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Fruit Fly Pancreas Points to Possible Diabetes Cures
Posted: Wednesday, September 22, 2004
Almost two years ago Seung Kim, MD, PhD, assistant professor of developmental biology and of medicine at the Stanford University School of Medicine, 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, now find the other crucial half of the pancreatic equation -- cells producing a glucagonlike hormone.
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.
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.
Kim and Rulifson found found that the protein in flies is so similar to the human protein that it responds to common drugs used by diabetics called sulfonylureas. 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.
"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.
Source: Diabetes In Control.com:
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