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 Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

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: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>