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 World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern

nachricht Therapy of preterm birth in sight?
19.07.2017 | Universitätsspital Bern

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: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>