Metformin alters insulin signaling and viability of human granulosa cells.
OBJECTIVE
To study whether insulin signaling pathways in the ovary are altered by metformin.


METHODS
In vitro human granulosa cell culture system.


METHODS
Academic research environment.


METHODS
Infertility patients undergoing oocyte retrieval for IVF/ICSI.


METHODS
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.


RESULTS
Basal cell viability of primary granulosa cells was significantly increased relative to control by metformin 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.


CONCLUSIONS
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.
Sonntag
Barbara
B
Department of Obstetrics and Gynecology, University Hospital of Münster, Münster, Germany. sonnta@uni-muenster.de
Götte
Martin
M
Wülfing
Pia
P
Schüring
Andreas N
AN
Kiesel
Ludwig
L
Greb
Robert R
RR
D000328:Adult; D000704:Analysis of Variance; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008687:Metformin / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*
D007328:Insulin; D008687:Metformin; D020928:Mitogen-Activated Protein Kinases