Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Key regulator of blood glucose levels discovered

08.09.2005


In many patients with type 2 diabetes, the liver acts like a sugar factory on overtime, churning out glucose throughout the day, even when blood sugar levels are high. Scientists at the Salk Institute for Biological Studies discovered a key cellular switch that controls glucose production in liver cells.

This switch may be a potential new target for the development of highly specific diabetes drugs that signal the liver to reduce the production of sugar. The Salk researchers, led by Marc Montminy, a professor in the Clayton Foundation Laboratories for Peptide Biology, published their findings in the Sept. 7th online issue of Nature.

"It is very exciting to understand how glucose production in the liver is regulated. Now, we can try to improve the way how type 2 diabetics handle blood sugar," says Montminy.



The newly discovered switch, a protein named TORC2, turns on the expression of genes necessary for glucose production in liver cells. When describing glucose’s role in health and disease, Montminy compares the human body to a hybrid car that runs on a mix of fuels depending on its activity status: gas, or glucose, is used for high-energy activities, and battery power, or body fat, for low-energy activities. During the day, when food refuels the "gas tank," the body burns mainly glucose, and during sleep, it burns primarily fat.

The body switches from glucose to fat burning mainly in response to two key hormones -- insulin and glucagon -- that are produced by the pancreas. During feeding, the pancreas releases insulin, which promotes the burning of glucose. At night, however, the pancreas releases glucagon into the bloodstream, which signals the body to fire up the fat burner.

But even during sleep, our brain needs a constant supply of glucose to function properly. For that reason, our body actually manufactures glucose during sleep or when we are fasting. That process, called gluconeogenesis, is carried out mainly in the liver.

Insulin normally shuts down the ability of the liver to produce glucose. In individuals with Type II diabetes, however, insulin is unable to inhibit sugar production in the liver, "either because the pancreas is not producing enough insulin or because insulin’s signal can’t be ’heard,’" says Montminy. When the liver is unable to hear the insulin signal, excess glucose builds up in the bloodstream.

In addition to so-called insulin sensitizing drugs that allow insulin to work better, researchers are looking for alternative ways to shut down the production of glucose in the liver of diabetics. "Figuring out how to control glucose production in the liver is critical because many complications of diabetes, such as heart disease, kidney failure and blindness, can be reduced by maintaining a very tight control over blood sugar levels," he says.

As glucose levels run low during fasting, the pancreas sends out the hormone glucagon and instructs the liver to produce glucose. This increase in glucagon turns on the TORC2 switch and allows the liver to make more glucose. Mice that were genetically modified to make more or less TORC2 produced more or less glucose depending on the amount of available TORC2 (transducer of regulated CREB activity).

Most of the time, TORC2 sits in the cellular compartment that surrounds the nucleus, where all the genes are located. When a glucagon signal arrives, the TORC2 switch crosses the nuclear membrane, teams up with the transcriptional activator CREB and turns on all the genes necessary for gluconeogenesis. "Being located in a different part of the cell is what keeps the TORC2 switch off," explains Montminy.

The researchers also discovered that a chemical modification on TORC2 itself sequesters the protein in the cytoplasm, the viscous substance inside the cell that surrounds the nucleus. "Since we now know the molecular mechanism by which TORC2 is inactivated we can start looking for small molecules that do the same thing," says Montminy.

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

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>