Browse > Article

Glucose Transporters and AMP-Activated Protein Kinase Modulation Effects of Decursin and Decursinol Angelate on Diabetic Rats  

Ok, Seon (Department of Pharmacy, Kyungsung University)
Lee, Ju-Hee (Department of Pharmacy, Kyungsung University)
Kim, Ik-Hwan (Department of Biotechnology, Korea University)
Kang, Jae-Seon (Department of Pharmacy, Kyungsung University)
Publication Information
YAKHAK HOEJI / v.55, no.4, 2011 , pp. 301-308 More about this Journal
Abstract
Diabetes has been one of major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has been focused as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK increases glucose uptake through independent insulin signal pathway. In this study, we investigated the anti-diabetic effect of Angelica gigas Nakai extract (AGNEX), a mixture of decursin and decursinol angelate (53 : 47), decursin and decursinol angelate on blood glucose, glucose transport (GLUT) and AMPK expression levels in streptozotocin (STZ)-induced diabetic rats. To induce diabetes, 50 mg/kg of STZ was injected via i.v. route and AGNEX 2 mg/kg (STZ+AG), decursin 2 mg/kg (STZ+D), decursinol angelate 2 mg/kg (STZ+DA), and metformin 100 mg/kg (STZ+M) were administered orally for 21 days. STZ+DA group showed a significant decrease in fasting blood glucose levels compared to the other groups. Decursinol angelate significantly upregulated expression of glucose transporter 4 (GLUT4) and phosphorylation of AMPK (p-AMPK) in skeletal muscle of rats. In pancreas of rats, decursinol angelate significantly increased expression of GLUT2 through down-regulation of p-AMPK. In addition to the result of pancreatic islets morphology, AGNEX, decursin, decursinol angelate, and metformin treated group recovered ${\beta}$-cell damage by hyperglycemia. These results indicate that decursinol angelate might be a potential anti-diabetic agent and AGNEX could be useful in the treatment of diabetes mellitus.
Keywords
decursin; decursinol angelate; metformin; GLUT; AMPK;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 da Silva Xavier, G., Leclerc, I., Varadi, A., Tsuboi, T., Moule, S. K. and Rutter, G. A. : Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression. Biochem. J. 371, 761 (2003).   DOI   ScienceOn
2 강재선, 황성우, 이진영, 김강민, 김천규, 홍용근, 최광진, 이상길 : 지질대사 개선효과가 있는 데커신 및 데커시놀안젤레이트를 유효 성분으로 하는 참당귀 및 세발당귀추출물과 그 추출방법, 한국특허 10-2009-0078267, 10-2008-0004122 (2008).
3 Olson, A. L. and Pessin, J. E. : Structure, function, and regulation of the mammalian facilitative glucose transporter gene family. Annu. Rev. Nutr. 16, 235 (1996).   DOI   ScienceOn
4 Thorens, B., Flier, J. S., Lodish, H. F. and Kahn, B. B. : Differential regulation of two glucose transporters in rat liver by fasting and refeeding and by diabetes and insulin treatment. Diabetes 39, 712 (1990).   DOI   ScienceOn
5 Kefas, B. A., Heimberg, H., Vaulont, S., Meisse, D., Hue, L., Pipeleers, D. and Van de Casteele, M. : AICA-riboside induces apoptosis of pancreatic beta cells through stimulation of AMPactivated protein kinase. Diabetologia 46, 250 (2003).   DOI
6 Kim, W. H., Lee, J. W., Suh, Y. H., Lee, H. J., Lee, S. H., Oh, Y. K., Gao, B. and Jung, M. H. : AICAR potentiates ROS production induced by chronic high glucose: roles of AMPK in pancreatic beta-cell apoptosis. Cell. Signal. 19, 791 (2007).   DOI   ScienceOn
7 Im, S. S., Kim, S. Y., Kim, H. I. and Ahn, Y. H. : Transcriptional regulation of glucose sensors in pancreatic beta cells and liver.Curr. Diabetes Rev. 2, 11 (2006).   DOI   ScienceOn
8 Tsuboi, T., da Silva Xavier, G., Leclerc, I. and Rutter, G. A. : 5'- AMP-activated protein kinase controls insulin-containing secretory vesicle dynamics. J. Biol. Chem. 278, 52042 (2003).   DOI
9 Brozinick, J. T., Jr., McCoid, S. C., Reynolds, T. H., Nardone, N. A., Hargrove, D. M., Stevenson, R. W., Cushman, S. W. and Gibbs, E. M. : GLUT4 overexpression in db/db mice dosedependently ameliorates diabetes but is not a lifelong cure. Diabetes 50, 593 (2001).   DOI   ScienceOn
10 Hardie, D. G. : The AMP-activated protein kinase pathwaynew players upstream and downstream. J. Cell. Sci. 117, 5479 (2004).   DOI   ScienceOn
11 Kim, K. M., Jung, J. Y., Hwang, S., W., Kim, M. J. and Kang, J. S. : Isolation and purification of decursin and decursinol angelate in Angelica gigas Nakai. The Korean Society of Food Science and Nutrition 38, 635 (2009).
