelph, Ontario, Canada N1G 2W1

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Coral L Murrant Departments of Biomedical Sciences, Human Health and Nutritional Sciences, University of Guelph, ANNU Bldg, Room 350, Guelph, Ontario, Canada N1G 2W1

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population (RXFP1) is present at the TA, Branch and capillary level but not on MI arterioles. There is evidence to support that RXFP1 is located on the endothelium of renal arteries ( Novak et al . 2006 ) and VSM of renal ( Novak et al . 2006 ) and cardiac

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Harman S Mattu Division of Metabolic and Vascular Health, University of Warwick Medical School, Gibbet Hill Road, Coventry CV4 7AL, UK

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Harpal S Randeva Division of Metabolic and Vascular Health, University of Warwick Medical School, Gibbet Hill Road, Coventry CV4 7AL, UK

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from endothelium and decreased blood flow to insulin target tissues, contributing to insulin resistance ( Kim et al . 2006 ). Systemic inflammation and abnormal production of adipose tissue-derived factors play a pivotal role in the genesis and

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Stefanie Ruhs Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Halle, Germany

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Alexander Nolze Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Halle, Germany

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Ralf Hübschmann Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Halle, Germany

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Claudia Grossmann Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Halle, Germany

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or GPER1 inhibitors, however, aldosterone-induced vasorelaxation was only dependent on MR ( Ferreira et al. 2015 ). Furthermore, aldosterone could endothelium-dependently inhibit phenylephrine-mediated vasoconstriction of aortic rings via GPER1

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