트레드밀 운동이 고지방 식이 유도 비만 쥐의 골격근 인슐린 신호 경로에 미치는 영향 = The Effects of Regular Treadmill Exercise on Skeletal Muscle Insulin Signaling Pathway in High Fat Diet Induced Obesity Rats

다국어 초록 (Multilingual Abstract)

The purpose of the study is to investigate how regular treadmill exercise for 8 weeks affects on expression of insulin pathway (IRS-1/PI3K/Akt) which is crucial signaling pathway to modulate insulin homeostasis on skeletal muscle for obese rats induced by high fat diet for 14 weeks and what is the relation between insulin pathway and mTORC1-S6K1 (mTOR pathway) which controls insulin pathway. The subject of this study was 24 white male rats of Sprague-dawley and we induced them to be obesity by diet for 14 weeks with water after the environmental adaptation for a week. Animals were divided three groups which are obesity diet group (OD, n=8), obesity diet training (ODT, n=8) and normal diet group (ND, n=8). They performed treadmill exercise for 40 minute 5 times a week for 1 to 4 weeks. For 5 to 8 weeks, treadmill exercise was performed for 60 minute 5 times a week. As a result, IRS-1 and PI3K were significantly decreased in OD group compared with ND group and significantly increased in ODT group compared with OD group (p<0.05). Although p-Akt was not significantly change, it tended to support previous studies (p<0.05). Also, mTORC1 was not significantly changed among groups. But S6K1 was significantly decreased in OD group compared with ND group and increased in ODT group compared with OD group. Therefore, we concluded that regular treadmill exercise for 8 weeks increased IRS-1 and PI3K protein levels affected on positive insulin signaling pathway. Furthermore, not overexpression of mTORC1-S6K1 but leading the change of S6K1 caused differentiation of insulin signaling steps according to muscular fiber.

참고문헌 (Reference)

1 Rivas, D. A., "mTOR function in skeletal muscle: A focal point for overnutrition and exercise" 34 : 807-816, 2009

2 Hay, N., "Upstream and downstream of mTOR" 18 : 1926-1945, 2004

3 Coffey, V. G., "The molecular bases of training adaptation" 37 : 737-763, 2007

4 Krebs, M., "The mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man" 56 : 1600-1607, 2007

5 Rasmussen, B. B., "The balancing act between the cellular processes of protein synthesis and breakdown: Exercise as a model to understand the molecular mechanisms regulating muscle mass" 106 : 1365-1366, 2009

6 Corcoran, M. P., "Skeletal muscle lipid deposition and insulin resistance: Effect of dietary fatty acids and exercise" 85 : 662-677, 2007

7 Sakamoto, K., "Role of Akt 2 in contraction-stimulated cell signaling and glucose uptake in skeletal muscle" 291 : 1031-1037, 2006

8 Kirwan, J. P., "Regular exercise enhances insulin activation of IRS‐1 associated PI3‐kinase in human skeletal muscle" 88 : 797-803, 2000

9 Um, S. H., "Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1" 3 : 393-402, 2006

10 Tremblay, F., "Modulation of insulin action by dietary proteins and amino acids: Role of the mammalian target of rapamycin nutrient sensing pathway" 8 : 457-462, 2005

11 Isotani, S., "Immunopurified mammalian target of rapamycin phosphorylates and activates p70S6 kinase alpha in vitro" 274 : 34493-34498, 1999

12 Tremblay, F., "Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient-and obesity- induced insulin resistance" 104 : 14056-14061, 2007

13 Medeiros, C., "Exercise reduces insulin resistance and upregulates the mTOR/p70S6k pathway in cardiac muscle of diet‐induced obesity rats" 226 : 666-674, 2011

14 Liao, B., "Exercise improves skeletal muscle insulin resistance without reduced basal mTOR/S6K1 signaling in rats fed a high‐fat diet" 111 : 2743-2752, 2011

15 이기업, "Effects of high-fat diet and exercise training on intracellular glucose metabolism in rats" AMER PHYSIOLOGICAL SOC 278 (278): 977-984, 200006

16 Houmard, J. A., "Effect of shortterm exercise training on insulin stimulated PI3-kinase activity in human skeletal muscle" 277 : 1055-1060, 1999

17 Sim, Y. J., "Effect of postnatal treadmill exercise on c‐Fos expression in the hippocampus of rat pups born from the alcoholintoxicated mothers" 30 : 118-125, 2008

18 Benziane, B., "Divergent cell signaling after short‐term intensified endurance training in human skeletal muscle" 295 : 1427-1438, 2008

19 Miyazaki, M., "Cellular mechanisms regulating protein synthesis and skeletal muscle hypertrophy in animals" 106 : 1519-1529, 2009

20 Powers, T., "Cell growth control: mTOR takes on fat" 31 : 775-776, 2008

21 Serrano, A. L., "Calcineurin controls nerve activity dependent specification of slow skeletal muscle fibers but not muscle growth" 98 : 13108-13113, 2001

22 Patti, M. E., "Bidirectional modulation of insulin action by amino acids" 101 : 1519-1529, 1998

23 Tremblay, F., "Amino acid and insulin signaling via the mTOR/p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells" 276 : 38052-38060, 2001

24 Bodine, S. C., "Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo" 3 : 1014-1019, 2001

25 Leger, B., "Akt signaling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy" 576 : 923-933, 2006

26 박수현, "12주 걷기 운동 프로그램의 운동강도가 비만여성의 신체조성, 복부지방, 심폐체력에 미치는 영향" 한국운동생리학회 16 (16): 1-10, 2007