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

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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Anti-Diabetic Effect of Sericultural Product in High Fat Diet-Fed Mice

고지방식이급여 마우스에서 잠상산물의 항당뇨 효능

  • Ahn, Eunyeong (Department of Food Science and Nutrition, Catholic University of Daegu) ;
  • Choi, Sang-Won (Department of Food Science and Nutrition, Catholic University of Daegu) ;
  • Kim, Eunjung (Department of Food Science and Nutrition, Catholic University of Daegu)
  • 안은영 (대구가톨릭대학교 식품영양학과) ;
  • 최상원 (대구가톨릭대학교 식품영양학과) ;
  • 김은정 (대구가톨릭대학교 식품영양학과)
  • Received : 2016.10.18
  • Accepted : 2017.02.07
  • Published : 2017.03.31
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Abstract

The objective of this study was to identify and compare the anti-diabetic effects of mulberry leave (ML), silkworm (SK), mulberry fruit (MF), and Cudrania tricuspidata BUREAU (CT) extracts in high fat diet (HFD)-induced obese and diabetic mice. C57BL/6N mice were assigned to six groups: normal diet (ND, n=7), HFD (n=10), HFD with 5% ML powder (ML, n=10), HFD with 2% SK powder (SK, n=10), HFD with 5% MF powder (MF, n=10), and HFD with 5% CT powder (CT, n=10). Mice were fed their assigned diet for 14 weeks. ML group showed significant reduction in levels of plasma glucose and insulin compared with the HFD group. Plasma total cholesterol (T-C) was significantly reduced by ML and SK compared with the HFD group. Plasma high-density lipoprotein cholesterol (HDL-C) and HTR (HDL-C to T-C ratio) levels of the ML, SK, MF, and CT groups were significantly elevated compared to the HFD group. Moreover, concentrations of hepatic T-C and triglycerides in the ML, SK, MF, and CT groups were significantly reduced in comparison to the HFD group. Levels of pAKT, pS6K, and pAMPK significantly increased in the ML group compared with the HFD group. Taken together, ML appears to be the most potent anti-diabetic and anti-dyslipidemic substance among sericultural products. ML could be developed as a potential agent for diabetes and its complication management.

본 연구는 고지방식이로 유도된 제2형 당뇨 동물모델에서 잠상산물의 항당뇨 및 지질개선 효과를 규명하기 위하여 C57BL/6N 마우스에 14주간 잠상산물 분말(ML, SK, MF, CT)을 급여한 후 제2형 당뇨의 임상적 지표 및 인슐린 신호 전달체계에 미치는 영향을 분석하였다. HFD군보다 잠상산물을 급여한 군들의 체중증가량이 감소하는 경향이었으며, 혈장 포도당 및 인슐린 농도는 HFD군보다 ML분말을 급여한 군에서 특히 감소하였다. 혈장 T-C 농도는 HFD군에 비하여 ML과 SK 분말 급여 군에서 유의적으로 감소하였으며, 혈장 HDL-C 농도 및 HTR은 HFD군보다 ML군과 SK군에서 현저히 증가하였다. 간 조직 지질 농도는 HFD군보다 잠상산물을 급여한 네 군 모두에서 TG와 T-C 농도의 유의적인 감소가 나타났다. 이상의 결과 잠상산물 중 ML분말이 혈장 포도당, 인슐린, T-C 및 TG 농도를 가장 효과적으로 감소시켰으며, 혈장 HDL-C 농도 및 HTR은 증가시켰다. 또한, 내장지방 조직의 AKT, S6K, 그리고 AMPK의 활성도 증가시킨 것으로 보아 고지방식이에 의한 인슐린 저항성 및 지질 대사를 개선한 것으로 생각된다. 향후 ML의 인슐린 저항성 개선 효과에 대해 더 깊이 있는 기전연구가 수행된다면 제2형 당뇨환자를 위한 건강기능성 식품으로 개발될 수 있을 것으로 생각한다.

