DOI QR코드

DOI QR Code

Effects of Green Tea Polyphenol and Vitamin C on Type 2 Diabetic Rats Induced by Low Dose Streptozotocin Following High Fat Diet

고지방식이와 저용량 스트렙토조토신으로 유도된 2형 당뇨병 흰쥐에서 녹차 폴리페놀과 비타민 C 병합 투여 효과

  • Lee, Byoung-Rai (Department of Molecular Biology & Biochemistry, College of Medicine Chosun University) ;
  • Yang, Hoon (Department of Molecular Biology & Biochemistry, College of Medicine Chosun University) ;
  • Park, Pyoung-Sim (Department of Food Nutrient and Culinary, Chosun College of Science & Technology)
  • 이병래 (조선대학교 의과대학 생화학분자생물학교실) ;
  • 양훈 (조선대학교 의과대학 생화학분자생물학교실) ;
  • 박평심 (조선이공대학교 식품영양조리과학과)
  • Received : 2015.09.30
  • Accepted : 2015.11.23
  • Published : 2016.02.29

Abstract

This study investigated the effects of green tea polyphenol and vitamin C on type 2 diabetes mellitus by administering polyphenon 60 (P60) and sodium ascorbate (SA) to diabetic rats induced by high fat diet/low-dose streptozotocin. The experimental group was divided into five different groups: non-diabetic control group (NC), diabetes control group (DC), diabetes+P60 group (DM+P60), diabetes+SA group (DM+SA), and diabetes+P60+SA group (DM+P60+SA). P60 and SA were dissolved in 0.1% drinking water. After P60 and SA were administered for 16 weeks, fasting blood glucose, plasma insulin, serum triglyceride, blood urea nitrogen (BUN), and creatinine levels as well as kidney alkaline phosphatase (AP) and ${\gamma}$-glutamyltranspeptidase (GGT) activities were measured. Fasting blood glucose level increased 5-fold in the DC group compared to the NC group. In the DM+P60 group, fasting blood glucose level decreased by 14%. In the DM+P60+SA group, fasting blood glucose level decreased by 28% compared to the DC group, whereas the DM+SA group did not show any significant difference. The homeostasis model assessment for insulin resistance index increased in the DC group and decreased in the DM+P60+SA group compared to the DC group. Serum creatinine level increased in the DC group, but decreased by 17% in the DM+P60 group and by 43% in the DM+P60+SA group compared to the DC group. The serum BUN level increased in the DC group, but decreased by 41% in the DM+P60+SA group compared to the DC group. Kidney GGT and AP activities decreased in the DC group compared to the NC group; however, they were reversed by DM+P60+SA group. These results show that combined administration of both green tea polyphenol and vitamin C had better effects on improving blood glucose level, insulin resistance, serum triglyceride level, and protecting kidneys than administration of either green tea polyphenol or vitamin C alone in the context of type 2 diabetes.

녹차 폴리페놀과 비타민 C가 2형 당뇨병에 미치는 영향을 관찰하기 위해 고지방식이와 저용량 스트렙토조토신을 이용하여 당뇨병이 유도된 흰쥐에 polyphenon 60(P60)과 sodium ascorbate(SA)를 16주간 투여한 후 공복 혈당, 혈장 인슐린, 혈청 중성지질, BUN 및 creatinine과 신장 GGT와 AP 활성도를 측정하였다. 당뇨병 흰쥐에 P60이나 SA 투여로 인한 식이섭취량과 체중의 변화는 없었다. 공복 혈당은 당뇨 대조군(DC 군)에서 대조군(NC 군)의 5배로 증가하였으며, 당뇨+녹차 폴리페놀(DM+P60) 군은 14%, 당뇨+녹차 폴리페놀+비타민 C(DM+P60+SA) 군은 28%가 DC 군보다 감소하였고, 당뇨+비타민 C(DM+SA) 군은 DC 군과 유의한 차이가 없었다. 혈장 인슐린 양은 각 실험군 사이에 유의한 차이가 없으며, 인슐린 저항성 지수 HOMA-IR은 DC 군에서 증가하였고 DM+P60+SA 군은 DC 군보다 감소하였다. 혈청 creatinine 양은 DC 군에서 증가하였고 DM+P60 군은 DC 군보다 17% 감소하였으며, DM+P60+SA 군은 DC 군보다 43% 감소하였다. 혈청 BUN 양은 DC 군에서 증가하였고 DM+P60+SA 군은 DC 군보다 41% 감소하였다. 신장 GGT와 AP 활성도는 DC 군에서 감소하였고 DM+P60+SA 군은 DC 군보다 감소가 적었으며, DM+SA 군은 DC 군과 유의한 차이가 없었다. 이상의 실험 결과 2형 당뇨병에서 녹차 폴리페놀과 비타민 C 복합 투여가 혈당, 인슐린 저항성 및 혈청 중성지질량 개선 및 신장 손상 방지효과가 녹차 폴리페놀이나 비타민 C를 단독으로 투여하였을 때보다 더 증가함을 확인할 수 있었다. 녹차 폴리페놀과 비타민 C의 혈당 상승 억제와 신장 손상 방지 효과에 대한 계속된 연구가 필요하며, 녹차 폴리페놀과 비타민 C는 당뇨병 환자에게 혈당을 조절하고 신장 손상을 방지하는 기능성 식품 제재로서 개발 가능성이 있는 것으로 생각한다.

