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Diabetes Publish Ahead of Print published online ahead of print April 4, 2008
DOI: 10.2337/db08-0127

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Original Research

Metformin Decreases the Adipokine Vaspin in Overweight Women with the Polycystic Ovary Syndrome: Concomitant Improvement in Insulin Sensitivity and a Decrease in Insulin Resistance

Bee K Tan, MBBS1, Dennis Heutling, MD2, Jing Chen, PhD1, S Farhatullah, MSc1, Raghu Adya, MBBS, MSc1, Stephen D Keay, FRCOG, MD1, C Richard Kennedy, FRCOG1, Hendrik Lehnert, FRCP, MD1,,2, and Harpal S Randeva, FRCP, MD, PhD1,,2

1Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
21st Medical Department, University of Lübeck Medical School, Lübeck, Germany

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and obesity. Vaspin levels increase with hyperinsulinemia and obesity. Currently, no data exists on vaspin in PCOS women.

Objective: To assess mRNA and protein levels of vaspin from subcutaneous (sc) and omental (om) adipose tissue (AT) of PCOS women and matched controls, including circulating vaspin. Ex vivo regulation of AT vaspin and the effects of metformin treatment on circulating vaspin levels in PCOS subjects were also studied.

Research Design and Methods: Real-time RT-PCR and western blotting were used to assess mRNA and protein expression of vaspin. Serum vaspin was quantified by ELISA. The effects of D-glucose, insulin, gonadal and adrenal steroids on AT vaspin were analysed ex vivo.

Results: There were significantly higher levels of circulating vaspin (P < 0.05), vaspin mRNA (P < 0.05) and protein (P < 0.05) in om AT of PCOS women. Interestingly, in om AT explants, glucose significantly increased vaspin protein levels and secretion into conditioned media (P < 0.001). Also, after 6 months of metformin treatment, there was a significant decrease in serum vaspin levels in PCOS women (P < 0.001). Furthermore, multivariate regression analysis revealed that following metformin therapy, changes in circulating glucose levels was predictive of changes in serum vaspin levels (P = 0.014).

Conclusions: We report for the first time elevated serum and om AT levels of vaspin in overweight PCOS women, and its ex vivo regulation mainly by glucose. More importantly, metformin treatment decreases serum vaspin levels, a novel observation.


Correspondence: Harpal.Randeva{at}warwick.ac.uk

Key Words: Metformin • vaspin • PCOS • adipose tissue • adipocyte • adipokine • insulin resistance • metabolic syndrome • glucose


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