title: Perturbations of the stress-induced GLUT4 localization pathway in slow-twitch muscles of obese Zucker rats.
abstract: Past studies have suggested that the stress-induced 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), 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-AS160-GLUT4 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.
authors.affiliation: Department and Institute of Physiology, School of Medicine, National Yang Ming University, Shih-Pai, Taipei, Taiwan, Republic of China.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
authors.forename: Shin-Ying
authors.initials: SY
authors.lastname: Hsih
authors.forename: Yung-Pei
authors.initials: YP
authors.lastname: Hsu
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: Low-Tone
authors.initials: LT
authors.lastname: Ho
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010766:Phosphorylation; D005082:Physical Exertion; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D011924:Rats, Zucker; D013312:Stress, Physiological
chemical_list: D001786:Blood Glucose; D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; C495694:Slc2a4 protein, rat; C533101:TBC1D4 protein, rat; D006003:Glycogen; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D000091162:AMP-Activated Protein Kinase Kinases; D000263:Adenylate Kinase