Source of Insulin-Secreting Cells Found

Discovery opens new avenues to type 1 diabetes research

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By
HealthDay Reporter

WEDNESDAY, May 5, 2004 (HealthDayNews) -- In a finding that might seem obscure but is nonetheless important to many people with diabetes, researchers have discovered where the body's insulin-making beta cells come from: other beta cells.

It is a discovery that will help guide research aimed at helping people with type 1 diabetes, a genetic condition in which the immune system attacks and destroys beta cells, said Dr. Douglas A. Melton, a professor of natural sciences at Harvard University and leader of the group reporting the finding in the May 6 issue of Nature. One goal is a treatment that will supply new beta cells to replace those destroyed by the immune attack.

Perhaps 10 percent of Americans with diabetes have type 1, which usually appears early in life. The rest have type 2 diabetes, which generally occurs in adulthood as the body gradually loses its ability to metabolize sugar.

The study, financed by the Howard Hughes Medical Institute, tested three possible sources of new beta cells: embryonic stem cells, which are made very early in life and can be transformed into any kind of specialized cell; adult stem cells, produced later in life, with a more limited ability to be transformed; and beta cells themselves.

The researchers developed a genetic tag that was taken up only by beta cells. They injected that tag into mice shortly after birth, after embryonic stem cells had begun to specialize and when adult stem cells had begun to appear.

Then they waited for half the life span of the mice and looked for the genetic tag. They found it in all the beta cells in those mice, showing that those beta cells had not come from adult stem cells, which had not taken up the tag. Instead, the original beta cells had divided to form new cells.

That was a surprise, Melton said, because no one had realized that beta cells had a potentially useful ability to produce more beta cells.

"It hadn't been appreciated how extensive this potential was," he said.

One important implication for research is that the emphasis shifts from the effort to produce beta cells from adult stem cells, Melton said.

"There are two likely avenues of research," he said. "One is seeing how to get beta cells to divide more efficiently. The other is to see how to get embryonic stem cells to differentiate into beta cells."

"This does point the field in a different direction, which is that apparently normal beta cells can replenish themselves," said Kenneth S. Zaret, leader of the cell and developmental biology program at the Fox Chase Cancer Center in Philadelphia, who wrote an accompanying editorial. "Until now, the field has largely focused on embryonic or adult stem cells."

There still is room for a different approach, Zaret said. "This doesn't exclude that other lineages can give rise to other beta cells," he said. "It does say that beta cells have an extensive replicative capacity, that beta cells can give rise to beta cells."

Melton said his group is working on ways to improve production of beta cells from both embryonic stem cells and beta cells. But that effort will solve only part of the type 1 diabetes problem, he acknowledged. The other part is protecting new beta cells from being destroyed by the immune system.

"We're working on the supply side of this," he said. "If we can solve the supply side problem, then we can turn attention to blocking the immune response."

More information

You can learn all about type 1 diabetes from the National Library of Medicine, which also has a primer on stem cells.

SOURCES: Douglas A. Melton, M.D., professor, natural sciences, Harvard University, Cambridge, Mass.; Kenneth S. Zaret, Ph.D, leader, cell and developmental biology program, Fox Chase Cancer Center, Philadelphia; May 6, 2004, Nature

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