12 Kang, S. Y., Lee, K. Y., Park, M. J., Kim, Y. C., Markelonis, G. J., Oh, T. H. and Kim, Y. C. : Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice. Neurobiology of Learning and Memory 79, 11 (2003).   DOI   ScienceOn
13 Kahn, B. B., Alquier, T., Carling, D. and Hardie, D. G. : AMPactivated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell. Metab. 1, 15 (2005).   DOI   ScienceOn
14 Bergeron, R., Previs, S. F., Cline, G. W., Perret, P., Russell, R. R. 3rd., Young, L. H. and Shulman, G. I. : 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 (2001).   DOI   ScienceOn
15 Towler, M. C. and Hardie, D. G. : AMP-activated protein kinase in metabolic control and insulin signaling. Circ. Res. 100, 328 (2007).   DOI   ScienceOn
16 Hardie, D. G. : AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat. Rev. Mol. Cell. Biol. 8, 774 (2007).   DOI   ScienceOn
17 Zhang, B. B., Zhou, G. and Li, C. : AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell. Metab. 9, 407 (2009).   DOI   ScienceOn
18 Arner, P. : Insulin resistance in type 2 diabetes: role of fatty acids. Diabetes Metab. Res. Rev. 18, S5 (2002).   DOI   ScienceOn
19 Delarue, J. and Magnan, C. : Free fatty acids and insulin resistance. Curr. Opin. Clin. Nutr. Metab. Care. 10, 142 (2007).   DOI   ScienceOn
20 김응진, 민헌기, 최영길, 이태희, 허갑범, 신순현, 강성구, 김광원 이현철 : 제 3판 당뇨병학. 대한당뇨병학회 310 (2005).
21 Cheng, J. T., Huang, C. C., Liu, I. M., Tzeng, T. F. and Chang, C. J. : Novel mechanism for plasma glucose-lowering action of metformin in streptozotocin-induced diabetic rats. Diabetes 55, 819 (2006).   DOI   ScienceOn
22 Unger, R. H. : Diabetic hyperglycemia: link to impaired glucose transport in pancreatic beta cells. Science 251, 1200 (1991).   DOI
23 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. : Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167 (2001).   DOI
24 Lee, S. H., Lee, Y. S., Jung, S. H., Shin, K. H., Kim, B. K. and Kang, S. S. : Anti-tumor activities of decursinol angelate and decursin from Angelica gigas. Arch. Pharm. Res. 26, 727 (2003).   DOI
25 Ziel, F. H., Venkatesan, N. and Davidson, M. B. : Glucose transport is rate limiting for skeletal muscle glucose metabolism in normal and STZ-induced diabetic rats. Diabetes 37, 885 (1988).   DOI   ScienceOn
26 Chomczynski, P. and Sacchi, N. : Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162, 156 (1987).