Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

In Type 2 Diabetes, Mitochondrial Damage Kills Insulin-Producing Cells

25.11.2009
Over time, patients with type 2 diabetes lose insulin-producing cells, a difficulty that aggravates their disease. Researchers at Joslin Diabetes Center now have identified a mechanism that triggers the problem, giving a chance to find targets for drugs to protect these crucial cells.

Curiously enough, the failure arises when the insulin-producing "beta" cells, located in the pancreas, themselves fail to import insulin properly. Similar failures throughout the body, producing a condition known as insulin resistance, are a common cause of type 2 diabetes.

Scientists in the lab of Joslin Principal Investigator Rohit N. Kulkarni, M.D., Ph.D., found that when a beta cell can't respond to circulating insulin, an altered molecular cascade ends up damaging the normal action of a certain molecular complex on the surface of the cell's mitochondria.

Mitochondria, known as the cell's powerhouses, produce most of every cell's supply of adenosine triphosphate, the prime fuel for cellular activity. When compromised in this way, the beta-cell's mitochondria begin to destroy it.

In research published online in PLoS ONE on November 24, Siming Liu, Ph.D., a postdoctoral fellow in the Kulkarni lab, began by studying genetically modified mice whose beta cells, and only beta cells, lacked a receptor on their cell surface that allows insulin to act.

"Experimenting with these cell lines, Siming noticed that they kept dying over a period of time, and then discovered that this cell death was linked to mitochondrial damage," says Dr. Kulkarni, who is also an Assistant Professor of Medicine at Harvard Medical School.

When Liu genetically modified these cells to restore the insulin receptor, he could fix most of the defects.

He tracked down the damage to a molecular complex on the mitochondrial surface that includes two key proteins. One is glucokinase, an enzyme that is key in metabolizing glucose. The other is Bcl-2-associated death promoter (BAD), a protein that is central to a pathway toward cell death.

Liu then examined beta cells from humans with type 2 diabetes and discovered that this mechanism also was at work there.

While researchers had known about the existence of the glucokinase/BAD complex, this was the first study to implicate it in the death of beta cells when the insulin signaling pathway breaks down, and to show that this mechanism also is triggered in humans with type 2 diabetes. Scientists elsewhere recently isolated a similar effect in hepatocytes, cells that make up the liver.

Following up on the discovery in beta cells, "we will try to figure out whether the proteins we isolated in the complex can be therapeutic targets," says Kulkarni. "Right now, no drugs are specifically targeted to prevent this kind of cell death, which can affect just about anyone with type 2 diabetes."

"Mitochondrial function is a very fundamental aspect of how beta cells produce insulin, and this research shows its direct relation with insulin signaling," notes co-author E. Dale Abel, M.D., Ph.D., Chief of the Division of Endocrinology and Metabolism at the University of Utah School of Medicine in Salt Lake City.

Other contributors include Terumasa Okada, Anke Assmann and Chong Wee Liew of Joslin; Jamie Soto and Heiko Bugger of the University of Utah School of Medicine; and Orian S. Shirihai of the Boston University School of Medicine. The research was funded by the National Institutes of Health.

Joslin Diabetes Center is the world's preeminent diabetes research and clinical care organization. Joslin is dedicated to ensuring people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure for the disease. Founded in 1898 by Elliott P. Joslin, M.D., Joslin is an independent nonprofit institution affiliated with Harvard Medical School. For more information about Joslin, visit www.joslin.org or call 1-800-JOSLIN-1.

Eric Bender | Newswise Science News
Further information:
http://www.joslin.harvard.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>