Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Joslin study finds clue to birth defects in babies of mothers with diabetes

17.10.2011
Stimulation of metabolism-sensing enzyme that can regulate crucial gene explains how free radicals generated during maternal hyperglycemia cause malformation of the neural tube

In a paper published today in Diabetologia, a team at Joslin Diabetes Center, headed by Mary R. Loeken, PhD, has identified the enzyme AMP kinase (AMPK) as key to the molecular mechanism that significantly increases the risk of neural tube defects such as spina bifida and some heart defects among babies born to women with diabetes.

Even if women with diabetes -- either type 1 or type 2 -- work vigilantly to control their blood sugar levels around the time of conception, the risk of a defect is still twice that of the general population. This finding could lead to strategies to interfere with the mechanism and reduce the chances of such birth defects occurring.

Previous studies published by Loeken's lab showed that maternal hyperglycemia (high blood sugar) causes oxidative stress in the embryo, and inhibits expression of the Pax3 gene. Pax3 is essential to the formation of the neural tube, which in the embryo is the precursor to the brain and spinal cord. Oxidative stress results when oxidized molecules - called free radicals - are created faster than they can be eliminated.

However, Loeken said, it was not known how the cells that express Pax3 could sense the oxidative stress and why oxidative stress, which occurs throughout the embryo, only damages selective structures such as the neural tube.

In the paper published today, Loeken's team identifies the key to the process as AMP kinase, which is activated by oxidative stress and was found to signal the cell nucleus to block the expression of Pax3.

"The stimulation of a metabolism-sensing enzyme that can regulate specific genes explains how oxidative stress, which is generated throughout the embryo during maternal hyperglycemia, causes malformation of specific embryo structures," Loeken said.

"We now know that we must do whatever we can to prevent AMPK from being stimulated," said Loeken, who is a research investigator in Joslin's Section on Islet Cell and Regenerative Biology.

Trying to keep the mother's blood glucose levels under control is currently the only way to do that, she noted. "That's the best we can do right now," she said. But armed with the findings of this study, she noted, other researchers may be able to come up with drugs or other strategies to inhibit AMPK activity,

Dr. Loeken added, however, that formulating a strategy could be tricky because it is not known if interfering with AMPK activity -- while a good thing in preventing neural tube birth defects -- might also have negative effects on the embryo.

In their study Loeken and her group, including Yichao Wu, Marta Viana, and Shoba Thirumangalathu, used mice and cell lines to test their hypothesis that AMPK might be stimulated in the embryo and that stimulation of AMPK was responsible for blocking Pax3 expression and causing neural tube defects in response to high glucose.

"We found in this study that AMPK is stimulated in embryo by both high glucose and oxidative stress," Loeken said.

The study used interventions including a drug that activates AMPK and another that blocks it. The paper showed that a drug that increased AMPK activity mimics the effects of oxidative stress to inhibit expression of Pax3, thus inducing neural tube defects.

This research was supported by a grant from the National Institutes of Health.

About Joslin Diabetes Center

Joslin Diabetes Center is the world's preeminent diabetes research and clinical care organization. Joslin is dedicated to ensuring that people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure. Joslin is an independent, nonprofit institution affiliated with Harvard Medical School. For more information about Joslin, visit http://www.joslin.org. Keep up with Joslin research and clinical news at Inside Joslin at http://www.joslin.org/news/inside_joslin.html, Become a fan of Joslin on Facebook at http://www.facebook.com/joslindiabetes and follow Joslin on Twitter at http://www.twitter.com/joslindiabetes

Jeffrey Bright | EurekAlert!
Further information:
http://www.joslin.org

More articles from Studies and Analyses:

nachricht Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

All articles from Studies and Analyses >>>

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

Pulverizing electronic waste is green, clean -- and cold

22.03.2017 | Materials Sciences

Astronomers hazard a ride in a 'drifting carousel' to understand pulsating stars

22.03.2017 | Physics and Astronomy

New gel-like coating beefs up the performance of lithium-sulfur batteries

22.03.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>