By Jennifer Couzin
ScienceNOW Daily News
24 January 2008
In people with diabetes, insulin-producing cells in the pancreas, called beta cells, have been destroyed or may behave sluggishly. This leaves the body unable to regulate its blood sugar. Coaxing the pancreas to make new beta cells is one of the great goals of diabetes research. Scientists debated for years whether the pancreas holds stem cells that could replenish beta cells, but in 2004, biologists led by Douglas Melton at Harvard looked for these stem cells in the pancreas of mice and failed to find them. His team instead reported that existing beta cells could multiply to form new ones (ScienceNOW, 5 May 2004).
Harry Heimberg of Vrije Universiteit in Brussels, Belgium, wondered whether there were additional sources of new beta cells. Earlier experiments in rats had found that clamping a pancreatic duct and stopping digestive enzymes from entering the small intestine roughly doubles the mass of beta cells in the pancreas. But which cells in the pancreas were generating these extra beta cells?
Heimberg and his colleagues caused the same severe injury in mice. Then they searched for pancreatic cells that might somehow turn into beta cells. To do this, they focused on the genetic marker neurogenin 3, which appears in cells slated to become beta cells when they're just beginning to develop in an embryo. Within 3 days of injury, the scientists found cells with this gene. Furthermore, preventing the gene's expression reduced beta-cell proliferation, the group reports in the 25 January issue of Cell. When these neurogenin 3 cells were taken from an adult mouse and injected into a pancreas removed from a mouse embryo, they developed into beta cells and produced insulin, suggesting that the cells were developing into new beta cells in the injured animal. Further studies found that the neurogenin 3 cells weren't making insulin before the injury. That means beta cells hadn't bolstered the beta-cell supply by themselves, as Melton had shown was possible in normal animals.
Many questions remain. Where do the cells come from, for example? The cells sit along the ducts of the organ, so they could originate as mature ductal cells that revert to an embryonic state after the injury and then become beta cells. Or, says Heimberg, they could be progenitor cells, which unlike stem cells cannot self-replenish. Other big questions are whether the neurogenin 3 cells can be coaxed to come forward in the normal human pancreas without damaging the organ, and whether they can be turned into insulin producers.
Melton suspects the cells began as mature pancreatic cells, likely from the ducts, as they don't have many characteristics of stem cells. The study, he says, shows that there's another mechanism to keep beta cells coming, which might offer a new cell source to consider in the hunt for ways to replenish beta cells.
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