DOI QR코드

DOI QR Code

Effects of Different Exercise Intensities on GLUT-4 and GRP-78 Protein Expression in Soleus Muscle of Streptozotocin-Induced Diabetic Rats with Caffeine Oral Administration

카페인 경구투여가 운동강도 차이에 따른 당뇨유발 흰쥐 가자미근의 GLUT4 및 GRP78 단백질 발현에 미치는 영향

  • Published : 2004.10.01

Abstract

This study investigated the response of GLUT-4 and GRP-78 protein expression in soleus muscle of Streptozotocin-induced diabetic rats with caffeine oral administration by imposing different exercise intensities. Rats were randomly divided into 5 groups (n=6 in each group): diabetic group (D), diabetic-caffeine group (DC), diabetic-caffeine group with low intensity exercise (DCL), diabetic-caffeine group with moderate intensity exercise (DCM) and diabetic-caffeine group with high intensity exercise (DCH). The rats in DCL, DCM and DCH groups were exercised acutely by treadmill running for 8 meter/m, 16 meter/m and 25 meter/m, respectively. Little difference in GLUT-4 protein expression was shown in DC and DCL compared to D. GLUT-4 protein expression was decreased in DCM and increased in DCH was observed. GRP-78 protein expressions in DCL, DCM and DCH were little lower than that of D. An increase in GRP-78 protein was observed in DC. Improved insulin sensitivity with acute high intensity exercise gives the rats important therapy that lowers insulin requirement. This improvement of insulin sensitivity for glucose transport in skeletal muscle results from translocation of the GLUT-4 protein from the endoplasmic reticilum to the cell surface and increase in total quantity of GLUT-4 protein. It is not clear what mechanism reduced GRP-78 protein level in exercise group. It is merely conjectured that caffeine-induced lipolysis provided cells with energy in abundance and this relieved stress which cells are subjected to receive when performing exercise.

본 연구는 운동강도 차이에 따른 카페인 구강 투여가 STZ-유발 당뇨 쥐 가자미근에서 GLUT-4와 GRP-78 단백질 발현에 미치는 영향을 규명하기 위하여 F344계 수컷 횐쥐를 무작위 표본추출에 의하여 당뇨유발군(n=6), 당뇨유발-카페인 투여군(n=6), 당뇨유발-카페인투여 저강도운동군(n=6), 당뇨유발-카페인투여 중강도운동군(n=6), 그리고 당뇨유발-카페인투여 고강도 운동군(n=6)으로 분류하였다. 저강도 운동은 트레드밀 경사도 0%에서 8 m/min 속도로, 중강도 운동은 트레드밀 경사도 0%에서 16 m/min 속도로, 고강도운동은 트레드밀 경사도 0%에서 25 m/min속도로 30분간 1회 운동을 실시하였다. GLUT4단백질 발현은 당뇨군에 비해서 당뇨유발군-카페인 투여군과 당뇨유발-카페인투여 저강도 운동군에서 차이가 없었으며, 당뇨유발-카페인투석 중강도 운동군에서는 다소 감소하였으나 당뇨유발-카페인투여 고강도 운동군에서 증가하였다. GRP-78 단백질 발현은 당뇨군에 비해서 당뇨유발-카페인투여 저강도 운동군, 당뇨유발-카페인투여 중강도 운동군, 그리고 당뇨유발-카페인투석 고강도 운동군에서 감소하였으나, 당뇨유발-카페인 투여군에서는 다소 증가한 것으로 나타났다 고강도 일회성 운동이 인슐린 민감도를 개선시켜 인슐린 요구량을 낮추는데 이러한 효과는 내형질세망에서 세포막으로의 GLUT-4 단백질의 전이와 GLUT-4 단백질 양의 증가 때문이다. 운동군에서의 GRP-78 단백질이 감소된 기전은 정확히 밝힐 수는 없지만, 카페인으로 인한 지질 동원이 운동 시 작업근의 세포에 많은 에너지를 공급하여 세포가 받는 스트레스를 완화시켜 주었기 때문이라고 추측된다.

