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

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:

Children's Hospital Boston | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

nachricht New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington

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: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

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

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>