4 March 2002

Drugs to combat effects of a couch potato lifestyle

photo of Prof Hardie

Discoveries made at the University of Dundee are helping in the development of drugs that fool your body into thinking that your are actively exercising even when you are not, and may help in the fight against the current increase in the incidence of obesity and Type 2 diabetes.

Professor Grahame Hardie - Professor of Cellular Signalling in the School of Life Sciences - recently rated a five star department in the Research Assessment Exercise- discovered a system called AMP-activated protein kinase (AMPK)in the 1980s. AMPK is switched on by exercise, and triggers the "burning off" of carbohydrate and fats by muscle, preventing them from being stored in fat tissue. The system is thought to be responsible for the beneficial effects of exercise in warding off obesity and Type 2 diabetes, and drugs that activate AMPK would mimic this.

The drug metformin (derived from the medieval herbal remedy, French lilac) is already widely used to treat Type 2 diabetes, although it was not previously understood how it worked. Now however an explanation has been provided: it switches on the AMPK system. Prof. Hardie is working with pharmaceutical companies to develop a new generation of AMPK-activating drugs that may be more effective than metformin.

Insulin is the hormone that stimulates tissues to take up glucose from the blood. Type 1 diabetes (more common in children) is due to a lack of insulin, whereas the Type 2 form is due to the body failing to respond properly to insulin. The incidence of the Type 2 form is rocketing across the world, probably due to the modern urban lifestyle of high-calorie, high-fat "junk" foods combined with lack of exercise. As many as 5% of the Scottish population may already have the disease, but because of its long-term consequences such as increased susceptibility to heart attacks, strokes, blindness, kidney damage and foot amputations, it is thought to account for over 10% of all health service expenditure. Although the Type 2 form was previously only diagnosed in older people, it has recently been found in young people who are overweight.

Professor Hardie said: "We discovered that the AMPK system is activated in cells when they run short of energy, and it triggers the uptake and metabolism of glucose and fats. Clearly the best policy is to eat sensibly and exercise regularly, which will greatly reduce your chances of becoming overweight and developing Type 2 diabetes. However when regular exercise is not possible, such as in older people where other health problems may prevent it, drugs that activate AMPK are an alternative. They may help to combat the effects of a sedentary lifestyle".

Professor Hardie is co-ordinator of a European commission project on AMPK worth 1.1 million. He also recently received a new grant (1 million) from the Wellcome Trust for his studies on the system, and holds grant worth 0.25 million from the charity, Diabetes UK. Professor Hardie is also organising an international conference on AMPK where experts from across the world will discuss these developments, to be held in the West Park Centre, Dundee, this September.