Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of maternal exercise on expression of GLUT-4, VAMP-2 in skeletal muscle and plasma insulin and leptin levels in pregnant rats

운동이 F344계 임신쥐에서 골격근의 VAMP-2 및 GLUT-4 단백질 발현과 혈중 인슐린, 렙틴 농도에 미치는 영향

  • Yoon, Jin-Hwan (Research Institute of Sports Medicine, Hannam University) ;
  • Lee, Hee-Hyuk (Research Institute of Sports Medicine, Hannam University) ;
  • Kim, Jong-Oh (Research Institute of Sports Medicine, Hannam University) ;
  • Oh, Myung-Jin (Research Institute of Sports Medicine, Hannam University) ;
  • Park, Seong-Tae (Research Institute of Sports Medicine, Hannam University) ;
  • Jee, Young-Seok (Research Institute of Sports Medicine, CheongJu University) ;
  • Seo, Tae-Beom (Department of Oriental Medicine, Daejeon Univeristy) ;
  • NamGung, Uk (Department of Oriental Medicine, Daejeon Univeristy)
  • 윤진환 (한남대학교 스포츠의학연구소) ;
  • 이희혁 (한남대학교 스포츠의학연구소) ;
  • 김종오 (한남대학교 스포츠의학연구소) ;
  • 오명진 (한남대학교 스포츠의학연구소) ;
  • 박성태 (한남대학교 스포츠의학연구소) ;
  • 지용석 (청주대학교 스포츠의학연구소) ;
  • 서태범 (대전대학교 한의대) ;
  • 남궁욱 (대전대학교 한의대)
  • Published : 2007.06.25
Download PDF
⟨ Previous Next ⟩

Abstract

The main objective of this study was to investigate the effects of exercise on serum insulin and leptin levels and GLUT-4 and VAMP-2 in skeletal muscles from the pregnant rats. F344 rats were randomly divided into four groups (n = 15 in each group): control group (CG), pregnant group (PG), pregnant running group (PR), and pregnant swimming group (PS). From the 15th day of pregnancy, animals in the running group were forced to run on treadmill for 30 min with a light intensity, while those in the swimming group were forced to swim in swimming pool for 10 min once a day for 6 consecutive days. The present result demonstrated that in pregnant rat group, serum insulin levels significantly in-creased and leptin levels significantly decreased. Skeletal GLUT-4 and VAMP-2 protein expression was significantly decreased in pregnant rats compared to non-pregnant rats. However, matenal running during gestational period alleviated pregnancy-induced changes in plasma insulin and leptin levels, and it significantly enhanced skeletal GLUT-4 and VAMP-2 protein expression. From those results, it can be suggested that running exercise during gestational period may improve glycemic control by up-regulating GLUT-4 and VAMP-2 protein expression.

본 연구는 임신횐쥐에서 운동이 혈중 인슐린과 렙틴 농도, 그리고 골격근의 GLUT-4와 VAMP-2단백질 발현에 변화를 조사하기 위하여 수행되었다. 본 연구에서 비임신 횐쥐에 비해 임신 횐쥐에서 혈중 인슐린 농도가 유의하게 증가되었고, 렙틴 농도는 유의하게 감소하는 것으로 나타났다. 임신횐쥐에게 달리기 운동을 적용한 결과 임신으로 증가된 인슐린 농도를 유의하게 감소시키면서 렙틴 농도의 감소를 억제시키는 것으로 나타났다. 골격근에서 GLUT-4와 VAMP-2 단백질 발현량을 조사한 결과 비임신 횐쥐에 비해 임신 횐쥐에서 이러한 단백질 발현이 유의하게 감소되었지만, 임신 중 달리기운동을 경험한 횐쥐에서 GLUT-4와 VAMP-2 발현 모두 유의하게 증가되는 것으로 나타났다. 이와 잘이 임신으로 인한 혈중 인슐린 및 렙틴의 변화가 골격근에서 당을 근조직으로 흡수하는 신호 전달 경로와 수송체의 발현 손상과 연관되어있음을 보여주는 것이다. 하지만 임신 횐쥐에서 달리기 운동은 인슐린과 렙틴 농도의 변화를 완화시킴으로써 골격근의GLUT-4와 VAMP-2발현을 유의하게 증가시키는 것으로 나타났다.

