JDRF-funded researchers in collaboration with the pharmaceutical company Hoffmann-La Roche, have discovered a protein that regulates growth of beta cells – the insulin-producing cells that are located within islets in the pancreas– and a chemical compound that stimulates it.
The discovery, led by Markus Stoffel, M.D., Ph.D., a professor at the Swiss Federal Institute of Technology in Zurich, represents a significant advance in identifying a new drug target for diabetes.
The work builds on a discovery made five years ago, when Dr. Stoffel and his team first showed that a once obscure protein, called Tmem27, is localized on the surface membrane of beta cells.
After screening possible molecules that could snip Tmem27, Dr. Stoffel and his team found the culprit: Bace2, an enzyme protein that, like Tmem27, also resides on the outer surface (known as the plasma membrane) of the beta cell.
The researchers then discovered that mice that lacked Bace2 had larger islets and the beta cells in the islets increased in number, a process known as proliferation or regeneration.
They also found that these mice were able to clear glucose from the blood more efficiently than control mice with Bace2.
Dr. Stoffel and his team next aimed to inhibit Bace2 in an effort to control and promote the growth of beta cells. To do so, they teamed up with scientists at Hoffmann-LaRoche who developed a chemical compound that could inhibit Bace2.
When the scientists gave this compound to mice, they saw that it inhibited Bace2 and stimulated the growth of new beta cells.
In addition to identifying a new drug target for promoting beta cell regeneration, Dr. Stoffel’s work may also help in developing tests to measure the amount of Tmem27 fragments in the blood – a biomarker that could be used as an index of beta cell number.
The work appears in the September 7 issue of Cell Metabolism.