Keywords

References

  1. Ministry for Health, Welfare and Family Affairs; Korea Centers for Disease Control and Prevention. 2014. National Health Nutrition Examination Survey Report. Korea Centers for Disease Control and Prevention, Cheongju, Korea.
  2. Choi CS, Park SW. 2002. The mechanism of development of insulin resistance in type 2 diabetes mellitus. Korean J Med 63: 613-625.
  3. Kaushik G, Satya S, Khandelwal RK, Naik SN. 2010. Commonly consumed Indian plant food materials in the management of diabetes mellitus. Diabetes Metab Syndr 4: 21-40. https://doi.org/10.1016/j.dsx.2008.02.006
  4. Van Gaal L, Scheen A. 2015. Weight management in type 2 diabetes: current and emerging approaches to treatment. Diabetes Care 38: 1161-1172. https://doi.org/10.2337/dc14-1630
  5. Publishing Committee of Pharmacognosy. 2000. Pharmacognosy. Dongmyongsa, Seoul, Korea. p 257.
  6. Tanabe K, Nakamura S, Omagari K, Oku T. 2011. Repeated ingestion of the leaf extract from Morus alba reduces insulin resistance in KK-Ay mice. Nutr Res 31: 848-854. https://doi.org/10.1016/j.nutres.2011.09.023
  7. Jang MJ, Rhee SJ. 2004. Hypoglycemic effects of pills made of mulberry leaves and silkworm powder in streptozotocininduced diabetic rats. J Korean Soc Food Sci Nutr 33: 1611-1617. https://doi.org/10.3746/jkfn.2004.33.10.1611
  8. Krol E, Jeszka-Skowron M, Krejpcio Z, Flaczyk E, Wojciak RW. 2016. The effects of supplementary mulberry leaf (Morus alba) extracts on the trace element status (Fe, Zn and Cu) in relation to diabetes management and antioxidant indices in diabetic rats. Biol Trace Elem Res 174: 158-165. https://doi.org/10.1007/s12011-016-0696-1
  9. Ann JY, Eo H, Lim Y. 2015. Mulberry leaves (Morus alba L.) ameliorate obesity-induced hepatic lipogenesis, fibrosis, and oxidative stress in high-fat diet-fed mice. Genes Nutr 10: 46. https://doi.org/10.1007/s12263-015-0495-x
  10. Wu T, Tang Q, Gao Z, Yu Z, Song H, Zheng X, Chen W. 2013. Blueberry and mulberry juice prevent obesity development in C57BL/6 mice. PLoS One 8: e77585. https://doi.org/10.1371/journal.pone.0077585
  11. Andallu B, Suryakantham V, Lakshmi Srikanthi B, Reddy GK. 2001. Effect of mulberry (Morus indica L.) therapy on plasma and erythrocyte membrane lipids in patients with type 2 diabetes. Clin Chim Acta 314: 47-53. https://doi.org/10.1016/S0009-8981(01)00632-5
  12. Park JH, Lee KW, Sung KS, Kim SS, Cho KD, Lee BH, Han CK. 2012. Effect of diets with Job's tears and Cudrania tricuspidata leaf mixed-powder supplements on body fat and serum lipid levels in rats fed a high-fat diet. J Korean Soc Food Sci Nutr 47: 943-949.
  13. Kim OK, Nam DE, Jun W, Lee J. 2015. Cudrania tricuspidata water extract improved obesity-induced hepatic insulin resistance in db/db mice by suppressing ER stress and inflammation. Food Nutr Res 59: 29165. https://doi.org/10.3402/fnr.v59.29165
  14. Folch J, Lees M, Sloane Stanley GH. 1957. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226: 497-509.
  15. Omodeo Sale F, Marchesini S, Fishman PH, Berra B. 1984. A sensitive enzymatic assay for determination of cholesterol in lipid extracts. Anal Biochem 142: 347-350. https://doi.org/10.1016/0003-2697(84)90475-5
