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Regulation of adipose tissue metabolism in women
Summary
In women, androgen excess may be a modifiable risk factor for metabolic syndrome and type 2 diabetes. We are investigating the mechanism by which androgens induce insulin resistance in female adipose tissue, and also the effects on adipose tissue metabolism of drugs commonly used in women with androgen excess, such as spironolactone.
Description
Insulin resistance is the key defect underpinning the development of the metabolic syndrome and type 2 diabetes.
In recent years it has been shown that adipose tissue, via communication with other tissues, plays a pivotal role in determining whole body insulin sensitivity.
The development of insulin resistance in adipose tissue is linked to inflammation which is mediated by adipose tissue macrophages.
Androgens have long been known to regulate various aspects of adipose tissue function. Our recent studies have shown that androgens impair insulin-mediated glucose uptake in the adipocytes of women. Androgen excess is a common problem in women from early adolescence onwards; in reproductive-aged women, the most frequent cause is polycystic ovary syndrome (PCOS).
It is therefore possible that androgens could contribute to the metabolic defects in PCOS by setting up a vicious cycle whereby hyperinsulinaemia causes increased ovarian androgen production which in turn contributes to insulin resistance.
In addition, we have found that spironolactone, a drug commonly used in women with androgen excess, has potentially beneficial effects on glucose metabolism and inflammation in adipose cells. These effects of spironolactone were independent of androgen receptor (AR) antagonism and are possibly mediated by mineralocorticoid receptor (MR) antagonism.
Our in vitro studies of the effects of androgens and MR antagonists on adipose tissue metabolism in women are ongoing. We hope that our studies will lead to targeted therapies for the metabolic syndrome in women.
Funding
National Health and Medical Research Council
Selected Publications
Corbould A. Effects of androgens on insulin action in women: is androgen excess a component of female metabolic syndrome? Diabetes-Metabolism Research and Reviews. 2008 Oct;24(7):520-32.
Corbould A. Effects of spironolactone on glucose transport and interleukin-6 secretion in adipose cells of women. Horm Metab Res. 2007 Dec;39(12):915-8.1.
Corbould A. Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women. J Endocrinol. 2007 Mar;192(3):585-94.