title: Does metformin influence the insulin-, IGF I- and IGF II-receptor gene expression and Akt phosphorylation in human decidualized endometrial stromal cells?
abstract: OBJECTIVE
  To assess the effects of metformin on insulin-, IGF I-, and IGF II-receptor gene expression and Akt phosphorylation in decidualized human endometrial stromal cells (ESC) after stimulation with insulin, IGF I and II.
  
  
  METHODS
  ESC were isolated from healthy, regularly cycling women and after two passages decidualized with estrogen/progesterone±metformin. Cells were incubated with insulin, IGF I or IGF II for 1, 5, and 10 min to assess Akt phosphorylation by Western blot. To investigate the insulin-, IGF I- and IGF II-receptor gene expression ESC were incubated with insulin, IGF I or IGF II for 6 and 24h.
  
  
  RESULTS
  Insulin- and IGF I-receptor gene expression in ESC changed significantly after incubation with insulin, IGF I or IGF II. This was further augmented in metformin pretreated cells, while IGF II-receptor gene expression changed particularly after pretreatment with metformin. Akt phosphorylation peaked after 5 min insulin, IGF I and IGF II stimulation in ESC in both control (control 0.08 ± 0.03 vs. insulin 0.74 ± 0.19, IGF I 0.68 ± 0.22, IGF II 0.53 ± 0.13, p<0.05) and metformin pretreated cells (control 0.03 ± 0.01 vs. insulin 0.75 ± 0.11, IGF I 0.74 ± 0.15, IGF II 0.67 ± 0.09, p<0.005). However, there was no significant difference between the control and metformin pretreated group.
  
  
  CONCLUSIONS
  Insulin, IGF I and IGF II lead to changes in their receptor gene expression and induced Akt phosphorylation in ESC. These effects were further highlighted in the presence of metformin.
authors.affiliation: Department of Gynecological Endocrinology and Reproductive Medicine, Ruprecht-Karls University Heidelberg, Heidelberg, Germany.
authors.forename: Edison
authors.initials: E
authors.lastname: Capp
authors.forename: Julia
authors.initials: J
authors.lastname: Jauckus
authors.forename: Helena
authors.initials: H
authors.lastname: von Eye Corleta
authors.forename: Bettina
authors.initials: B
authors.lastname: Toth
authors.forename: Thomas
authors.initials: T
authors.lastname: Strowitzki
authors.forename: Ariane
authors.initials: A
authors.lastname: Germeyer
mesh_terms: D002478:Cells, Cultured; D004717:Endometrium / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D012102:Reproductive Control Agents / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects
chemical_list: D007328:Insulin; D017527:Receptor, IGF Type 2; D012102:Reproductive Control Agents; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D008687:Metformin; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt