JDRF-Funded Researchers Reprogram Human Alpha Cells to Produce Insulin and Reverse Diabetes in Mice

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Human cells, including pancreatic islet cells which produce hormones that regulate blood sugar levels, are much more adaptive than scientists previously thought. A new study from the journal Nature shows that human alpha and gamma cells, which typically produce the hormones glucagon and pancreatic polypeptide, can become like beta cells, the cells lost in T1D, and produce insulin.

For the first time ever, researchers at the University of Geneva, led by JDRF-funded investigator Pedro Herrera, Ph.D., separated human islets, which normally contain 5 different types of hormone-producing cells, to obtain just the alpha and gamma cells. They then transplanted only these pure cell populations into mice with diabetes. They found that if the alpha or gamma cells were given one or two key beta cell genes, the cells would begin to behave like beta cells, produce insulin and reverse diabetes in the mice.

“Human cells proved to be very effective. The mice recovered!” said Dr. Herrera, professor at the University of Geneva.

The team repeated the experiments, this time using islets recovered from people with diabetes, and found that the alpha cells from donors with diabetes had the same ability to turn on insulin and become like beta cells—raising the possibility that this process could be harnessed to restore insulin production in people with T1D.

“The idea of using the intrinsic regenerative capacities of the human body makes sense here,” says Herrera. He adds that much work remains before a viable treatment can be developed without having adverse effects on other cells in the body, suggesting the exploration of drug or gene therapies as potential options.

Type 1 diabetes (T1D) is an autoimmune disorder, which destroys insulin-producing beta cells in the pancreas. In T1D, beta cells are stressed, hastening the autoimmune process that leads to their death. Beta cells, however, can persist long after T1D diagnosis, and in certain situations, the body can even regrow new beta cells. JDRF’s Beta Cell Regeneration program has three goals: to make more beta cells, promote their survival and improve the function of those that remain.

To learn more about the JDRF Beta Cell Regeneration Program, click here.

The JDRF-funded (either now or in the past) authors of the study also included Bart O. Roep, Ph.D., Markus Grompe, M.D., Domenico Bosco, Ph.D., Thierry Berney, M.D., and Craig Dorrell, Ph.D.

By Alexandra Mulvey