DOI QR코드

DOI QR Code

Fagopyritol, a Derivative of D-chiro-inositol, Induces GLUT4 Translocation via Actin Filament Remodeling in L6-GLUT4myc Skeletal Muscle Cells

랫드 근육세포에서 fagopyritol이 액틴 필라멘트 구조와 포도당 수송체 4에 미치는 영향

  • Nam, Hajin (Institute of Natural Medicine, Hallym University) ;
  • Hwang, In Koo (Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University) ;
  • Jung, Harry (Department of Medical Genetics, College of Medicine, Hallym University) ;
  • Kwon, Seung-Hae (Korea Basic Science Institute Chuncheon Center) ;
  • Park, Ok Kyu (Korea Basic Science Institute Chuncheon Center) ;
  • Suh, Jun Gyo (Institute of Natural Medicine, Hallym University)
  • 남하진 (한림대학교 천연의약연구소) ;
  • 황인구 (서울대학교 수의학과) ;
  • 정혜리 (한림대학교 의학유전학교실) ;
  • 권승해 (한국기초과학지원연구원 춘천센터) ;
  • 박옥규 (한국기초과학지원연구원 춘천센터) ;
  • 서준교 (한림대학교 천연의약연구소)
  • Received : 2013.08.07
  • Accepted : 2013.09.24
  • Published : 2013.09.30

Abstract

Insulin induces glucose transporter 4 (GLUT4) translocation to the muscle cell surface. As fagopyritol has insulin-like effects, the effects of fagopyritol on GLUT4 translocation and filamentous (F) actin remodeling in L6-GLUT4myc skeletal muscle cells were investigated. Fagopyritol significantly increased plasma membrane GLUT4 levels compared with the basal control in L6-GLUT4myc myoblast cells. Phosphatidylinositol (PI) 3-kinase inhibitor (LY294002) treatment prevented GLUT4 translocation to the plasma membrane in the myoblasts. Fagopyritol treatment apparently stimulates F-actin remodeling in myoblasts. In addition, fagopyritol treatment induced GLUT4 translocation and F-actin remodeling in myotubes. Taken together, these results suggest that fagopyritol promotes GLUT4 translocation and F-actin remodeling by activating the PI 3-kinase-dependent signaling pathway.

인슐린은 근육세포 표면으로 포도당 수송체 4(glucose transporter 4, GLUT4)를 유도하여 혈액 속의 포도당을 세포 내로 유입시키도록 작용한다고 알려져 있다. Fagopyritol은 인슐린과 유사한 작용을 하는 것으로 알려져 있으므로, 본 연구에서는 혈당강하 효과가 있다고 알려진 fagopyritol을 랫드의 근육세포주(L6GLUT4myc 세포)에 처리하여, 아직 명확하게 밝혀지지 않은 fagopyritol의 혈당강하 기전을 규명하고자 수행하였다. Fagopyritol의 혈당강하 기전을 규명하기 위하여 근원세포(myoblast)와 근관세포(myotube)에 fagopyritol을 처리하여 액틴 필라멘트의 구조와 GLUT4에 미치는 영향을 분석하였다. Fagopyritol을 myoblast에 처리하였을 때, GLUT4가 처리군에서 대조군과 비교하여 유의 있게 원형질막 쪽으로 유도되는 것을 확인하였고, 액틴 필라멘트의 구조가 재조정되면서 GLUT4의 이동을 돕는 것으로 생각된다. 또한 fagopyritol이 인슐린과 유사한 작용 경로를 가지는지 확인하기 위하여, 인슐린 작용 경로에서 중요한 역할을 하는 것으로 알려진 phosphatidylinositol 3-kinase (PI3K)의 억제제인 LY294002를 fagopyritol과 함께 처리하였을 때 GLUT4가 원형질막 쪽으로 유도되지 않는 것을 확인하였다. Fagopyritol을 myotube에 처리하였을 때, myoblast에 처리하였을 때와 유사한 결과를 나타내었다. 이러한 결과를 종합하면 fagopyritol이 인슐린과 유사한 작용을 하여 액틴 필라멘트의 구조 변경과 GLUT4의 이동을 촉진시키는 것으로 사료된다.

