Insulin and metformin regulate circulating and adipose tissue chemerin

Diabetes. 2009 Sep;58(9):1971-7. doi: 10.2337/db08-1528. Epub 2009 Jun 5.

Abstract

Objective: To assess chemerin levels and regulation in sera and adipose tissue from women with polycystic ovary syndrome (PCOS) and matched control subjects.

Research design and 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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Adolescent
  • Adult
  • Androstenedione / pharmacology
  • Dehydroepiandrosterone Sulfate / pharmacology
  • Dose-Response Relationship, Drug
  • Estradiol / pharmacology
  • Female
  • Glucose / administration & dosage
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacology
  • Insulin / administration & dosage*
  • Insulin / pharmacology
  • Insulin Resistance
  • Male
  • Metformin / administration & dosage*
  • Metformin / pharmacology
  • Omentum / drug effects
  • Omentum / metabolism
  • Organ Culture Techniques
  • Polycystic Ovary Syndrome / drug therapy*
  • Polycystic Ovary Syndrome / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Chemokine / blood*
  • Receptors, Chemokine / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Testosterone / pharmacology
  • Up-Regulation / drug effects
  • Young Adult

Substances

  • CMKLR1 protein, human
  • Hypoglycemic Agents
  • Insulin
  • RNA, Messenger
  • Receptors, Chemokine
  • Testosterone
  • Androstenedione
  • Estradiol
  • Dehydroepiandrosterone Sulfate
  • Metformin
  • Glucose