AMPK signaling in skeletal muscle under chronic catabolic stress

• Main Authors: Chung-Yu Chen, 陳宗與
• Other Authors: Ying-Lan Tsai
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/33772817495135589710

博士 === 國立體育大學 === 體育研究所 === 98 === Hypoxia and exercise training are the well known factors, which can cause functional changes in skeletal muscle. Glucose metabolism in skeletal muscle is mediated by AMPK and CAMK II signaling pathway, which is crucial in normal and obese subjects. The first study was purposed to investigate the different duration of mild hypoxia exposure on AMPK signaling and insulin sensitivity. The second study was aimed to compare the acute exercise and exercise training effect on glucose tolerance in obese Zucker rat. This study also demonstrate the role of AMPK signaling and CAMK II protein expression in Zucker rats. Methods: In the first study, Spargue Dawley (n=56) rats were divided into two groups; 8 hr/day mild hypoxia exposure group and 1 hr/day mild hypoxia exposure group. Each group was followed 3 treatments: control, acute mild hypoxia and 8-week mild hypoxia. In the second study, obese Zucker rats (n=24) and lean littermates (n=24) were assigned into following 3 treatments; control, acute 1-hr exercise and six-week chronic exercise training. Results: In first part of the study, significantly decreased epididymal fat mass, improved glucose tolerance, enhanced insulin sensitivity, and increased capillary density was observed with 8 hr/day with 8-week mild hypoxia treatment. Only in insulin sensitivity and capillary density were significantly increased in 1 hr/day with 8-week mild hypoxia treated group. Furthermore, acute 8-hour mild hypoxia exposure significantly elevated PGC-1α, VEGF and GLUT4 mRNA levels. However, the protein expression of AMPK, phospho-AMPK, PGC-1α, GLUT4 and VEGF in both red and white quadriceps muscles were not significantly different among groups under acute and chronic mild hypoxia conditions. In second study, exercise training significantly improved glucose tolerance and increased citrate synthase activity in both obese and lean Zucker rats. However, no significant difference in GLUT1, GLUT4, and PGC-1α mRNA levels were observed in red gastrocnemius muscle between the control and acute exercise groups. Interestingly, the phosphorylation of AMPK-thr 172, CAMK II-thr 286, and PGC-1α protein level in obese Zucker rat were significantly higher than lean littermates under basal state, but this phenomenon could be reversed after six-week exercise training. In addition, the PGC-1α level was significantly increased in lean Zucker rats following six-week exercise training. Conclusions: The first study demonstrated significant improvements in glucose tolerance and insulin sensitivity by 8 hr/day with 8-week mild intermittent hypoxia. However, this beneficial effect was not apparent in 1 hr/day with 8-week mild intermittent hypoxia group. This improvement in glucose tolerance and insulin sensitivity appears to be related to the elevated muscle capillary density and decreased fat accumulation; it seems not to be related with increased GLUT4, VEGF, and PGC-1α protein expression. The second study showed significantly higher CAMK II-thr 286 and AMPK-thr 172 phosphorylation in obese Zucker rat than in lean rats; however, six weeks exercise training could reverse this phenomenon. Improved glucose tolerance by exercise training in both obese and lean Zucker rats appear to be related to increased mitochondria density rather than elevated GLUT1, GLUT4, and PGC-1α protein expression. This study confirmed that mild intermittent hypoxia and exercise training would be affective to improve glucose tolerance and increase insulin sensitivity, which can adopt as therapeutic strategy for type 2 diabetic patients.