Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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Administration of Triticum aestivum Sprout Water Extracts Reduce the Level of Blood Glucose and Cholesterol in Leptin Deficient ob/ob Mice

Leptin 결핍 ob/ob 마우스에서 소맥엽 추출물의 혈당 강하 및 혈중 콜레스테롤에 미치는 효과

  • Lee, Sun-Hee (Dept. of Immunology and Institute of Medical Science, Chonbuk National University Medical School) ;
  • Lim, Sung-Won (Dept. of Immunology and Institute of Medical Science, Chonbuk National University Medical School) ;
  • Mihn, Nguyen Van (Dept. of Immunology and Institute of Medical Science, Chonbuk National University Medical School) ;
  • Hur, Jung-Mu (Chong Kun Dang Healthcare Corp. Research Center) ;
  • Song, Bong-Joon (Chong Kun Dang Healthcare Corp. Research Center) ;
  • Lee, Young-Mi (Dept. of Oriental Pharmacy, College of Pharmacy, Wonkwang University) ;
  • Lee, Hoi-Seon (Faculty of Biotechnology and Center for Agricultural Science and Technology, College of Agriculture and Life Science, Chonbuk National University) ;
  • Kim, Dae-Ki (Dept. of Immunology and Institute of Medical Science, Chonbuk National University Medical School)
  • 이선희 (전북대학교 의과대학 및 의과학연구소) ;
  • 임성원 (전북대학교 의과대학 및 의과학연구소) ;
  • 응웬반민 (전북대학교 의과대학 및 의과학연구소) ;
  • 허정무 (종근당 건강(주)) ;
  • 송봉준 (종근당 건강(주)) ;
  • 이영미 (원광대학교 약학대학 한약학과) ;
  • 이회선 (전북대학교 농업생명과학대학 응용생물공학부) ;
  • 김대기 (전북대학교 의과대학 및 의과학연구소)
  • Received : 2010.12.21
  • Accepted : 2011.03.03
  • Published : 2011.03.31
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Abstract

Type 2 diabetes mellitus (NIDDM) is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. In order to control the type 2 diabetes mellitus, anti-hyperglycemic effect of Triticum aestivum L. water extracts (TAWE) was investigated in 7 week old male diabetic C57BL6/J-ob/ob mice. For the experiments, the diabetic animal model ob/ob mice and non-diabetic animal model lean mice were divided into 3 groups: non-treatment control group (Control), and two experimental groups orally treated with 25 or 100 mg/kg/day dose of TAWE (TAWE-25 and TAWE-100, respectively). The lean mice were used as the non-diabetic normal control. TAWE was orally administrated for 6 weeks and the diabetic clinical markers, including blood glucose level, body weight, organs weight and insulin level were determined. The oral administration of TAWE-100 in ob/ob diabetic mice significantly decreased blood glucose level (78.4%) and body weight (11.9%) compared with diabetic control group. The weights of organs, including spleen, liver, kidneys, heart and lung were not different among groups, while the treatments of TAWE-100 in ob/ob diabetic mice significantly reduced blood total cholesterol (24.35%) and triglyceride (23.97%) levels compared with the diabetic control group. The levels of serum insulin and glucose tolerance were improved after TAWE-100 treatment in ob/ob diabetic mice. Moreover, the immunohistochemical staining for insulin detection in pancreatic islet $\beta$-cells expressed high level of insulin in TAWE-100 treated ob/ob mice. From the above results, the intake of TAWE may be effective in anti-hyperglycemia by the attenuation of glucose and lipid levels. TAWE-containing diets or drugs may be beneficial for controlling diabetes mellitus type 2 in human.

