Abstract
Panax ginseng is a best-selling medicinal plant showing an antidiabetic activity via human, animal and in vitro studies. Among bioactive constituents found in ginseng, ginsenosides are known to be responsible for antidiabetic activity of ginseng. Ginsenoside Rb2, one of the major ginsenosides found in Asian ginseng, is shown to inhibit palmitate-induced gluconeogenesis in H4IIE rat hepatocytes via AMP-activated protein kinase (AMPK)-induced up-regulation of orphan nuclear receptor small heterodimer partner (SHP). Up to now, about thirteen articles were published to demonstrate that the pharmacological or physiological activities of ginsenosides are associated with AMPK, and only protopanaxatriol-type ginsenosides such as Re, Rg1 and Rg2, have been shown to suppress the hepatic glucose production. Therefore, Rb2 is the first protopanaxadiol-type ginsenoside shown to inhibit hepatic gluconeogenesis through AMPK activation. Further work will reveal whether activation of AMPK pathway by Rb2 would be beneficial to diabetic animals or type 2 diabetic patients.
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Chanda, D., Kim, S. J., Lee, I. K., Shong, M., and Choi, H. S., Sodium arsenite induces orphan nuclear receptor SHP gene expression via AMP-activated protein kinase to inhibit gluconeogenic enzyme gene expression. Am. J. Physiol. Endocrinol. Metab., 295, E368–E379 (2008).
Gao, D., Nong, S., Huang, X., Lu, Y., Zhao, H., Lin, Y., Man, Y., Wang, S., Yang, J., and Li, J., The effects of palmitate on hepatic insulin resistance are mediated by NADPH Oxidase 3-derived reactive oxygen species through JNK and p38MAPK pathways. J. Biol. Chem., 285, 29965–29973 (2010).
He, L., Sabet, A., Djedjos, S., Miller, R., Sun, X., Hussain, M. A., Radovick, S., and Wondisford, F. E., Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell, 137, 635–645 (2009).
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., and Hotamisligil, G. S., A central role for JNK in obesity and insulin resistance. Nature, 420, 333–336 (2002).
Horike, N., Sakoda, H., Kushiyama, A., Ono, H., Fujishiro, M., Kamata, H., Nishiyama, K., Uchijima, Y., Kurihara, Y., Kurihara, H., and Asano, T., AMP-activated protein kinase activation increases phosphorylation of glycogen synthase kinase 3beta and thereby reduces cAMP-responsive element transcriptional activity and phosphoenolpyruvate carboxykinase C gene expression in the liver. J. Biol. Chem., 283, 33902–33910 (2008).
Kamata, H., Honda, S., Maeda, S., Chang, L., Hirata, H., and Karin, M., Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell, 120, 649–661 (2005).
Kim, S. J., Yuan, H. D., and Chung, S. H., Ginsenoside Rg1 suppresses hepatic glucose production via AMP-activated protein kinase in HepG2 cells. Biol. Pharm. Bull., 33, 325–328 (2010).
Kim, Y. D., Park, K. G., Lee, Y. S., Park, Y. Y., Kim, D. K., Nedumaran, B., Jang, W. G., Cho, W. J., Ha, J., Lee, I. K., Lee, C. H., and Choi, H. S., Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP. Diabetes, 57, 306–314 (2008).
Koo, S. H., Flechner, L., Qi, L., Zhang, X., Screaton, R. A., Jeffries, S., Hedrick, S., Xu, W., Boussouar, F., Brindle, P., Takemori, H., and Montminy, M., The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature, 437, 1109–1111 (2005).
Lee, J. M., Seo, W. Y., Song, K. H., Chanda, D., Kim, Y. D., Kim, D. K., Lee, M. W., Ryu, D., Kim, Y. H., Noh, J. R., Lee, C. H., Chiang, J. Y., Koo, S. H., and Choi, H. S., AMPK-dependent repression of hepatic gluconeogenesis via disruption of CREB·CRTC2 complex by orphan nuclear receptor small heterodimer partner. J. Biol. Chem., 285, 32182–32191 (2010).
Lee, K. T., Jung, T. W., Lee, H. J., Kim, S. G., Shin, Y. S., and Whang, W. K., Ginsenoside Rb2 inhibits palmitateinduced gluconeogenesis in H4IIE cells via AMPK-induced upregulation of the orphan nuclear receptor SHP. Arch. Pharm. Res., 34, 1201–1208 (2011).
Lowell, B. B. and Shulman, G. I., Mitochondrial dysfunction and type 2 diabetes. Science, 307, 384–387 (2005).
MacLean, P. S., Zheng, D., and Dohm, G. L., Muscle glucose transporter (GLUT 4) gene expression during exercise. Exerc. Sport Sci. Rev., 28, 148–152 (2000).
Ozcan, U., Cao, Q., Yilmaz, E., Lee, A. H., Iwakoshi, N. N., Ozdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., and Hotamisligil, G. S., Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science, 306, 457–461 (2004).
Saha, A. K., Avilucea, P. R., Ye, J. M., Assifi, M. M., Kraegen, E. W., and Ruderman, N. B., Pioglitazone treatment activates AMP-activated protein kinase in rat liver and adipose tissue in vivo. Biochem. Biophys. Res. Commun., 314, 580–585 (2004).
Tuncman, G., Hirosumi, J., Solinas, G., Chang, L., Karin, M., and Hotamisligil, G. S., Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proc. Natl. Acad. Sci. U. S. A., 103, 10741–10746 (2006).
Wang, X. R., Zhang, M. W., Chen, D. D., Zhang, Y., and Chen, A. F., AMP-activated protein kinase rescues the angiogenic functions of endothelial progenitor cells via manganese superoxide dismutase induction in type 1 diabetes. Am. J. Physiol. Endocrinol. Metab., 300, E1135–E1145 (2011).
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M. F., Goodyear, L. J., and Moller, D. E., Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest., 108, 1167–1174 (2001).
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Jung, M.S., Chung, S.H. AMP-activated protein kinase: A potential target for ginsenosides?. Arch. Pharm. Res. 34, 1037–1040 (2011). https://doi.org/10.1007/s12272-011-0700-4
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DOI: https://doi.org/10.1007/s12272-011-0700-4