Removing the “Brake Signals” Could Benefit Beta Cell Regeneration

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The loss of the pancreas’s beta cells, which produce insulin, leads to type 1 diabetes (T1D). But there are other cells in the pancreas besides beta cells. There are alpha cells, which normally make the hormone glucagon, and delta cells, which make the hormone somatostatin. In a surprise twist, though, alpha and delta cells can spontaneously engage in insulin production when beta cells are lost. This gives scientists an inroad into, potentially, converting alpha and delta cells, after they start producing insulin, into beta cells, possibly leading to a cure for T1D.

Pedro Herrera, Ph.D., and his team of investigators, though, wanted to access the alpha cells and find out why they weren’t converting all the way into beta cells after turning on insulin. In a paper published in Nature Cell Biology, they found that, while they activate insulin production, they also increased expression of other alpha cell genes, seemingly enforcing the alpha cell fate and opposing conversion into beta cells. But “taking the brakes off” the local signals could lead to alpha to beta cell conversion, potentially.

“Now that we are beginning to understand the mechanisms of this cellular plasticity, we believe that these adaptive cell identity changes could be exploited in future new treatments,” says Dr. Herrera.

This study was co-funded by JDRF and Eli Lilly. In addition to Dr. Herrera, JDRF supported investigators, either now or in the past, who were authors include Mark A. Magnuson, M.D., Takeshi Miyatsuka, Ph.D., Maike Sander, M.D., and Melissa K. Thomas, M.D., Ph.D.

By Alexandra Mulvey