Replacements for some diabetics’ missing insulin-producing cells might be found in the patients’ own pancreases, a new study in mice suggests.
Alpha cells in the pancreas can spontaneously transform into insulin-producing beta cells, researchers from the University of Geneva in Switzerland report online in Nature April 4. The study, done in mice, is the first to reveal the pancreas’s ability to regenerate missing cells. Scientists were surprised to find that new beta cells arose from alpha cells in the pancreas, rather than stem cells.
If the discovery translates to people, scientists may one day be able to coax type 1 diabetics’ own alpha cells into replacing insulin-producing cells. Type 1 diabetes, also known as juvenile diabetes, results when the immune system destroys beta cells in the pancreas. People with the disease must take lifelong injections of insulin in order to keep blood sugar levels from rising too high.
“The exciting discovery from this study is that alpha cells can spontaneously convert to beta cells without any interference from the researchers,” says Andrew Rakeman, the scientific program manager for the Juvenile Diabetes Research Foundation’s beta cell therapies program. “It’s very early and very basic research right now, but it opens up the idea that reprogramming is not just something we have to force cells to do, that it’s an intrinsic property of the cells.”
Although the immune system continually wipes out beta cells in people with type 1 diabetes, some studies have found a small number of beta cells in the pancreases of people who have had the disease for years. Some researchers thought the cells could be ones that had somehow survived the immune system’s ongoing assault, but that “is very unlikely, because the immune system is very, very efficient,” says Pedro Herrera, a developmental biologist at the University of Geneva Medical School and a leader of the new study. So that suggested to Herrera and his colleagues that the pancreas was making new beta cells.
Researchers treated mice to destroy beta cells in the pancreas, and kept the mice alive by giving them insulin. After six months, the mice no longer needed the extra insulin because their pancreases had regenerated between 4 percent and 17 percent of the beta cells that had been present before the treatment. Although only a fraction of beta cells regenerated, it was enough to provide the insulin the mice needed to maintain nearly normal blood sugar levels.
When the researchers examined the mice they found that some of the insulin-producing cells also made glucagon, which is normally made by alpha cells. The finding suggested that the beta cells in the mice had once been alpha cells.
The researchers confirmed that hypothesis by genetically tagging alpha cells in other mice, then killing their beta cells. Newly generated beta cells carried the tags, indicating that a switch had indeed occurred.
About 5 percent of alpha cells converted to beta cells, says Fabrizio Thorel, a developmental biologist in Herrera’s group and a coauthor of the new study. “What we don’t know at the moment is whether all alpha cells have the ability to be converted to beta cells,” he says. The researchers also don’t know what signals prompt alpha cells to begin their conversion, Thorel says, but it is clear that the transformation happens only after nearly all beta cells have been wiped out.
Even if human pancreases can perform the alpha to beta conversion — and Herrera says he believes it is possible — the immune system in type 1 diabetics would kill the newly transformed cells unless researchers could figure out how to stop the immune system attack and reduce inflammation in the pancreas that accompanies diabetes. Herrera says that efforts to control the immune system could give the pancreases of type 1 diabetic patients a chance to recover at least some function. “The life of diabetics would change even if the pancreas is only able to produce 1 or 2 percent of normal insulin levels,” he says.
The team is now trying to determine if older mice retain the regenerative capacity seen in the young mice used in the study and which signal tells alpha cells to begin transforming into beta cells.
