Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Unexpected function for a key regulator of blood glucose levels

10.11.2005


An unexpected twist to a discovery reported just two months ago may significantly improve our understanding about the molecular origins of diabetes.



Scientists at the Salk Institute for Biological Studies then reported their discovery of a key cellular switch that instructs the liver to produce more glucose when blood sugar levels run low. Their paper was published in Nature.

Now, in the November issue of Cell Metabolism, they report that the very same switch limits its own activity to prevent the amount of produced glucose from overshooting healthy levels.


"This crucial fine-tuning is missing in diabetic individuals," explains Marc Montminy, a professor in the institute’s Clayton Foundation Laboratories for Peptide Biology. "When you measure glucose levels in diabetic patients in the morning or after they have been fasting, their glucose levels are very high because the body is unable to control the production of glucose," he adds.

Two hormones with opposite effects - insulin and glucagon - act together to maintain a steady level of glucose circulating in our bloodstream, to provide a constant and readily available energy supply for the cells in our body.

Right after a meal, when nutrient levels in the blood are high, the pancreas releases insulin, which tells muscle and liver cells to squirrel away glucose for later use. In addition, insulin stimulates the production of fat and shuts down the ability of the liver to produce glucose.

At night or between meals, however, when glucose supplies run low, the pancreas releases glucagon into the bloodstream, to signal the body to fire up the fat burner. But even during sleep, our brain relies solely on glucose for fuel. To keep the brain well supplied with energy, the liver actually manufactures glucose during sleep or when we are fasting.

In response to low blood sugar levels, the glucagon signal flips a switch that triggers glucose production in liver cells. This switch is a protein called TORC2 that, when activated by glucagon, turns on the expression of genes necessary to make glucose from scratch.

At the same time TORC2 sets the stage to be shut off quickly when glucose levels start rising. "We were quite surprised to find that activated TORC2 makes the liver more sensitive to insulin, allowing it to respond more effectively to rising glucose levels," says Salk research fellow and co-author Seung-Hoi Koo, who also is affiliated with the Sungkyunkwan University School of Medicine in Korea

TORC2 does so by increasing the amount of a protein called IRS2 (insulin receptor substrate 2) mainly in liver and pancreas cells. IRS2 acts as a molecular bridge between the insulin receptor and downstream targets in the insulin signaling pathway. With more IRS2 available, liver cells can react to minute amounts of insulin and stop churning out glucose.

Mice that lack IRS2 are severely diabetic since the insulin signal can’t "get through". However, when the Salk scientists treated them with gene therapy that delivered the missing gene for IRS2, healthy glucose levels were restored within a week.

"Understanding the regulation of insulin sensitivity represents a major challenge in the field of diabetes," says co-author Gianluca Canettieri, formerly a research fellow at Salk, now at the University of Rome, "La Sapienzia", Italy. "I think this finding could have significant implications in human therapy," he adds.

Other co-authors of the paper are Rebecca Berdeaux, Jose Heredia, Susan Hedrick and Xinmin Zhang, all at the Salk Institute for Biological Studies.

Cathy Yarbrough | EurekAlert!
Further information:
http://www.salk.edu

More articles from Health and Medicine:

nachricht Electrical 'switch' in brain's capillary network monitors activity and controls blood flow
27.03.2017 | Larner College of Medicine at the University of Vermont

nachricht Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

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: 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

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>