New Findings Might Help in Developing Better Drugs for Diabetes

Diabetes presently impacts millions of people globally. For years, investigators have been attempting to substitute the insulin cells of the pancreas that are damaged by the disease. Innovative research may have identified a method to genetically transform alpha cells into insulin producing beta cells.

Type 1 diabetes is characterized by the incapability of the pancreas to generate insulin. More particularly, the body’s own immune system halts recognizing the beta cells usually accountable for generating insulin. Instead, it strikes and destroys them.

Without insulin – which usually tells the body to begin decreasing the levels of glucose – the blood sugar can’t enter the cells, where it is generally transformed into energy. As a outcome, glucose gets stuck in the bloodstream, resulting in diabetes.

For years, researchers have been attempting to obtain a way to substitute these beta cells – often referred to as islet cells due to the fact they are located in an endocrine area of the pancreas well-known as the islets of Langerhans.

Investigators have tried to replace damaged beta cells with new ones using stem cells and adult cells. Even though the outcomes have looked encouraging, they have yet to be successful.

Now, scientists from the CeMM Research Center for Molecular Medicine in Austria appear to have identified the missing association, providing hope of a cure for type 1 diabetes.

The role of alpha and beta cells

A group of investigators led by Stefan Kubicek, group leader at CeMM – analyzed the role of a wide range of approved medicines on alpha and beta cell transformation. Their results were presented in the journal Cell.

Additionally to beta cells, alpha cells and 3 other kinds of cells form the islets of Langerhans in the pancreas, where they are accountable for controlling blood sugar levels.

While beta cells assist signal a decrease in blood sugar, alpha cells do the opposite, by generating glucagon. However, alpha cells are adaptable: they can transform into beta cells.

In cases of extreme beta cell depletion, alpha cells have been proven to change into insulin producing beta cells, with the assist of an epigenetic regulator well-known as Arx.

Endocrine cells require regulators to maintain their identity. For example, current studies have proven that following the endocrine cells have differentiated, in order for beta cells to manage their identity, the alpha cell epigenetic regulator Arx has to be actively repressed.

“Arx manages many genes that are essential for the functionality of an alpha cell,” states Kubicek. “Previous work of our collaborator, Patrick Collombat’s team revealed that a genetic knockout of Arx results in a transformation of alpha cells into beta cells.”

So, at this point, investigators knew that they required Arx to transform the cells, but they did not know whether there were other aspects in the human organism that influenced the process.

To examine this, Kubicek and team developed alpha and beta cell lines and isolated them from their environment. They examined the cells and exhibited that a deprivation of Arx is sufficient to give a cell its alpha identification, and no other aspects from the human body are needed.

Malaria medicine transforms alpha cells into insulin-producing cells

Now, researchers were capable to test the results of a wide variety of approved medicines on cultured alpha cells using a exclusively designed, completely automated assay.

Investigators identified that artemisinins – a group of medicines generally used to treat malaria – had the same impact as a loss in Arx.

In other terms, artemisinins transformed pancreatic alpha cells into functional, insulin producing beta-like cells.

Commenting on their study Kubicek said,

“With our research, we could present that artemisinins transform the epigenetic program of glucagon producing alpha cells and induce profound alterations of their biochemical function.”