Keywords

References

  1. Atawi, F. A., A. S. Warsy, Z. Babay and M. Addar. 2004. Leptin concentration during different stages of pregnancy. Clin. Exp. Obstet. Gynecol. 31, 211-216
  2. Avery, M. D. and A. J. Walker. 2001. Acute effect of exercise on blood glucose and insulin levels in women with gestational diabetes. J. Matern. Fetal. Med. 10, 52-58 https://doi.org/10.1080/jmf.10.1.52.58-4
  3. Brankston, G. N., B. F. Mitchell, E. A. Ryan and N. B. Okun. 2004. Resistance exercise decreases the need for insulin in overweight women with gestational diabetes mellitus. Am. J. Obstet. Gynecol. 190, 188-193 https://doi.org/10.1016/S0002-9378(03)00951-7
  4. Brelje, T. C., D. W. Scharp, P. E. Lacy, L. Ogren, F. Talamantes, M. Robertson, H. G. Friesen and R. L. Sorenson. 1993. Effect of homologous placental lactogens, prolactins, and growth hormones on islet B-cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of islet function during pregnancy. Endocrinology 132, 879-887 https://doi.org/10.1210/en.132.2.879
  5. Bung, P.. R. N. Artal, N. Khodiguian and S. Kjos. 1991. Exercise in gestational diabetes: An optional therapeutic approach?. Diabetes 40, 182-185 https://doi.org/10.2337/diab.40.2.S182
  6. Catalano, P. M., E. D. Tyzbir and R. R. Wolfe. 1993. Carbohydrate metabolism during pregnancy in control subject and women with gestational diabetes. Am. J. Physiol. 264, 60-670
  7. Catalano, P. M., L. Huston, S. B. Amini and S. C. Kalhan. 1999. Longitudinal change in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am. J. Obstet. Gynecol. 180, 903-916 https://doi.org/10.1016/S0002-9378(99)70662-9
  8. Catalano, P. M., N. M. Drago and S. B. Amini. 1995. Maternal carbohydrate metabolism and its relationship to fetal growth and body composition. Am. J. Obstet. Gynecol. 172, 1464-1470 https://doi.org/10.1016/0002-9378(95)90479-4
  9. Cong, L. and J. Chen. 2001. Effect of exercise on leptin in streptozotocin-induced diabetic rats. Wei. Sheng. Yan. Jiu. 30, 158-159
  10. Dela, F., T. Ploug, A. Handberg, L. N. Petersen, J. J. Larsen, K. J. Mikines and H. Galbo. 1994. Physical training increases muscle GLUT4 protein and mRNA in patients with NIDDM. Diabetes 43, 862-865 https://doi.org/10.2337/diabetes.43.7.862
  11. Despres, J. P., M. C. Pouliot, S. Moorjani, A. Nadeau, A. Tremblay, P. J. Lupien, G. Theriault and C. Bouchard. 1991. Loss of abdominal fat and metabolic response to exercise training in obese women. Am. J. Physiol. 261, 159-167
  12. Di Cianni, G., R. Miccoli, L. Volpe, C. Lencioni and S. Del Prato. 2003. Intermediate metabolism in normal pregnancy and in gestational diabetes. Diabetes Metab. Res. Rev. 19, 259-270 https://doi.org/10.1002/dmrr.390
  13. Ebihara, K., Y. Ogawa, H. Masuzaki, M. Shintani, F. Miyanaga, M. Aizawa-Abe, T. Hayashi, K. Hosoda, G. Inoue, Y. Yoshimasa, O. Gavrilova, M. L. Reitman and K. NakaoK. 2001. Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes. Diabetes 50, 1440-1448 https://doi.org/10.2337/diabetes.50.6.1440
  14. Etgen, G. J., J. T. Brozinick, H. Y. Kang and J. L. Ivy. 1993. Effects of exercise training on skeletal muscle glucose uptake and transport. Am. J. Physiol. 264, 723-733 https://doi.org/10.1152/ajpcell.1993.264.3.C723
