DOI QR코드

DOI QR Code

Insulin sensitivity improvement of fermented Korean Red Ginseng (Panax ginseng) mediated by insulin resistance hallmarks in old-aged ob/ob mice

  • Cheon, Jeong-Mu (Department of Veterinary Toxicology, College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Dae-Ik (Daegu Technopark Oriental Medicine Industry Support Center) ;
  • Kim, Kil-Soo (Department of Veterinary Toxicology, College of Veterinary Medicine, Kyungpook National University)
  • Received : 2014.08.12
  • Accepted : 2015.03.10
  • Published : 2015.10.15

Abstract

Background: The biological actions of various ginseng extracts have been studied for treating obesity and diabetes mellitus. However, few studies have evaluated the effects of fermented Korean Red Ginseng (Panax ginseng Meyer) on metabolic syndrome. The present study evaluated the antiobesity and antidiabetic effects of fermented red ginseng (FRG) on old-aged, obese, leptin-deficient (B6.V-Lepob, "ob/ob") mice. Methods: The animals were divided into three groups and given water containing 0%, 0.5%, and 1.0% FRG for 16 wk. The effect of FRG on ob/ob mice was determined by measuring changes in body weight, levels of blood glucose, serum contents of triglycerides, total cholesterol and free fatty acids, messenger RNA (mRNA) expressions of key factors associated with insulin action, such as insulin receptor (IR), lipoprotein lipase (LPL), glucose transporter 1 and 4 (GLUT1 and GLUT4), peroxisome proliferators-activated receptor gamma ($PPAR-{\gamma}$), and phosphoenolpyruvate carboxykinase (PEPCK) in the liver and in muscle, and histology of the liver and pancreas. Results: FRG-treated mice had decreased body weight and blood glucose levels compared with control ob/ob mice. However, anti-obesity effect of FRG was not evident rather than hypoglycemic effect in old aged ob/ob mice. The hyperlipidemia in control group was attenuated in FRG-treated ob/ob mice. The mRNA expressions of IR, LPL, GLUT1, GLUT4, $PPAR-{\gamma}$, and PEPCK in the liver and in muscle were increased in the FRG-treated groups compared with the control group. Conclusion: These results suggest that FRG may play a vital role in improving insulin sensitivity relative to reducing body weight in old-aged ob/ob mice.

