RESEARCHERS say high doses of aspirin block action of enzyme, cause blood sugar levels to drop in type 2 diabetics

Thursday, August 30th 2001, 12:00 am

By: News On 6

WASHINGTON (AP) _ In a discovery that may lead to new therapies for type 2 diabetes, researchers have solved a decades-old mystery of why high doses of aspirin lower blood sugar levels and make cells more sensitive to insulin.

In 1876, a doctor discovered that his diabetic patients improved with doses of an aspirin-like drug. He reported the result, but there was little interest by others.

In 1901 and later in the 1950s, still other doctors also found that diabetics seemed to get better for a time on large doses of aspirin. But nobody knew why this happened and there was no follow up.

Until now. Researchers at Harvard University and the University of California, San Diego, report Friday in the journal Science that in studies using diabetic mice they have found that high doses of aspirin block the action of an enzyme called ikB kinase Beta, or ikkBeta, and that this, in turn, causes the body to be more sensitive to insulin. The result is that blood sugar levels drop.

``This study helps us understand what causes insulin insensitivity due to obesity and a high fat diet,'' said Dr. Steven E. Shoelson, a researcher at the Joslin Diabetes Center and the Harvard Medical School in Boston and lead author of the study.

Although aspirin can have some effect against diabetes over time, Shoelson said the dosage required is dangerous. To lower blood sugar in a diabetic, he said, would require 6-8 grams of aspirin for long periods of time. Two regular aspirin tablets are about 0.65 grams.

High doses of aspirin, although used for some disorders, can cause serious side effects, such as intestinal bleeding, dizziness and nausea.

``We strongly recommend against anybody considering treating their diabetes with aspirin,'' Shoelson said.

What Shoelson and his co-workers are now looking for is a chemical molecule that blocks the action of ikkBeta without the side effects of aspirin.

``We now have a defined protein target and we are trying to find drugs against it,'' he said.

Some preliminary studies in mice have been promising, said Shoelson, but it will take years of research before any result can be tried in humans.

Dr. Marjorie Mau, a diabetes researcher at the University of Hawaii, said ``it would be exciting'' if the researchers develop a new enzyme target for a diabetes drug, but she cautioned that much more study is needed before such a drug could ever be offered to patients.

``There is a lot of stuff that looks promising in mice that just doesn't pan out over time,'' she said. ``It is a long way to the clinic and mice are not humans.''