Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New protein provides clue to diabetes

16.10.2003


Although cases of adult-onset diabetes have skyrocketed in the United States, researchers still don’t know much about the biological processes that predispose so many people to the disease. But in research that will be published in the Oct. 16 issue of the journal Nature, scientists say they’ve found a protein that plays an essential role in regulating a cell’s ability to absorb glucose, an important step toward gaining a better understanding of the underlying causes of diabetes.



Now that researchers know how this crucial protein reacts in normal cells, they can study how it functions in diabetic patients. The findings ultimately may lead to new drug targets for diabetes medications, says Harvey Lodish, a scientist at Whitehead Institute for Biomedical Research and co-author of the new study.

The researchers discovered the protein – which they call TUG – following a five-year search for molecules that control a glucose transporter named GLUT4, according to Jonathan Bogan, lead author on the paper and former scientist in both Lodish’s laboratory and the Diabetes Unit at Massachusetts General Hospital.


"This discovery has all the attributes of being extremely important to understanding, and maybe treating, Type 2 diabetes," says Lodish.

Nearly 17 million Americans have Type 2 (adult-onset) diabetes, a disorder in which cells lose their ability to absorb glucose from the blood stream. This is different from Type 1 (juvenile onset) diabetes, in which the immune system attacks insulin-producing cells. Normally, when blood sugar levels rise, the pancreas secretes the hormone insulin, which travels through the blood and interacts with "receptors" on the surface of cells in muscle and fat, instructing the cells to absorb and store the excess glucose.

But in Type 2 diabetes, the cells become deaf to insulin’s signals, a condition known as insulin resistance. "No one really knows what causes it," says Bogan, who now is an assistant professor at Yale University School of Medicine. "We don’t even know very much about how the process works in normal cells. Learning the normal process is the first step in learning more about insulin resistance."

Key to this are glucose transporters, a class of proteins that shuttles glucose molecules through the membrane and into the body of the cell. The first glucose transporter was discovered in 1985 in Lodish’s lab. Several others, including GLUT4, have been discovered since then. While most glucose transporters reside at the cell surface, GLUT4 is usually deep inside the cell, only moving to the surface when insulin sends a signal. It is the only transporter that responds exclusively to the presence of insulin.

For the study, Bogan engineered GLUT4 proteins so that they contained two distinct fluorescent tags, and studied them in cultured fat cells. One tag glowed only when GLUT4 appeared at the cell surface. The other was detectable at any location in the cell, enabling Bogan to measure GLUT4 distribution within the cells. He then tested a collection of approximately 2.4 million proteins to see which ones had an effect on GLUT4 distribution.

"By using the tags," Bogan says, "we were able to sift through all the cells and find this needle in a haystack."

Bogan found that one protein, TUG, had a significant effect on GLUT4, acting as a tether that binds GLUT4 inside the cell. When insulin reaches the cell surface, it signals TUG to release GLUT4, which then moves to the cell surface to allow glucose absorption. These study results suggest that excess tethering may somehow contribute to insulin resistance.

Lodish proposes that discovering this key component of the GLUT4 pathway is a significant clue for possibly identifying a diabetes drug target. "Insulin shots just overwhelm the cell and hopefully make it respond to insulin," he says. "But so far, there aren’t any drugs that act directly on this pathway. Now we can begin to speculate, for example, that a drug which blocks TUG might enhance a cell’s ability to absorb glucose. It’s an hypothesis, but an easy one to test."

Joseph Avruch, professor at Harvard Medical School and chief of the diabetes unit at Massachusetts General Hospital, is no stranger to the world of diabetes research. "This is probably the most important discovery in the insulin glucose transport field that’s come along in years," he says. "This is a big step in understanding how insulin resistance works, and opens the way to possibly getting around the impediments that exist in Type 2 diabetes."

While Lodish continues to explore other molecular mechanisms of diabetes, Bogan is continuing the TUG research in his laboratory at Yale, identifying other proteins that interact with TUG and studying mice in which TUG has been genetically altered or deleted. Whitehead Institute and Massachusetts General Hospital own the patent for the technology used to discover TUG and are licensing it to pharmaceutical companies who are employing it in the search for diabetes drug targets.

Says Avruch, "TUG might turn out to be a target, or it might be the key that opens the door to understanding how the system works. Either way, this is still a very important step forward."

David Cameron | EurekAlert!
Further information:
http://www.wi.mit.edu/home.html

More articles from Health and Medicine:

nachricht Antibiotic effective against drug-resistant bacteria in pediatric skin infections
17.02.2017 | University of California - San Diego

nachricht Tiny magnetic implant offers new drug delivery method
14.02.2017 | University of British Columbia

All articles from Health and Medicine >>>

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

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>