  15. Flores, M. B., M. F. Fernandes, E. R. Ropelle, M. C. Faria, M. Ueno, L. A. Velloso, M. J. Saad and J. B. Carvalheira. 2006. Exercise improves insulin and leptin sensitivity in hypothalamus of Wistar rats. Diabetes 55, 2554-2561 https://doi.org/10.2337/db05-1622
  16. Foster, L. J. and A. Klip. 2000. Mechanism and regulation of GLUT-4 vesicle fusion in muscle and fat cells. Am. J. Physiol. Cell Physiol. 279, 877-890 https://doi.org/10.1152/ajpcell.2000.279.4.C877
  17. Gorski, J., D. Hood, H. Kaciuba-Uscilko and R. L. Terjung. 1986. Effects of muscle stimulation in situ in pregnant rats. Eur. J. Appl. Physiol. 55, 390-394 https://doi.org/10.1007/BF00422738
  18. Havel, P. J. 2002. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr. Opin. Lipidol. 13, 51-59 https://doi.org/10.1097/00041433-200202000-00008
  19. Hayashi, T., J. F. Wojtaszewski and L. J. Goodyear. 1997. Exercise regulation of glucose transport in skeletal muscle. Am. J. Physiol. 273, 1039-1051
  20. Host, H. H., P. A. Hansen, L. A. Nolte, M. M. Chen and J. O. Holloszy. 1998. Glycogen supercompensation masks the effect of a traininginduced increase in GLUT-4 on muscle glucose transport. J. Appl. Physiol. 85, 133-138 https://doi.org/10.1152/jappl.1998.85.1.133
  21. Ishihara, H., T. Asano, H. Katagiri, J. L. Lin, K. Tsukuda, K. Inukai, Y. Yazaki and Y. Oka. 1993. Expression of GLUT-4 and glucose transporter in unweighted soleus muscle of normal and STZ-induced diabetic rats. Am. J. Physiol. Endocrinol. Metab. 264, 301-307 https://doi.org/10.1152/ajpendo.1993.264.2.E301
  22. Kawai, M. and K. Kishi. 1997. In vitro studies of the stimulation of insulin secretion and B-cell proliferation by rat placental lactogen-II during pregnancy in rats. J. Reprod. Fertil. 109, 145-152 https://doi.org/10.1530/jrf.0.1090145
  23. Kawanaka, K., I. Tabata, S. Katsuta and M. Higuchi. 1997. Changes in insulin-stimulated glucose transport and GLUT-4 protein in rat skeletal muscle after training. J. Appl. Physiol. 83, 2043-2047 https://doi.org/10.1152/jappl.1997.83.6.2043
  24. Kim, C. H., Y. H. Leem, I. H. Cho, S. C. Kim, S. S. Bang, J. Y. Cho and K. S. Lee. 2003. The effect of exercise training and catechins supplementation on skeletal muscle GLUT-4, VAMP-2 and Syntaxin-4 protein expression in obese Zucker rats. Exercise Science 12, 633-678
  25. Kirwan, J. P., S. Hauguel-De Mouzon, J. Lepercq, J. C. Challier, L. Huston-Presley, J. E. Friedman, S. C. Kalhan and P. M. Catalano. 2002. TNF-alpha is a predictor of insulin resistance in human pregnancy. Diabetes 51, 2207-2213 https://doi.org/10.2337/diabetes.51.7.2207
  26. Kristiansen, S., M. Hargreaves and E. A. Richter. 1996. Exercise-induced increase in glucose transport, GLUT-4, and VAMP-2 in plasma membrane from human muscle. Am. J. Physiol. 270, 197-201
  27. Kuo, C. H., D. G. Hunt, Z. Ding and J. L. Ivy. 1999. Effect of carbohydrate supplementation on postexercise GLUT-4 protein expression in skeletal muscle. J. Appl. Physiol. 87, 2290-2295 https://doi.org/10.1152/jappl.1999.87.6.2290
  28. Kuo, C. H., H. Hwang, M. C. Lee, A. L. Castle and J. L. Ivy. 2004. Role of insulin on exercise-induced GLUT-4 protein expression and glycogen supercompensation in rat skeletal muscle. J. Appl. Physiol. 96, 621-627 https://doi.org/10.1152/japplphysiol.00830.2003
