DOI QR코드

DOI QR Code

지구성 운동과 셀레니움 투여가 당뇨 Goto-kakizaki 쥐의 골격근의 MCT1과 MCT4단백질 발현수준에 미치는 효과

Effects of Exercise Training and Selenium on MCT1 and MCT4 Protein Levels in Skeletal Muscles of Diabetic Goto-Kakizaki Rats

  • 김승석 (한국체육대학교 운동생화학실) ;
  • 강은범 (한국체육대학교 운동생화학실) ;
  • 엄현섭 (한국체육대학교 운동생화학실) ;
  • 김범수 (한국체육대학교 운동생화학실) ;
  • 임예현 (한국체육대학교 운동생화학실) ;
  • 박준영 (한국체육대학교 운동생화학실) ;
  • 조인호 (한국체육대학교 운동생화학실) ;
  • 오유성 (서울시립대학교 체육학과) ;
  • 곽이섭 (동의대학교 레저스포츠학과) ;
  • 조준용 (한국체육대학교 운동생화학실)
  • Kim, Seung-Seok (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Kang, Eun-Bum (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Eum, Hyun-Sub (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Kim, Bum-Su (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Lim, Yea-Hyun (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Park, Joon-Young (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Cho, In-Ho (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Oh, Yoo-Sung (Department of Physical Education, Seoul city University) ;
  • Kwak, Yi-Sub (Department of Leisure Sports, Dong-Eui University) ;
  • Cho, Joon-Yong (Exercise Biochemistry Laboratory, Korea National Sport University)
  • 발행 : 2008.01.31

초록

이 연구는 지구성 운동과 셀레니움 투여가 Coto-Kakizaki 쥐의 젖산수송 능력에 독립적으로 혹은 상호작용하여 영향을 미치는가를 구명하는데 그 목적이 있다. 실험동물들의 집단은 비교집단(n=10, SED), 지구성 운동집단(n=10, EXER), 셀레니움 투여집단(n=10, SELE)과 지구성 운동과 셀레니움 투여 병행 집단(n=10, COMBI)으로 분류하여 6주간 실험을 실시하였다. 6주간 실험 처치 후 체중은 비교집단에 비해 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 현저하게 감소하였으며 당 부하검사를 실시한 결과에서도 비교집단에 비해 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 90분과 120분 사이에서 혈당 수준이 유의한 낮은 것으로 나타났다. 간 글리코겐 수준은 비교집단과 셀레니움 투여집단에 비해 지구성 운동집단과 지구성 운동과 셀레니움 투여 병행 집단이 유의하게 높은 것으로 나타났다. 가자미근과 족저근의 글리코겐 수준도 비교집단과 셀레니움 투여집단에 비해 지구성 운동집단과 지구성 운동과 셀레니움 투여 병행 집단이 현저하게 높은 것으로 나타났다. 혈액 생화학 성분의 경우, 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 비교집단에 비해 고밀도 지단백 수준 증가와 함께 혈장 젖산, 혈청 중성지방, 인슐린, 총 콜레스테롤과 HOMA-IR 수준이 현저하게 감소한 것으로 나타났다. 특히 혈청 중성지방 수준은 지구성 운동집단과 지구성 운동과 셀레니움 투여 병행 집단이 셀레니움 투여집단에 비해 유의하게 낮은 것으로 나타났다. 이 연구에 가장 중요한 결과는 혈당과 젖산 수송과 관련된 단백질 발현 수준이 6주간의 실험처치 후에 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 비교집단에 비해 가자미근의 MCT1과 미토콘드리아 MCT1 단백질 발현수준이 현저하게 증가하였다는 결과와 함께 가자미근과 족저근의 MCT4 단백질 발현 수준도 지구성 운동집단, 셀레니움 투여집단과 지구성 운동과 셀레니움 투여 병행 집단이 비교집단에 비해 현저하게 증가하였다는 결과이다. 이러한 결과를 근거로 볼 때 지구성 운동과 셀레니움 투여는 독립적으로 혹은 상호작용하여 혈당과 젖산수송 능력을 개선시키는데 도움이 된다는 것을 알 수 있으며 특히 인슐린 저항 특성과 함께 고젖산혈증을 나타내는 제 II형 당뇨 환자들의 당뇨 처치를 위한 방법으로 활용할 만한 가치가 있는 것으로 생각된다.

