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Single gene cause of insulin sensitivity may offer insight for treating diabetes
Date:9/12/2012

hought to affect perhaps one in 200,000 people, with around 300 people with the condition in the UK. PTEN's role in cell growth sees people with Cowden syndrome develop many benign polyps in their skin, mouth and bowel, and have a higher risk than the general population of developing breast cancer, thyroid cancer and womb cancer.

'PTEN is a gene that is heavily involved in processes for both cell growth and metabolism,' says first author Dr Aparna Pal of the University of Oxford. 'Given PTEN's dual role, we were interested in understanding the metabolic profile of people with Cowden syndrome. It was possible that mutations in PTEN could improve metabolism.'

The team carried out glucose tolerance tests with 15 people with Cowden syndrome and 15 matched controls. Those with Cowden syndrome had significantly higher insulin sensitivity. In collaboration with their colleagues at the Babraham Institute, the team showed that this was caused by increased activity in the insulin signalling pathway.

The researchers also noticed that the body mass index of those with Cowden syndrome appeared greater than the controls. They carried out a comparison with a much larger control group of over 2,000 individuals from the Oxford Biobank, a data and tissue resource for research established by Professor Fredrik Karpe.

This confirmed that those with Cowden syndrome had higher levels of obesity as a group than the controls. The extra body weight appeared to be caused by extra fat, and there were no differences in where the fat was stored compared to controls.

'This was a surprise. Normally insulin sensitivity goes with being lean,' says Professor Karpe.

Dr Gloyn concludes: 'We now know that mutations that inactivate the PTEN gene result in increased cancer risk and obesity, but also increase insulin sensitivity which is very likely to protect against type 2 diabetes.

'The study shows how in
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Contact: University of Oxford press office
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University of Oxford
Source:Eurekalert

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