*2.4. SR, CR and Combined Extracts Activated Insulin Signaling Pathway in Liver*

Insulin resistance was derived from systemic inflammation in T2DM [23]. Our researches suggested that LSC and HSC could markedly inhibit inflammation in liver, and subsequent investigation was carried out to determine whether this action contributed to improve insulin signaling. As the qPCR results show in Figure 5A–D, mRNA expressions of IRS1, PI3K, Akt2, and Glut2 were markedly decreased in T2DM rats. Additionally, protein levels of p-PI3K, p-Akt, and Glut2 were notably lower in T2DM rats than those in normal rats (Figure 5E–G). After treatment, mRNA expressions of IRS1, PI3K, Akt2, and Glut2 were remarkably increased to a range from 102% to 171% and protein levels of p-PI3K, p-Akt and Glut2 were notably increased. However, protein levels of PI3K, Akt were not significantly different among groups. Furthermore, LSC and HSC were more effective than individual SR and CR.

**Figure 5.** The effect of metformin (P), scutellaria Radix (SR), coptidis Rhizome (CR), low dose of combined extracts group (LSC) and high dose of combined extracts (HSC) on insulin signaling pathway. (**A**–**D**) mRNA expression levels of Insulin receptor substrate 1 (IRS1), Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), Protein kinase B (Akt2) and Glucose transporter 2 (Glut2) in liver of the N, M, P, SR, CR, LSC, and HSC by qPCR; (**E**–**G**) Protein expression levels of PI3K, phosphorylated PI3K (p-PI3K), Akt2, phosphorylated Akt2 (p-Akt2), Glut2 in liver of the N, M, P, SR, CR, LSC, and HSC by Western blot. The values are shown as mean ± SD. # *p* < 0.05, ## *p* < 0.01, ### *p* < 0.001 vs. normal group; \* *p* < 0.05, \*\* *p* < 0.01, \*\*\* *p* < 0.001 vs. model group. Data were analyzed by One-way-ANOVA.

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