4 March 2002
Drugs to combat effects of a couch potato lifestyle
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
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.