Keywords

References

  1. Banks EA, Brozinick JT Jr, Yaspelkis BB 3rd, Kang HY and Ivy JL. 1992. Muscle glucose transport, GLUT-4 content, and degree of exercise training in obese Zucker rats. Am J Physiol. 263(5 Pt 1), E1010-5
  2. Baron AD, Brechtel G, Wallace P and Edelman SV. 1988. Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans. Am J Physiol. 255, E769-E774
  3. Bonen A, Tan MH and Watson-Wright WM. 1984. Effects of exercise on insulin binding and glucose metabolism in muscle. Can J Physiol Pharmacol. 62(12), 1500-4 https://doi.org/10.1139/y84-248
  4. Bonen A, Tan MH and Watson-Wright WM. 1981. Insulin binding and glucose uptake differences in rodent skeletal muscles. Diabetes. 30(8), 702-4 https://doi.org/10.2337/diabetes.30.8.702
  5. Brozinick JT Jr, Etgen GJ Jr, Yaspelkis BB 3rd, Kang HY and Ivy JL. 1993. Effects of exercise training on muscle GLUT-4 protein content and translocation in obese Zucker rats. Am J Physiol. 265(3 Pt 1), E419-27
  6. DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J and Felber JP. 1981. The effect of insulin on the disposal of intravenous glucose: results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes. 30, 1000-1007 https://doi.org/10.2337/diab.30.12.1000
  7. Defronzo RA, Simonson D and Ferrannini E. 1982. Hepatic and peripheral insulin resistance: a common feature of type II (non-insulin-dependent) and type I (insulin dependent) diabetes mellitus. Diabetologia. 23, 313-319 https://doi.org/10.1007/BF00253736
  8. Dela F, Ploug T, Handberg A, Petersen LN, Larsen JJ, Mikines KJ and Galbo H. 1994. Physical training increases muscle GLUT4 protein and mRNA in patients with NIDDM. Diabetes. 43(7), 862-5 https://doi.org/10.2337/diabetes.43.7.862
  9. Dohm GL, Tapscott EB, Pories WJ, Dabbs DJ, Flickinger EG, Meelheim D, Fushiki T, Atkinson SM, Elton EC and Caro JF. 1988. An in vitro human muscle preparation suitable for metabolic studies: decreased insulin stimulation of glucose transport in muscle from morbidly obese and diabetic subjects. J Clin Invest. 82, 486-494 https://doi.org/10.1172/JCI113622
  10. Frank, Brosius. 2003. Low-dose streptozotocin induction protocol (Mouse). Animal Model of Diabetic Complications Consortium
  11. Garvey WT, Maianu L, Hancock JA, Golichowski AM, Baron A. 1992. Gene expression of GLUT4 in skeletal muscle from insulin-resistant patients with obesity, IGT, GDM, and NIDDM. Diabetes. 41(4), 465-75 https://doi.org/10.2337/diabetes.41.4.465
  12. Goodyear LJ, Hirshman MF, Smith RJ and Horton ES. 1991. Glucose transporter number, activity, and isoform content in plasma membranes of red and white skeletal muscle. Am J Physiol. 261(5 Pt 1), E556-61
  13. Guenther Boden. 2001. Obesity, free fatty acids, and insulin resistance. Current opinion in endocrinology & diabetes. 8(5), 235-239 https://doi.org/10.1097/00060793-200110000-00002
  14. Henriksen EJ, Bourey RE, Rodnick KJ, Koranyi L, Permutt MA and Holloszy JO. 1990. Glucose transporter protein content and glucose transport capacity in rat skeletal muscles. Am J Physiol. 259(4 Pt 1), E593-8
  15. Houmard JA, Egan PC, Neufer PD, Friedman JE, Wheeleer WS, Israel RG and Dohm GL. 1991. Elevated skeletal muscle glucose transporter levels in exercise-trained middle-aged men. American Journal of Physiology. 261, 437-443
