Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify new drug target that stimulates

07.09.2011
JDRF-funded scientists collaborate with pharmaceutical company to uncover new ways to stimulate pancreatic beta cell growth

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 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. Importantly, Bace2, and not its close relative Bace1, which is implicated in other diseases, cleaves the Tmem27 protein, suggesting the potential for developing a Bace2 inhibitor as a diabetes-specific therapy.

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.

"This is an exciting and potentially impactful finding," says Patricia Kilian, Ph.D., scientific program director of regeneration research at JDRF. "It's an example of how researchers make an early observation and follow up on it, and then take it to the next level where it has translational potential – the potential to be developed into a drug that promotes the growth of beta cells for diabetes."

About JDRF

JDRF is the worldwide leader for research to cure type 1 diabetes (T1D). It sets the global agenda for diabetes research, and is the largest charitable funder and advocate of diabetes science worldwide. The mission of JDRF is to find a cure for diabetes and its complications through the support of research. T1D is an autoimmune disease that strikes children and adults suddenly, and can be fatal. Until a cure is found, people with T1D have to test their blood sugar and give themselves insulin injections multiple times or use a pump—each day, every day of their lives. And even with that intensive care, insulin is not a cure for diabetes, nor does it prevent its potential complications, which may include kidney failure, blindness, heart disease, stroke, and amputation. Since its founding in 1970 by parents of children with T1D, JDRF has awarded more than $1.5 billion to diabetes research, including $107 million last year. More than 80 percent of JDRF's expenditures directly support research and research-related education. For more information, please visit www.jdrf.org.

Joana Casas | EurekAlert!
Further information:
http://www.jdrf.org

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>