Effects of the Combined Extracts of Grape Pomace and Omija Fruit on Hyperglycemia and Adiposity in Type 2 Diabetic Mice

  • Cho, Su-Jung (Department of Food Science and Nutrition, Kyungpook National University) ;
  • Jung, Un Ju (Department of Food Science and Nutrition, Kyungpook National University) ;
  • Kim, Hye-Jin (Food R&D, CJ Cheiljedang Corp.) ;
  • Ryu, Ri (Department of Food Science and Nutrition, Kyungpook National University) ;
  • Ryoo, Jae Young (School of Life Sciences, Kyungpook National University) ;
  • Moon, Byoung Seok (Food R&D, CJ Cheiljedang Corp.) ;
  • Choi, Myung-Sook (Department of Food Science and Nutrition, Kyungpook National University)
  • Received : 2015.03.06
  • Accepted : 2015.06.02
  • Published : 2015.06.30


Grape products have been known to exert greater antioxidant and anti-obesity than anti-hyperglycemic effects in animals and humans. Omija is used as an ingredient in traditional medicine, and it is known to have an anti-hyperglycemic effect. We investigated whether the combined extracts of grape pomace and omija fruit (GE+OE) could reduce fat accumulation in adipose and hepatic tissues and provide beneficial effects against hyperglycemia and insulin resistance in type 2 diabetic mice. C57BL/KsJ-db/db mice were fed either a normal control diet or GE+OE (0.5% grape pomace extract and 0.05% omija fruit extract, w/w) for 7 weeks. GE+OE decreased plasma leptin and resistin levels while increasing adiponectin levels and reducing the total white adipose tissue weight. Furthermore, GE+OE lowered plasma free fatty acid (FFA), triglyceride, and total-cholesterol levels as well as hepatic FFA and cholesterol levels. Hepatic fatty acid synthase and glucose 6-phosphate dehydrogenase activities were decreased in the GE+OE group, whereas hepatic ${\beta}$-oxidation activity was increased. Furthermore, GE+OE supplementation not only reduced hyperglycemia and pancreatic ${\beta}$-cell failure but also lowered blood glycosylated hemoglobin and plasma insulin levels. The homeostasis model assessment of insulin resistance levels was also decreased and the decrease seems to be mediated by the lowered activities of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinases. The present data suggest that GE+OE may have the potential to reduce hyperglycemia, insulin resistance, and obesity in patients with type 2 diabetes.


