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db/db 마우스 동물모델에서 Vigna nakashimae 클로로포름층 분획물의 항당뇨 효능

Antidiabetic Activity of a Chloroform Fraction of Vigna nakashimae in db/db mice

  • 남정수 (부산대학교 양산캠퍼스 한의학전문대학원) ;
  • 하태정 (국립식량과학원 기능성작물부) ;
  • 박재홍 (부산대학교 양산캠퍼스 한의학전문대학원) ;
  • 정명호 (부산대학교 양산캠퍼스 한의학전문대학원)
  • Nam, Jeong-Su (School of Korean Medicine, Pusan National University) ;
  • Ha, Tae Joung (Department of Functional Crops, National Institute of Crop Science, RDA) ;
  • Park, Jae Hong (School of Korean Medicine, Pusan National University) ;
  • Jung, Myeong Ho (School of Korean Medicine, Pusan National University)
  • 투고 : 2013.02.19
  • 심사 : 2013.04.09
  • 발행 : 2013.04.30

초록

최근 식생활의 변화에 따라 당뇨병, 비만 등의 만성대사질환의 발병률이 증가함에 따라 예방과 치료를 위한 물질연구가 많이 진행되고 있다. 본 연구에서는 선행 연구에서 항당뇨 효능이 확인된 Vigna nakashimae (VN) 메탄올 추출물로부터 VN 클로로포름층 분획물과 물층 분획물을 얻어 각 분획물의 항당뇨 효능과 분자적 기전을 살펴보았다. 각각의 VN 분획물을 제 2형 당뇨병질환모델인 db/db 마우스에 경구투여하여 VN 분획물의 혈당 및 지질 대사 변화 등을 측정하였다. VN 클로로포름층 분획물은 공복 혈당과 당화혈색소를 물층 분획물보다 더 효과적으로 감소시켰다. 또한 내당능도 개선하였으며, 혈중 지방산과 중성지방도 감소시켰다. VN 클로로포름층 분획물은 HepG2와 C2C12세포에서 인산화된 AMPK와 AMPK 하위 유전자인 CPT-1의 유전자 발현을 증가시켰다. VN 클로로포름층 분획물은 AMPK의 활성화와 일치하게 HepG2에서 당 생성 효소인 PEPCK와 G-6Pase의 발현을 감소시켰으며, C2C12에서는 당 유입을 증가시켰다. 이상의 결과는 VN 클로로포름층 분획물은 AMPK의 활성화를 통해 공복혈당을 감소시켰으며, 이러한 효과는 물층 분획물보다 더 효과적이었다.

In this study, we evaluated the antidiabetic effect of a chloroform fraction of a methanol extract of Vigna nakashimae (designated VN) and compared it with that of a water fraction. Both fractions were administrated to eight-week old db/db mice for two weeks, after which the plasma glucose, triglyceride, and total cholesterol levels were measured. The chloroform fraction (VN-C) lowered the fasting glucose and blood glycated hemoglobin in the db/db mice more effectively than those of the water fraction (VN-W). VN-C also improved the glucose tolerance and led to a significant decrease in the plasma levels of free fatty acids and triglycerides. VN-C enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and increased the expression of carnitine palmitoyltransferase-1 (CPT-1) in HepG2 and C2C12 cells more significantly than VN-W. Consistent with AMPK activation, VN-C inhibited cAMP/Dex-stimulated expression of gluconeogenic genes and increased glucose uptake in C2C12. Collectively, these results suggest that VN-C has an antidiabetic effect, which is exerted via AMPK activation, and that this effect is stronger than that of VN-W.

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참고문헌

  1. Bergeron, R., Previs, S. F., Cline, G. W., Perret, P., Russell, R. R., Young, L. H. and Shulman, G. I. 2001. Effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 50, 1076-1082. https://doi.org/10.2337/diabetes.50.5.1076
  2. Carling, D. 2004. The AMP-activated protein kinase cascade--a unifying system for energy control. Trends Biochem Sci 29, 18-24. https://doi.org/10.1016/j.tibs.2003.11.005
  3. Goldstein, B. J. 2002. Insulin resistance as the core defect in type 2 diabetes mellitus. J Cardiol 90, 3G-10G.
  4. Itoh, T. and Furuichi, Y. 2009. Hypoglycemic effect of hot-water extract of adzuki (Vigna angularis) in spontaneously diabetic KK-A(y) mice. Nutrition 25, 318-321. https://doi.org/10.1016/j.nut.2008.08.011
  5. Itoh, T., Kita, N., Kurokawa, Y., Kobayashi, M., Horio, F. and Furuichi, Y. 2004. Suppressive effect of a hot water extract of adzuki beans (Vigna angularis) on hyperglycemia after sucrose loading in mice and diabetic rats. Biosci Biotechnol Biochem 68, 2421-2426. https://doi.org/10.1271/bbb.68.2421
  6. Koistinen, H. A., Galuska, D., Chibalin, A. V., Yang, J., Zierath, J. R., Holman, G. D. and Wallberg-Henriksson, H. 2003. 5-amino-imidazole carboxamide riboside increases glucose transport and cell-surface GLUT4 content in skeletal muscle from subjects with type 2 diabetes. Diabetes 52, 1066-1072 https://doi.org/10.2337/diabetes.52.5.1066
  7. Madar, Z. and Stark, A. H. 2002. New legume sources as therapeutic agents. Br J Nutr 88, S287-292. https://doi.org/10.1079/BJN2002719
  8. Prinyawiwatkul, W., McWatters, K. H., Beuchat, L. R. and Phillips, R. D. 1996. Cowpea flour: a potential ingredient in food products. Crit Rev Food Sci Nutr 36, 413-436. https://doi.org/10.1080/10408399609527734
  9. Saltiel, A. R. and Kahn, C. R. 2001. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414, 799-806. https://doi.org/10.1038/414799a
  10. Solanki, Y. B. and Jain, S. M. 2010. Antihyperlipidemic activity of Clitoria ternatea and Vigna mungo in rats. Pharm Bio 48, 915-923. https://doi.org/10.3109/13880200903406147
  11. Stumvoll, M., Nurjhan, N., Perriello, G., Dailey, G. and Gerich, J. E. 1995. Metabolic effects of metformin in non-insulin- dependent diabetes mellitus. N Engl J Med 333, 550-554. https://doi.org/10.1056/NEJM199508313330903
  12. Yeo, J. Y., Ha, T. J., Nam, J. and Jung, M. H. 2011. Antidiabetic effects of Vigna nakashimae extract in db/db mice. Biosci Biotechnol Biochem 75, 2223-2228 https://doi.org/10.1271/bbb.110538
  13. Zhang, B. B., Zhou, G. and Li, C. 2009. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab 9, 407-416. https://doi.org/10.1016/j.cmet.2009.03.012
  14. Zimmet, P., Alberti, K. G. and Shaw, J. 2001. Global and societal implications of the diabetes epidemic. Nature 414, 782-787. https://doi.org/10.1038/414782a
  15. Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M. F., Goodyear, L. J. and Moller, D. E. 2001. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108, 1167-1174. https://doi.org/10.1172/JCI13505