New Findings about the Transformers: Alpha Cells

Alpha cells and beta cells are the yin and yang of the pancreas. Whereas beta cells secrete the hormone insulin and lower blood glucose levels, alpha cells secrete the hormone glucagon, which raises them. Normally, the two work in tandem to regulate blood glucose levels and keep them in check. So what happens when nearly all of the alpha cells are destroyed? Surprisingly little, according to new research from the University of Geneva in Switzerland.

Led by Pedro Herrera, Ph.D., the researchers found that when they destroyed nearly all the alpha cells in the pancreas of a mouse, the body was able to maintain tight glucose control nearly as well as in a mouse with a full set of alpha cells. The results show that alpha cells are largely dispensable for maintaining tight glucose control and are, for the most part, not needed for beta cells to function.

“And that’s really good news,” says Dr. Herrera, the 2011 recipient of JDRF’s Gerold & Kayla Grodsky Basic Research Scientist Award. “Because now we know that if we can come up with some treatment that could convert almost all alpha cells to beta cells, it wouldn’t disrupt the body’s ability to maintain tight glucose control.”

In 2010, Dr. Herrera and his team made a breakthrough in the field of beta cell regeneration. They showed that when they destroyed all of the beta cells in the pancreas, approximately 5 to 10 percent of the glucagon-producing alpha cells began spontaneously converting into insulin-producing beta cells, in an apparent attempt to restore balance between these two important cell types.

Even though only a small number of alpha cells converted into beta cells, Dr. Herrera and his team saw it as an opportunity. If the body is able to spontaneously convert alpha cells into beta cells, then perhaps there are opportunities to design drugs that mimic this effect and “reprogram” alpha cells to convert them to beta cells. If so, scientists could try to exploit those mechanisms to reprogram a large portion of alpha cells into beta cells—enough to restore glucose control in people with T1D.

But before they could take on that feat, the researchers first had to make sure that in fixing one problem, they did not introduce another. That is, they had to first see how the body responded when nearly all its alpha cells in the pancreas were depleted.

Amazingly, with 98 percent of the alpha cells destroyed, the few remaining alpha cells were able to keep up with the entire workload of secreting glucagon when glucose levels were low. Furthermore, the body’s response to high levels of blood glucose remained unaffected, showing that a loss of alpha cells didn’t change the way that beta cells perform, either.

“This work suggests that if you switch most of the alpha cells in your body into beta cells, you will still be able to make enough of the hormone glucagon,” says Andrew Rakeman, Ph.D., senior program manager of beta cell therapies at JDRF. “It’s an important advance because it provides further support that a therapeutic strategy for converting alpha cells to beta cells is feasible.”