Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A new strategy normalizes blood sugars in diabetes

29.03.2010
Novel approach may circumvent lost response in insulin due to obesity
Researchers at Children's Hospital Boston have identified a new strategy for treating type 2 diabetes, identifying a cellular pathway that fails when people become obese. By activating this pathway artificially, they were able to normalize blood glucose levels in severely obese and diabetic mice. Their findings will be published online by Nature Medicine on March 28.

Epidemiologists have long known that obesity contributes to type 2 diabetes. In previous work, researcher Umut Ozcan, MD, in Division of Endocrinology at Children's, showed that the brain, liver and fat cells of obese mice have increased stress in the endoplasmic reticulum (ER), a structure in the cell where proteins are assembled, folded into their proper shapes, and dispatched to do jobs for the cell.

In the presence of obesity, the ER is overwhelmed and its operations break down. This so-called "ER stress" activates a cascade of events that suppress the body's response to insulin, and is a key link between obesity and type 2 diabetes.

Until now, however, researchers haven't known precisely why obesity causes ER stress to develop. Ozcan and colleagues now show that a transcription factor that normally helps relieve ER stress, called X-box binding protein 1 (XBP-1), is unable to function in obese mice. Instead of traveling to the cell nucleus and turning on genes called chaperones, necessary for proper ER function, XBP-1 becomes stranded.

Probing further, the researchers found the reason: XBP-1 fails to interact with a protein fragment called p85, part of an important protein that mediates insulin's effect of lowering blood glucose levels (phosphotidyl inositol 3 kinase or PI3K). Ozcan's group identified a new complex of p85 proteins in the cell, and showed that normally, when stimulated by insulin, p85 breaks off and binds to XBP-1, helping it get to the nucleus.

"What we found is, in conditions of obesity, XBP1 cannot go to the nucleus and there is a severe defect in the up-regulation of chaperones," says Ozcan. "But when we increase levels of free p85 in the liver of obese, severely diabetic mice, we see a significant increase in XBP1 activity and chaperone response and, consequently, improved glucose tolerance and reduced blood glucose levels."

When people are obese, the insulin signaling that normally increases free p85 is impaired, leading to more ER stress and more insulin resistance, ultimately leading to type 2 diabetes. But Ozcan thinks this vicious cycle can be circumvented through strategies that increase levels of free p85. His group is taking further steps to activate this novel pathway to create new treatment strategies for type 2 diabetes.

The study was funded the National Institutes of Health, a Translational Research award from Children's Hospital Boston, and Timothy Murphy funds.

Citation: Sang Won Park, Yingjiang Zhou, Justin Lee, Allen Lu, Cheng Sun, Jason Chung, Kohijiro Ukei and Umut Ozcan. The regulatory subunits of PI3K, p85á and p85â, interact with XBP-1 and increase its nuclear translocation. Nature Medicine advance online publication, March 28, 2010. DOI 10.1038/nm.2099.

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 397-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School.

Andrea Duggan | EurekAlert!
Further information:
http://www.childrens.harvard.edu
http://www.childrenshospital.org/newsroom

More articles from Health and Medicine:

nachricht How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine

nachricht Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center

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: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Thanks for the memory: NIST takes a deep look at memristors

22.01.2018 | Materials Sciences

Radioactivity from oil and gas wastewater persists in Pennsylvania stream sediments

22.01.2018 | Earth Sciences

Saarland University bioinformaticians compute gene sequences inherited from each parent

22.01.2018 | Life Sciences

VideoLinks Wissenschaft & Forschung
Overview of more VideoLinks >>>