Keywords

References

  1. World Health Organization. Obesity. Available from: http://www.who.int/topics/obesity/en/. [2015.03.08]
  2. May AL, Freedman D, Sherry B, Blanck HM. Obesity-United States, 1999-2010. MMWR Surveill Summ 2013;62:120-8.
  3. Kopelman PG. Obesity as a medical problem. Nature 2000;404:635-43. https://doi.org/10.1038/35007508
  4. World Health Organization. Diabetes. Available from: http://www.who.int/topics/diabetes_mellitus/en/. [2015.03.08]
  5. Rose DP, Haffner SM, Baillargeon J. Adiposity, The metabolic syndrome, and breast cancer in African-American and white American women. Endocr Rev 2007;28:763-77. https://doi.org/10.1210/er.2006-0019
  6. Singla P, Bardoloi A, Parkash AA. Metabolic effects of obesity: a review. World J Diabetes 2010;1:76-88. https://doi.org/10.4239/wjd.v1.i3.76
  7. Lee L. Introducing herbal medicine into conventional health care settings. J Nurse Midwifery 1999;44:253-66. https://doi.org/10.1016/S0091-2182(99)00042-7
  8. Cicero AFG, Derosa G, Gaddi A. What do herbalists suggest to diabetic patients in order to improve glycemic control? Evaluation of scientific evidence and potential risks. Acta Diabetol 2004;41:91-8. https://doi.org/10.1007/s00592-004-0150-2
  9. Hasani-Ranjbar S, Larijani B, Abdollahi M. A systematic review of Iranian medicinal plants useful in diabetes mellitus. Arch Med Sci 2008;4:285-92.
  10. Hasani-Ranjbar S, Nayebi N, Larijani B, Abdollahi M. A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity. World J Gastroenterol 2009;15:3073-85. https://doi.org/10.3748/wjg.15.3073
  11. Kim ST, Jang JH, Kwon JH, Moon KD. Change in the chemical components of red and white ginseng after puffing. Korean J Food Preserv 2009;16:355-61.
  12. Xie JT, Zhou YP, Dey L, Attele AS, Wu JA, Gu M, Polonsky KS, Yuan CS. Ginseng berry reduces blood glucose and body weight in db/db mice. Phytomedicine 2002;9:254-8. https://doi.org/10.1078/0944-7113-00106
  13. Zhao SJ, Li CY, Qian YC, Luo XP, Zhang X, Wang XS, Kang BY. Induction of hairy roots of Panax ginseng and studies on suitable culture condition of ginseng hairy roots. Chin J Biotechnol 2004;20:215-20.
  14. Xie JT, Wang CZ, Ni M, Wu JA, Mehendale SR, Aung HH, Foo A, Yuan CS. American ginseng berry juice intake reduces blood glucose and body weight in ob/ob mice. J Food Sci 2007;72:S590-4. https://doi.org/10.1111/j.1750-3841.2007.00481.x
  15. Jung JW, Kang HR, Ji GE, Park MS, Song WJ, Kim MH, Kwon JW, Kim TW, Park HW, Cho SH, et al. Therapeutic effects of fermented red ginseng in allergic rhinitis: a randomized, double-blind, placebo-controlled study. Allergy Asthma Immunol Res 2011;3:103-10. https://doi.org/10.4168/aair.2011.3.2.103
  16. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995;269:540-3. https://doi.org/10.1126/science.7624776
  17. Kim HJ, Chae IG, Lee SG, Jeong HJ, Lee EJ, Lee IS. Effects of fermented red ginseng extracts on hyperglycemia in streptozotocin-induced diabetic rats. J Ginseng Res 2010;34:104-12. https://doi.org/10.5142/jgr.2010.34.2.104
  18. Biggs ML, Mukamal KJ, Luchsinger JA, Ix JH, Carnethon MR, Newman AB, de Boer IH, Strotmeyer ES, Mozaffarian D, Siscovick DS. Association between adiposity in midlife and older age and risk of diabetes in older adults. J Am Med Assoc 2010;303:2504-12. https://doi.org/10.1001/jama.2010.843
  19. Yuan CS, Attele AS, Zhang L, Lynch JP, Xie JT, Shi JQ. Leptin reduces body weight gain in neonatal rats. Pediatr Res 2000;48:380-3. https://doi.org/10.1203/00006450-200009000-00021
  20. Kim SH, Hyun SH, Choung SY. Anti-diabetic effect of cinnamon extract on blood glucose in db/db mice. J Ethnopharmacol 2006;104:119-23. https://doi.org/10.1016/j.jep.2005.08.059
  21. Muoio DM, Lynis DG. Peripheral metabolic actions of leptin. Best Pract Res Clin Endocrinol Metab 2002;16:653-66. https://doi.org/10.1053/beem.2002.0223
  22. Lindstrom P. The physiology of obese-hyperglycemic mice [ob/ob mice]. ScientificWorldJournal 2007;7:666-85. https://doi.org/10.1100/tsw.2007.117
  23. Bruning JC, Winnay J, Bonner-Weir S, Taylor SI, Accili D, Kahn CR. Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles. Cell 1997;88:561-72. https://doi.org/10.1016/S0092-8674(00)81896-6
  24. Eckel RH. Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases. N Engl J Med 1989;320:1060-8. https://doi.org/10.1056/NEJM198904203201607
  25. Zechner R. The tissue-specific expression of lipoprotein lipase: implications for energy and lipoprotein metabolism. Curr Opin Lipidol 1997;8:77-88. https://doi.org/10.1097/00041433-199704000-00005
