Researchers in Austria have discovered that a well known malaria drug can induce alpha cell transdifferentiation – the process by which pancreatic alpha cells turn into insulin producing, beta-like cells. Their findings, published in the prestigious journal Cell, are a further step along the road towards a beta cell replacement in type 1 diabetes.
What are alpha cells?
Alpha cells are a type of cell found in the pancreas, and make up about 20 per cent of the organ. When glucose levels in the blood get too low, alpha cells secrete glucagon, a hormone that triggers glucose release from stores in the liver. For many years, type 1 research has been trying to find a way to convert alpha cells into beta-like cells, so that they could produce insulin in place of beta cells destroyed by the autoimmune response that defines type 1 diabetes.
An old drug that can do new tricks
It has long been known that under certain conditions, including extreme beta cell loss, alpha cells can start producing insulin, but it has been difficult to replicate this process in the lab. The Austrian team, led by Stefan Kubicek, and based at the CeMM Research Center for Molecular Medicine, tested the effect of a number of existing drugs on alpha cells in the lab to see if any could recreate this switch in alpha cell role.
One group of drugs tested were artemisinins, which are already approved by regulatory bodies for treating malaria. When applied to alpha cells, the artemisinins were able to switch on a long chain of biochemical reactions that result in insulin production.
The paper published in Cell shows that artemisinin can change alpha cells in the pancreases of zebrafish and mice, both used as animal models because of the similarities in alpha and beta cell biochemistry. The team were also able to replicate the results using human cells in the lab. They did this by sourcing groups of pancreas cells, called islets, from the JDRF funded ECIT Islet for Basic Research Program, and destroying the beta cells within the islets. When they then introduced the artemisinins, they were able to see an increase in insulin secretion, suggesting that the alpha cells were now producing insulin.
How can this help people with type 1?
The biggest challenge in developing this finding into a treatment will be to recreate these results in vivo – in people in clinical trials. The researchers hope that their work will provide enough evidence to support clinical trials of the malaria drug for type 1. The fact that artemisinins are already found in an approved drug means that any clinical trials could proceed more quickly than with a completely new treatment.
Converting alpha cells into beta cells would be a particularly useful method compared to beta cell transplants – currently offered to people with type 1 with additional, related health problems – because these cells would already be part of the affected person’s body, and so there would be no need for immunosuppressant drugs. However, just as with islet transplants, while converting alpha cells into beta cells would mean a person with type 1 would be able to produce their own insulin again, these new alpha cells could still be vulnerable to the underlying autoimmune attack, and could eventually be destroyed.
We need, therefore, to continue investigating a range of treatments, including those that aim to make the immune system tolerant of beta cells, so that a wide combination of approaches could, in the future, create a cure for type 1.