New research on Diabetes

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Multi-tasking diabetes pill shows promise

14:53 18 July 03

NewScientist.com news service

An experimental multi-tasking drug for diabetes has shown promising results in mouse experiments. It could lead to a new medication for type 2 diabetes, say US researchers.

People with diabetes have difficulty balancing their body's blood sugar levels. In type 2 diabetes, people may have reduced sensitivity to the hormone insulin that enables the body's cells to take up glucose from the blood. This means that sugar in the blood can build up to dangerous levels.

Most diabetes drugs act either to increase the amount of insulin in the blood or to enhance the body's sensitivity to glucose. But the team led by scientists at Hoffman-La Roche in Nutley, New Jersey believe they have found a molecule which can do both.

The molecule, called RO-28-1675, acts on a special "glucose-sensing" enzyme called glucokinase (GK). It helps GK persuade the pancreas to make more insulin, and at the same time stimulate the liver to take up more glucose.

"There have not been that many new diabetes drugs ever discovered, and this one is unique in its mechanism of action," says team member Mark Magnuson, at Vanderbilt University, Nashville, Tennessee. "It has dramatic effects in animals, suggesting it has the potential to be a very powerful new drug."

Joseph Grippo, another team member and vice-president of metabolic diseases at Roche, says that human trials should begin in about a year. If all goes well, the drug could be on the market within five or six years, he told New Scientist.

Genetic clues

Researchers at Vanderbilt had previously cloned the gene for GK. Studies of people with rare forms of diabetes and related disorders by other research groups revealed mutations in the GK gene that both reduced and enhanced the enzyme's activity.

These clues put scientists at Hoffman La-Roche on a hunt for compounds that would alter GK activity. After trawling through a chemical library of over 120,000 compounds, the team hit upon a molecule that increased the activity of GK. From this, the more potent RO-28-1675 was developed.

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Weblinks

Hoffman-La Roche, New Jersey

American Diabetes Association

Glucokinase, Human Protein Reference Database

Diabetes UK

Science

RO-28-1675 was then tested as an oral drug in control and diabetic mice. "We essentially found that in many, many models of diabetes we could lower very high levels of blood glucose towards normal," says Grippo.

And he is very hopeful that this success will transfer to the treatment of people: "We do believe this will work - the human genetics are really compelling." Magnuson adds that the drug should be effective in nearly all cases of type 2 diabetes, not just rare kinds.

"Overall I would say that this is an interesting development in the regulation of glucose metabolism," says Matt Hunt, science information team manager at Diabetes UK. But he cautions that the drug has only been tested in rodents so far and success in humans is not guaranteed.

Journal reference: Science: (vol 301, p 370)

Shaoni Bhattacharya

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