JDRF-funded researchers make pancreatic ductal cells sense and release insulin

Researcher Safiya Naina Marikar

In a JDRF-funded research project in Australia, scientists have turned human pancreatic ductal cells into insulin-producing cells, offering promise for restoring the ability to make insulin in people living with type 1 diabetes. The researchers stimulated ductal cells taken from a human pancreas with small molecule inhibitors to influence the cells to sense glucose and release insulin.

This study builds on the team’s research from 2022, where they used the same drug to turn the insulin gene back in cells taken from the pancreas donated by someone who was living with type 1. You can find out more about this research in our news story.

What are ductal cells?

The tubes running through the pancreas are lined with ductal cells. While our bodies are still developing, ductal cells can turn into hormone-producing cells, thanks to certain genes. Unfortunately, this function is lost by adulthood, so people living with type 1 diabetes can’t grow new beta cells to replace those destroyed by the immune attack. But this exciting research suggests we may be able to influence the ductal cells to restore insulin secretion.

A diagram of the pancreas and part of the small intestine.

Regenerating beta cells

This JDRF-funded research study showed that, by changing their genes, ductal cells can be influenced to produce insulin and effectively replacing the lost beta cell function. The experiment was done on human cells in a dish, so researchers are hopeful that it could be the start of a treatment to regenerate beta-like cells in people living with type 1 diabetes.

Lead researcher Safiya Marikar said: “Our research shows great promise at reducing the insulin dependency of people with type 1 around the world. By stimulating the cells already present in the ducts of the pancreas, in theory we should be able to re-awaken their insulin producing capabilities. Although, we need to research this further to determine how this could be used as a treatment for type 1.”

An alternative to islet transplants

Safiya Marikar said: “Since we are trying to stimulate cells that people with type 1 already have, we hope to rely less on organ donors to replace lost beta cells. We are currently facing a massive shortage of donors for islet transplants. This is because multiple donors are required to get enough islets to resolve the insulin dependency in just one person living with type 1 diabetes.”

Islets are clusters of cells including the insulin-producing beta cells. Other issues with islet transplants include the risks associated with any surgery and the need for immunosuppressants drugs. This means only people who are really struggling to manage their type 1 are offered islet transplants.

What is a proof-of-concept study?

This study is a proof-of-concept study, which is a type of research project that comes early in the research pipeline. These studies are crucial to establish how theories work so that new treatments can be developed from a solid foundation of knowledge.

Professor Sam El-Osta, who supervises Safiya, who is undertaking her doctoral studies, said: “Until now, we haven’t fully understood the molecular process of regenerating beta cells in the pancreas. We had seen that stimulating cells with small molecule inhibitors influence regenerative genes and the secretion of insulin release from cells derived from pancreas. More importantly, our studies show this regenerative capacity exists in pancreatic cells from type 1 donors with absolute destruction of beta cells. Our research group has demonstrated that we can partly restore the critical switch that turns these genes back on by reprogramming ductal cells to release insulin in response to glucose.”

What are the next steps for this research?

Safiya’s research has filled some of the gaps in our knowledge, but we need more studies to develop the idea further. Her work adds evidence for a proposed epigenetic theory, but we need to learn more about the exact mechanism before we can take it forward to trials in animals and humans. We also need to figure out which of the ductal cells are being targeted and fine tune this to develop a method that can be used to treat people living with type 1.

Supporting early career researchers

Researchers who are early in their careers don’t have the experience behind them to secure large grants, like the JDRF funding Professor El-Osta previously received. Working with established scientists on large projects is a great way for early career scientists to gain this vital experience.

Discussing the role of early career scientists in clinical research, Professor El-Osta said: “Safiya is quite simply one of the two or three most outstanding young students that I have encountered in the last 20 years. By connecting university students with accomplished scientists in technology fields, our new Human Epigenomics Program at the Baker Heart and Diabetes Institute aims to increase student numbers going into regenerative biology and clinical diabetes research.”

We are proud to work with scientists like Professor El-Osta who champion and support the next generation of type 1 diabetes researchers.

You can access the full research paper, published in the journal Clinical Epigenetics.