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Conversion of Alpha Cells to Beta Cells in Pancreas May Help Treat Type 1 Diabetes

In individuals with type 1 diabetes (T1D), the immune system erroneously destroys insulin-producing beta cells. In turn, this leads to an inability of the body to control blood sugar. As a result, individuals must monitor and adjust their blood sugar on their own using a combination of finger sticks, continuous glucose monitors (CGM), insulin pumps, or insulin injections.

However, in a recent study, researchers explored the potential of reprogramming alpha cells in the pancreas to either become or function as beta cells. They used an adeno-associated virus to administer two different transcription factors – Pdx1 and MafA – into the pancreases of diabetic mice. With the overexpression of these factors, alpha cells developed into beta-like cells.

Alpha cells are ideal for reprogramming for numerous reasons including the fact that they naturally occur in abundance in the pancreas, they already function alongside beta cells in islets, and there are no apparent negative effects on glucose metabolism from reducing alpha cell levels, among other reasons.

Upon administering the transcription factors, euglycemia was restored within two weeks and maintained for four months. In addition, glucose response improved as well. After four months, autoimmune diabetes returned. However, this sheds light on potential therapeutic approaches for treating and managing diabetes and could be used in conjunction with immunosuppression for improved insulin production and blood glucose management.

Further testing is needed to determine if this approach is as effective in human pancreatic cells as it is in mouse models, though there have been some studies involving human islets in which alpha-to-beta-cell conversion occurred.

It is these types of studies that increase understanding of T1D and potential therapeutic treatment options. The Diabetes Research Connection (DRC), though not involved in this study, strives to support early career scientists in pursuing novel research studies aligned with preventing and curing T1D as well as improving quality of life for those living with the disease. DRC raises critical funds to enable these projects to move forward.

 

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Could Reprogramming Cells Help Treat Type 1 Diabetes?

More than 300 million people around the world are living with diabetes. Currently, there is no cure, but scientists are continually researching and testing different methods for treating and managing this disease. One of the major obstacles faced in treating type 1 diabetes is that the body’s immune system attacks and destroys insulin-producing beta cells, whether these cells are naturally occurring or introduced through medical treatment.

Some researchers are looking at ways to reprogram the body’s own cells to function as insulin-producing cells to help better control blood sugar. The human pancreas contains small niches where hormone-making cells reside. Within these niches, two different cells predominate: alpha cells, which make glucagon, and beta cells, which make insulin. In individuals with type 1 diabetes, insulin-producing cells are destroyed, but glucagon cells are not.

Scientists developed a method using viruses as carriers to deliver two genes that are present in insulin but glucagon cells to the glucagon cells allowing the cells to be able to produce insulin. Glucagon cells are a good option for this process because they are similar to insulin cells and appear in abundance in islets within the pancreas already. A decrease in these cells as they were reprogrammed did not appear to affect glucose metabolism.

These experiments have been performed in NOD mice, which are mice that develop diabetes very close to human diabetes. Following the experiment, the diabetes disease appeared to have resolved in the diabetic NOD mice thanks to the new source of cells making insulin in their pancreas. However, human application of this technique will take time since targeting specific cells is complicated, and the use of viral elements creates side effects that need to be resolved.

It is this type of research and these experiments that lead to breakthroughs in the treatment, management, prevention, and improvement in the quality of life for individuals living with type 1 diabetes. Though not involved in this particular study, the Diabetes Research Connection supports early-career scientists through funding for novel research on type 1 diabetes. Learn more about current projects and support their advancement by visiting http://diabetesresearchconnection.org.

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