Keywords

References

  1. Al-Nozha, O., Habib, F., Mojaddidi, M. and El-Bab, M. F. 2013. Body weight reduction and metformin: Roles in polycystic ovary syndrome. Pathophysiology 20, 131-137. https://doi.org/10.1016/j.pathophys.2013.03.002
  2. Bai, L., Wang, Y., Fan, J., Chen, Y., Ji, W., Qu, A., Xu, P., James, D. E. and Xu, T. 2007. Dissecting multiple steps of GLUT4 trafficking and identifying the sites of insulin action. Cell Metab 5, 47-57. https://doi.org/10.1016/j.cmet.2006.11.013
  3. Chung, M. J., Lee, Y. S., Kim, B. C., Lee, S. B., Moon, T. H., Lee, S. J. and Park, K. H. 2006. The hypoglycemic effects of acarviosine-glucose modulate hepatic and intestinal glucose transporters in vivo. Food Sci Biotechnol 15, 851-855.
  4. Cid, M. B., Alfonso, F. and Martín-Lomas, M. 2004. Synthesis of fagopyritols A1 and B1 from D-chiro-inositol. Carbohydr Res 339, 2303-2307. https://doi.org/10.1016/j.carres.2004.06.021
  5. Antonescu, C. N., Randhawa, V. K. and Klip, A. 2008. Dissecting GLUT4 traffic components in L6 myocytes by fluorescence- based, single-cell assays. Methods Mol Biol 457, 367-378. https://doi.org/10.1007/978-1-59745-261-8_27
  6. Emoto, M., Langille, S. E. and Czech, M. P. 2001. A role for kinesin in insulin-stimulated GLUT4 glucose transporter translocation in 3T3-L1 adipocytes. J Biol Chem 276, 10677-10682. https://doi.org/10.1074/jbc.M010785200
  7. Fabjan, N., Rode, J., Kosir, I. J., Wang, Z., Zhang, Z. and Kreft, I. 2003. Tartary buckwheat (Fagopyrum tataricum Gaertn.) as a source of dietary rutin and quercitrin. J Agric Food Chem 51, 6452-6455. https://doi.org/10.1021/jf034543e
  8. Horbowicz, M. and Obendorf, R. L. 2005. Fagopyritol accumulation and germination of buckwheat seeds matured at 15, 22, and 30${^{\circ}C}$. Crop Sci 45, 1264-1270. https://doi.org/10.2135/cropsci2004.0431
  9. Ishikura, S., Bilan, P. J. and Klip, A. 2007. Rabs 8A and 14 are targets of the insulin-regulated Rab-GAP AS160 regulating GLUT4 traffic in muscle cells. Biochem Biophys Res Commun 353, 1074-1079. https://doi.org/10.1016/j.bbrc.2006.12.140
  10. Jordan, S. D., Konner, A. C. and Bruning, J. C. 2010. Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis. Cell Mol Life Sci 67, 3255-3273. https://doi.org/10.1007/s00018-010-0414-7
  11. Kanzaki, M., Watson, R. T., Khan, A. H. and Pessin, J. E. 2001. Insulin stimulates actin comet tails on intracellular GLUT4-containing compartments in differentiated 3T3L1 adipocytes. J Biol Chem 276, 49331-49336. https://doi.org/10.1074/jbc.M109657200
  12. Karlsson, H. K. and Zierath, J. R. 2007. Insulin signaling and glucose transport in insulin resistant human skeletal muscle. Cell Biochem Biophys 48, 103-113. https://doi.org/10.1007/s12013-007-0030-9
  13. Kawa, J. M., Taylor, C. G. and Przybylski, R. 2003. Buckwheat concentrate reduces serum glucose in streptozotocin-diabetic rats. J Agric Food Chem 51, 7287-7291. https://doi.org/10.1021/jf0302153
  14. Khayat, Z. A., Tong, P., Yaworsky, K., Bloch, R. J. and Klip, A. 2000. Insulin-induced actin filament remodeling colocalizes actin with phosphatidylinositol 3-kinase and GLUT4 in L6 myotubes. J Cell Sci 113, 279-290.
  15. Kishi, K., Muromoto, N., Nakaya, Y., Miyata, I., Hagi, A., Hayashi, H. and Ebina, Y. 1998. Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway. Diabetes 47, 550-558. https://doi.org/10.2337/diabetes.47.4.550
  16. Klip, A., Li, G. and Logan, W. J. 1984. Induction of sugar uptake response to insulin by serum depletion in fusing L6 myoblasts. Am J Physiol 247, 291-296.
  17. Leto, D. and Saltiel, A. R. 2012. Regulation of glucose transport by insulin: traffic control of GLUT4. Nat Rev Mol Cell Biol 13, 383-396. https://doi.org/10.1038/nrm3351
  18. Omata, W., Shibata, H., Li, L., Takata, K. and Kojima, I. 2000. Actin filaments play a critical role in insulin-induced exocytotic recruitment but not in endocytosis of GLUT4 in isolated rat adipocytes. Biochem J 346, 321-328. https://doi.org/10.1042/0264-6021:3460321
  19. Ostlund, R. E. Jr., McGill, J. B., Herskowitz, I., Kipnis, D. M., Santiago, J. V. and Sherman, W. R. 1993. D-chiro-inositol metabolism in diabetes mellitus. Proc Natl Acad Sci USA 90, 9988-9992. https://doi.org/10.1073/pnas.90.21.9988
