title: Metformin alters insulin signaling and viability of human granulosa cells.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital of Münster, Münster, Germany. sonnta@uni-muenster.de
authors.forename: Barbara
authors.initials: B
authors.lastname: Sonntag
authors.forename: Martin
authors.initials: M
authors.lastname: Götte
authors.forename: Pia
authors.initials: P
authors.lastname: Wülfing
authors.forename: Andreas N
authors.initials: AN
authors.lastname: Schüring
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kiesel
authors.forename: Robert R
authors.initials: RR
authors.lastname: Greb
mesh_terms: 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*
chemical_list: D007328:Insulin; D008687:Metformin; D020928:Mitogen-Activated Protein Kinases