Diosgenin and 5-Methoxypsoralen Ameliorate Insulin Resistance through ER-αPI3KAkt-Signaling Pathways in HepG2 Cells

الملخص EN

To determine the effects and the underlying mechanism of diosgenin (DSG) and 5-methoxypsoralen (5-MOP), two main active components in the classical Chinese prescription Hu-Lu-Ba-Wan (HLBW), on insulin resistance, HepG2 cells were incubated in medium containing insulin.

Treatments with DSG, 5-MOP, and their combination were performed, respectively.

The result showed that the incubation of HepG2 cells with high concentration insulin markedly decreased glucose consumption and glycogen synthesis.

However, treatment with DSG, 5-MOP, or their combination significantly reversed the condition and increased the phosphorylated expression of estrogen receptor-α (ERα), sarcoma (Src), Akt/protein kinase B, glycogen synthase kinase-3β (GSK-3β), and the p85 regulatory subunit of phosphatidylinositol 3-kinase p85 (PI3Kp85).

At the transcriptional level, expression of the genes mentioned above also increased except for the negative regulation of GSK-3β mRNA.

The increased expression of glucose transport-4 (GLUT-4) was meanwhile observed through immunofluorescence.

Nevertheless, the synergistic effect of DSG and 5-MOP on improving glycometabolism was not obvious in the present study.

These results suggested that DSG and 5-MOP may improve insulin resistance through an ER-mediated PI3K/Akt activation pathway which may be a new strategy for type 2 diabetes mellitus, especially for women in an estrogen-deficient condition.