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 Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

nachricht Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>