Research points to another path toward giving diabetics the insulin-producing cells they need

Type 1 diabetes is such a life-changing illness that scores of teams around the world are looking for ways to replace the insulin-producing pancreatic cells that are destroyed in the disease.

Many of these researchers use stem cells of various types to try to generate large quantities of insulin producing cells that could be transplanted. But a few are trying to directly reprogram other pancreas cells into desired beta cells. Often called transdifferentiation, this process could be a great shortcut to getting the needed cells.

Fred Levine and his CIRM-funded colleagues at the Sanford-Burnham Medical Research Institute in La Jolla have succeeded in causing this identity change using a single peptide, which you can think of as a very small protein. The islet cells in our pancreas contain beta cells and alpha cells in close proximity. When a diabetic’s immune system destroys the insulin-producing beta cells it does not harm the alpha cells, so they are a ready supply of cells that could be reprogrammed that are already in the right location. Levine’s team did this with the peptide caerulein. In a press release Levine noted:

“We have found a promising technique for type 1 diabetics to restore the body’s ability to produce insulin. By introducing caerulein to the pancreas we were able to generate new beta cells—the cells that produce insulin—potentially freeing patients from daily doses of insulin to manage their blood-sugar levels.”

Injecting the peptide worked in both a mouse model of diabetes and in human pancreas tissue from cadavers. But it also caused enough inflammation of the pancreas that the team is now tracking down the molecular target where the peptide does its magic. With that knowledge they hope to develop a more specific drug without the side effect.

Levine is well aware that a second step would be needed to protect any new beta cells they create from immune system attack. In a video that the institute produced a collaborator talked about preliminary work to prevent this immune rejection [starting at 2:45 into the video]. She is trying to super charge the type of immune cell called T-regulatory cells that are responsible for maintaining a balanced immune response.

The team published their work online in Cell Death and Disease, July 31.

Don Gibbons

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