  29. Lee, A. D., P. A. Hansen and J. O. Holloszy. 1995. Wortmannin inhibits insulin-stimulated but not contraction- stimulated glucose transport activity in skeletal muscle. FEBS 361, 51-54 https://doi.org/10.1016/0014-5793(95)00147-2
  30. Lee, H. H., H. Kim, J. W. Lee, Y. S. Kim, H. Y. Yang, H. K. Chang, T. H. Lee, M. C. Shin, M. H. Lee, M. S. Shin, S. Park, S. Baek and C. J. Kim. 2005. Maternal swimming during pregnancy enhances short-term memory and neurogenesis in the hippocampus of rat pups. Brain Dev. 28, 147-154 https://doi.org/10.1016/j.braindev.2005.05.007
  31. Lopez-Luna, P., M. A. Iglesias, C. Munoz and E. Herrera. 1998. Aerobic exercise during pregnancy reverts maternal insulin resistance in rats. Med. Sci. Sports Exerc. 30, 1510-1514 https://doi.org/10.1097/00005768-199810000-00007
  32. Malide, D., N. K. Dwyer, D. J. Blanchette-Mackiec and S. W. Cushmanb. 1997. Immunocytochemical Evidence that GLUT4 Resides in a Specialized Translocation Post-endosomal VAMP2- positive Compartment in Rat Adipose Cells in the Absence of Insulin. J. Histochem. Cytochem. 45, 1083-1096 https://doi.org/10.1177/002215549704500806
  33. Martin, S., J. Tellam, C. Livingstone, J. W. Slot, G. W. Gould and D. E. James. 1996. The glucose transporter (GLUT-4) and vesicle-associated membrane protein-2 (VAMP-2) are segregated from recycling endosomes in insulin- sensitive cells. J. Cell Biol. 134, 625-635 https://doi.org/10.1083/jcb.134.3.625
  34. Masuzaki, H., Y. Ogawa, M. Aizawa-Abe, K. Hosoda, J. Suga, K. Ebihara, N. Satoh, H. Iwai, G. Inoue, H. Nishimura, Y. Yoshimasa and K. Nakao. 1999. Glucose metabolism and insulin sensitivity in transgenic mice overexpressing leptin with lethal yellow agouti mutation: usefulness of leptin for the treatment of obesity-associated diabetes. Diabetes 48, 1615-1622 https://doi.org/10.2337/diabetes.48.8.1615
  35. Munoz, C., P. Lopez-Luna and E. Herrera. 1999. Treadmill training enhances glucose tolerance more in pregnant than in virgin rats. Biol. Neonate. 75, 337-342 https://doi.org/10.1159/000014112
  36. Ogawa, Y., H. Masuzaki, K. Hosoda, M. Aizawa-Abe, J. Suga, M. Suda, K. Ebihara, H. Iwai, N. Matsuoka, N. Satoh, H. Odaka, H. Kasuga, Y. Fujisawa, G. Inoue, H. Nishimura, Y. Yoshimasa and K. Nakao. 1999. Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin. Diabetes 48, 1822-1829 https://doi.org/10.2337/diabetes.48.9.1822
  37. Park, S. T., T. B. Seo, S. S. Baek, Y. S. Chung, M. J. Oh, J. O. Kim, H. H. Lee, I. G. Jeong and J. H. Yoon. 2005. The effect of running exercise training on GLUT4 and VAMP2 protein expression in muscle of streptozotocin-induced diabetes rats. Exercise Science 14, 545-554
  38. Park, S., J. S. Jang, D. W. Jun and S. M. Hong. 2005. Exercise enhances insulin and leptin signaling in the cerebral cortex and hypothalamus during dexamethasone-induced stress in diabetic rats. Neuroendocrinology 82, 282-293 https://doi.org/10.1159/000093127
  39. Parsons, J. A., A. Bartke and R. L. Sorenson. 1995. Number and size of islets of Langerhans in pregnant, human growth hormone-expressing transgenic, and pituitary dwarf mice: effect of lactogenic hormones. Endocrinology 136, 2013-2021 https://doi.org/10.1210/en.136.5.2013
  40. Parsons, J. A., T. C. Brelje and R. L. Sorenson. 1992. Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinology 130, 1459-1466 https://doi.org/10.1210/en.130.3.1459
