Increasing effect of Tangzhiqing formula on IRS-1-dependent PI3K/AKT signaling in muscle

BACKGROUND Tangzhiqing fomula (TZQ-F), the mixture of Red Paeony root, Mulberry leaf, Lotus leaf, Danshen root and Hawthorn leaf, regulates the abnormal glucose and lipids in prediabetic patients. In this study, we focus on the mechanism of TZQ-F and its fractions on glucose metabolism. METHODS After orally administration of TZQ-F for 4 weeks in KK-Ay mice, we dissected out the liver and muscle, and employed PCR and western blotting to screening the PI3K/AKT pathway. The following PI3K/AKT signaling pathway were performed in L-6 myotube and HepG2 cells. RESULTS In the liver of KK-Ay mice, no significance was observed on PI3K, AKT and their phosphorylation between TZQ-F and controls , while, in the muscle, up-regulation of PI3K, AKT, Glycogen synthase (GYS) and their phosphorylation type, as well as GluT4, was deteced in TZQ-F. In HepG2 cells, TZQ-F increased IRS-2 by 10 folds, without interrupting AKT, IRS-1 and GluT4. In L-6 myotube cells, TZQ-F and its fractions treatment significantly increased IRS-1 and AKT at mRNA level. CONCLUSION TZQ-F prevents pre-diabetes through increasing effect on IRS-1-dependent PI3K/AKT signaling pathway in muscle.