title: Insulin and metformin regulate circulating and adipose tissue chemerin.
abstract: OBJECTIVE
  To assess chemerin levels and regulation in sera and adipose tissue from women with polycystic ovary syndrome (PCOS) and matched control subjects.
  
  
  METHODS
  Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of chemerin. Serum chemerin was measured by enzyme-linked immunosorbent assay. We investigated the in vivo effects of insulin on serum chemerin levels via a prolonged insulin-glucose infusion. Ex vivo effects of insulin, metformin, and steroid hormones on adipose tissue chemerin protein production and secretion into conditioned media were assessed by Western blotting and enzyme-linked immunosorbent assay, respectively.
  
  
  RESULTS
  Serum chemerin, subcutaneous, and omental adipose tissue chemerin were significantly higher in women with PCOS (n = 14; P < 0.05, P < 0.01). Hyperinsulinemic induction in human subjects significantly increased serum chemerin levels (n = 6; P < 0.05, P < 0.01). In adipose tissue explants, insulin significantly increased (n = 6; P < 0.05, P < 0.01) whereas metformin significantly decreased (n = 6; P < 0.05, P < 0.01) chemerin protein production and secretion into conditioned media, respectively. After 6 months of metformin treatment, there was a significant decrease in serum chemerin (n = 21; P < 0.01). Importantly, changes in homeostasis model assessment-insulin resistance were predictive of changes in serum chemerin (P = 0.046).
  
  
  CONCLUSIONS
  Serum and adipose tissue chemerin levels are increased in women with PCOS and are upregulated by insulin. Metformin treatment decreases serum chemerin in these women.
authors.affiliation: Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, U.K.
authors.forename: Bee K
authors.initials: BK
authors.lastname: Tan
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Syed
authors.initials: S
authors.lastname: Farhatullah
authors.forename: Raghu
authors.initials: R
authors.lastname: Adya
authors.forename: Jaspreet
authors.initials: J
authors.lastname: Kaur
authors.forename: Dennis
authors.initials: D
authors.lastname: Heutling
authors.forename: Krzysztof C
authors.initials: KC
authors.lastname: Lewandowski
authors.forename: J Paul
authors.initials: JP
authors.lastname: O'Hare
authors.forename: Hendrik
authors.initials: H
authors.lastname: Lehnert
authors.forename: Harpal S
authors.initials: HS
authors.lastname: Randeva
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000735:Androstenedione / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D009852:Omentum / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000097:blood* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: C102741:CMKLR1 protein, human; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D008687:Metformin; D005947:Glucose