After a meal, pancreatic beta cells leap into action to produce insulin—a vital hormone that regulates blood sugar and ensures the energy from food reaches the right cells. When these cells malfunction, as in type 1 and type 2 diabetes, blood sugar levels spiral out of control, leading to serious health complications.
Weiping Han, Divisional Director at the Institute of Molecular and Cell Biology (IMCB) explained that islet transplantation—a beta cell replacement therapy—offers a minimally invasive treatment for patients whose beta cells have failed. “Successful islet transplantation provides long-term glycaemic control for insulin-dependent diabetes with minimal risk of hypoglycaemic episodes,” said Han. However, the procedure remains limited by the scarcity of high-quality islets suitable for transplantation.
In response, Han and Wing Yan So, a Senior Scientist at IMCB, set out to improve islet transplantation by genetically enhancing suboptimal islet cells that would otherwise be unsuitable. They focused on modifying the PAX6 gene, a regulator of beta cell function and identity.
To do this, they used adeno-associated virus (AAV), a common gene therapy tool, to introduce the PAX6 gene into beta cells from diabetic mice and human islets. They then investigated its effect on beta cell survival, blood sugar regulation and the success of islet transplantation in diabetic mouse models.
In collaboration with Universite de Montreal, Canada, the IMCB team of researchers found that overexpressing the PAX6 gene in beta cells enhanced insulin and incretin signallings and reduced cell death under diabetic conditions. In diabetic mice, PAX6 gene therapy lowered blood glucose by up to 50 percent, with the effects lasting at least six weeks. Similarly, human islet transplants showed a marked increase in insulin production and improved long-term graft survival.
Han highlighted the significance of these findings: “The study shows that PAX6 gene therapy can greatly expand access to islet transplantation by boosting the function and survival of compromised islets, ultimately reducing the number of donor islets needed to restore healthy blood sugar levels.”
For people with diabetes, this breakthrough may mean wider access to life-changing transplants, requiring fewer donor islets and offering the prospect of better long-term blood sugar control and a reduced reliance on insulin injections.
However, some challenges remain before this approach can be applied in clinical settings. “Future studies are needed to determine the optimal dosage and expression levels of PAX6 to ensure therapeutic efficacy while minimising side effects,” added Han.
The team also plans to tackle another major hurdle—reducing the immune response triggered by islet transplantation—to extend the lifespan of transplants and promote longer-term insulin independence for patients.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology (IMCB).
