In a breakthrough, diabetics damaged cells regenerated to produce insulin

For many years, research has focused on identifying novel therapies that stimulate beta-cell growth and function to restore insulin production in type 1 diabetics. Now, in an exciting breakthrough, researchers at the Baker Heart and Diabetes Institute in Melbourne, Australia, have brought us a step closer to making this a reality, regenerating damaged pancreatic cells so they can produce insulin and functionally respond to blood glucose levels.

“We consider this regenerative approach an important advance towards clinical development,” said Sam El-Osta, the study’s corresponding author. “Until now, the regenerative process has been incidental and lacking confirmation; more importantly, the epigenetic mechanisms that govern such regeneration in humans remains poorly understood.”

Enhancer of zeste homolog 2 (EZH2) is an enzyme that forms part of the protein group polycomb repressive complex 2 (PRC2), which regulates gene expression. EZH2 is also critical in stem cell renewal, maintenance, and differentiation into specific cell lineages. Mutation and overexpression of EZH2 results in the suppression of genes responsible for cell cycle control, leading to uncontrolled growth and cancer. That’s why EZH2 inhibitors are used to treat some cancers.

In the current study, the researchers looked at the ability of two FDA-approved EZH2 inhibitors normally used to treat rare forms of cancer, GSK126 and tazemetostat (Tazverik), to reactivate pancreatic progenitor cells.

Inhibiting EZH2 pharmacologically with GSK and tazemetostat caused the pancreatic cells from the juvenile and adult diabetic donors to shift towards a beta-like cell identity. After 48 hours of stimulation with the drugs, the reprogrammed cells produced and secreted insulin in response to a physiological glucose challenge.