  26. Pulawa LK, Eckel RH. Overexpression of muscle lipoprotein lipase and insulin sensitivity. Curr Opin Clin Nutr Metab Care 2002;5:569-74. https://doi.org/10.1097/00075197-200209000-00017
  27. Wang H, Knaub LA, Jensen DR, Jung DY, Hong EG, Ko HJ, Coates AM, Goldberg IJ, Becky A, Janssen RC, et al. Skeletal muscle-specific deletion of lipoprotein lipase enhances insulin signaling in skeletal muscle but causes insulin resistance in liver and other tissues. Diabetes 2009;58:116-24. https://doi.org/10.2337/db07-1839
  28. Cruz WS, Kwon G, Marshall CA, McDaniel ML, Semenkovich CF. Glucose and insulin stimulate heparin-releasable lipoprotein lipase activity in mouse islets and INS-1 cells. J Biol Chem 2001;276:12162-8. https://doi.org/10.1074/jbc.M010707200
  29. Lopez V, Saraff K, Medh JD. Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells. Biochem Biophys Res Commun 2009;389:34-9. https://doi.org/10.1016/j.bbrc.2009.08.081
  30. Craik JD, Young JD, Cheeseman CI. GLUT-1 mediation of rapid glucose transport in dolphin (tursiops truncatus) red blood cells. Am J Physiol Regul Integr Comp Physiol 1998;274:R112-9. https://doi.org/10.1152/ajpregu.1998.274.1.R112
  31. Shepherd PR, Kahn BB. Glucose transporters and insulin action-implications for insulin resistance and diabetes mellitus. N Engl J Med 1999;341:248-57. https://doi.org/10.1056/NEJM199907223410406
  32. Zisman A, Peroni OD, Abel ED, Michael MD, Mauvais-Jarvis F, Lowell BB, Wojtaszewski JFP, Hirshman MF, Virkamaki A, Goodyear LJ, et al. Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat Med 2000;6:924-8. https://doi.org/10.1038/78693
  33. Hruz PW, Mueckler MM. Structural analysis of the GLUT1 facilitative glucose transporter. Mol Membr Biol 2001;18:183-93. https://doi.org/10.1080/09687680110072140
  34. Levine KB, Cloherty EK, Hamill S, Carruthers A. Molecular determinants of sugar transport regulation by ATP. Biochemistry 2002;41:12629-38. https://doi.org/10.1021/bi0258997
  35. Thorens B, Mueckler M. Glucose transporters in the 21st century. Am J Physiol Endocrinol Metab 2010;298:E141-5. https://doi.org/10.1152/ajpendo.00712.2009
  36. Barroso I, Gurnell M, Crowley VEF, Agostini M, Schwabe JW, Soos MA, Maslen GLI, Williams TDM, Lewis H, Schafer AJ, et al. Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 1999;402:880-3. https://doi.org/10.1038/47254
  37. Herzig S, Hedrick S, Morantte I, Koo SH, Galimi F, Montminy M. CREB controls hepatic lipid metabolism through nuclear hormone receptor PPAR-gamma. Nature 2003;426:190-3. https://doi.org/10.1038/nature02110
  38. Rangwala SM, Lazar MA. Peroxisome proliferator-activated receptor ${\gamma}$ in diabetes and metabolism. Trends Pharmacol Sci 2004;25:331-6. https://doi.org/10.1016/j.tips.2004.03.012
  39. Rangwala SM, Rhoades B, Shapiro JS, Rich AS, Kim JK, Shulman GI, Kaestner KH, Lazar MA. Genetic modulation of PPAR ${\gamma}$ phosphorylation regulates insulin sensitivity. Dev Cell 2003;5:657-63. https://doi.org/10.1016/S1534-5807(03)00274-0
  40. Hevener AL, He W, Barak Y, Le J, Bandyopadhyay G, Olson P, Wilkes J, Evans RM, Olefsky J. Muscle-specific Pparg deletion causes insulin resistance. Nat Med 2003;9:1491-7. https://doi.org/10.1038/nm956
  41. Newsholme EA, Williams T. The role of phosphoenolpyruvate carboxykinase in amino acid metabolism in muscle. Biochem J 1978;176:623-6. https://doi.org/10.1042/bj1760623
  42. Nye CK, Hanson RW, Kalhan SC. Glyceroneogenesis is the dominant pathway for triglyceride glycerol synthesis in vivo in the rat. J Biol Chem 2008;283:27565-74. https://doi.org/10.1074/jbc.M804393200
  43. Yang J, Kalhan SC, Hanson RW. What is the metabolic role of phosphoenolpyruvate carboxykinase? J Biol Chem 2009;284:27025-9. https://doi.org/10.1074/jbc.R109.040543
  44. She P, Burgess SC, Shiota M, Flakoll P, Donahue EP, Malloy CR, Sherry AD, Magnuson MA. Mechanisms by which liver-specific PEPCK knockout mice preserve euglycemia during starvation. Diabetes 2003;52:1649-54. https://doi.org/10.2337/diabetes.52.7.1649
  45. Cha JY, Park JC, Ahn HY, Eom KE, Park BK, Jun BS, Lee CH, Cho YS. Effect of Monascus purpureus-Korean Red Ginseng power on the serum lipid levels and antioxidative activity in rats. J Korean Soc Food Sci Nutr 2009;38:1153-60. https://doi.org/10.3746/jkfn.2009.38.9.1153
  46. Mollah ML, Kim GS, Moon HK, Chung SK, Cheon YP, Kim JK, Kim KS. Anti-obesity effects of wild ginseng (Panax ginseng CA Meyer) mediated by PPAR-${\gamma}$, GLUT4 and LPL in ob/ob mice. Phytother Res 2009;23:220-5. https://doi.org/10.1002/ptr.2593

