Journal of Food and Nutrition Research
ISSN (Print): 2333-1119 ISSN (Online): 2333-1240 Website: Editor-in-chief: Prabhat Kumar Mandal
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Journal of Food and Nutrition Research. 2018, 6(4), 242-249
DOI: 10.12691/jfnr-6-4-6
Open AccessArticle

Effects of Ginseng-Added Brown Rice Cookie on the Regulation of Hepatic Glucose Metabolism Mediated through the Insulin Signaling Pathway in db/db Obese Mice

Sun Hee Hong1, Minji Woo1, Jeong Sook Noh2 and Yeong Ok Song1,

1Department of Food Science and Nutrition, Kimchi Research Institute, Pusan National University, Busan 46241, Republic of Korea

2Department of Food Science and Nutrition, Tongmyong University, Busan 48520, Republic of Korea

Pub. Date: April 27, 2018

Cite this paper:
Sun Hee Hong, Minji Woo, Jeong Sook Noh and Yeong Ok Song. Effects of Ginseng-Added Brown Rice Cookie on the Regulation of Hepatic Glucose Metabolism Mediated through the Insulin Signaling Pathway in db/db Obese Mice. Journal of Food and Nutrition Research. 2018; 6(4):242-249. doi: 10.12691/jfnr-6-4-6


In the present study, the effects of ginseng-added brown rice cookie (GBRC) on the regulation of hepatic glucose and lipid metabolism mediated through the insulin signaling pathway were examined in db/db mice. Isocaloric diets, prepared by adding the individual ingredients of rice cookie (RC) or GBRC to AIN-93G diet (10%, w/w), were fed to the animals for 10 weeks (n = 7 per group). The plasma insulin level and oral glucose tolerance test-derived area under the curve were lower in the GBRC group than in the RC group (P < 0.05). In the GBRC group, the insulin signaling pathway was significantly elevated through phospho-insulin receptor substrate-1 and phospho-Akt upregulation (P < 0.05), indicating that glucose utilization was increased. Subsequently, hepatic triacylglycerol synthesis was inhibited via the downregulation of fatty acid synthase, regulated by sterol regulatory element binding protein-1. In addition, fatty acid oxidation was increased. Protein expression levels of the lipolytic enzymes carnitine palmitoyltransferase I and acetyl-CoA oxidase 1, regulated by peroxisome proliferator-activated receptor-alpha, were increased (P < 0.05). Consequently, gluconeogenesis was suppressed via the downregulation of gluconeogenic enzymes, such as pyruvate carboxykinase and glucose-6-phosphatase, regulated by phospho-5′ adenosine monophosphate-activated protein kinase (P < 0.05). Protein expression levels of the nuclear factor kappa B-regulated cyclooxygenase-2 and inducible nitric oxide synthase were inhibited, thereby diminishing reactive oxygen species and peroxynitrite generation (P < 0.05). In conclusion, GBRC revealed antidiabetic effects by promoting hepatic glucose utilization mediated through the insulin signaling pathway, which enhanced lipid oxidation rather than triacylglycerol synthesis.

