To analyze the effects of aucubin on the PI3K/Akt/NF-κB signaling pathways in diabetic mice, 10 C57BL/6J mice were used as the normal control (NC) group. Mice successfully modeled by feeding a high fat diet for 28 days combined with intraperitoneal injection of streptozotocin for 3 days were randomly divided into 6 groups: the model group, the low dose aucubin group (aucubin 1 mg/kg, the low dose group), a high dose aucubin group (aucubin 5 mg/kg, the high dose group), the high dose + insulin-like growth factor 1(IGF-1) group (aucubin 5 mg/kg + IGF-1 50 μg/kg), and the IGF-1 alone group (IGF-1 50 μg/kg). Fasting plasma glucose (FPG) was recorded; levels of glycosylated hemoglobin (HbA1c) and fasting insulin (FINS) were measured by electrochemiluminescence; the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated; inflammatory markers (TNF-α, IL-1β, IL-6) were detected by ELISA; mRNA expression levels of PI3K, Akt, and NF-κB p65 in pancreatic tissue were measured by qRT-PCR; and the phosphorylation ratios of pAkt/Akt and pNF-κB p65/NF-κB p65, as well as the protein expression level of inhibitor of nuclear factor κB α (IκBα), were detected by Western blotting. The results showed that, compared to those of the NC group, the body weight and health status scores of mice in the model group, low dose group, high dose group, high dose + IGF-1 group, and IGF-1 alone group were significantly decreased (P<0.05), while serum levels of FPG, HbA1c, FINS, HOMA-IR, TNF-α, IL-1β, and IL-6, as well as the mRNA expression of PI3K, Akt, and NF-κB p65 and the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 in pancreatic tissue, were significantly increased (P<0.05), and IκBα expression was significantly decreased (P<0.05). Compared to the model group, the low-dose and high-dose groups showed increased body mass and health status scores (P<0.05); decreased serum levels of FPG, HbA1c, FINS, HOMA-IR, TNF-α, IL-1β, and IL-6; decreased pancreatic mRNA expressions of PI3K, Akt, and NF-κB p65; decreased p-Akt/Akt and p-NF-κB p65/NF-κB p65 ratios(P<0.05); as well as increased IκBα expression (P<0.05). The changes in the above indicators were more significant in the high-dose group than in the low-dose group (P<0.05). Compared to the high-dose group, the high-dose+IGF-1 group showed decreased body mass and health status scores (P<0.05); increased serum levels of FPG, HbA1c, FINS, HOMA-IR, TNF-α, IL-1β, and IL-6; increased pancreatic mRNA expressions of PI3K, Akt, and NF-κB p65; increased p-Akt/Akt and p-NF-κB p65/NF-κB p65 ratios (P<0.05); and decreased IκBα expression (P<0.05). There were no significant difference in any indicators between the IGF-1 alone group and the model group (P>0.05). Together, the study suggests that aucubin improves glucose metabolism and insulin resistance to alleviates inflammatory responses in diabetic mice, and the mechanism of action is associated with the inhibition of the PI3K/Akt/NF-κB signaling pathways.
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