Diabetes currently affects 29 million Americans. For decades researches have been trying to replace the insulin cells of the pancreas that are destroyed by the diseases. Groundbreaking research may have found a way to genetically transform alpha cells in to insulin-producing beta cells.
Diabetes rank as the seventh leading cause of death in the United States ,according to the centers for disease and prevention (CDC)
The CDC report that 29 million Americans currently live with the disease, and another 86 million have prediabetes.
Type 1 diabetes is characterized by the inability of the pancreas to produce insulin. More specifically, the bodys own immune system stops recognizing the beta cells normally responsible for producing insulin. Instead, It attacks and destroy them.
Without insulin – which normally “tells” the body to start reducing the levels of glucose- the blood sugar cannot enter the cells, where it is normally transformed in to energy. As a result glucose get stuck in the bloodstream, leading to diabetes.
The role of alpha and beta cells
A team of researchers – led by Stefan Kubicek, group leader at CeMM- examined the role of a variety of approved drugs on alpha and beta cells transformation.
In addition to beta cells, alpha cells from the islets of Langerhans in the pancreas , where they are responsible for regulating blood sugar levels.
While beta cells help signal a reduction in blood sugar, alpha cells do the opposite, by producing glucagon. However, alpha cells are flexible : they can transform in to beta cells.
In case of extreme beta cell depletion, alpha cells have been shown to turn in to insulin-producing bets cells, with the help of an epigenetic regulator known as Arx.
Endocrine cells need regulator to keep their identity. For instance, recent studies have shown that after the endocrine cells have differentiated, in order for beta cell to maintain their identity, the alpha cells epigenetic regulator Arx need to be actively repressed.
“Arx regulates many genes that are crucial for the functionality of an alpha cells,” says Kubicek. “preceding work of our collaborator, Patrick Collombats team showed that a genetic knockout of Arx leads to transformation of alpha cells into beta cells.
So, at this point researchers knew that they needed Arx to transform the cells, but they didn’t know whether there were other factors in the human organism that influenced the process.
To investigate this, kubicek and team designed alpha and beta cells lines and isolated them from their environment. They analysed the cells alpha identity, and no other from the human body are required.
Malaria drug turns alpha cells into insulin-producing cells
Researches found that artemisinins – a group of drug commonly used to treat malaria – had the same effect as a loss in Arx.
In other words , artemisinis transformed pancreatic alpha cells in to functional, insulin-producing beta-like cells.
“artemisinins change the epigastric program of glucagon-producing alterations of their biochemical function,” explains kubicek.
The way this happens is through the activation of GABA receptors.
The effect of GABA receptors in rodents and humans
GABA is amajor neurotransmitter produced by islet beta cells. It works by islet beta cells. It work as atrasmitter with in the islet cells, where it regulates the secretion and function of the islet.
Artemisinins reshapes alpha cells by binding to a protein called gephyrin. This protein activates the GABA receptors, which are like central switches of the cellular signaling. At the end of a longer chain of biochemical reaction, GABA triggers the production of insulin.
Kubiceks study confirms previous mouse studies that have been shown GABA to help transform alpha cells into beta cells. One of these studies is led by Patrick collombat and is published in the same issue of cell.
The beneficial effects of artimisinins were shown not only in isolated cell lne experiments, but also in model organisms. Kubicek and team showed that the malaria drug increased beta cell mass and improved homeostasis in zebrafish, mice, and rats.