Tan, Bee K., Heutling, Dennis, Chen, Jing, Farhatullah, S., Adya, Raghu, Keay, Stephen D., Kennedy, C. Richard, Lehnert, Hendrik and Randeva, Harpal S.. (2008) Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance. Diabetes, Vol.57 (No.6). pp. 1501-1507. ISSN 0012-1797

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Abstract

OBJECTIVE-Polycystic ovary syndrome (PCOS) is associated with insulin resistance and obesity. Vaspin (visceral adipose tissue-derived serine protease inhibitor) levels increase with hyperinsulinemia and obesity. Currently, no data exists on vaspin in PCOS women. We therefore assessed mRNA and protein levels of vaspin, including circulating vaspin, from subcutaneous and omental adipose tissue of PCOS women and matched control subjects. Ex vivo regulation of adipose tissue 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 enzyme-linked immunosorbent assay. The effects of D-glucose, insulin, and gonadal and adrenal steroids on adipose tissue vaspin were analyzed 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 omental adipose tissue of PCOS women. Interestingly, in omental adipose tissue 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 were predictive of changes in serum vaspin levels (P = 0.014). CONCLUSIONS-We report, for the first time, elevated serum and omental adipose tissue levels of vaspin in overweight PCOS women and ex vivo regulation of vaspin, predominantly by glucose. More importantly, metformin treatment decreases serum vaspin levels, a novel observation.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology R Medicine > RG Gynecology and obstetrics
Divisions:	Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Metformin, Polycystic ovary syndrome, Adipose tissues, Serine proteinases -- Inhibitors, Insuline resistance, Overweight women -- Health and hygiene
Journal or Publication Title:	Diabetes
Publisher:	American Diabetes Association
ISSN:	0012-1797
Date:	June 2008
Volume:	Vol.57
Number:	No.6
Number of Pages:	7
Page Range:	pp. 1501-1507
Identification Number:	10.2337/db08-0127
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	General Charities of the City of Coventry
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URI:	http://wrap.warwick.ac.uk/id/eprint/29923

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