Cited by

  1. Anti-aging effects of Piper cambodianum P. Fourn. extract on normal human dermal fibroblast cells and a wound-healing model in mice vol.11, pp.None, 2015, https://doi.org/10.2147/cia.s107734
  2. Targeting Cancer Metabolism - Revisiting the Warburg Effects vol.32, pp.3, 2015, https://doi.org/10.5487/tr.2016.32.3.177
  3. Involvement of S6K1 in mitochondria function and structure in HeLa cells vol.28, pp.12, 2015, https://doi.org/10.1016/j.cellsig.2016.09.003
  4. Wu-Mei-Wan Reduces Insulin Resistance via Inhibition of NLRP3 Inflammasome Activation in HepG2 Cells vol.2017, pp.None, 2015, https://doi.org/10.1155/2017/7283241
  5. Herbal Medicine for the Treatment of Obesity: An Overview of Scientific Evidence from 2007 to 2017 vol.2017, pp.None, 2017, https://doi.org/10.1155/2017/8943059
  6. Recognition of Transmembrane Protein 39A as a Tumor-Specific Marker in Brain Tumor vol.33, pp.1, 2015, https://doi.org/10.5487/tr.2017.33.1.063
  7. Pectin lyase-modified red ginseng extract exhibits potent anti-glycation effects in vitro and in vivo vol.21, pp.2, 2017, https://doi.org/10.20463/jenb.2017.0011
  8. Ginsenoside Rb2 Alleviates Hepatic Lipid Accumulation by Restoring Autophagy via Induction of Sirt1 and Activation of AMPK vol.18, pp.6, 2017, https://doi.org/10.3390/ijms18051063
  9. GS-E3D, a new pectin lyase-modified red ginseng extract, inhibited diabetes-related renal dysfunction in streptozotocin-induced diabetic rats vol.17, pp.None, 2015, https://doi.org/10.1186/s12906-017-1925-7
  10. Ginseng for the treatment of diabetes and diabetes-related cardiovascular complications: a discussion of the evidence vol.97, pp.4, 2019, https://doi.org/10.1139/cjpp-2018-0440
  11. Enhanced Intestinal Permeability and Plasma Concentration of Metformin in Rats by the Repeated Administration of Red Ginseng Extract vol.11, pp.4, 2015, https://doi.org/10.3390/pharmaceutics11040189
  12. Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies vol.198, pp.None, 2015, https://doi.org/10.1016/j.pharmthera.2019.02.013
  13. Extension of Drosophila lifespan by Korean red ginseng through a mechanism dependent on dSir2 and insulin/IGF-1 signaling vol.11, pp.21, 2015, https://doi.org/10.18632/aging.102387
  14. Review of Ginseng Anti-Diabetic Studies vol.24, pp.24, 2015, https://doi.org/10.3390/molecules24244501
  15. Supplementation with Korean Red Ginseng Improves Current Perception Threshold in Korean Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Trial vol.2020, pp.None, 2020, https://doi.org/10.1155/2020/5295328
  16. 고려인삼과 당뇨병: 세포와 동물 및 인체실험을 통한 고려인삼의 당뇨병에 대한 효능 vol.51, pp.1, 2015, https://doi.org/10.22889/kjp.2020.51.1.001
  17. Effect of Korean Red Ginseng on metabolic syndrome vol.45, pp.3, 2015, https://doi.org/10.1016/j.jgr.2020.11.002
  18. Antidiabetic Effect of Noodles Containing Fermented Lettuce Extracts vol.11, pp.8, 2015, https://doi.org/10.3390/metabo11080520
  19. The effects of ginseng on the metabolic syndrome: An updated review vol.9, pp.9, 2021, https://doi.org/10.1002/fsn3.2475