  20. Patel, N., Rudich, A., Khayat, Z. A., Garg, R. and Klip, A. 2003. Intracellular segregation of phosphatidylinositol-3,4,5- trisphosphate by insulin-dependent actin remodeling in L6 skeletal muscle cells. Mol Cell Biol 23, 4611-4626. https://doi.org/10.1128/MCB.23.13.4611-4626.2003
  21. Patki, V., Buxton, J., Chawla, A., Lifshitz, L., Fogarty, K., Carrington, W., Tuft, R. and Corvera, S. 2001. Insulin action on GLUT4 traffic visualized in single 3T3-L1 adipicytes by using ultra-fast microscopy. Mol Biol Cell 12, 129-141. https://doi.org/10.1091/mbc.12.1.129
  22. Rowland, A. F., Fazakerley, D. J. and James, D. E. 2011. Mapping insulin/GLUT4 circuitry. Traffic 12, 672-681. https://doi.org/10.1111/j.1600-0854.2011.01178.x
  23. Sbrissa, D., Ikonomov, O. C., Strakova, J. and Shisheva, A. 2004. Role for a novel signaling intermediate, phosphatidylinositol 5-phosphate, in insulin-regulated f-actin stress fiber breakdown and GLUT4 translocation. Endocrinology 145, 4853-4865. https://doi.org/10.1210/en.2004-0489
  24. Song, H. Y., Nam, Y., Kim, S. M., Kwon, S. O., Yeo, K. M., Kim, B. N. and Suh, J. G. 2009. Fagopyritol promote glucose uptake in L6 muscle cells. Lab Anim Res 25, 335-339.
  25. Steadman, K. J., Burgoon, M. S., Schuster, R. L., Lewis, B. A., Edwardson, S. E. and Obendorf, R. L. 2000. Fagopyritols, D-chiro-inositol, and other soluble carbohydrates in buckwheat seed milling fractions. J Agric Food Chem 48, 2842-2847.
  26. Thong, F. S., Dugani, C. B. and Klip, A. 2005. Turning signals on and off: GLUT4 traffic in the insulin-signalling highway. Physiology (Bethesda) 20, 271-284. https://doi.org/10.1152/physiol.00017.2005
  27. Tong, P., Khayat, Z. A., Huang, C., Patel, N., Ueyama, A. and Klip, A. 2001. Insulin-induced cortical actin remodeling promotes GLUT4 insertion at muscle cell membrane ruffles. J Clin Invest 108, 371-381. https://doi.org/10.1172/JCI200112348
  28. Tsakiridis, T., Vranic, M. and Klip, A. 1994. Disassembly of the actin network inhibits insulin-dependent stimulation of glucose of glucose transport and prevents recruitment of glucose transporters to the plasma membrane. J Biol Chem 269, 29934-29942.
  29. Ueyama, A., Yaworsky, K. L., Wang, Q., Ebina, Y. and Klip, A. 1999. GLUT-4myc ectopic expression in L6 myoblasts generates a GLUT-4-specific pool conferring insulin sensitivity. Am J Physiol 277, 572-578.
  30. Wang, Q., Bilan, P. J., Tsakiridis, T., Hinek, A. and Klip, A. 1998. Actin filaments participate in the relocalizastion of phosphatidylinositol3-kinase to glucose transporter-containing compartments and in the stimulation of glucose uptake in 3T3-L1 adipocytes. Biochem J 331, 917-928.
  31. Wang, Q., Khayat, Z., Kishi, K., Ebina, Y. and Klip, A. 1998. GLUT4 translocation by insulin intact muscle cells: detection by a fast and quantitative assay. FEBS Lett 427, 193-197. https://doi.org/10.1016/S0014-5793(98)00423-2
  32. Wang, Q., Somwar, R., Bilan, P.J., Liu, Z., Jin, J., Woodgett, J. R. and Klip, A. 1999. Protein kinase B/Akt participtes in GLUT4 translocation by insulin in L6 myoblasts. Mol Cell Biol 19, 4008-4018.
  33. Whiting, L., Danaher, R. N., Ruggiero, K., Lee, C. C., Chaussade, C., Mulvey, T., Phillips, A. and Loomes, K. M. 2013. D-chiro-Inositol attenuates epinephrine-stimulated hepatic glucose output in the isolated perfused liver independently of insulin. Horm Metab Res 45, 394-397.
  34. Yao, Y., Shan, F., Bian, J., Chen, F., Wang, M. and Ren, G. 2008. D-chiro-inositol-enriched tartary buckwheat bran extract lowers the blood glucose level in KK-Ay mice. J Agric Food Chem 56, 10027-10031. https://doi.org/10.1021/jf801879m
  35. Yap, A., Nishiumi, S., Yoshida, K. and Ashida, H. 2007. Rat L6 myotubes as an in vitro model system to study GLUT4-dependent glucose uptake stimulated by inositol derivatives. Cytotechnology 55, 103-108. https://doi.org/10.1007/s10616-007-9107-y

Cited by

  1. Localization of Glucose Transporter 10 to Hair Cells’ Cuticular Plate in the Mouse Inner Ear vol.2018, pp.2314-6141, 2018, https://doi.org/10.1155/2018/7817453