- December 9, 2016
- Posted by: emobile
- Category: Researcher's Corner
Emobileclinic Researchers Corner
The Journal of Cell has published the findings of researchers from the CeMM Research Center for Molecular Medicine in Austria who made a landmark discovery to genetically transform alpha cells into insulin-producing beta cells with the aim of finding permanent cure for type 1 diabetes.
Diabetes ranks as the seventh leading cause of death in the United States according to the Centers for Disease Control and Prevention (CDC). Type 1 diabetes resulted from the inability of the pancreas to produce insulin. Simply put, the body immune system fails to recognize the beta cells normally responsible for producing insulin. Instead, it attacks and destroys them.
For years, scientists have been trying to uncover a way to replace these beta cells – sometimes referred to as islet cells because they are located in an endocrine area of the pancreas known as the islets of Langerhans. Researchers have attempted to replace destroyed beta cells with new ones using stem cells and adult cells. Although the results appeared encouraging, however; no appreciable success has been recorded. It is laudable to know that this team seems to have found the missing link, giving hope of a cure for type 1 diabetes.
The team led by Stefan Kubicek, examined the role of a variety of approved drugs on alpha and beta cell transformation. In addition to beta cells, alpha cells and three other types of cells from the islets of Langerhans in the pancreas, where they are responsible for regulating blood sugar levels.
Beta cells signal a reduction in blood sugar, alpha cells do the opposite, by producing glucagon. However, alpha cells are flexible: they can transform into beta cells.
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. According to Kubiecek, “Arx regulates many genes that are crucial for the functionality of an alpha cell,” and added that “preceding work of our collaborator, Patrick Collombat’s team showed that a genetic knockout of Arx leads to a transformation of alpha cells into beta cells.”
Kubicek and team designed alpha and beta cell lines and isolated them from their environment. They analyzed 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. Now, scientists were able to test the effects of a wide range of approved drugs on cultured alpha cells using a specially designed, fully automated assay.
Researchers found that artemisinins – a group of drugs commonly used to treat malaria – had the same effect as a loss in Arx. In other words, artemisinins transformed pancreatic alpha cells into functional, insulin-producing beta-like cells. Kubicek explains further that “with our study, we could show that artemisinins change the epigenetic program of glucagon-producing alpha cells and induce profound alterations of their biochemical function”. This way this was done through the activation of GABA receptors.
Jin li et.al (2016): Artemisinins Target GABAa Receptor signaling and Impair a Cell Identity. Cell, doi:10:1016/j.cell.2016.11.010