Diabetes News: Pharmacological Stimulation Regenerates Beta-like Cells to Release Insulin

Posted on 07.08.2023

A proof-of-concept study by DDA-funded Visiting Professor Sam El-Osta’s team demonstrates that ductal cells derived from the human pancreas can be influenced by pharmacological stimulation to regenerate beta-like cells that functionally release insulin.

– While pharmaceutical options receive warranted attention for the treatment of diabetes help control blood glucose levels, they do not prevent, retard or reverse the decline in insulin-secreting beta-cells. Until now, the regenerative process and default suppression have been incidental, lacking confirmation, says Professor Sam El-Osta.

Therefore, El-Osta’s group has proposed that activation of insulin expression as a result of EZH2 inhibition could originate from human pancreatic ductal progenitors.

Central to this hypothesis is the regenerative state of beta-like cells influenced by histone H3 lysine 27 trimethylation or H3K27me3, which is a gene modification written by the EZH2 methyltransferase enzyme. Pharmacological inhibition of EZH2 reduces H3K27me3 on core gene targets that influence the regenerative beta-like state including the expression of the insulin gene and glucose-sensitive insulin protein secretion originating from human pancreatic ductal cells. This new work improves our understanding of treatment refractory genes emphasising the regenerative barrier of ductal cells derived from the pancreas appears to be tightly controlled by EZH2 dependent gene modification.

New Human Epigenomics Pogramme Engages Early Career Scientists

The next year will see a tremendous expansion of Professor El-Osta’s research and training curriculum offered by the Human Epigenomics Program in collaboration with international partners such as University College Copenhagen and Steno Diabetes Centre Copenhagen. The aim is to push forward fundamental biology and clinical research. By connecting university students with accomplished scientists in technology fields, the new Human Epigenomics Program at the Baker Heart and Diabetes Institute located in Melbourne aims to engage the next generation of students and early career scientists into regenerative research using state of the art facilities in genomics, cell biology and bioinformatics.

– The ultimate aim is to provide new hope for people living with diabetes, says El-Osta.

Read the article

June 12, 2023; issue of Clinical Epigenetics entitled “Pharmacological inhibition of human EZH2 can influence a regenerative β-like cell capacity with in vitro insulin release in pancreatic ductal cells” 15, 101.

https://doi.org/10.1186/s13148-023-01491-z (2023)

Contact information

Professor Sam El-Osta
Baker Heart and Diabetes Institute
Epigenetics in Human Health and Disease Program

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