  16. Lee JS, Lee MK, Ha TY, Bok SH, Park HM, Jeong KS, Woo MN, Do GM, Yeo JY, Choi MS. 2006. Supplementation of whole persimmon leaf improves lipid profiles and suppresses body weight gain in rats fed high-fat diet. Food Chem Toxicol 44: 1875-1883. https://doi.org/10.1016/j.fct.2006.06.014
  17. Park SH, Jang MJ, Hong JH, Rhee SJ, Choi KH, Park MR. 2007. Effects of mulberry leaf extract feeding on lipid status of rats fed high cholesterol diets. J Korean Soc Food Sci Nutr 36: 43-50. https://doi.org/10.3746/jkfn.2007.36.1.043
  18. Kim AJ, Kim SY, Choi MK, Kim MH, Han MR, Chung KS. 2005. Effects of mulberry leaves powder on lipid metabolism in high cholesterol-fed rats. Korean J Food Sci Technol 37: 636-641.
  19. Do SG, Park JH, Nam H, Kim JB, Lee JY, Oh YS, Suh JG. 2012. Silk fibroin hydrolysate exerts an anti-diabetic effect by increasing pancreatic ${\beta}$ cell mass in C57BL/KsJdb/db mice. J Vet Sci 13: 339-344. https://doi.org/10.4142/jvs.2012.13.4.339
  20. Cho YS, Shon MY, Lee MK. 2007. Lipid-lowering action of powder and water extract of mulberry leaves in C57BL/6 mice fed high-fat diet. J Korean Soc Food Sci Nutr 36: 405-410. https://doi.org/10.3746/jkfn.2007.36.4.405
  21. Lim HH, Yang SJ, Kim Y, Lee M, Lim Y. 2013. Combined treatment of mulberry leaf and fruit extract ameliorates obesity-related inflammation and oxidative stress in high fat diet-induced obese mice. J Med Food 16: 673-680. https://doi.org/10.1089/jmf.2012.2582
  22. Cha JY, Kim HJ, Cho YS. 2000. Effects of water-soluble extract from leaves of Morus alba and Cudrania tricuspidata on the lipid peroxidation in tissues of rats. J Korean Soc Food Sci Nutr 29: 531-536.
  23. Kim SH, Kang JS, Lee SJ, Chung YJ. 2008. Antidiabetic effect of Korean red ginseng by puffing process in streptozotocin-induced diabetic rats. J Korean Soc Food Sci Nutr 37: 701-707. https://doi.org/10.3746/jkfn.2008.37.6.701
  24. O'Meara NMG, Devery RAM, Owens D, Collins PB, Johnson AH, Tomkin GH. 1990. Cholesterol metabolism in alloxan-induced diabetic rabbits. Diabetes 39: 626-633. https://doi.org/10.2337/diab.39.5.626
  25. Nikkila EA, Kekki M. 1973. Plasma triglyceride transport kinetics in diabetes mellitus. Metabolism 22: 1-22. https://doi.org/10.1016/0026-0495(73)90024-3
  26. Biddinger SB, Almind K, Miyazaki M, Kokkotou E, Ntambi JM, Kahn CR. 2005. Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome. Diabetes 54: 1314-1323. https://doi.org/10.2337/diabetes.54.5.1314
  27. Guo J, Jou W, Gavrilova O, Hall KD. 2009. Persistent dietinduced obesity in male C57BL/6 mice resulting from temporary obesigenic diets. PLoS One 4: e5370. https://doi.org/10.1371/journal.pone.0005370
  28. Chiu CY, Chan IL, Yang TH, Liu SH, Chiang MT. 2015. Supplementation of chitosan alleviates high-fat diet-enhanced lipogenesis in rats via adenosine monophosphate (AMP)-activated protein kinase activation and inhibition of lipogenesis-associated genes. J Agric Food Chem 63: 2979-2988. https://doi.org/10.1021/acs.jafc.5b00198
  29. Yang X, Yang L, Zheng H. 2010. Hypolipidemic and antioxidant effects of mulberry (Morus alba L.) fruit in hyperlipidaemia rats. Food Chem Toxicol 48: 2374-2379. https://doi.org/10.1016/j.fct.2010.05.074
  30. Holt RIG, Cockram C, Flyvbjerg A, Goldstein BJ. 2010. Textbook of diabetes. 4th ed. Wiley-Blackwell, West Sussex, UK. p 56-60.
