Insulin and Metformin Regulate Circulating and Adipose Tissue Chemerin
- Bee K. Tan1,
- Jing Chen1,
- Syed Farhatullah1,
- Raghu Adya1,
- Jaspreet Kaur1,
- Dennis Heutling2,
- Krzysztof C. Lewandowski1,3,
- J. Paul O'Hare1,
- Hendrik Lehnert1,4 and
- Harpal S. Randeva1
- 1Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, U.K.;
- 2Division of Endocrinology and Metabolism, Magdeburg University Hospital, Magdeburg, Germany;
- 3Department of Endocrinology and Metabolic Diseases, The Medical University of Lodz and Polish Mother's Memorial Research Institute, Lodz, Poland;
- 41st Medical Department, University of Lübeck Medical School, Lübeck, Germany.
- Corresponding author: Harpal S. Randeva, harpal.randeva{at}warwick.ac.uk.
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.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received November 3, 2008.
- Accepted May 19, 2009.
- © 2009 by the American Diabetes Association.
