Stanford scientists manipulate gene expression to make insulin-producing cells

Li Ka Shing Center for Learning and Knowledge
Cadaver studies showed that pancreatic alpha cells naturally, but slowly, turn into insulin-secreting beta cells in diabetic humans. This process could be a target for new diabetes treatments.

Stanford University scientists converted pancreatic alpha cells to insulin-producing beta cells in mice by blocking the production of a pair of proteins. If translatable to humans, this method could be used to replenish faulty beta cells and ease diabetes symptoms.

"It is important to carefully evaluate any and all potential sources of new beta cells for people with diabetes," said Dr. Seung Kim, a professor of developmental biology and of medicine at Stanford, in a statement. "Now we've discovered what keeps an alpha cell as an alpha cell, and found a way to efficiently convert them in living animals into cells that are nearly indistinguishable from beta cells."

Kim’s team built on existing research showing that, when beta cells are destroyed in mice, a tiny percentage of alpha cells begin to resemble beta cells. Seeking to unlock the mechanism by which this occurs, they looked at two proteins involved in the development of alpha cells, Arx and DNMT1.

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The researchers engineered mice that would stop producing these proteins in their alpha cells when given a certain chemical. Within seven weeks of blocking these proteins, the alpha cells made a “rapid conversion” into beta cells. Studies of gene expression and electrophysiology showed the converted alpha cells to be “remarkably similar” to native beta cells.

Studying pancreatic tissue from cadavers, the team found that the conversion of alpha cells into beta cells happens naturally in diabetic humans, but at a smaller scale. This transformation could be a target for diabetes therapies.

"This indicates that it might be possible to use targeted methods to block these genes or the signals controlling them in the pancreatic islets of people with diabetes to enhance the proportion of alpha cells that convert into beta cells,” Kim said.

Meanwhile, a number of players are trying to tackle diabetes by boosting beta cell count. A University of Oregon team is working on identifying the mechanism by which a zebrafish-derived protein triggers beta cells to multiply. Stanford and University of Tokyo scientists grew genetically-matched mouse pancreases in rats that, when transplanted into mice, reversed their diabetes. And, after testing hundreds of combinations of agents, Harvard scientists figured out how to coax embryonic stem cells to become beta cells.

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