Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse with designer liver has enhanced glucose tolerance and improved insulin response

13.04.2005


Liver-specific knock out mouse has improved liver function



A collaborative effort led by The Burnham Institute’s Gen-Sheng Feng has created a mouse with improved glucose tolerance and insulin activity in the liver, and generated new findings about insulin-signaling in the liver that could prove useful in understanding the pathogenesis of type 2 diabetes. These results, to be published by Nature Medicine in May, were made available to the scientific community by advance posting online at the journal’s website on April 10th.

The liver plays a major role in the uptake of glucose from the bloodstream, its storage, and regulation. Insulin resistance in the liver is a crucial factor in the development of hyperglycemia and hypertriglyceridemia in individuals who suffer type 2-diabetes. Precisely how insulin-initiated signals are modulated in liver cells for glucose uptake and metabolism is unknown.


Gen-Sheng Feng, Ph.D., a Professor in The Burnham Institute’s Signal Transduction Program, has focused his efforts on a recently discovered protein called Gab1. Gab1 has a structure that is similar to other proteins in a family known as Insulin Receptor-Signaling, or IRS, proteins. IRS proteins relay signals initiated by insulin receptors and thus play a critical role in insulin regulation inside cells. Biochemical studies on Gab1 in cell cultures suggested that Gab1 is also involved in insulin signaling, but it is not clear how Gab1 acts to control insulin activity in the liver.

To learn how Gab1 functions in the liver, Feng used a highly advanced genetic engineering technology, called tissue-specific gene deletion, to create a mouse in which the Gab1 gene was deleted, or "knocked out", from the liver, and only the liver. Offsprings were termed "LGKO" for liver-Gab1 knockout mice.

Dr. Feng’s laboratory, in collaboration with Drs. Andrea Hevener and Jerrold Olefsky at the University of California, San Diego, conducted a thorough investigation of the glucose metabolism and insulin activity in this newly-created mouse strain. Interestingly, the LGKO mice had reduced blood glucose levels and lower levels of serum insulin. The mice retained triglycerides in the liver with a commensurate decrease of circulating triglycerides in the bloodstream. Insulin response to glucose load was diminished in LGKO mice, thus glucose tolerance in the liver was significantly improved in the absence of Gabl protein.

The Feng team conducted biochemical analyses on the LGKO mice, homing in on enzymatic pathways critical to insulin response in cells. Upon stimulation with insulin, they found an elevated level of Akt/PkB kinase, an enzyme needed for insulin signaling, and elevated activity of IRS proteins. There was no activation of another enzyme, Erk, which is elevated in normal liver in reaction to insulin stimulation. Dr. Feng concluded that the function of Gab1 in normal liver cells is to promote signaling in the Erk pathway, which reduces insulin response signals flowing through IRS and Akt proteins.

"We propose that Gab1 acts as a negative regulator on insulin signal strength in the liver," said Dr. Feng. "In this work, by making a new liver-specific gene knockout mouse model, we found a novel balancing mechanism for control of liver insulin signaling. Our observation might be instrumental for understanding better the pathogenesis of type II diabetes and designing anti-diabetes drugs."

Co-authors on this study from Dr. Feng’s laboratory were Emilie Bard-Chapeau, Ph.D., and Shinong Long, Ph.D., postdoctoral fellows, and Eric Zhang, graduate student in the Burnham Institute-UCSD’s joint graduate training program in Molecular Pathology.

Jerrold Olefsky, Ph.D. and Andrea Hevener, Ph.D. are Professor and Adjunct Associate Professor, respectively, in the Department of Medicine at the University of Calfornia, San Diego.

Nancy Beddingfield | EurekAlert!
Further information:
http://www.burnham.org

More articles from Life Sciences:

nachricht When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

All articles from Life Sciences >>>

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

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>