Author: Phuongmai Truong
Institution: UC Berkeley
Date: June 2010
A recent study on diabetic mice showed that the pancreas can recreate insulin-producing cells through a cell conversion process. This process, as the scientists discovered, can effectively treat Type I diabetes. Researchers from the University of Geneva, Switzerland report this exciting result in the April 4 issue of Nature.
The pancreas has two types of cells: alpha cells that produce glucagon to raise blood sugar level, and beta cells that produce insulin to lower blood sugar level. Type I diabetes, also known as juvenile diabetes, occurs when the immune system destroys beta cells. Due to the lack of insulin-producing cells in the pancreas, people with this disease must take lifelong insulin injections to prevent their blood sugar level from rising too high.
In the new discovery at the University of Geneva Medical School, developmental biologist Pedro Herrera and his colleagues found that alpha cells in mice could transform into beta cells without any artificial interference. Initially, beta cells in the pancreas were destroyed and the mice were kept alive by insulin injections. After six months, the pancreases regenerated 4-17% of the beta cells that the mice possessed before the experiment. Although the regenerated cells are only a small fraction of the original cells, they can provide sufficient insulin to keep their blood sugar level nearly normal without insulin injections.
A closer examination revealed that some of the new insulin-producing cells also made glucagon, suggesting that the cells were once alpha cells. To confirm this hypothesis, the researchers repeated the experiment, adding a genetic tag in the alpha cells in the mice before killing the beta cells. The tags found in the newly formed beta cells suggested that cell conversion had occurred.
The result indicates a plausible explanation for cases in which a small number of beta cells are found in the pancreases of people with Type I diabetes. Since the immune system is very efficient, existing beta cells are unlikely to survive from its continuous attack. The small amount of existing beta cells must come from the alpha-beta conversion that is confirmed in mice. Biologist Fabrizio Thorel, a co-author of the new study, says that about 5% of alpha cells converted to beta cells but it is unclear whether all alpha cells are capable of such a conversion. The right conditions for this conversion are also unknown, although the researchers believe that the conversion only occurs after nearly all beta cells are killed. However, it is promising that human intervention is unnecessary to force the pancreas into creating new beta cells since the pancreas can do that on its own.
Nevertheless, one problem remains in this hopeful solution to Type I diabetes. Even if the pancreas can regenerate beta cells, the immune system eliminates them continuously, and thus there are never enough beta cells present at one time. Thus, researchers are looking for a way to control the attacks by the immune system and reduce inflammation in the pancreas, a symptom of diabetes. The immune system does not have to be stopped completely, as "the life of diabetics would change even if the pancreas is only able to produce 1-2% of normal insulin level," says Herrera.
Herrera's research group is studying whether older mice have the same capability to reproduce beta cells like the young mice in previous experiments. In addition, the biologists are trying to look for the specific signal that commands alpha cells to convert to beta cells. The results of this study and the future studies to follow offer a bright new hope in the effort to cure diabetes, which can change many lives.