The project began with a straightforward goal: to understand the chemical basis of lifestyle-related diabetes. But the results raised the possibility of a solution to a very different medical problem: helping physically disabled people get the benefits of exercise.
The project – which was backed by a European Research Council (ERC) grant in 2008 – is a great example of the importance of frontier research according to its leader Professor Juleen Zierath, a physiologist at the Karolinska Institute in Stockholm. ‘I could hardly have imagined that our research would take us in this direction,’ she said.
Since 1986, Prof. Zierath has been investigating how lifestyle-related diabetes, known as Type 2 diabetes, develops. Her group had discovered that the DNA of people with the disease is chemically ‘marked’ with more methyl groups – a hydrocarbon – than normal.
That’s important because these methyl groups inhibit the ability of the muscles to metabolise sugar and fat. With fewer methyl groups in place, the muscle finds exercise easier.
Her team had also discovered that these markers disappear when obese people – who are at greater risk of Type 2 diabetes – undergo weight-loss surgery. Using her ERC grant, Prof. Zierath then went on to prove that exercise, which is known to reduce susceptibility to Type 2 diabetes, had the same effect on the number of methyl group markers.
But the study did not end there. The research team artificially contracted rodent muscle cells in culture in the lab by stimulating them with caffeine, and found that the same loss of methyl groups occurred. This suggested that artificial stimulation could give people the benefits of exercise, even if a physical disability – for example, being confined to a wheelchair – prevented them from exercising normally.
Such therapy is probably a long way off, but the prospect has at least been raised – and that would not have come about without the ERC grant, said Prof. Zierath. ‘Five years of sustained funding at a high level allowed us a lot of breathing room, a lot of freedom, and an opportunity to relax and test different ideas,’ she added.
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