October 12, 2023  Print

In a world first, researchers at WIMR have discovered that altering the way a protein called CD47 is expressed can change how pancreatic islet cells secrete insulin.

The implications of this finding, published in Science Translational Medicine, could help improve glucose control for people with both type 1 and type 2 diabetes.

The study was conceptualised and conducted by Dr Kedar Ghimire and Professor Natasha Rogers.  Team leader and senior author of the study, Professor Rogers is Deputy Director of WIMR’s Centre for Transplant and Renal Research and Head of Transplantation at Westmead Hospital.  She explains, “Pancreatic islets are cells in your pancreas that make insulin.

“CD47 is a kind of protein that is found on the surface of all cells in the body, including pancreatic islets. Essentially, CD47 tells immune cells whether or not to destroy whatever cell it is attached to.

“Our study shows that CD47 also plays a significant role in how the pancreas secretes insulin.”

Within a pancreatic islet, large amounts of insulin sit within granules and these are released in waves, as needed.  The first wave of insulin sits just under the cell membrane. 

Professor Rogers says, “If the pancreatic islet registers that you have high glucose, it will release that initial pool of insulin, and the next wave of granules then move up in position to replace the insulin that has just been released.”

First author, Dr Kedar Ghimire says the study found that CD47 plays a significant role in this process.

“We discovered that CD47 regulates how these insulin-filled granules move to the surface; how they ‘dock’ at the surface; and how they interact.

“With this new understanding of the role of CD47, we have been able to show that targeting its function can improve glucose control.”

PhD student Atharva Kale, who is supervised by Professor Rogers (pictured) and Dr Ghimire, and is a co-author on the paper, says that while the research is still in its early stages, these findings have a number of potential benefits for glucose control in diabetics.

“We hope that people with a predisposition for getting diabetes or who have recently been diagnosed will be able to delay the need for treatment." 
Dr Ghimire adds, “When someone is diagnosed with type 1 diabetes, they can go through a ‘honeymoon phase’ where they don’t require any treatment and their islets are still working.  If these people can be identified in this early phase, or as having a predisposition to type 1 diabetes, we can hopefully delay their onset.
“We believe that type 2 diabetics may also benefit from this finding as targeting the function of CD47 can improve overall blood glucose control.”
Another potential benefit of this finding involves pancreatic islet transplantation, a procedure that was pioneered at WIMR by Executive Director, Professor Philip O’Connell who undertook Australia’s first successful clinical trial of islet transplantation and has been responsible for its transition into the Australian healthcare system.
Professor Natasha Rogers says, “One of the challenges we face with pancreatic islet transplantation is that islet cells are very fragile.  The process of isolating islet cells and transplanting them into someone is damaging to the cells and this can impact their function. We think that by targeting the CD47 molecule, we can actually improve how the islets function after transplant. 
“We’ve also shown you can target CD47 in the pancreatic islet cells outside the body, before they are transplanted.  This seems to protect them so that even after the islets have been transplanted, they continue to function well.  This could potentially reduce the number of transplants required in order for a patient to gain better or full glucose control.”
While the research is in its early stages, the WIMR team is confident that these findings will have broader implications.
Professor Rogers says, “There is a lot more work to do in the lab. We believe that CD47 affects more than just insulin secretion.  We think there are a lot of other biological mechanisms, relevant to people with any form of diabetes, and we hope to explore these further.”