The purpose of this study was to determine the possible additive effects of endurance exercise training (EXER) and selenium (SELE) on the improvements of glucose and lactate transport capacities in diabetic Goto-kakizaki rats. Animals either remained sedentary control (SED) or performed EXER or received SELE [$5{\mu}mol$ kg body wt (-1) day (-1)], or underwent both EXER and SELE (COMBI), which lasted for 6 wk. Compared with sedentary control, EXER alone or the SELE alone group, or the combined treatment group had significant reduction in glucose response measured at 90 min and 120 min during an intraperitoneal glucose tolerance test (IPGTT) and body weight after 6week treatment. EXER alone, or combined group individually had significantly higher glycogen contents in liver compared with SED or SELE groups. EXER alone increased glycogen content in soleus and plantaris compared with SED, and this parameter was increased to greatest extent in the combined treatment groups compared with SED or SELE groups. EXER alone, SELE alone or COMBI, caused significant decreases in the plasma lactates, serum glucose, insulin, total cholesterol and HOMA-IR along with a significant increase in high-density lipoprotein cholesterol compared with SED. In addition, EXER or COMBI individually had significantly lower serum triacylglycerol compared with SED or SELE. With respect to protein expression related to glucose and lactate transport capacities, EXER alone, SELE alone, or COMBI increased in MCT1 and MCT4 protein level in soleus and plantaris. Furthermore, EXER alone, SELE alone or COMBI caused significant increases in mt MCT1 protein level in soleus and plantaris. The findings of the current study suggest that endurance exercise training and selenium treatment may provide therapeutic values to type II diabetic patients with peripheral insulin resistance and hyperlactatecemia by improving glucose and lactate transport capacities, leading to improvements in plasma lactate, serum glucose, insulin and lipid profiles (TC, TG, HDL).

