Controlling Beta Cell Proliferation and Apoptosis to Manage Type 1 Diabetes

A key indicator of type 1 diabetes is lack of insulin-producing beta cells in the pancreas. These cells are mistakenly attacked and destroyed by the immune system leaving individuals unable to naturally manage their blood sugar. With little to no production of insulin, the body cannot effectively process sugars and use them as fuel. Instead, individuals must constantly monitor their blood glucose levels and administer insulin as needed.

However, a recent study uncovered how an FDA-approved drug for treating breast cancer may also be effective in diabetes care. Neratinib is a dual inhibitor of HER2 and EGFR kinases, but researchers have also found that it is incredibly effective at blocking mammalian sterile 20-like kinase 1 (MST1) as well. MST1 plays a key role in regulating beta cell proliferation and apoptosis. By inhibiting MST1 expression, insulin-producing beta cells may be protected from this process leading to greater beta cell survival and improved function.

In addition, when mouse models and human islets were treated with neratinib, they showed a marked improvement in glucose control and maintained lower overall glucose levels. The drug also restored expression of specific transcription factors such as PDX1 that contribute to glucose metabolism and insulin production.

Neratinib is an FDA-approved cancer treatment drug currently being used for breast cancer, but its effectiveness in treating other forms of cancer is being explored as well. Now researchers are examining whether its indications could be expanded to include diabetes.  While it has been proven safe in cancer treatment, scientists are looking at ways to decrease its toxicity and improve specificity for diabetes.

In its current form, neratinib does not only target MST1 – it inhibits other kinases as well. Furthermore, there is concern that an extreme decrease in beta cell apoptosis could lead to increased expression of other cell types which could impact health. However, researchers can use this study as a foundation for exploring ways in which to refine the drug and improve beta-cell protection and function while minimizing other effects.

Diabetes Research Connection (DRC) is interested to see how this study impacts future treatment and prevention efforts in regard to type 1 diabetes. The DRC provides critical funding to early career scientists pursuing novel, peer-reviewed research projects focused on prevention, treatment, and improvement of quality of life for individuals living with the disease. This support can lead to scientific breakthroughs and have a significant impact on understanding of type 1 diabetes. To learn more about current projects and how to support these efforts, visit http://diabetesresearchconnection.org.

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