title: Metformin inhibits expression and secretion of PEDF in adipocyte and hepatocyte via promoting AMPK phosphorylation.
abstract: OBJECTIVE
  Pigment epithelium-derived factor (PEDF) plays an important role in obesity-induced insulin resistance (IR). The study aims to investigate the effect of metformin, a widely used agent to improve IR, on PEDF production both in vivo and in vitro.
  
  
  METHODS
  SD rats were divided into normal control group, high fat group (HF group), and metformin group (MET group). Hyperinsulinemic euglycemic clamp was performed to evaluate insulin sensitivity. IR models of 3T3-L1 and HepG2 cells were established and then treated with metformin and inhibitor of AMP activated protein kinase (AMPK).
  
  
  RESULTS
  In vivo, the HF group showed increased serum PEDF which is negatively correlated with insulin sensitivity, while the MET group revealed decreased serum PEDF and downregulated PEDF expression in fat and liver, concomitant with significantly improved IR. In vitro, the IR cells showed enhanced PEDF secretion and expression, whereas metformin lowered PEDF secretion and expression, accompanied with increased glucose uptake. Metformin stimulated AMPK phosphorylation in fat and liver of the obese rats, while in vitro, when combined with AMPK inhibitor, the effect of metformin on PEDF was abrogated.
  
  
  CONCLUSIONS
  Metformin inhibits the expression and secretion of PEDF in fat and liver via promoting AMPK phosphorylation, which is closely associated with IR improvement.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Street, Chongqing 400016, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Yang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lv
authors.forename: Ting
authors.initials: T
authors.lastname: Luo
authors.forename: Lulu
authors.initials: L
authors.lastname: Liu
authors.forename: Rufei
authors.initials: R
authors.lastname: Gao
authors.forename: Shumei
authors.initials: S
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Ye
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Cheng
authors.forename: Qifu
authors.initials: Q
authors.lastname: Li
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D005136:Eye Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000493:pharmacokinetics; D015309:Glucose Clamp Technique; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015843:Serpins / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D055372:AMP-Activated Protein Kinases; D005136:Eye Proteins; D005947:Glucose; D007004:Hypoglycemic Agents; D008687:Metformin; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor