Friday, August 12, 2022

A pathway to the regeneration of insulin in pancreatic stem cells

New discovery could pave the way for improved treatments for diabetes.

As the number of people with diabetes worldwide exceeds 500 million, scientists must find ways to improve a limited number of available medications with unclear effectiveness. A new study by Monash University is an important step forward toward developing new therapies.

Scientists have discovered a pathway to the regeneration of insulin in pancreatic stem cells. They successfully reactivated type 1 diabetic donor’s pancreas stem cells to become insulin-expressing and functionally resemble beta-like cells using a drug licensed by the US Food and Drug Administration.

Though more research is necessary, the novel strategy could, in principle, replace destroyed insulin-producing cells (beta cells) in people with type 1 diabetes with brand-new insulin-generating cells.

Diabetes expert Prof Sam Ei- Osta said, “We consider our research novel and an important step towards developing new therapies. It may lead to a potential treatment option for insulin-dependent diabetes, diagnosed in seven Australian children every day, resulting in a lifetime testing of blood glucose and daily insulin injections to replace the insulin no longer produced by a damaged pancreas.”

FOr restoration of insulin expression in damaged pancreas, scientists had to overcome several challenges since the diabetic pancreas was often thought to be too damaged to heal.

Professor El-Osta said, “By the time an individual is diagnosed with Type 1 diabetes (T1D), many of their pancreatic beta cells, which produce insulin, have been destroyed. These studies show that the diabetic pancreas is not incapable of expressing insulin” and that the proof-of-concept experiments “address unmet medical needs in T1D. The advances in the genetics of diabetes have brought a “greater understanding and a resurgence of interest in the development of potential therapies.”

“Patients rely on daily insulin injections to replace what would have been produced by the pancreas. Currently, the only other effective therapy requires pancreatic islet transplantation. While this has improved health outcomes for individuals with diabetes, transplantation relies on organ donors, so it has limited widespread use.”

Co-author of the study, Dr. Al-Hasani, says that “as we face a globally aging population and the challenges of escalating numbers of Type 2 diabetes which is strongly correlated with increases in obesity, the need for a cure for diabetes is becoming more urgent.”

“Before you get to patients, many issues must be resolved. More work is required to define the properties of these cells and establish protocols to isolate and expand them. I would think therapy is pretty far away. However, this represents an important step to devising a lasting treatment that might apply to all types of diabetes.”

Prof El-Osta, Drs Al-Hasani, and Khurana have developed a revolutionary method to regenerate insulin cells without the ethical concerns commonly associated with embryonic stem cells.

Journal Reference:

  1. Al-Hasani, K., Khurana, I., Mariana, L. et al. Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor. Sig Transduct Target Ther 7, 248 (2022). DOI: 10.1038/s41392-022-01034-7
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