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Discovery of Fruit Fly Pancreas Points to Possible Diabetes Cures, Say Stanford Researchers
Discovery of Fruit Fly Pancreas Points to Possible Diabetes Cures, Say Stanford Researchers -- Posted by Gumbo on 11-02-04 18:35
Discovery of Fruit Fly Pancreas Points to Possible Diabetes Cures, Say
Stanford Researchers
STANFORD, Calif., Sep 15, 2004 (BUSINESS WIRE) -- Fruit flies have cells
that function like a miniature pancreas. That's good news not only for the
flies, but also for researchers hoping to use the tiny insects to develop
cures for diabetes.
Almost two years ago Seung Kim, MD, PhD, assistant professor of
developmental biology and of medicine at the Stanford University School of
Medicine, and colleagues including then-postdoctoral scholar Eric Rulifson,
PhD, found cells in the fruit fly brain that make insulin. These cells tell
the fly's energy-storing organ, called a fat body, to store sugar and fat
after a meal. In research published in the Sept. 16 issue of Nature the
scientists report finding the other crucial half of the pancreatic
equation -- cells producing a glucagon like hormone.
Together, glucagon and insulin act as a thermostat keeping blood sugar
within a normal range. Islet cells produce insulin to lower blood sugar
after a meal. When the amount of sugar in the blood dips between meals,
other pancreatic cells produce glucagon to raise it.
"Without glucagon or insulin you're in big trouble," Kim said. "We found
that's also true in flies."
Kim thinks the two cell types in flies represent a primordial pancreas that
scientists can study to better understand how the insulin- and
glucagon-producing cells develop and function in humans. An immediate
application could be testing new drugs before trying them in more expensive
lab animals such as mice.
The flies could also provide insights into how pancreatic islet cells
form -- information that could help Kim and his colleagues devise ways of
coaxing stem cells to develop into pancreatic cells. "We can try to find out
what regulates the development of those cells and use that information to
help make human islet cells," he said, adding that stem cells could
potentially be used to replace the lost insulin-producing cells in people
with diabetes.
About 300,000 people in the United States have type-1 diabetes, in which the
body's immune system destroys pancreatic cells that produce insulin. Without
insulin, the muscles and liver don't receive a signal to take up sugar from
the blood after a meal. The excess sugar binds to proteins including those
that line the blood vessels. If people don't carefully control their blood
sugar using injected insulin they can end up with heart disease, blindness,
kidney disease or require amputations.
Although the insulin- and glucagon-making cells in fruit flies aren't
clumped together in a solid organ such as the human pancreas, they
faithfully mimic the functions of their human counterparts. When Kim and
Rulifson destroyed the insulin-producing cells, causing the equivalent of
human diabetes, the fat body no longer received a signal to store sugar and
the fly's blood sugar skyrocketed. Wiping out the glucagon-producing cells
caused the blood sugar to plummet, as in the potentially fatal human
condition known as hypoglycemia.
In addition to producing similar molecules, flies and humans have a
comparable mechanism for regulating blood sugar, the researchers found. A
protein on the insulin-producing and glycogen-producing cells in humans
alters its shape when it detects changes in energy levels within the cell.
This change triggers the cell to release insulin or glucagon as needed to
keep blood sugar and energy levels within a normal range.
Fruit flies have that same protein, but it's found only on the cell that
makes the glucagon like protein, called AKH. Kim and Rulifson, now an
assistant professor at the University of Pennsylvania, speculate this means
that the most ancient hormonal regulators of metabolism first secreted
glucose.
Kim and Rulifson found that the conserved protein, called the sulfonylurea
receptor or Sur, regulates the release of AKH, similar to its role in human
cells. They found that the protein in flies is so similar to the human
protein that it responds to common drugs used by diabetics called
sulfonylureas. Prescribed to millions of people with diabetes, these drugs
work by helping Sur change shape and allow islet cells to release insulin.
These same drugs act on Sur in flies, but the result is a release of AKH
rather than insulin.
With so many similarities in how the cells detect and regulate blood sugar,
Kim thinks the fruit fly's primordial pancreas will be a useful tool for
scientists studying both diabetes and hypoglycemia in humans.
"This innovative research by Drs. Kim and Rulifson raises the exciting
possibility that the fruit fly may serve as a model organism for discovering
drugs that affect glucose regulation and hypoglycemia and for better
understanding beta cell and islet development," said Richard Insel, MD,
executive vice president for research at the Juvenile Diabetes Research
Foundation in New York.
Stanford University Medical Center integrates research, medical education
and patient care at its three institutions -- Stanford University School of
Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital
at Stanford. For more information, please visit the Web site of the medical
center's Office of Communication & Public Affairs at
http://mednews.stanford.edu.
SOURCE: Stanford University Medical Center
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