키워드

참고문헌

  1. Adamo, K. B. and T. E. Graham. 1998. Comaparison of traditional measurements with macro glycogen and pro-glycogen anna lysis of muscle glycogen. Journal of Applied Physiology 84(3), 908-913. https://doi.org/10.1152/jappl.1998.84.3.908
  2. Almind, K., A. Dorio and C. R. Kahn. 2001. Putting the genes for type II diabetes on the map. Nat. Med. 7, 277-279. https://doi.org/10.1038/85405
  3. Becker, D. J., B. Reul, A. T. Ozcelikay, J. P. Buchetm, J. C. Henquin and S. M. Brichard, 1996. Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogenic enzymes in diabetic rats. Diabetologia 39(1), 3-11. https://doi.org/10.1007/BF00400407
  4. Bo, S., A. Lezo, G. Menato, M. L. Gallo, C. Bardelli, A. Signorile, C. Berutti, M. Massobrio and G. F. Pagano. 2005. Gestational hyperglycemia, zinc, selenium, and antioxidant vitamins. Nutrition 21(2), 186-191. https://doi.org/10.1016/j.nut.2004.05.022
  5. Bonen, A. 2001. Expression of lactate transporters (MCT1, MCT4) in heart and muscle. European. Journal of Applied Physiology 86, 6-11. https://doi.org/10.1007/s004210100516
  6. Brooks, G. A. 2000. Intra and extra-cellular lactate shuttles, Medicine and Science and Sports Exercise 32, 790-799. https://doi.org/10.1097/00005768-200004000-00011
  7. Carey, P. E., J. Halliday, J. E. Snaar, P. G. Morris and R. Taylor. 2003. Direct assessment of muscle glycogen storage after mixed meals in normal and type 2 diabetic subjects. American Journal of Physiological Endocrinology Metabolism 284(4), E688-E694. https://doi.org/10.1152/ajpendo.00471.2002
  8. Czech, M. P. and S. Corvera. 1999. Signaling mechanisms that regulate glucose transport. Journal of Biological Chemistry 274(4), 1865-1868. https://doi.org/10.1074/jbc.274.4.1865
  9. Enoki, T., Y. Yoshida, H. Hatta and A. Bonen, 2003. Exercise training alleviates MCT1 and MCT4 reductions in heart and skeletal muscle of STZ-induced diabetic rats. Journal of Applied Physiology 94, 2433-2438. https://doi.org/10.1152/japplphysiol.01155.2002
  10. Ferrannini, E., A. Lanfranchi, F. Rohner-Jeanrenaud, G. Manfredini and Van de G. Werve. 1990. Influence of long-term diabetes on liver glycogen metabolism in the rat. Metabolism 39(10), 1082-1088. https://doi.org/10.1016/0026-0495(90)90170-H
  11. Ghosh, R, B. Mukherjee and M. A. Chatterjee. 1994. Novel effect of selenium on streptozotocin-induced diabetic mice. Diabetes Research 25(4), 165-171.
  12. Goodyear, L. J., M. F. Hirshman, R. J. Smith and E. S. Horton. 1991. Glucose transporter number, activity and isoform content in plasma membranes of red and white skeletal muscle. American Journal of Physiology 261, E556-E561.
  13. Goto, Y., M. Kakizaki and N. Masaki. 1976. Production of spontaneous diabetic rats by repetition of selective breeding. Tohoku Journal of Experimental Medicine 119(1), 85-90. https://doi.org/10.1620/tjem.119.85
  14. Halestrap, A. P. and N. T. Price. 1999. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochemical Journal 343, 281-299. https://doi.org/10.1042/0264-6021:3430281
  15. Hajduch, E., Heyes, R. R., Watt, P. W. and Hundal, H. S. 1999. Lactate transport in rat adipocyte: identification of monocarboxylate transport 1 (MCT1) and its modulation during streptozotocin-induced diabetes. FEBS Lett. 479, 281-299.
  16. Juel, C. and A. P. Halestrap. 1999. Lactate transport in skeletal muscle-role and regulation of the monocarboxylate transporter. Journal of Physiology 517, 633-642. https://doi.org/10.1111/j.1469-7793.1999.0633s.x
  17. Khamaisi, M., R. Potashnik, A. Tirosh, E. Demshchak, A. Rudich, H. Tritschler, K. Wessel and N. Bashan. 1997. Lipoic acid reduces glycemia and increases muscle GLUT4 content in streptozotocin-diabe tic rats. Metabolism 46, 763-768. https://doi.org/10.1016/S0026-0495(97)90120-7
  18. Metz, L., M. Vermaelen, K. Lambert, C. Broca, P. Sirvent, C. Raynaud and J. Mercier. 2005. Endurance training increases lactate transport in male Zucker falfa rats. Biochemical and Biophysical Research Communications 331, 1338-1345. https://doi.org/10.1016/j.bbrc.2005.04.054
  19. Mondon, C. E., I. R. Jones, S. Azhar, C. B. Hollenbeck and G. M. Reaven. 1992. Lactate production and pyruvate dehydrogenase activity in fat skeletal muscle from diabetic rats. Diabetes 41, 1547-1554. https://doi.org/10.2337/diabetes.41.12.1547
  20. Muller, A. S., E. Most and J. Pallauf. 2005. Effects of a supranutritional dose of selenate compared with selenite on insulin sensitivity in type II diabetic dbdb mice. J. Anim. Physiol. Anim. Nutr. 89(3-6), 94-104. https://doi.org/10.1111/j.1439-0396.2005.00559.x
  21. Mueller, A. S. and J. Pallauf. 2006. Compendium of the antidiabetic effects of supranutritional selenate doses. In vivo and in vitro investigations with type II diabetic db/db mice. Journal of Nutritional Biochemistry 17(8), 548-560. https://doi.org/10.1016/j.jnutbio.2005.10.006
  22. Py, G., N. Eydoux, A. Perez-Martin, E. Raynaud, J. F. Brun, C. Prefaut and J. Mercier. 2001. Streptozotocin-induced diabetes decreases rat sarcolemmal lactate transport. Metabolism 50, 418-424. https://doi.org/10.1053/meta.2001.21692
  23. Py, G., K. Lambert, O. Milhavet, N. Eydoux, C. Prefaut and J. Mercier. 2002. Effect of streprozotocin-induced diabetes in markers of skeletal muscle metabolism and monocarboxylate transporter 1 to monocarboxylate transporter 4 transporters. Metabolism 51, 807-813. https://doi.org/10.1053/meta.2002.33343
  24. Tan, M. H., A. Bonen, W. Watson-Wright, D. Hood, M. Sopper, D. Currie, A. N. Belcastro and G. Pierce. 1984. Muscle glycogen repletion after exercise in trained normal and diabetic rats. Journal of Applied Physiology 57(5), 1404-1408. https://doi.org/10.1152/jappl.1984.57.5.1404
  25. Tan, M. H., A. Bonen, J. B. Garner and A. N. Belcastro. 1982. Physical training in diabetic rats: effect on glucose tolerance and serum lipids. Journal of Applied Physiology 52(6), 1514-8. https://doi.org/10.1152/jappl.1982.52.6.1514
  26. Tancrede, G., S. Rousseau-Migneron and A. Nadeau. 1982. Beneficial effects of physical training in rats with a mild streptozotocin-induced diabetes mellitus. Diabetes 31 (5Pt1), 406-409. https://doi.org/10.2337/diabetes.31.5.406
  27. Ulusu, N. N. and B. Turan. 2005. Beneficial effects of selenium on some enzymes of diabetic rat heart. Biol. Trace. Elem. Res. 103(3), 207-216. https://doi.org/10.1385/BTER:103:3:207