brown rice diabetes mellitus ginseng insulin lipid metabolism

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[1]  Tangvarasittichai, S., “Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus.” World Journal of Diabetes 6(3). 456-480. 2015.
[2]  Srivastava, R. A. K., Pinkosky, S. L., Filippov, S., Hanselman, J. C., Cramer, C. T., and Newton, R. S., “AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases Thematic Review Series: New Lipid and Lipoprotein Targets for the Treatment of Cardiometabolic Diseases.” Journal of Lipid Research 53(12): 2490-2514. 2012.
[3]  Kim, O. K., Nam, D. E., Jun, W., and Lee, J., “Cudrania tricuspidata water extract improved obesity-induced hepatic insulin resistance in db/db mice by suppressing ER stress and inflammation.” Food & Nutrition Research 59(1). 29165. 2015.
[4]  Carmena, R., “Type 2 diabetes, dyslipidemia, and vascular risk: rationale and evidence for correcting the lipid imbalance.” American Heart Journal 150(5). 859-870. 2005.
[5]  Fabbrini, E., Magkos, F., Mohammed, B. S., Pietka, T., Abumrad, N. A., Patterson, B. W., Okunade, A. and Klein, S., “Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity.” Proceedings of the National Academy of Sciences 106(36). 15430-15435. 2009.
[6]  Samuel, V. T., Petersen, K. F., and Shulman, G. I., “Lipid-induced insulin resistance: unravelling the mechanism.” The Lancet 375(9733). 2267-2277. 2010.
[7]  Strable, M. S., and Ntambi, J. M., “Genetic control of de novo lipogenesis: role in diet-induced obesity.” Critical Reviews in Biochemistry and Molecular Biology 45(3). 199-214. 2010.
[8]  Hardie, D., “AMPK: a key regulator of energy balance in the single cell and the whole organism.” International Journal of Obesity 32. S7-S12. 2008.
[9]  Goldberg, R. B., Kendall, D. M., Deeg, M. A., Buse, J. B., Zagar, A. J., Pinaire, J. A., Tan, M. H., Khan, M. A., Perez, A. T., and Jacober, S. J., “A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia.” Diabetes Care 28(7). 1547-1554. 2005.
[10]  Ndife, J., Abdulraheem, L., and Zakari, U., “Evaluation of the nutritional and sensory quality of functional breads produced from whole wheat and soya bean flour blends.” African Journal of Food Science 5(8). 466-472. 2011.
[11]  Kārkliņa, D., Gedrovica, I., Reca, M., and Kronberga, M., Production of biscuits with higher nutritional value. Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences. 3. 113-116. 2012.
[12]  Hong, S. H., Kim, M. J., Woo, M. J., and Song, Y. O., “Rice Cookie Decreases Plasma and Hepatic Lipid Levels in High-Fat Diet-fed Mice: A Comparison Study with Traditional Western Style Cookies.” Journal of Food and Nutrition Research 5(7). 451-457. 2017.
[13]  Hong, S. H., Kim, M., Woo, M., Noh, J. S., Lee, J., Chung, L., and Song, Y. O., “The amelioration of plasma lipids by Korean traditional confectionery in middle-aged women: A cross-over study with western cookie.” Nutrition Research and Practice 10(6). 590-596. 2016.
[14]  Son, M. J., Rico, C. W., Nam, S. H., and Kang, M. Y., “Influence of oryzanol and ferulic acid on the lipid metabolism and antioxidative status in high fat-fed mice.” Journal of Clinical Biochemistry and Nutrition 46(2). 150-156. 2010.
[15]  Cho, W. C., Chung, W.-S., Lee, S. K., Leung, A. W., Cheng, C. H., and Yue, K. K., “Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats.” European Journal of Pharmacology 550(1). 173-179. 2006.
[16]  Kim, H. J., Lee, S. G., Chae, I. G., Kim, M. J., Im, N. K., Yu, M. H., Lee, E. J., and Lee, I. S., “Antioxidant effects of fermented red ginseng extracts in streptozotocin-induced diabetic rats.” Journal of Ginseng Research 35(2). 129. 2011.
[17]  Merino-Aguilar, H., Arrieta-Baez, D., Jiménez-Estrada, M., Magos-Guerrero, G., Hernández-Bautista, R. J., Susunaga-Notario, A. d. C., Almanza-Pérez, J. C., Blancas-Flores, G., Román-Ramos, R., and Alarcón-Aguilar, F. J., “Effect of fructooligosaccharides fraction from Psacalium decompositum on inflammation and dyslipidemia in rats with fructose-induced obesity.” Nutrients 6(2). 591-604. 2014.
