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Introduction Akt is a serine/threonine protein kinase bearing multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. Akt includes three closely related isoforms Akt1, Akt2, and Akt3
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/2, AKT and PKCε activation ( Brar et al . 2002 , 2004 , Lawrence et al . 2005 ). UCN2 and CRFR2 are both expressed in mouse skeletal muscle ( Chen et al . 2004 , Keipert et al . 2013 ), where they inhibit atrophy and promote hypertrophy ( Hinkle
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Exercise Health and Performance, Faculty of Health and Medical Sciences, Department of Neuroscience and Pharmacology, School of Medicine and Pharmacology, UMR CNRS 9214, Physiology Department, Department of Endocrinology, Inflammation and Infection Research, Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
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Exercise Health and Performance, Faculty of Health and Medical Sciences, Department of Neuroscience and Pharmacology, School of Medicine and Pharmacology, UMR CNRS 9214, Physiology Department, Department of Endocrinology, Inflammation and Infection Research, Faculty of Health Sciences, and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
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), SPA-810, 1/2000, Victoria, BC, Canada) or Cell Signaling (AKT (9272), P-AKT (Ser473) (9271), Danvers, MA, USA), and secondary antibodies were purchased from Sigma–Aldrich (sheep anti-mouse, A5906) or Cell Signaling (goat anti-rabbit, 7074). Serum
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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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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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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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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Signalling Technology unless otherwise stated): anti phospho-CREB (Ser 133, 1:2000 overnight; 4 °C); anti total-CREB (1:1000, room temperature, 1 h; Santa CruzBiotechnology, Santa Cruz, CA, USA); anti phospho-Akt (Thr 308, 1:1000, 4 °C, overnight); anti total-Akt
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(1:100 dilution, Sigma-Aldrich). Insulin receptor, IGF1 receptor and AKT (thr308) phosphorylation, as a percentage of total protein, was determined using MesoScale Discovery phospho and total protein assays, performed according to the manufacturer
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expression or activity. Broken arrow: indirect effect. P indicates phosphorylation. ACT2BR, activin 2B receptor; AMPK, AMP-activated protein kinase; AS160, Akt substrate of 160 kDa; CRFR2, corticotrophin-releasing factor receptor 2; FOXO, forkhead
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Department of Endocrinology, School of Medicine, Pontificia Universidad Catolica De Chile, Santiago, Chile
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, magnification 600×. Data presented as mean ± s.e.m. , n = 6–8 mice/group. (D) pAkt/Akt renal cortex protein analysis by western immunoblot. Data presented as mean ± s.e.m. , n = 6–8 mice/group. Statistical analysis, * = P < 0.05, ** = P < 0
Department of Anatomy, Department of Medicine, Integrated Metabolomics Research Group, Department of Life Science, Korea University College of Medicine, Seoul 136-701, South Korea
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Department of Anatomy, Department of Medicine, Integrated Metabolomics Research Group, Department of Life Science, Korea University College of Medicine, Seoul 136-701, South Korea
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Isoeugenol exerts various beneficial effects on human health. However, the mechanisms underlying these effects are poorly understood. In this study, we observed that isoeugenol activated AMP-activated protein kinase (AMPK) and increased glucose uptake in rat L6 myotubes. Isoeugenol-induced increase in intracellular calcium concentration and glucose uptake was inhibited by STO-609, an inhibitor of calcium/calmodulin-dependent protein kinase kinase (CaMKK). Isoeugenol also increased the phosphorylation of protein kinase C-α (PKCα). Chelation of calcium with BAPTA-AM blocked isoeugenol-induced AMPK phosphorylation and glucose uptake. Isoeugenol stimulated p38MAPK phosphorylation that was inhibited after pretreatment with compound C, an AMPK inhibitor. Isoeugenol also increased glucose transporter type 4 (GLUT4) expression and its translocation to the plasma membrane. GLUT4 translocation was not observed after the inhibition of AMPK and CaMKK. In addition, isoeugenol activated the Akt substrate 160 (AS160) pathway, which is downstream of the p38MAPK pathway. Knockdown of the gene encoding AS160 inhibited isoeugenol-induced glucose uptake. Together, these results indicate that isoeugenol exerts beneficial health effects by activating the AMPK/p38MAPK/AS160 pathways in skeletal muscle.
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Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
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Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
Department of Physiology, University of Toronto, Department of Medicine, Mount Sinai Hospital, Toronto General Research Institute and Banting and Best Diabetes Centre, University Health Network, Muscle Health Research Center and Physical Activity and Chronic Disease Unit, Faculty of Health, School of Kinesiology and Health Science, York University, Department of Internal Medicine, University of Manitoba, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
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serine 307-phosphorylated IRS-1 (Millipore, Temecula, CA, USA), rabbit polyclonal anti-IRS-1 antibody (Millipore), rabbit polyclonal antibody against serine 473-phosphorylated Akt (Cell Signaling Technology, Danvers, MA, USA), rabbit polyclonal anti-Akt