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Researchers identify new drug target that stimulates
Date:9/6/2011

NEW YORK, N.Y., Sept. 6, 2011 -- One of the holy grails in diabetes research is to discover molecules that stimulate beta cell growth and to find drugs that target these molecules. Now, JDRF-funded researchers in collaboration with the pharmaceutical company Hoffmann-La Roche, have done both, discovering not only a protein that regulates beta cell growth, but also a chemical compound that stimulates it. The work appears in the September 7 issue of Cell Metabolism.

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 beta cell regeneration.

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, the insulin-producing cells that are located within islets in the pancreas. At the time, they found that increased levels of Tmem27 on beta cells were associated with increased islet mass in mice. They also found that if Tmem27 is cleaved, it left the protein completely inactivated.

"We hypothesized that if we could prevent Tmem27 from being cleaved and increase the levels of this protein, we could get more beta cell growth," says Dr. Stoffel, who is also a 2010 recipient of JDRF's Gerold & Kayla Grodsky Basic Research Scientist Award. "This observation gave us the rationale to look for what was inactivating Tmem27."

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 confirmed their theory by finding 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 the
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Contact: Joana Casas
mcasas@jdrf.org
212-479-7560
Juvenile Diabetes Research Foundation International
Source:Eurekalert

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