Keywords

References

  1. International Diabetes Federation. 2014. IDF diabetes atlas. 6th ed. Brussels, Belgium. p 7-17.
  2. Akkati S, Sam KG, Tungha G. 2011. Emergence of promising therapies in diabetes mellitus. J Clin Pharmacol 51: 796-804. https://doi.org/10.1177/0091270010376972
  3. Philippe J, Raccah D. 2009. Treating type 2 diabetes: how safe are current therapeutic agents?. Int J Clin Pract 63: 321-332. https://doi.org/10.1111/j.1742-1241.2008.01980.x
  4. Babu PV, Liu D, Gilbert ER. 2013. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J Nutr Biochem 24: 1777-1789. https://doi.org/10.1016/j.jnutbio.2013.06.003
  5. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. 2004. Polyphenols: food sources and bioavailability. Am J Clin Nutr 79: 727-747. https://doi.org/10.1093/ajcn/79.5.727
  6. Graf BA, Milbury PE, Blumberg JB. 2005. Flavonols, flavones, flavanones, and human health: epidemiological evidence. J Med Food 8: 281-290. https://doi.org/10.1089/jmf.2005.8.281
  7. Arts IC, Hollman PC. 2005. Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr 81: 317S-325S. https://doi.org/10.1093/ajcn/81.1.317S
  8. Hanhineva K, Torronen R, Bondia-Pons I, Pekkinen J, Kolehmainen M, Mykkanen H, Poutanen K. 2010. Impact of dietary polyphenols on carbohydrate metabolism. Int J Mol Sci 11: 1365-1402. https://doi.org/10.3390/ijms11041365
  9. Wedick NM, Pan A, Cassidy A, Rimm EB, Sampson L, Rosner B, Willett W, Hu FB, Sun Q, van Dam RM. 2012. Dietary flavonoid intakes and risk of type 2 diabetes in US men and women. Am J Clin Nutr 95: 925-933. https://doi.org/10.3945/ajcn.111.028894
  10. Song Y, Manson JE, Buring JE, Sesso HD, Liu S. 2005. Associations of dietary flavonoids with risk of type 2 diabetes, and markers of insulin resistance and systemic inflammation in women: a prospective study and cross-sectional analysis. J Am Coll Nutr 24: 376-384. https://doi.org/10.1080/07315724.2005.10719488
  11. Wang Y, Ho CT. 2009. Polyphenolic chemistry of tea and coffee: a century of progress. J Agric Food Chem 57: 8109-8114. https://doi.org/10.1021/jf804025c
  12. Iso H, Date C, Wakai K, Fukui M, Tamakoshi A; JACC Study Group. 2006. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med 144: 554-562. https://doi.org/10.7326/0003-4819-144-8-200604180-00005
  13. Wolfram S, Raederstorff D, Preller M, Wang Y, Teixeira SR, Riegger C, Weber P. 2006. Epigallocatechin gallate supplementation alleviates diabetes in rodents. J Nutr 136: 2512-2518. https://doi.org/10.1093/jn/136.10.2512
  14. Ishikawa A, Yamashita H, Hiemori M, Inagaki E, Kimoto M, Okamoto M, Tsuji H, Memon AN, Mohammadio A, Natori Y. 2007. Characterization of inhibitors of postprandial hyperglycemia from the leaves of Nerium indicum. J Nutr Sci Vitaminol 53: 166-173. https://doi.org/10.3177/jnsv.53.166
  15. Fukino Y, Shimbo M, Aoki N, Okubo T, Iso H. 2005. Randomized controlled trial for an effect of green tea consumption on insulin resistance and inflammation markers. J Nutr Sci Vitaminol 51: 335-342. https://doi.org/10.3177/jnsv.51.335
  16. Strobel P, Allard C, Perez-Acle T, Calderon R, Aldunate R, Leighton F. 2005. Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. Biochem J 386: 471-478. https://doi.org/10.1042/BJ20040703