Supported by : National Research Foundation of Korea


  1. Leahy JL. 2005. Pathogenesis of type 2 diabetes mellitus. Arch Med Res 36: 197-209.
  2. Matsuzawa Y, Funahashi T, Nakamura T. 1999. Molecular mechanism of metabolic syndrome X: contribution of adipocytokines . adipocyte-derived bioactive substances. Ann NY Acad Sci 892: 146-154.
  3. Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW, Shulman GI. 1996. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 97: 2859-2865.
  4. Rajala MW, Scherer PE. 2003. Minireview: The adipocyte− at the crossroads of energy homeostasis, inflammation, and atherosclersis. Endocrinology 144: 3765-3773.
  5. Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, Magnuson MA, Kahn CR. 2000. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell 6: 87-97.
  6. DeFronzo RA. 1999. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 131: 281-303.
  7. Takahashi Y, Soejima Y, Fukusato T. 2012. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol 18: 2300-2308.
  8. Perez-Jimenez J, Saura-Calixto F. 2008. Grape products and cardiovascular disease risk factors. Nutr Res Rev 21: 158-173.
  9. Cordain L, Melby CL, Hamamoto AE, O'Neill DS, Cornier MA, Barakat HA, Israel RG, Hill JO. 2000. Influence of moderate chronic wine consumption on insulin sensitivity and other correlates of syndrome X in moderately obese women. Metabolism 49: 1473-1478.
  10. Ceriello A, Bortolotti N, Motz E, Lizzio S, Catone B, Assaloni R, Tonutti L, Taboga C. 2001. Red wine protects diabetic patients from meal-induced oxidative stress and thrombosis activation: a pleasant approach to the prevention of cardiovascular disease in diabetes. Eur J Clin Invest 31: 322-328.
  11. Jo SH, Ha KS, Moon KS, Lee OH, Jang HD, Kwon YI. 2011. In vitro and in vivo anti-hyperglycemic effects of omija (Schizandra chinensis) fruit. Int J Mol Sci 12: 1359-1370.
  12. Wang XY, Yu ZL, Pan SY, Zhang Y, Sun N, Zhu PL, Jia ZH, Zhou SF, Ko KM. 2014. Supplementation with the extract of Schisandrae Fructus pulp, seed, or their combination influences the metabolism of lipids and glucose in mice fed with normal and hypercholesterolemic diet. Evid Based Complement Alternat Med 2014: 472638.
  13. Cho SJ, Jung UJ, Park HJ, Kim HJ, Park YB, Kim SR, Choi MS. 2013. Combined ethanol extract of grape pomace and omija fruit ameliorates adipogenesis, hepatic steatosis, and inflammation in diet-induced obese mice. Evid Based Complement Alternat Med 2013: 212139.
  14. Kobayashi K, Forte TM, Taniguchi S, Ishida BY, Oka K, Chan L. 2000. The db/db mouse, a model for diabetic dyslipidemia: molecular characterization and effects of western diet feeding. Metabolism 49: 22-31.
  15. 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.
  16. Hulcher FH, Oleson WH. 1973. Simplified spectrophotometric assay for microsomal 3-hydroxy-3-methylglutaryl CoA reductase by measurement of coenzyme A. J Lipid Res 14: 625-631.
  17. Davidson AL, Arion WJ. 1987. Factors underlying significant underestimations of glucokinase activity in crude liver extracts: physiological implications of higher cellular activity. Arch Biochem Biophys 253: 156-167.
  18. Alegre M, Ciudad CJ, Fillat C, Guinovart JJ. 1988. Determination of glucose-6-phosphatase activity using the glucose dehydrogenase-coupled reaction. Anal Biochem 173: 185-189.
  19. Bentle LA, Lardy HA. 1976. Interaction of anions and divalent metal ions with phosphoenolpyruvate carboxykinase. J Biol Chem 251: 2916-2921.
  20. Bradford MM. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254.
  21. Lazarow PB. 1981. Assay of peroxisomal ${\beta}$-oxidation of fatty acids. Methods Enzymol 72: 315-319.
  22. Nepokroeff CM, Lakshmanan MR, Porter JW. 1975. Fatty acid synthase from rat liver. Mothods Enzymol 35: 37-44.
  23. Pitkanen E, Pitkanen O, Uotila L. 1997. Enzymatic determination of unbound D-mannose in serum. Eur J Clin Chem Clin Biochem 35: 761-766.
  24. Ochoa S. 1955. "Malic" enzyme. A. "Malic" enzyme from pigeon liver and wheat germ. Methods Enzymol 1: 739-753.
  25. Walton PA, Possmayer F. 1985. $Mg_2$-dependent phosphatidate phosphohydrolase of rat lung: development of an assay employing a defined chemical substrate which reflects the phosphohydrolase activity measured using membranebound substrate. Anal Biochem 151: 479-486.
  26. Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, Lakey ND, Culpepper J, Moore KJ, Breitbart RE, Duyk GM, Tepper RI, Morgenstern JP. 1996. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 84: 491-495.
  27. Nishina PM, Lowe S, Wang J, Paigen B. 1994. Characterization of plasma lipids in genetically obese mice: the mutants obese, diabetes, fat, tubby, and lethal yellow. Metabolism 43: 549-553.
  28. Lombardo YB, Hron WT, Sobocinski KA, Menahan LA. 1984. A metabolic profile of fed and fasting genetically obese mice at 4-5 months of age. Horm Metab Res 16: 37-42.
  29. Schaffler A, Scholmerich J, Buchler C. 2005. Mechanisms of disease: adipocytokines and visceral adipose tissue− emerging role in nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol 2: 273-280.
  30. Diraison F, Dusserre E, Vidal H, Sothier M, Beylot M. 2002. Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity. Am J Physiol Endocrinol Metab 282: E46-E51.
  31. Kelley DE, McKolanis TM, Hegazi RA, Kuller LH, Kalhan SC. 2003. Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance. Am J Physiol Endocrinol Metab 285: E906-E916.
  32. Likimani TA, Wilson RP. 1982. Effects of diet on lipogenic enzyme activities in channel catfish hepatic and adipose tissue. J Nutr 112: 112-117.
  33. Miedema K. 2004. Towards worldwide standardisation of $HbA_1c$ determination. Diabetologia 47: 1143-1148.
  34. Kasuga M. 2006. Insulin resistance and pancreatic ${\beta}$ cell failure. J Clin Invest 116: 1756-1760.
  35. Prentki M, Nolan CJ. 2006. Islet ${\beta}$ cell failure in type 2 diabetes. J Clin Invest 116: 1802-1812.
  36. Hanley AJ, Williams K, Festa A, Wagenknecht LE, D'Agostino RB Jr, Kempf J, Zinman B, Haffner SM. 2004. Elevations in markers of liver injury and risk of type 2 diabetes: the Insulin Resistance Atherosclerosis Study. Diabetes 53: 2623-2632.
  37. Reaven GM. 1988. Role of insulin resistance in human disease. Diabetes 37: 1595-1607.
  38. Davies GF, Khandelwal RL, Wu L, Juurlink BH, Roesler WJ. 2001. Inhibition of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by troglitazone: a peroxisome proliferator- activated receptor-${\gamma}$ (PPAR${\gamma}$)-independent, antioxidant- related mechanism. Biochem Pharmacol 62: 1071-1079.
  39. Tataranni PA, Ortega E. 2005. A burning question: does an adipokine-induced activation of the immune system mediate the effect of overnutrition on type 2 diabetes? Diabetes 54: 917-927.
  40. Paquot N, Tappy L. 2005. Adipocytokines: link between obesity, type 2 diabetes and atherosclerosis. Rev Med Liege 60: 369-373.
  41. Tong J, Fujimoto WY, Kahn SE, Weigle DS, McNeely MJ, Leonetti DL, Shofer JB, Boyko EJ. 2005. Insulin, C-peptide, and leptin concentrations predict increased visceral adiposity at 5- and 10-year follow-ups in nondiabetic Japanese Americans. Diabetes 54: 985-990.
  42. Steppan CM, Lazar MA. 2002. Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab 13: 18-23.
  43. Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ. 1997. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389: 374-377.
  44. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. 2001. The hormone resistin links obesity to diabetes. Nature 409: 307-312.
  45. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. 2001. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86: 1930-1935.

Cited by

  1. Omija fruit ethanol extract improves adiposity and related metabolic disturbances in mice fed a high-fat diet vol.41, 2017,
  2. Low-dose grape pomace and omija fruit extract is more effective than high-dose in lowering oxidative stress and fat-pad mass in db/db mice vol.26, pp.6, 2017,