[18]  Nakamura, Y., Natsume, M., Yasuda, A., Ishizaka, M., Kawahata, K., and Koga, J., “Fructooligosaccharides suppress high-fat diet-induced fat accumulation in C57BL/6J mice.” Biofactors 43(2). 145-151. 2017.
[19]  Hong, S. H., Kim, M., Woo, M., and Song, Y. O. “Effects of ingredients of Korean brown rice cookies on attenuation of cholesterol level and oxidative stress in high-fat diet-fed mice.” Nutrition Research and Practice, 11(5), 365-372. 2017.
[20]  Jeon, W. J., Oh, J. S., Park, M. S., and Ji, G. E., “Anti‐Hyperglycemic Effect of Fermented Ginseng in Type 2 Diabetes Mellitus Mouse Model.” Phytotherapy Research 27(2). 166-172. 2013.
[21]  Folch, J., Lees M., and Sloane-Stanley, G., “A simple method for the isolation and purification of total lipids from animal tissues.” Journal of Biological Chemistry 226(1). 497-509. 1957.
[22]  Ohkawa, H., Ohishi, N., and Yagi, K., “Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.” Analytical Biochemistry 95(2). 351-358. 1979.
[23]  Ali, S., LeBel, C., and Bondy, S., “Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity.” Neurotoxicology 13(3). 637-648. 1991.
[24]  Kooy, N. W., Royall, J. A., Ischiropoulos, H., and Beckman, J. S., “Peroxynitrite-mediated oxidation of dihydrorhodamine 123.” Free Radical Biology and Medicine 16(2). 149-156. 1994.
[25]  Jung, K., Hong, S. H., Kim, M., Han, J.-S., Jang, M.-S., and Song, Y. O., “Antiatherogenic effects of Korean cabbage kimchi with added short arm octopus.” Food Science and Biotechnology 24(1). 249-255. 2015.
[26]  Field, A. E., Austin, S. B., Gillman, M. W., Rosner, B., Rockett, H. R., and Colditz, G. A., “Snack food intake does not predict weight change among children and adolescents.” International journal of obesity 28(10): 1210-1216.
[27]  Farley, T. A., Baker, E. T., Futrell, L., and Rice, J. C., “The ubiquity of energy-dense snack foods: a national multicity study.” American Journal of Public Health 100(2). 306-311. 2010.
[28]  Choi, K., and Kim, Y. B., “Molecular mechanism of insulin resistance in obesity and type 2 diabetes.” The Korean Journal of Internal Medicine 25(2). 119-129. 2010.
[29]  Mokdad, A. H., Ford, E. S., Bowman, B. A., Dietz, W. H., Vinicor, F., Bales, V. S., and Marks, J. S., “Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001.” Jama 289(1). 76-79. 2003.
[30]  Yuan, H. D., Shin, E. J., and Chung, S. H., “Anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice.” Journal of Ginseng Research 32(3). 187-193. 2008.
[31]  Lee, W. K., Kao, S. T., Liu, I. M., and Cheng, J. T., “Ginsenoside Rh2 is one of the active principles of Panax ginseng root to improve insulin sensitivity in fructose-rich chow-fed rats.” Hormone and Metabolic Research 39(05). 347-354. 2007.
[32]  Kozuka, C., Yabiku, K., Sunagawa, S., Ueda, R., Taira, S. I., Ohshiro, H., Ikema, T., Yamakawa, K., Higa, M. and Tanaka, H., “Brown rice and its component, γ-oryzanol, attenuate the preference for high-fat diet by decreasing hypothalamic endoplasmic reticulum stress in mice.” Diabetes 61(12). 3084-3093. 2012.
[33]  Kaume, L., Gilbert, W., Gadang, V., and Devareddy, L., “Dietary supplementation of fructooligosaccharides reduces hepatic steatosis associated with insulin resistance in obese Zucker rats.” Functional Foods in Health and Disease 1(5). 199-213. 2011.
[34]  Seo, Y. S., Shon, M. Y., Kong, R., Kang, O. H., Zhou, T., Kim, D. Y., and Kwon, D. Y., “Black ginseng extract exerts anti-hyperglycemic effect via modulation of glucose metabolism in liver and muscle.” Journal of Ethnopharmacology 190. 231-240. 2016.
[35]  Son, M. J., Rico, C. W., Nam, S. H., & Kang, M. Y., “Effect of Oryzanol and Ferulic Acid on the Glucose Metabolism of Mice Fed with a High‐Fat Diet.” Journal of Food Science 76(1). 2011.
[36]  Yu, X., Ye, L., Zhang, H., Zhao, J., Wang, G., Guo, C., and Shang, W., “Ginsenoside Rb1 ameliorates liver fat accumulation by upregulating perilipin expression in adipose tissue of db/db obese mice.” Journal of Ginseng Research 39(3): 199-205. 2015.
[37]  Kaul, K., Hodgkinson, A., M Tarr, J., M Kohner, E., and Chibber, R., “Is inflammation a common retinal-renal-nerve pathogenic link in diabetes?” Current diabetes reviews 6(5). 294-303. 2010.