Discovery links a tumour suppressor to diabetes drug target

Two professors in the School of Life Sciences have combined their expertise to crack a major scientific problem - with their research potentially leading to the development of improved drugs to treat diabetes.

Dario Alessi, working at the Medical Research Council Protein Phosphorylation Unit, and Grahame Hardie, at the Wellcome Trust Biocentre, have discovered that a tumour suppressor called LKB1 is the long sought after enzyme that switches on AMPK, an enzyme important in regulating the level of glucose in the blood.

This is likely to stimulate the development of improved drugs to treat Type II diabetes. Remarkably, a lack of LKB1 activity is known to be the cause of Peutz-Jeghers Syndrome, a rare inherited disease that predisposes people to many types of cancer. The discovery that LKB1 switches on AMPK therefore raises the possibility that AMPK is also important in preventing cancer and that drugs that activate AMPK may be useful for the treatment of some cancers, as well as diabetes.

Commenting on their discovery Grahame Hardie said, "The idea that LKB1 might switch on AMPK came from work I did on a related system in the simple single-cell organism, brewer’s yeast with another colleague in Dundee, Mike Stark. The idea that LKB1 might be the key was a genuine ‘Eureka’ moment, especially when I realised that Dario Alessi was already working on it and had all of the expertise necessary to test the idea. By lunchtime the following day we had done the first successful experiment to prove the idea. This shows the benefit of working in a major biomedical research centre like Dundee, where the whole is much more than the sum of its parts.

This was an extraordinary and totally unexpected result that has important implications for our general understanding of diabetes and cancer. It also demonstrates the strength of this area of research in Dundee."


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