title: Effect of mild intermittent hypoxia on glucose tolerance, muscle morphology and AMPK-PGC-1alpha signaling.
abstract: The main goal of this study was to investigate the long-term effect of daily 8-hour mild intermittent hypoxia (14-15% O2) on glucose tolerance and muscle morphology of Sprague-Dawley rats. The involvement of AMPK-PGC-1alpha-VEGF signaling pathways in the skeletal muscle was also determined during the first 8 hours of hypoxia. We found that mRNA levels of VEGF and PGC-1alpha were significantly increased above control after 8-h mild hypoxia without a change in AMPK phosphorylation. After 8 weeks of mild intermittent hypoxia treatment, plasma glucose and insulin levels in oral glucose tolerance test (OGTT), epididymal fat mass, and body weight were significantly lower compared to the control group. While soleus muscle weight was not changed, capillary and fiber densities in the hypoxia group were 33% and 35% above the control suggesting reorganization of muscle fibers. In conclusion, our data provide strong evidence that long-term mild intermittent hypoxia decreases the diffusion distance of glucose and insulin across muscle fibers, and decreases adiposity in rats. These changes may account for the improved glucose tolerance observed following the 8-week hypoxia treatment, and provides grounds for investigating the development of a mild non-pharmacological intervention in the treatment of obesity and type 2 diabetes.
authors.affiliation: Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei 111, Taiwan, ROC.
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Tsai
authors.forename: Chung-Lan
authors.initials: CL
authors.lastname: Kao
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
authors.forename: Ming-Chieh
authors.initials: MC
authors.lastname: Wu
authors.forename: K
authors.initials: K
authors.lastname: Mallikarjuna
authors.forename: Yi-Hung
authors.initials: YH
authors.lastname: Liao
authors.forename: John L
authors.initials: JL
authors.lastname: Ivy
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D050154:Adiposity / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D018149:Glucose Intolerance / Q000378:metabolism*; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000033:anatomy & histology* / Q000166:cytology / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C495694:Slc2a4 protein, rat; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases