Metformin alters insulin signaling and viability of human granulosa cells

Objective: To study whether insulin signaling pathways in the ovary are altered by metformin. Design: In vitro human granulosa cell culture system. Setting: Academic research environment. Patient(s): Infertility patients undergoing oocyte retrieval for IVF/ICSI. Main Outcome Measure(s): Cell viability and phosphorylated protein kinase B (PKB/AKT) and p44/42 mitogen-activated protein kinase (MAPK) expression of human primary and HGL5 granulosa cells. Result(S): Basal cell viability of primary granulosa cells was significantly increased relative to control by nietformin preincubation, without an additional stimulatory effect of insulin or IGF. Phosphorylated AKT expression in lysates of the human granulosa cell line HGL5 was significantly increased in contrast to decreased phosphorylated MAPK expression by metformin preincubation. Conclusion(s): Besides systemic effects, the ovulation inducing action of metformin may at least partially be due to direct effects on insulin signaling intermediates and follicular growth patterns in the ovary.