運動模擬藥物設計之分子基礎與可行性

The Molecular Basis in Developing Exercise-Simulating Drugs and Practical Applications

廖翊宏(Yi-Hung Liao) ； 陳秀華(Hsiu-Hua Chen) ； 李麗珍(Li-Chen Lee) ； 陳宗與(Chung-Yu Chen)

《大專體育》 110期 (2010/10) Pp. 92-99

https://doi.org/10.6162/SRR.2010.110.14

摘要

已知規律身體活動可增進運動表現，同時預防數種退化性代謝疾病發生。然而，根據流行病學研究顯示，現今仍有大部分的人會因無運動意願或喪失運動能力而無法養成規律運動的習慣。由於缺乏運動，此類族群罹患糖尿病或心血管疾病的風險則明顯高於規律運動族群，因此，運動科學家們開始思考開發特殊藥物以模擬運動訓練效益的可行性。最近，數種天然與人工合成的AMPK(AMP-activated protein kinase)與PPAR δ(peroxisome-proliferator-activated receptor δ) 活化劑陸續被發現，並在數種動物模式中被證實可有效提高有氧能力、降低體脂肪、提昇胰島素敏感度等運動適應效應。這些令人振奮的結果進一步提供科學界發展「運動藥錠」的契機與線索；然而，目前這些藥物在穩定性與安全性上仍有技術與實用面的問題亟需克服。在本文中，我們將探討這類化合物如何引起類似運動訓練之生理變化的分子機制，同時在實際應用與該領域未來研究方向上亦有深入討論。

關鍵字

運動訓練 ； 胰島素敏感度 ； AMPK ； PPARδ ； 糖尿病

並列摘要

Regular physical activity is capable of improving exercise performance and preventing from several degenerative metabolic diseases. According to the epidemiological evidence, there is still large proportion of the population showing an inability or unwillingness to perform regular exercise, and these people with low physical activity usually face higher risks of diabetes, cardiovascular diseases, etc. Exercise scientists therefore start pursuing a possible compound to simulate the adaptive benefits of physical exercise training. Recently, some natural and pharmacological activators of AMP-activated protein kinase (AMPK) and peroxisome-proliferatoractivated receptor δ (PPAR δ) had been discovered and found to enhance aerobic capacity, reduce body fat, and improve insulin sensitivity in several experimental animal models. These exciting findings seem to point out a new avenue for developing the ”exercise pill”. However, there are still many technical and practical problems needed to be solved. In this article, the molecular mechanisms for the effects of these exercise simulating compounds on improving aerobic capacity and metabolic fitness are reviewed. Additionally, the practical applications and the prospects in this research field are discussed as well.

並列關鍵字

exercise training ； insulin sensitivity ； AMPK ； PPAR δ ； diabetes

參考文獻

Abu-Elheiga, L.,Matzuk, M. M.,Kordari, P.,Oh, W.,Shaikenov, T.,Gu, Z.(2005).Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal.Proceedings of the National Academy of Sciences of the United States of America.102,12011-12016.

Baldwin, K. M.(2000).Research in the exercise sciences: Where do we go from here?.Journal of Applied Physiology.88,332-336.

Choi, C. S.,Savage, D. B.,Abu-Elheiga, L.,Liu, Z.-X.,Kim, S.,Kulkarni, A.(2007).Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity.Proceedings of the National Academy of Sciences.104,16480-16485.

Finkelstein, E.,Fiebelkorn, I.,Wang, G.(2004).Statelevel estimates of annual medical expenditures attributable to obesity.Obesity Research.12,18-24.

Goodyear, L. J.(2008).The exercise pill-Too good to be true?.New England Journal of Medicine.359,1842-1844.