본 연구에서는 소맥엽 물추출물을 제2형 당뇨동물모델 ob/ob 마우스에게 6주간 경구투여 하여 혈중 포도당 및 혈중 지질에 미치는 영향에 대하여 연구하였다. TAWE를 투여한 결과, lean 마우스 대조군 및 실험군들의 혈중 포도당 농도와 체중은 유의적인 변화가 없었다. 반면, ob/ob 마우스에서 대조군은 실험기간 내내 혈중 포도당 농도 및 체중이 높은 증가율을 보였으나, TAWE를 투여한 ob/ob 마우스에서는 혈중 포도당 및 체중 증가가 TAWE 투여용량 의존적으로 감소되었으며, 특히 TAWE-100 투여군에서 대조군에 비하여 체중 약 11.9%, 혈중 포도당 약 78.4% 감소되는 효과를 보였다. 또한 TAWE 투여가 실험동물의 장기무게에 미치는 영향을 알아보기 위해 비장, 신장, 심장 및 폐의 무게를 측정한 결과, lean 마우스 및 ob/ob 마우스 실험군 사이에 각각의 장기에 대한 유의적인 무게 차이는 나타나지 않았다. 혈중 인슐린 농도는 lean 마우스 대조군 및 실험군의 평균 농도(3.93 ng/mL)에 비하여 ob/ob 마우스 대조군(15.60 ng/mL), TAWE-100 투여군(20.19 ng/mL) 및 TAWE-25 투여군(19.66 ng/mL)에서 모두 높게 나타나는 경향을 보였지만 ob/ob 마우스 TAWE-100 투여군에서는 보다 증가된 인슐린 수치를 확인하였으며, 면역조직화학염색 시험법에서도 췌장 $\beta$세포의 인슐린 발현정도가 TAWE-100 투여군에서 가장 높게 나타났다. TAWE는 lean 마우스의 총콜레스테롤, 중성지방 및 HDL에 유의적인 영향을 미치지 않았지만, ob/ob 마우스 TAWE-100 투여군에서 대조군에 비해 총콜레스테롤 24.35%, 중성지방 23.97%가 감소하였고, HDL은 29.80% 증가하였다. 포도당 내당능에 대한 평가를 위해 당부하 검사를 실시한 결과 ob/ob 마우스 TAWE-100 투여군에서 60분부터 당부하가 유의적으로 개선되는 효과를 보였다. 결과적으로, TAWE의 인슐린 저항성 제2형 당뇨병 동물모델 ob/ob 마우스에 6주간의 장기투여는 혈당 및 혈중 지질대사를 개선할 수 있음을 의미하며, 임상학적 당뇨 증상완화 및 당뇨 합병증 예방 및 치료제로 음용할 수 있을 것으로 사료된다.

