Pancreatic puzzles, better beta cells and cellular handymen: latest type 1 diabetes research

At the Type 1 Diabetes Grand Challenge, we support cutting-edge research aimed at bringing us closer to better treatments and, potentially, a cure. One of the most promising routes towards a cure is restoring the body’s ability to produce insulin through beta cell therapies. The researchers we fund are helping make this vision a reality, from uncovering why beta cells are lost to developing better ways to grow, replace and protect them. Here are some of their latest discoveries. 

A new clue to what happens inside the pancreas in type 1 diabetes

Type 1 diabetes develops when the immune system destroys insulin-producing beta cells in the pancreas. But beta cells do not work alone. Other cells in the pancreas, including alpha cells, help keep glucose levels within a healthy range. Alpha cells produce glucagon, a hormone that raises blood glucose when levels fall too low. Researchers are increasingly interested in understanding how these different cell types change in type 1 diabetes and whether those changes could point to new opportunities for treatment.

Grand Challenge researcher Professor David Hodson and a UK-wide team have now discovered that a protein called eNAMPT may play a role in these changes. Previous studies have shown that elevated levels of eNAMPT can impair the function of beta cells. But until now, researchers did not know whether it could also affect the balance of different cell types within the pancreas.

Using cell samples from mice and human pancreases, the team found that higher levels of eNAMPT reduced the number of beta cells while increasing the number of alpha cells. They also found evidence that some beta cells had started to take on characteristics of alpha cells, suggesting that cells within the pancreas may be changing identity.

The team also found that alpha cells exposed to eNAMPT were less able to release glucagon when blood sugar levels fell, potentially weakening the body’s natural protection against low blood sugar (hypoglycaemia).

These findings suggest that eNAMPT may contribute to both beta cell loss and alpha cell dysfunction in type 1 diabetes. By helping researchers build a clearer picture of what happens inside the pancreas, this work could support efforts to develop treatments that protect insulin producing cells, potentially slowing the progression of type 1 diabetes.

Full study: eNAMPT induces alpha-cell mass expansion but impaired glucagon counter regulatory response | Endocrinology | Oxford Academic

Growing better beta cells for transplantation

One part of a solution to curing type 1 diabetes is to replace the beta cells that have been destroyed by the immune system. Scientists can now grow beta cells in the laboratory from stem cells, and early clinical trials of beta cell replacement therapies are already showing encouraging results. However, lab grown beta cells do not yet perform as well as those found naturally in the pancreas.

Our Grand Challenge researchers are exploring how to grow better beta cell. Researchers often use tiny 3D clusters of cells called organoids. These miniature tissues mimic some of the features of developing organs, allowing scientists to study how cells form and mature. Researchers are increasingly using pancreatic organoids to understand how beta cells develop and identify ways to improve the quality of cells grown in the laboratory.

Using this approach, researchers, including the Grand Challenge’s Dr Rocio Sancho, set out to create the first detailed map of the developing human pancreas. They wanted to learn more about the physical environment surrounding developing cells. They found that the pancreas tissue gradually becomes firmer as it matures and that cells experience different physical environments in different parts of the pancreas.

The team then recreated these conditions using soft gel-like materials called hydrogels. When pancreatic organoids were grown in hydrogels that closely matched the developing pancreas, they were more successful at developing beta cells. Organoids grown in softer or firmer environments were less successful.

These findings provide important clues about how to produce lab grown beta cells that more closely resemble those found naturally in the pancreas. By helping researchers better understand the conditions that support beta cell development, this work could help move us closer to a new era in type 1 diabetes, where people can make their own insulin again.

Full study: Microscale stiffness mapping of the human foetal pancreas defines hydrogels that promote the differentiation of pancreatic organoids – ScienceDirect

Giving transplanted islets a helping hand

Islet transplants, where pancreas cells from donors are transplanted into people with type 1 diabetes, already exist and are used to help some people who experience severe hypos. They have the potential to be life-changing, but currently this treatment is far from a cure. There is a shortage of donor cells available, and many of the transplanted cells become damaged during the isolation and transplantation process, reducing the number that survive and continue producing insulin.

Researchers from across London, including Grand Challenge researchers Professor Aileen King and Professor Shanta Persaud, have been investigating ways to give these cells the best possible chance of success.

The team turned their attention to mesenchymal stromal cells (MSCs), sometimes described as the body’s cellular handymen because they help support and repair other cells. Rather than using the MSCs themselves, the researchers focused on tiny messengers released by these cells, which carry proteins and genetic instructions between cells.

They found that when donor islets from mice were treated with these messengers, they released more insulin and were better protected from inflammatory damage. The treatment also helped more cells stay alive and improved their ability to produce the energy needed to function properly.

These findings suggest that MSC-derived messengers could one day provide a simpler way to strengthen donor islets before transplantation. More research is needed to understand whether these benefits translate into better transplant outcomes, but this work offers a promising new approach to helping transplanted insulin-producing cells survive and function for longer, moving us that one step closer to a cure.

Full study: Mesenchymal Stromal Cells Improve Islet β-Cell Functional Survival: Analysis of Extracellular Vesicle-Trafficked Proteins and miRNAs