Perturbations of the stress-induced GLUT4 localization pathway in slow-twitch muscles of obese Zucker rats
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ORIGINAL PAPER
Perturbations of the stress-induced GLUT4 localization pathway in slow-twitch muscles of obese Zucker rats Yu-Ching Chen & Shin-Da Lee & Shin-Ying Hsih & Yung-Pei Hsu & Chia-Hua Kuo & Low-Tone Ho
Received: 16 July 2010 / Accepted: 17 January 2011 / Published online: 24 February 2011 # University of Navarra 2011
Abstract Past studies have suggested that the stressinduced GLUT4 localization pathway is damaged in fast-twitch muscles (white muscles) of obese subjects. In this study, we used obese rodents in an attempt to determine whether the stress-induced GLUT4 localization pathway is abnormal in slow-twitch muscles (red muscles), which are responsible for most daily activities. Protein expression levels of the intracellular stress sensor AMP-activated protein kinase (AMPK), Chia-Hua Kuo and Low-Tone Ho equally contributed to this work. Y.-C. Chen : S.-Y. Hsih : Y.-P. Hsu : L.-T. Ho (*) Department and Institute of Physiology, School of Medicine, National Yang Ming University, Shih-Pai, Taipei 11221, Taiwan, Republic of China e-mail: [email protected] Y.-C. Chen : S.-Y. Hsih : Y.-P. Hsu : L.-T. Ho Department of Medical Research and Education, and Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei 11221, Taiwan, Republic of China S.-D. Lee Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung 40202, Taiwan, Republic of China C.-H. Kuo Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei 11153, Taiwan, Republic of China
its upstream kinase LKB1, its downstream protein AS160 and the glucose transporter protein 4 (GLUT4) in the red gastrocnemius muscle were measured under either resting or stress conditions (1 h of swimming or 14% hypoxia) in both lean and obese Zucker rats (n= 7 for each group). At rest, obese rats displayed higher fasting plasma insulin levels and increased muscle AMPK and AS160 phosphorylation levels compared with lean controls. No significant difference was found in the protein levels of LKB1, total GLUT4, or membrane GLUT4 between the obese and lean control groups. After one hour of swimming, AMPK and AS160 phosphorylation levels and the amount of GLUT4 translocated to the plasma membrane were significantly elevated in lean rats but remained unchanged in obese rats relative to their resting conditions. One hour 14% hypoxia did not cause significant changes in the LKB1-AMPK-AS160GLUT4 pathway in either lean or obese rats. This study demonstrated that the AMPK-AS160-GLUT4 pathway was altered at basal levels and after exercise stimulation in the slow-twitch muscle of obese Zucker rats. Keywords Obese . Exercise . Hypoxia . Slow-twitch muscle . Glucose uptake . AMPK
Introduction Obesity is a serious health problem worldwide and may predispose sufferers to glucose intolerance and
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the development of metabolism-related syndromes such as type 2 diabetes mellitus and cardiovascular disease [6]. However, the mechanisms causing glucose intolerance in obese subjects, whic
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