Keywords

References

  1. Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL. 1998.Overweight and obesity in the United States: prevalence and trends, 1960-1994. J Obes Relat Metab Disord 22:39-47. https://doi.org/10.1038/sj.ijo.0800541
  2. Boden G. 1997. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 46: 3-10. https://doi.org/10.2337/diabetes.46.1.3
  3. Muniyappa R, Montagnani M, Koh KK, Quon MJ. 2007.Cardiovascular actions of insulin. Endocr Rev 28: 463-491. https://doi.org/10.1210/er.2007-0006
  4. Semenkovich CF. 2006. Insulin resistance and atherosclerosis.J Clin Invest 116: 1813-1822. https://doi.org/10.1172/JCI29024
  5. Reaven GM. 1998. Role of insulin resistance in human disease. Diabetes 37: 1595-1607.
  6. Polonsky KS, Given BD, Van Cauter E. 1998. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest 2: 442-448.
  7. Bagg W, Plank LD, Gamble G, Drury PL, Sharpe N,Braatvedt GD. 2001. The effects of intensive glycaemic control on body composition in patients with type 2 diabetes.Diabetes Obes Metab 3: 410-416. https://doi.org/10.1046/j.1463-1326.2001.00153.x
  8. Srinivasan BT, Jarvis J, Khunti K, Davies MJ. 2008. Recent advances in the management of type 2 diabetes mellitus: a review. Postgrad Med J 84: 524-531. https://doi.org/10.1136/pgmj.2008.067918
  9. MacLennan AH, Wilson DH, Taylor AW. 1996. Prevalence and cost of alternative medicine in Australia. Lancet 347: 569-573. https://doi.org/10.1016/S0140-6736(96)91271-4
  10. Tapsell LC, Hemphill I, Cobiac L, Patch CS, Sullivan DR,Fenech M, Roodenrys S, Keogh JB, Clifton PM, WilliamsPG, Fazio VA, Inge KE. 2006. Health benefits of herbs and spices: the past, the present, the future. Med J Aust 185: S4-24.
  11. Vaaler S, Hanssen KF, Dahl-Jørgensen K, Frolich W, Aaseth J, Odegaard B, Aagenaes O. 1986. Diabetic control is improved by guar gum and wheat bran supplementation.Diabet Med 3: 230-233.
  12. Bonfili L, Amici M, Cecarini V, Cuccioloni M, Tacconi R,Angeletti M, Fioretti E, Keller JN, Eleuteri AM. 2009.Wheat sprout extract-induced apoptosis in human cancer cells by proteasomes modulation. Biochimie 91: 1131-1144. https://doi.org/10.1016/j.biochi.2009.06.001
  13. Tudek B, Peryt B, Miłoszewska J, Szymczyk T, Przybyszewska M, Janik P. 1998. The effect of wheat sprout extract on benzo(a)pyrene and 7,2-dimethylbenz(a)anthracene activity. Neoplasma 35: 515-523.
  14. Borowicki A, Stein K, Scharlau D, Glei M. 2010. Fermentation supernatants of wheat (Triticum aestivum L.) aleurone beneficially modulate cancer progression in human colon cells. J Agric Food Chem 58: 2001-2007. https://doi.org/10.1021/jf9032848
  15. Watzl B. 2008. Anti-inflammatory effects of plant-based foods and of their constituents. Int J Vitam Nutr Res 78: 293-298. https://doi.org/10.1024/0300-9831.78.6.293
  16. Lee SH, Lee YM, Lee HS, Kim DK. 2009. Anti-oxidative and anti-hyperglycemia effect of Triticum aestivum wheat sprout water extracts on the streptozotocin-induced diabetic mice. Kor J Pharmacogn 40: 408-414.
  17. Ingalls AM, Dickie MM, Snell GD. 1950. Obese, a new mutation in the house mouse. J Hered 41: 317-318. https://doi.org/10.1093/oxfordjournals.jhered.a106073
  18. Park ST, Jeong JC. 2007. Effects of Sotosajahwan on blood glucose, hyperlipidemia, polyol pathway and antioxidativemechanism in ob/ob mouse. Korean J Oriental Physiologyand Pathology 21: 1163-1169.
  19. Park ST, Jeong JC. 2008. Effects of Cheonghyul-san on blood glucose, hyperlipidemia, polyol pathway and reactive oxygen species in ob/ob mice. Korean J Oriental Physiologyand Pathology 22: 350-356.
  20. AOAC. 2005. Official methods of analysis. 18th ed. Association of Official Analytical Chemists, Washington, DC, USA.Vol 45, p 21-22.
  21. Reeves PG. 1997. Components of the AIN-93 diets as improvements in the AIN-76A diet. Nature 127: 838S-841S.
  22. Mordes JP, Rossini AA. 1981. Animal models of diabetes mellitus. Am J Med 70: 353-360. https://doi.org/10.1016/0002-9343(81)90772-5
  23. Eleazar S. 1992. Animal models of non-insulin-dependent diabetes. Diabetes Metabolism Reviews 8: 179-208. https://doi.org/10.1002/dmr.5610080302
  24. Niall MG, Rosaleen AM, Daphne O, Patrick BC, Alan HJ,Gerald HT. 1990. Cholesterol metabolism in alloxan-induced diabetic rabbits. Diabetes 39: 626-636. https://doi.org/10.2337/diabetes.39.5.626
  25. Choi SP, Choi HT, Lee HJ, Moon SY, Kim SH, Lee BG,Lee DS, Ham SS. 2004. Hypoglycemic effect of the functional food manufactured by fermented soybean as main materials in streptozotosin-induced diabetic rats. J KoreanSoc Food Sci Nutr 33: 1126-1132. https://doi.org/10.3746/jkfn.2004.33.7.1126
  26. Westman S. 1968. Development of the obese-hyperglycemic syndrome in mice. Diabetologia 4: 141-149. https://doi.org/10.1007/BF01219435
  27. Gepts W, Christophe J, Mayer J. 1960. Pancreatic islets in mice with the obese-hyperglycemic syndrome. Diabetes 9: 63-69. https://doi.org/10.2337/diab.9.1.63
  28. Westman S. 1968. The endocrine pancreas of old obese hyperglycemic mice. Acta Soc Med Ups 73: 81-89.
  29. Lindström P. 2007. The physiology of obese-hyperglycemic mice (ob/ob mice). Scientific World J 7: 666-685. https://doi.org/10.1100/tsw.2007.117
  30. Friedman JM, Halaas JL. 1998. Leptin and the regulation of body weight in mammals. Nature 395: 763-770. https://doi.org/10.1038/27376
  31. Koerner A, Kratzsch J, Kiess W. 2005. Adipocytokines: leptin-the classical, resistin-the controversical, adiponectinthe promising, and more to come. Best Pract Res Clin Endocrinol Metab 19: 525-546. https://doi.org/10.1016/j.beem.2005.07.008
  32. Morton GJ, Gelling RW, Niswender KD, Morrison CD, Rhodes CJ, Schwartz MW. 2005. Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metab 2: 411-420. https://doi.org/10.1016/j.cmet.2005.10.009
  33. Bleisch VR, Mayer J, Dickie MM. 1952. Familial diabetes mellitus in mice, associated with insulin resistance, obesity, and hyperplasia of the islands of langerhans. Am J Pathol28: 369-385.
  34. Hanefeld M, Koehler C, Henkel E, Fuecker K, Schaper F,Temelkova-Kurktschiev T. 2000. Post-challenge hyperglycaemia relates more strongly than fasting hyperglycaemia with carotid intima-media thickness: the RIAD study. Diabetic Medicine 17: 835-840. https://doi.org/10.1046/j.1464-5491.2000.00408.x
  35. Hanefeld M, Temelkova-Kurktschiev T, Schaper F, HenkelE, Siegert G, Koehler C. 1996. Impaired fasting glucose is not a risk factor for atherosclerosis. Diabet Med 16: 212-218.
  36. Georg P, Ludvik B. 2000. Lipids and diabetes. J Clin Basic Cardiol 3: 159-162.
  37. Hong HS, Park JS, Ryu HK, Kim WY. 2008. The association of plasma HDL-cholesterol level with cardiovasculardisease related factors in Korean type 2 diabetic patients.Korean Diabetes J 32: 215-223. https://doi.org/10.4093/kdj.2008.32.3.215

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