  16. Houmard JA, Shinebarger MH, Dolan PL, Leggett-Frazier N, Bruner RK, McCammon MR, Israel RG and Dohm GL. 1993. Exercise training increases GLUT-4 protein concentration in previously sedentary middle-aged men. Am J Physiol. 264(6 Pt 1), E896-901
  17. John W. Kennedy, Michael F. Hirshman, Ernest V. Gervino, Jeffrey V. Ocel, R. Armour Forse, Stephen J. Hoenig, Doron Aronson, Laurie J, Goodyear, and Edward S. Horton. 1999. Acute exercise induces GLUT4 Translocation in Skeletal Muscle of normal human subjects and subjects with type 2 diabetes. Diabetes. 48, 1-6 https://doi.org/10.2337/diabetes.48.5.1192
  18. Jill A. Barnes, Ida W. Smoak, and Stacy Branch. 1999. Expression of glucose-regulated proteins (GRP78 and GRP94) in hearts and fore-limb buds of mouse embryos exposed to hypoglycemia in vitro. Cell stress & chaperones. 4(4), 250-258 https://doi.org/10.1379/1466-1268(1999)004<0250:EOGRPG>2.3.CO;2
  19. Kelley DE, Mintun MA, Watkins SC, Simoneau JA, Jadali F, Fredrickson A, Beattie J and Theriault R. 1996. The effect of non-insulin-dependent diabetes mellitus and obesity on glucose transport and phosphorylation in skeletal muscle. J Clin Invest. 15;97(12), 2705-13 https://doi.org/10.1172/JCI118724
  20. Kern M, Wells JA, Stephens JM, Elton CW, Friedman JE, Tapscott EB, Pekala PH and Dohm GL. 1990. Insulin responsiveness in skeletal muscle is determined by glucose transporter (Glut4) protein level. Biochem J. 1;270(2), 397-400
  21. Lund S, Vestergaard H, Andersen PH, Schmitz O, Gotzsche LB and Pedersen O. 1993. GLUT-4 content in plasma membrane of muscle from patients with non-insulin- dependent diabetes mellitus. Am J Physiol. 265(6 Pt 1), E889-97
  22. McArdle William D, Katch Frank I and Katch Victor L. 2001. Exercise Physiology. Lippincott Williams & Wilkins. 84, 143
  23. Phillips SM, Han XX, Green HJ, Bonen A. 1996. Increments in skeletal muscle GLUT-1 and GLUT-4 after endurance training in humans. Am J Physiol. 270(3 Pt 1), E456-62
  24. Ploug T, Stallknecht BM, Pedersen O, Kahn BB, Ohkuwa T, Vinten J and Galbo H. 1990. Effect of endurance training on glucose transport capacity and glucose transporter expression in rat skeletal muscle. Am J Physiol. 259(6 Pt 1), E778-86
  25. Song Min Sup, Park Yong Keun, Lee Je-Ho and Park Kyoung sook. 2001. Induction of glucose-regulated protein 78 by chronic hypoxiz in human gasric tumor cells through a protein kinase C-$\varepsilon$/ERK/AP-1 signaling Cascade. Cancer Research. 61, 8322-8330
  26. Spriet LL. 2000. Caffeine protentiates low-frequency skeletal muscle force in habitual and nonhabitual caffeine consumers. Int J Sport Nutr. 5, S84-S99
  27. Terjung RL, Clarkson PM, Eichner ER, Greenhaff PL, Hespel P, Israel RG, Kraemer WJ, Meyer RA, Spriwt LL, Tarnopolsky MA, Wagenmarkers AJM and Williams MH. 2000. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc. 32, 706-717 https://doi.org/10.1097/00005768-200003000-00024
  28. Thong FS, Derave W, Kiens B, Graham TE, Urso B, Wojtaszewski JF, Hansen BF and Richter EA. 2002. Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise. Diabetes. 51, 583-590 https://doi.org/10.2337/diabetes.51.3.583
  29. Watchman A, Hattner RS, George B and Bernstein DS. 1970. Effects of decaffeineated and nondecaffeinated coffee ingestion on blood glucose and plasma radioimmunoreactive insulin responses to rapid intravenous infusion of glucose in nomal men. Metabolism. 19, 539-546 https://doi.org/10.1016/0026-0495(70)90009-0