Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gladstone Scientists identify key mechanism involved in Type 2 diabetes

29.03.2012
Findings may lead to new strategies to address insulin resistance

Scientists at the Gladstone Institutes have discovered a key protein that regulates insulin resistance—the diminished ability of cells to respond to the action of insulin and which sets the stage for the development of the most common form of diabetes. This breakthrough points to a new way to potentially treat or forestall type 2 diabetes, a rapidly growing global health problem.

In a paper being published online this week in the Proceedings of the National Academy of Sciences, researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, describe an unexpected role of the p75 neurotrophin receptor in controlling how the body processes sugar. Called p75NTR, this receptor protein is usually associated with functions in neurons.

"We identified that p75NTR is a unique player in glucose metabolism," said Dr. Akassoglou, who is also an associate professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "Therapies targeted at p75NTR may represent a new therapeutic approach for diabetes."

The pancreas makes a hormone called insulin that processes glucose, moving it from the bloodstream into the body's cells where it is used for energy. Insulin resistance is a key feature of Type 2 diabetes, in which glucose builds up in the bloodstream and the body's cells are unable to function properly. According to the Centers for Disease Control and Prevention, more than 20 million Americans have type 2 diabetes.

"Type 2 diabetes has become a very serious health problem and it is increasing at an alarming rate," said Lennart Mucke, MD, who directs the institute in which the research was conducted. "These findings provide an important new avenue for developing better therapies to combat this deadly disease—the seventh leading cause of death in the United States."

Complex signaling interactions between several different types of tissue—including fat, liver, muscle and brain—regulate glucose metabolism. Because p75NTR is found in fat and muscle tissue and participates in many important functions in the cell, Gladstone scientists hypothesized that p75NTR might also help to regulate glucose metabolism.

To study this, the researchers used mice that lacked the genes for p75NTR. They compared these mice to normal mice and discovered that those lacking p75NTR were more responsive to insulin when fed a normal diet. Second, they used some molecular biology tricks to block the action of the p75NTR protein in fat cells. This also resulted in increased glucose absorption in response to insulin. In contrast, when they caused the fat cells to make more p75NTR, glucose absorption was reduced. Additionally, the researchers found that another important regulatory molecule, Rab5, played a key role in p75NTR's impact on metabolism.

"Importantly, regulation by p75NTR enhanced insulin's effectiveness in normal lean mice on a normal diet," said Bernat Baeza-Raja, PhD, postdoctoral fellow and lead author of the study. "Because these mice already process glucose efficiently, the actions of p75NTR on glucose transport indicate a direct role of this protein in the regulation of glucose metabolism."

"Our studies of p75NTR's unanticipated role in regulating glucose metabolism suggest a new target for drug therapies," said Dr. Akassoglou. "Future work is needed to test whether this finding may translate into a potential treatment."

This study was a collaborative work between scientists at Gladstone, the University of California, San Diego (UCSD), the University of Michigan and the University of Houston. Other scientists who participated in this research at Gladstone include Natacha Le Moan, PhD, Christian Schachtrup, PhD, Dimitrios Davalos, PhD, and Eirini Vagena. Jerrold Olefsky, PhD, and Pingping Li, PhD, at UCSD were co-senior and co-first authors, respectively. Funding was provided by a variety of sources, including the National Institutes of Health, the University of California San Francisco Liver Center and Diabetes and Endocrinology Center and the R. A. Welch Foundation.

About the Gladstone Institutes

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.

Diane Schrick | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

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

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>