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 Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>