Malaria drugs could help replace lost insulin producing cells in type 1 diabetics

by Barbara Hewitt on December 5, 2016

Ground breaking research involving malaria drugs is hailed as a step forward in being able to replace insulin producing beta cells that are destroyed in people with type 1 diabetes.

Scientists have been trying to find a way to replace these cells, also known as islet cells, for decades and now a team in Austria believe they have found the missing link, which could pave the way to genetically transform alpha cells into insulin producing beta cells.

medications-pillsThe researchers from the CeMM Research Centre for Molecular Medicine, led by Stefan Kubicek, examined the role of a variety of approved drugs on alpha and beta cell transformation.

The process involved looking at beta cells which help signal a reduction in blood sugar and alpha cells which do the opposite, by producing glucagon. However, alpha cells are flexible and they can transform into beta cells and in cases of extreme beta cell depletion, alpha cells have been shown to turn into insulin producing beta cells, with the help of an epigenetic regulator known as Arx.

Kubicek explained that Arx regulates many genes that are crucial for the functionality of an alpha cell. While researchers knew that they needed Arx to transform the cells, they did not know whether there were other factors in the human organism that influenced the process.

To investigate this, Kubicek and his team designed alpha and beta cell lines and isolated them from their environment. They analysed the cells and demonstrated that a deprivation of Arx is enough to give a cell its alpha identity, and no other factors from the human body are required.

They were then able to test the effects of a wide range of approved drugs on cultured alpha cells using a specially designed, fully automated assay and found that artemisinins, a group of drugs commonly used to treat malaria, could transform pancreatic alpha cells into functional, insulin producing beta like cells.

‘With our study, we could show that artemisinins change the epigenetic programme of glucagon producing alpha cells and induce profound alterations of their biochemical function,’ said Kubicek, adding that the way this happens is through the activation of GABA receptors.

GABA is a major neurotransmitter produced by islet beta cells. It works as a transmitter within the islet cells, where it regulates the secretion and function of the islet. Artemisinins reshape alpha cells by binding to a protein called gephyrin. This protein activates the GABA receptors, which are like central switches of the cellular signalling. At the end of a longer chain of biochemical reactions, GABA triggers the production of insulin.

Overall, Kubicek and his team showed that the malaria drug increased beta cell mass and improved homeostasis in zebrafish, mice, and rats and they believe that it is very likely that the same effect will happen in humans because the molecular targets for artemisinins in fish, rodents, and humans are very similar.

‘Obviously, the long term effect of artemisinins needs to be tested. Especially the regenerative capacity of human alpha cells is yet unknown. Furthermore, the new beta cells must be protected from the immune system. But we are confident that the discovery of artemisinins and their mode of action can form the foundation for a completely new therapy of type 1 diabetes,’ Kubicek added.

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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