  41. Randhawa, V. K., P. J. Bilan, Z. A. Khayat, N. Daneman, Z. Liu, T. Ramlal, A. Volchuk, X. R. Peng, T. Coppola, R. Regazzi, W. S. Trimble and A. Klip. 2000. VAMP2, but not VAMP3/cellubrevin, mediates insulin-dependent incorporation of GLUT4 into the plasma membrane of L6 myoblasts. Mol. Biol. Cell. 11, 2403-2417 https://doi.org/10.1091/mbc.11.7.2403
  42. Rea, S. and D. E. James. 1997. Moving GLUT4: the biogenesis and trafficking of GLUT4 storage vesicles. Diabetes 46, 1667-1677 https://doi.org/10.2337/diabetes.46.11.1667
  43. Rodnick, K. J., W. L. Haskell, A. L. Swislocki, J. E. Foley and G. M. Reaven. 1987. Improved insulin action in muscle, liver, and adipose tissue in physically trained human subjects. Am. J. Physiol. 253, 489-495
  44. Ronnemaa, T., K. Mattila, A. Lehtonen and V. Kallio. 1986. A controlled randomized study on the effect of long-term physical exercise on the metabolic control in type 2 diabetic patients. Acta. Med. Scand. 220, 219-224
  45. Ryan, E. A., M. J. O'Sullivan and J. S. Skyler. 1985. Insulin action during pregnancy. Studies with the euglycemic clamp technique. Diabetes 34, 380-389 https://doi.org/10.2337/diabetes.34.4.380
  46. Salvatores, M., G. Gennarelli, G. Menato, M. Massobrio and M. 2006. Leptin as a possible marker of augmented metabolic risk during pregnancy. Minerva. Ginecol. 58, 1-10
  47. Shi, Z. Q., A. Nelson, L. Whitcomb, J. Wang and A. M. Cohen. 1998. Intracerebroventricular administration of leptin markedly enhances insulin sensitivity and systemic glucose utilization in conscious rats. Metabolism 47, 1274-1280 https://doi.org/10.1016/S0026-0495(98)90336-5
  48. Sivan, E., X. Chen, C. J. Homko, E. A. Reece and G. Boden. 1997. Longitudinal study of carbohydrate metabolism in healthy obese pregnant women. Diabetes Care 20, 1470-1475 https://doi.org/10.2337/diacare.20.9.1470
  49. Steinberg, G. R., A. C. Smith, S. Wormald, P. Malenfant, C. Collier and D. J. Dyck. 2004. Endurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle. Am. J. Endo. Metab. 286, 57-63 https://doi.org/10.1152/ajpendo.00302.2003
  50. Szanto, I. and C. R. Kahn. 2000. Selective interaction between leptin and insulin signaling pathways in a hepatic cell line. Proc. Natl. Acad. Sci. 97, 2355-2360 https://doi.org/10.1073/pnas.050580497
  51. Thomas, H. R., T. B. Joseph, M. L. Lisa and W. C. Samuel. 2000. Transient enhancement of GLUT-4 levels in rat epitrochlearis muscle after exercise training. J. Appl. Physiol. 88, 2240-2245 https://doi.org/10.1063/1.1287758
  52. Toyoda, N., T. Deguchi, K. Murata, T. Yamamoto and Y. Sugiyama. 1991. Postbinding insulin resistance around parturition in the isolated rat epitrochlearis muscle. Am. J. Obstet. Gynecol. 165, 1475-1480 https://doi.org/10.1016/S0002-9378(12)90788-7
  53. Treadway, J. L. & J. C. Young. 1989. Decreased glucose uptake in the fetus after maternal exercise. Med. Sci. Sports Exerc. 21, 140-145
  54. Zisman, A., O. D. Peroni, E. D. Abel, M. D. Michael, F. Mauvais-Jarvis, B. B. Lowell, J. F. P. Wojtaszewski, M. F. Hirshman, A. Virkamaki and L. Goodyear. 2000. Targets disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat. Med. 6, 924-928 https://doi.org/10.1038/78693