By
Dan Vergano, Medical Tribune News Service
A rain-forest fungus may someday provide diabetics with a pill
that corrects their ailment, according to pharmaceutical corporation
researchers.
People
with diabetes suffer from increased blood sugar because their
bodies either lack insulin or produce too little of the hormone.
Some 16 million individuals endure the disease nationwide, according
to the American Diabetes Association in Alexandria, Va. At least
half a million of them must inject themselves with insulin, which
cannot be taken by mouth because it is broken down by stomach
acids.
After
sifting through some 50,000 natural and man-made compounds, researchers
led by Bei Zhang of Merck Research Laboratories in Rahway, N.J.,
found an extract from an African forest that triggered insulin
pathways in hamster cells floating in a Petri dish.
Furthermore,
researchers significantly reduced diabetes signs -- low insulin
production, high blood sugar and limited ability to respond to
insulin -- in diabetic mice with oral doses of the active molecule
from the fungus. In one week, blood sugar levels dropped more
than 50 percent of the way toward normal in these obese mice,
which were genetically engineered to have diabetes.
``It
just worked phenomenally well,'' said study co-author Roy G. Smith,
director of the Huffington Center on Aging at Baylor College of
Medicine in Houston. ``The breakthrough here is a small molecule
that mimics the activity of insulin,'' he said of the study, which
appeared in this week's issue of the journal Science.
Stomach
acids fail to destroy the molecule as they do insulin, leading
the researchers to speculate it may one day form the basis for
an insulin pill, according to Smith. In healthy people, insulin
instructs cells to remove sugar from the bloodstream by bonding
to a chemical keyhole on the outside of cells called a receptor.
After a large meal, the body releases insulin into the bloodstream.
In
some individuals, the pancreas cells that secrete insulin don't
function at all, causing so-called type 1 or juvenile-onset diabetes.
In others, metabolic changes associated with obesity or genetics
can trigger insensitivity to insulin among cells, causing type
2 or adult-onset diabetes.
Diabetes,
the seventh leading cause of death in the United States, can cause
kidney damage, blindness and circulation problems and has been
linked to hardening of the arteries.
The
molecule discovered by Merck's researchers, dubbed L-783,281,
activates a part of the insulin receptor from within cells, instead
of outside them as the larger insulin molecule does, according
to the researchers.
``The
amazing thing is how it discriminates between receptors,'' commented
Smith, whose colleagues tested the molecule to ensure it didn't
trigger other pathways associated with tumor growth in cells.
Not
only did the molecule reduce the blood sugar taken in by test
mice, said Smith. It boosted cells' sensitivity to insulin as
well, increasing their blood-sugar-lowering power.
According
to Merck, research on turning the molecule into a pill remains
at the basic science level. Merck has not completed animal toxicity
tests on L-783,281, the first steps in testing a new drug, according
to Zhang. ``What [the molecule] will accomplish remains to be
seen,'' said Dr. Gerald Bernstein of the American Diabetes Association.
Some research indicates the pathway on the insulin receptor triggered
by L-783,281 may not be the most important one, a reason for caution,
he added.
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