Scientists at Westmead Institute for Medical Research (WIMR) have discovered that modifying the expression of the protein CD47 can influence the insulin secretion of pancreatic islet cells. This discovery, detailed in Science Translational Medicine, carries significant implications for enhancing glucose regulation in individuals with type 1 and type 2 diabetes.
The research, led by Dr. Kedar Ghimire and Professor Natasha Rogers, was conceived and executed at WIMR. Professor Rogers, serving as the team leader and senior author, holds positions as the Deputy Director of WIMR’s Centre for Transplant and Renal Research and as the Head of Transplantation at Westmead Hospital. She says, “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.”
Inside a pancreatic islet, substantial quantities of insulin reside within granules, awaiting release in sequential waves as required. The initial wave of insulin is positioned directly beneath the cell membrane.
Professor Rogers explains, “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.”
According to the first author, Dr. Kedar Ghimire, the research reveals that CD47 plays an important 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.”
Atharva Kale, a PhD student under the supervision of Professor Rogers and Dr. Ghimire, and also a co-author of the paper, highlights that although the research is in its preliminary phases, these discoveries hold promise for several advantages in managing glucose levels among people with diabetes.
“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 notes, “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.”
This discovery also carries potential advantages for pancreatic islet transplantation, a procedure initiated at WIMR by Executive Director Professor Philip O’Connell. Professor O’Connell spearheaded Australia’s inaugural successful clinical trial of islet transplantation and facilitated its integration 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.”
Despite being in the initial phases, the WIMR team expresses confidence that these findings will have far-reaching implications.
Professor Rogers adds, “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.”
The breakthrough research conducted at WIMR demonstrates the critical role of the protein CD47 in influencing insulin secretion by pancreatic islet cells. This study sheds light on how modifying CD47 function can enhance glucose regulation in individuals with both type 1 and type 2 diabetes. By elucidating the mechanisms by which CD47 regulates insulin-filled granules’ movement and docking at the cell surface, this research paves the way for novel therapeutic approaches aimed at improving diabetic glucose control.
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DISCLAIMER: This article is for informational purposes only and is not meant to replace medical advice on diabetes. The Australian Seniors Advisory Group is not affiliated with any medical research centre. Please consult your GP.