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[IP] Maybe pass this stuff to roche???
Possible new way to deliver insulin
Research in mice deemed promising for diabetes patients
Feb. 3 — A technique that allows insulin hormone to be stored in cells and
then released as needed by a pill eventually may offer a treatment for
diabetes that does not require daily injections, researchers say.
THE EXPERIMENTS, thus far, have been performed only on mice, but researchers
say a system using an implanted insulin gene may be ready for human testing
within two years.
In a study to be published Friday in the journal Science, researchers at Ariad
Pharmaceuticals in Cambridge, Mass., and at Memorial Sloan-Kettering Cancer
Center in New York said the cell engineering technique was able to control
diabetes in a group of laboratory mice and is now being tested on larger
Tim Clackson, senior author of the study, said that the technique causes
insulin, or some other protein, to clump inside a cell with another protein,
forming a molecule that is too large to leave the cell. A drug, given as a
pill, breaks up the clump, allowing the insulin to flow into the blood stream
in a way that mimics the spurt of hormone normally secreted by the pancreas.
The amount of protein (such as insulin) that gets released is directly related
to the amount of drug that is given,” said Clackson. “The more drug you give,
the more protein gets released into circulation.”
In diabetes, the technique theoretically would allow a patient to precisely
control insulin levels in the blood by a pill. Many diabetics now must control
insulin levels by injection.
A common type of diabetes is caused by the failure of the pancreas to produce
an appropriate amount of insulin to metabolize glucose, or sugar, levels in
the blood stream. Normally, the pancreas releases insulin in response to the
detected level of glucose.
Dr. Richard Furlanetto, scientific director of the Juvenile Diabetes
Foundation, said the experimental technique “is very clever science” but might
To be truly useful, it would have to be coupled to a system that would release
the hormone in direct response to the levels of glucose in the blood,” said
However, Furlanetto said the technique could be very useful in treating
conditions that require periodic secretion, or pulsed release, of some needed
protein, such as growth hormone.
In the experiment, Clackson and his colleagues inserted into laboratory cells
genes that produce insulin and a protein that naturally clumps, or aggregates,
with insulin. Once inside the cells, the genes produce the two proteins. They
form clusters that are too large to pass through pores in the walls of the
The engineered cells were then injected into the muscles of mice that are
diabetic and normally develop high levels of glucose in the blood.
When these mice were fed a drug that caused the protein clusters to split
apart, insulin was released into the bloodstream and glucose levels dropped to
In control mice, which had the engineered cells but were not given the oral
drug, insulin did not appear in the bloodstream and glucose levels stayed
The insulin stays in the compartments of the cell and has no toxicity or
adverse effects. It just sits there,” said Clackson. “Only when the animal
receives the drug do the aggregates break apart and then flow into the
Clackson said the experiment was only a “proof of concept” for the technique.
The next step is to transfer genes directly into body muscle cells, a common
gene therapy technique. To do this, the target genes will be put into a virus
that would be injected and deliver the genes into muscle cells, he said.
Although the initial target of the research is diabetes, Clackson said the
protein clustering technique could also be used to deliver any protein that
the body needs in spurts. For instance, the technique could be used to
administer growth hormone, or proteins that would provide pain relief,
appetite control or correct brain chemistry, he said.
© 2000 Associated Press. All rights reserved. This material may not be
published, broadcast, rewritten or redistributed.
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