  31. Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR. 1999. Tissue-specific knockout of the insulin receptor in pancreatic ${\beta}$ cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96: 329-339. https://doi.org/10.1016/S0092-8674(00)80546-2
  32. Konner AC, Bruning JC. 2012. Selective insulin and leptin resistance in metabolic disorders. Cell Metab 16: 144-152. https://doi.org/10.1016/j.cmet.2012.07.004
  33. Harrington LS, Findlay GM, Lamb RF. 2005. Restraining PI3K: mTOR signalling goes back to the membrane. Trends Biochem Sci 30: 35-42. https://doi.org/10.1016/j.tibs.2004.11.003
  34. Lee YS, Cha BY, Saito K, Yamakawa H, Choi SS, Yamaguchi K, Yonezawa T, Teruya T, Nagai K, Woo JT. 2010. Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice. Biochem Pharmcol 79: 1674-1683. https://doi.org/10.1016/j.bcp.2010.01.034
  35. Chakraborty A, Koldobskiy MA, Bello NT, Maxwell M, Potter JJ, Juluri KR, Maag D, Kim S, Huang AS, Dailey MJ, Saleh M, Snowman AM, Moran TH, Mezey E, Snyder SH. 2010. Inositol pyrophosphates inhibit Akt signaling, regulate insulin sensitivity and weight gain. Cell 143: 897-910. https://doi.org/10.1016/j.cell.2010.11.032
  36. Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, Rooyackers O, Zhou G, Williamson JM, Ljunqvist O, Efendic S, Moller DE, Thorell A, Goodyear LJ. 2002. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51: 2074-2081. https://doi.org/10.2337/diabetes.51.7.2074
  37. 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
  38. Kuo YH, Lin CH, Shih CC. 2015. Ergostatrien-$3{\beta}$-ol from Antrodia camphorata inhibits diabetes and hyperlipidemia in high-fat-diet treated mice via regulation of hepatic related genes, glucose transporter 4, and AMP-activated protein kinase phosphorylation. J Agric Food Chem 63: 2479-2489. https://doi.org/10.1021/acs.jafc.5b00073
  39. Lu J, Wu DM, Zheng YL, Hu B, Cheng W, Zhang ZF, Shan Q. 2011. Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and $I{\kappa}B$ kinase ${\beta}$/nuclear factor-${\kappa}B$-mediated inflammatory pathways in mice. Brain Behav Immun 25: 1658-1667. https://doi.org/10.1016/j.bbi.2011.06.009
  40. Reynolds TH IV, Cinquino N, Anthony M, Phelps CB, Zachary Berk E. 2009. Insulin resistance without elevated mammalian target of rapamycin complex 1 activity in muscles of mice fed a high-fat diet. J Appl Physiol 107: 1479-1485. https://doi.org/10.1152/japplphysiol.00574.2009
  41. Dasuri K, Zhang L, Kim SOKF, Bruce-Keller AJ, Keller JN. 2016. Dietary and donepezil modulation of mTOR signaling and neuroinflammation in the brain. Biochim Biophys Acta 1862: 274-283. https://doi.org/10.1016/j.bbadis.2015.11.002
  42. Gao Y, Zhang M, Wu T, Xu M, Cai H, Zhang Z. 2015. Effects of D-pinitol on insulin resistance through the PI3K/Akt signaling pathway in type 2 diabetes mellitus rats. J Agric Food Chem 63: 6019-6026. https://doi.org/10.1021/acs.jafc.5b01238
  43. Jo YH, Choi KM, Liu Q, Kim SB, Ji HJ, Kim M, Shin SK, Do SG, Shin E, Jung G, Yoo HS, Hwang BY, Lee MK. 2015. Anti-obesity effect of 6,8-diprenylgenistein, an isoflavonoid of Cudrania tricuspidata fruits in high-fat diet-induced obese mice. Nutrients 7: 10480-10490. https://doi.org/10.3390/nu7125544

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