New Hope to 'cure' type 1 & 2 diabetes?
(Top Posts - Social/Legal - 062008)

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Stomaching diabetes
By Patrick Barry
June 19th, 2008

A radical technique for treating diabetes
could recruit cells in the gut to make insulin
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Excerpts [with inserts, not part of original
article, in brackets]:

SAN DIEGO - If your pancreas fails you,
go with your gut.

Inserting a gene into gut cells in mice enabled
those cells to take over the pancreas's job,
producing insulin after meals, according to
unpublished research announced June 18 in
San Diego at the Biotechnology Industry
Organization International Convention. The
work may offer a novel way to treat diabetes.

"This is the first time that we've engineered
a tissue that is not the pancreas to manufac-
ture insulin" in animals, says researcher
Anthony Cheung, a molecular biologist
and cofounder of enGene, a biotechnology
company based in Vancouver, British Col-

"It's going to be very beneficial to patients,"
comments Christopher Rhodes, research
director of the Kovler Diabetes Center at
the University of Chicago, who enGene
asked to critique the research. "It's a very
promising approach." Cheung says that he
and his colleagues hope to begin safety
trials in people by 2010.


Existing treatments include frequent intra-
venous injections of insulin [oral medica-
tions for type 2 diabetics, insulin pumps
for type 1 diabetics] and transplant of pan-
creas cells from cadavers into diabetes
patients [usually only used for the most
severe cases, and availability of trans-
plants is only sufficient enough to treat
the most severe cases].

Scientists have also proposed using stem
cells to make fresh pancreas cells for trans-
plant. The new research presents the possi-
bility of recruiting cells at the junction
between the stomach and small intestines
to make insulin instead.

"It's a lot simpler than transplanting beta
cells," the insulin-producing cells of the
pancreas, Cheung says. The new approach
could potentially treat both juvenile [type 1]
and late-onset [type 2] diabetes, Rhodes

New gene, new job

The gut cells, called K cells, sit at the sur-
faces of tiny, fingerlike projections in the
gut lining. These cells normally release a
hormone called glucose-dependent insulin-
otropic polypeptide, or GIP, into the blood-
stream after meals. This hormone helps pre-
pare the pancreas to make insulin to respond
to the post-meal surge of blood sugar, so the
K cells are roughly synchronized with the

Cheung's team created tiny rings of DNA
containing the gene for insulin. To coax the
cells into releasing insulin at the right time,
they also included a snippet of DNA on the
ings that normally activates GIP after a meal.
But because the snippet was linked to insulin
instead of GIP, once the rings were inserted
into K cells, the cells that produced GIP also
produced insulin when the body needed it.

Using viruses to deliver DNA into cells is a
common technique in gene therapy, but it
risks triggering cancerous mutations. Instead,
the researchers developed a new gene-delivery
method that bundles the ring of DNA inside
microscopic spheres made of a material called
chitosan, which is extracted from shrimp shells.

These spheres, each about 100 nanometers
across, also contain a second ring of DNA
encoding a gene that controls where along the
animals' chromosomes the insulin gene gets
inserted. Previous research by Michèle Pamela
Calos of Stanford University and her colleagues
showed that none of the 370 possible insertion
points trigger cancer.

Rather than injecting a dose of these micro-
scopic spheres into the bloodstream, Cheung's
team sprayed the spheres directly onto the gut
lining using a modified endoscope, a tube-
shaped tool that doctors use to look down a
person's throat at their intestines. That way,
the spheres only get absorbed by cells of the
gut lining.

Cheung says that it might also be possible for
patients to ingest the spheres in a drink or a

In the experiments, the genetically altered K
cells responded when the animals ate sugar
by producing insulin with the same timing as
a healthy pancreas. The K cells performed the
new task for about five months. Because cells
of the gut lining are constantly replaced, the
treatment would have to be reapplied periodic-
ally, Cheung says.

Previous work by Cheung and his colleagues
showed that mice engineered to have the alt-
ered K cells from birth remained alive and
healthy after the insulin-producing beta cells
of the pancreas had been destroyed. In separ-
ate experiments using mice with a juvenile
[type 1] diabetes-like condition in which beta
cells are attacked by the animals' immune
systems, K cells were not attacked even when
altered to produce insulin.

The team has begun testing the technique on
pigs, whose intestines are very similar to human

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