The ginsenoside Rg3 has a stimulatory effect on insulin signaling in L6 myotubes

The ginsenoside Rg3 is known to have a protective effect against hyperglycemia, obesity and diabetes in vivo. In this study, we examined the effect of Rg3 on insulin signaling and glucose uptake in cultured L6 myotubes. Rg3 increased glucose uptake both in the basal and insulin-induced states of L6 myotubes. Consistent with the increase in glucose uptake, Rg3 stimulated the phosphorylation of IRS-1 and Akt. Interestingly, Rg3 dramatically increased IRS-1 protein levels, while the protein level of Akt was not affected. Rg3 regulated IRS-1 expression at the transcriptional level and also increased the level of GLUT4 mRNA. Treatment of ginsam, in which Rg3 is the major compound of ginsenosides, increased the IRS-1 protein levels in OLEFT rats. In addition, we found that this effect of Rg3 on insulin signaling was not mediated by the AMPK pathway. In conclusion, these results suggest that Rg3 improves insulin signaling and glucose uptake primarily by stimulating the expression of IRS-1 and GLUT4. (C) 2009 Elsevier Inc. All rights reserved.Hwang JT, 2009, PHYTOTHER RES, V23, P262, DOI 10.1002/ptr.2606Lim S, 2009, METABOLISM, V58, P8, DOI 10.1016/j.metabol.2008.07.027Choi KT, 2008, ACTA PHARMACOL SIN, V29, P1109, DOI 10.1111/j.1745-7254.2008.00869.xNakagawa Y, 2006, NAT MED, V12, P107, DOI 10.1038/nm1334Huang C, 2005, J BIOL CHEM, V280, P19426, DOI 10.1074/jbc.M412317200Kim JH, 2005, J PHARMACOL SCI, V97, P124Yun SN, 2004, ARCH PHARM RES, V27, P790Attele AS, 2002, DIABETES, V51, P1851, DOI 10.2337/diabetes.51.6.1851Zheng DH, 2001, J APPL PHYSIOL, V91, P1073Cho H, 2001, SCIENCE, V292, P1728Saltiel AR, 2001, CELL, V104, P517CARVALHO E, 2001, FASEB J, V15, P1101Kubota N, 2000, DIABETES, V49, P1880Kido Y, 2000, J CLIN INVEST, V105, P199Blair AS, 1999, J BIOL CHEM, V274, P36293Holmes BF, 1999, J APPL PHYSIOL, V87, P1990Friedman JE, 1999, DIABETES, V48, P1807Wang QH, 1999, MOL CELL BIOL, V19, P4008Virkamaki A, 1999, J CLIN INVEST, V103, P931White MF, 1998, MOL CELL BIOCHEM, V182, P3Gillis CN, 1997, BIOCHEM PHARMACOL, V54, P1