Metformin modulates PI3K and GLUT4 expression and Akt/PKB phosphorylation in human endometrial stromal cells after stimulation with androgen and insulin.

OBJECTIVE: To assess the effect of metformin on expression of Akt, ERK, PI3K and GLUT4, proteins associated with the growth factor signaling cascade, in human endometrial stromal cells after stimulation with androgen and insulin.

STUDY DESIGN: Primary culture of endometrial stromal cells were stimulated in different groups with estrogen, progesterone, androgen and insulin and treated with metformin for 10min, 24h and 48h. After 14 days, proteins were extracted for Western blot analysis.

RESULTS: PI3K and GLUT4 expression were increased in the insulin-treated group and further attenuated when metformin was added. The ERK protein was not affected, whereas the Akt phosphorylation was significantly decreased by the action of metformin.

CONCLUSION: Metformin affects human endometrial stromal cells by acting on proteins related to growth factors, usually increasing their expression when combined with insulin. Akt phosphorylation was inhibited by metformin, possibly due to its anti-proliferative action.