  17. Gao M, Zhao Z, Lv P, Li Y, Gao J, Zhang M, Zhao B. 2015. Quantitative combination of natural anti-oxidants prevents metabolic syndrome by reducing oxidative stress. Redox Biol 6: 206-217. https://doi.org/10.1016/j.redox.2015.06.013
  18. Chen ZY, Zhu QY, Wong YF, Zhang Z, Chung HY. 1998. Stabilizing effect of ascorbic acid on green tea catechins. J Agric Food Chem 46: 2512-2516. https://doi.org/10.1021/jf971022g
  19. Forbes JM, Cooper ME. 2013. Mechanisms of diabetic complications. Physiol Rev 93: 137-188. https://doi.org/10.1152/physrev.00045.2011
  20. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. 1985. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412-419. https://doi.org/10.1007/BF00280883
  21. Tate SS, Meister A. 1985. ${\gamma}$-Glutamyl transpeptidase from kidney. In Methods in Enzymology. Meister A, ed. Academic Press, New York, NY, USA. Vol 113, p 400-437.
  22. Tenenhouse HS, Scriver CR, Vizel EJ. 1980. Alkaline phosphatase activity does not mediate phosphate transport in the renal-cortical brush-border membrane. Biochem J 190: 473-476. https://doi.org/10.1042/bj1900473
  23. Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, Reaven GM. 2000. A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism 49: 1390-1394. https://doi.org/10.1053/meta.2000.17721
  24. Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. 2005. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res 52: 313-320. https://doi.org/10.1016/j.phrs.2005.05.004
  25. Nagao T, Meguro S, Hase T, Otsuka K, Komikado M, Tokimitsu I, Yamamoto T, Yamamoto K. 2009. A catechin-rich beverage improves obesity and blood glucose control in patients with type 2 diabetes. Obesity 17: 310-317. https://doi.org/10.1038/oby.2008.505
  26. Wein S, Schrader E, Rimbach G, Wolffram S. 2013. Oral green tea catechins transiently lower plasma glucose concentrations in female db/db mice. J Med Food 16: 312-317. https://doi.org/10.1089/jmf.2012.0205
  27. Khan SA, Priyamvada S, Khan W, Khan S, Farooq N, Yusufi AN. 2009. Studies on the protective effect of green tea against cisplatin induced nephrotoxicity. Pharmacol Res 60: 382-391. https://doi.org/10.1016/j.phrs.2009.07.007
  28. Ahad A, Ganai AA, Mujeeb M, Siddiqui WA. 2014. Ellagic acid, an NF-${\kappa}B$ inhibitor, ameliorates renal function in experimental diabetic nephropathy. Chem Biol Interact 219: 64-75. https://doi.org/10.1016/j.cbi.2014.05.011
  29. Khan SA, Priyamvada S, Farooq N, Khan S, Khan MW, Yusufi AN. 2009. Protective effect of green tea extract on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Pharmacol Res 59: 254-262. https://doi.org/10.1016/j.phrs.2008.12.009
  30. Groebler LK, Wang XS, Kim HB, Shanu A, Hossain F, McMahon AC, Witting PK. 2012. Cosupplementation with a synthetic, lipid-soluble polyphenol and vitamin C inhibits oxidative damage and improves vascular function yet does not inhibit acute renal injury in an animal model of rhabdomyolysis. Free Radic Biol Med 52: 1918-1928. https://doi.org/10.1016/j.freeradbiomed.2012.02.011
  31. Gaede P, Poulsen HE, Parving HH, Pedersen O. 2001. Doubleblind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients. Diabet Med 18: 756-760. https://doi.org/10.1046/j.0742-3071.2001.00574.x

Cited by

  1. 생여주의 산화방지, 알파글루코시데이스 저해 활성 및 여주초절임의 카란틴과 루테인 함량 변화 vol.50, pp.4, 2018, https://doi.org/10.9721/kjfst.2018.50.4.430