Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New tactic for controlling blood sugar in diabetes contradicts current view of the disease

05.09.2011
Study finds inflammation may be part of the solution, not the problem

Increased low-grade inflammation in the body resulting from obesity is widely viewed as contributing to type 2 diabetes. Going against this long-held belief, researchers from Children's Hospital Boston report that two proteins activated by inflammation are actually crucial for maintaining good blood sugar levels – and that boosting the activity of these proteins can normalize blood sugar in severely obese and diabetic mice.

The research, led by Umut Ozcan, MD, in the Division of Endocrinology at Children's, is reported in the October issue of Nature Medicine, published online September 4.

"This finding is completely contrary to the general dogma in the diabetes field that low-grade inflammation in obesity causes insulin resistance and type 2 diabetes," says Ozcan. "For 20 years, this inflammation has been seen as detrimental, whereas it is actually beneficial."

Ozcan's team previously showed that obesity places stress on the endoplasmic reticulum (ER), a structure in the cell where proteins are assembled, folded and dispatched to do jobs for the cell. This so-called "ER stress" impairs the body's response to insulin in maintaining appropriate blood glucose levels, and is a key link between obesity and type 2 diabetes. Last year, Ozcan and colleagues showed that a protein that relieves ER stress, called XBP1s, cannot function in obese mice. Earlier this year, they showed that activating XBP1s artificially in the liver normalized high blood sugar in obese, insulin-resistant type 2 diabetic mice (as well as lean, insulin-deficient type 1 diabetic mice).

The new study shows that a second protein triggered by inflammatory signals, p38 MAPK, chemically alters XBP1s, enhancing its activity -- and that without these alterations, XBP1s cannot function to maintain normal glucose levels. The study further showed that obese mice have reduced p38 MAPK activity, and that re-activating p38 MAPK in the liver reduced their ER stress, increased insulin sensitivity and glucose tolerance, and significantly reduced blood glucose levels.

Together, the findings suggest that either increasing p38 MAPK activity -- despite its being an inflammatory signal -- or increasing XBP-1 activity by other means could represent new therapeutic options for diabetes.

The study also suggests a new model for understanding type 2 diabetes, in which obesity may interfere with the ability of people's cells to respond to inflammatory signals. "It may be that inflammatory pathways are not working optimally and there could be a resistance to cytokines which mediates the inflammation," Ozcan says. "This could be a paradigm shift for the field."

The researchers also raise a possible down side in using p38 MAPK inhibitors to treat inflammatory diseases such as Crohn's disease, psoriasis and asthma. "These therapeutic approaches should … be evaluated within the context of our results, and in light of the possibility that inhibition of XBP1s activity also decreases the ability of the cell to cope with the inflammatory conditions," they write.

The study (doi:10.1038/nm.2449) was supported by the National Institutes of Health and the Timothy Murphy funds provided to the Division of Endocrinology, Children's Hospital Boston. Jaemin Lee, PhD, and Cheng Sun, PhD, were co-first authors on the paper.

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 1,100 scientists, including nine members of the National Academy of Sciences, 11 members of the Institute of Medicine and nine 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 396 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. For more information about research and clinical innovation at Children's, visit: http://vectorblog.org.

Children's Hospital Boston | EurekAlert!
Further information:
http://vectorblog.org

More articles from Health and Medicine:

nachricht Cardiac diseases: when less is more
30.03.2017 | Universitätsspital Bern

nachricht TSRI researchers develop new method to 'fingerprint' HIV
29.03.2017 | Scripps Research Institute

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: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

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...

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

NASA laser communications to provide Orion faster connections

30.03.2017 | Physics and Astronomy

Reusable carbon nanotubes could be the water filter of the future, says RIT study

30.03.2017 | Studies and Analyses

Unique genome architectures after fertilisation in single-cell embryos

30.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>