Researchers have successfully coerced pancreatic cells of a type 1 diabetic donor to produce insulin. Their strategy could lead to new therapies for patients with this disease.

The research team, led by Keith Al-Hasani, PhD, Ishant Khurana, PhD, and Assam El-Osta, PhD, from Monash University in Melbourne, Australia, published their findings in the article “Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor” in Signal Transduction and Targeted Therapy.

During Type 1 diabetes (T1D), the insulin-producing cells of the pancreas, called β cells, are destroyed. Patients with T1D, therefore, depend on insulin shots or an insulin pump for survival.

Because of a shortage of organ donors and problems associated with immunosuppressive drugs, transplantation strategies have limited clinical utility. Therefore, Al-Hasani, Khurana, El-Osta, and their team looked at the possibility of regenerating β cells.

“Pancreatic duct cells have been suggested as a source of progenitors for β cell regeneration,” the team wrote in their article. “The objective of this study was to investigate the specific regulation of H3K27me3 writing enzyme EZH2 that is considered responsible for default suppression (transcriptional gene silencing) critical to the ductal progenitor’s developmental program by enabling them to differentiate into functioning insulin-secreting β-cells.”

They examined the effect of GSK126, a highly selective inhibitor of EZH2, in pancreatic tissues from donors. And then they measured the expression of the insulin gene, as well as the expression of genes associated with progenitor identity. All of the genes were expressed in both the non-diabetic and diabetic donors.

“These results support the notion that EZH2 inhibition restores exocrine multipotency even in chronic disease with total β-cell destruction,” the researchers wrote. In other words, treating the ductal cells with the drug GSK126 caused them to functionally resemble β cells and to produce insulin.

In principle, this new approach would allow insulin-producing β cells that are destroyed in T1D patients to be replaced with new insulin-generating cells. “We consider the research novel and an important step forward towards developing new therapies,” El-Osta said.

However, more work needs to be done.

“The case is an isolated one, of a T1D child with hallmark islet damage and significant destruction of β-cells. Thus, it is unknown if the results will generalize,” the researchers wrote.

“More work is required to define the properties of these cells and establish protocols to isolate and expand them,” Al-Hasani said.

“I would think therapy is pretty far away,” he added. “However, this represents an important step along the way to devising a lasting treatment that might be applicable for all types of diabetes.”

GSK126 is approved for use by the FDA but is not currently licensed for diabetes treatment. 

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