Navigation Links
Joslin study finds clue to birth defects in babies of mothers with diabetes
Date:10/16/2011

BOSTON -- October 17, 2011-- 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.


'/>"/>
Contact: Jeffrey Bright
jeffrey.bright@joslin.harvard.edu
Joslin Diabetes Center
Source:Eurekalert  

Related biology news :

1. Joslin researchers identify pathways leading to activation of good fat
2. Joslin researchers identify new target for treatment of type 2 diabetes and prediabetes
3. Joslin research finds nearly three-quarters of youths with diabetes insufficient in vitamin D
4. First genome-wide association study for dengue identifies candidate susceptibility genes
5. Largest ever genetic study of liver function could point the way to new treatments
6. Study reveals new role for RNA interference during chromosomal replication
7. Method of studying roots rarely used in wetlands improves ecosystem research
8. Southampton scientists herald significant breakthrough in study of chlamydia
9. Einstein College of Medicine given $6.7 million to study congenital heart defect genetics
10. National Science Foundation selects University of Colorado Denver team to study city sustainability
11. Worms among first animals to surface after K-T extinction event, CU-led study finds
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Joslin study finds clue to birth defects in babies of mothers with diabetes
(Date:6/3/2016)... June 3, 2016 ... Nepal hat ein ... hochsicherer geprägter Kennzeichen, einschließlich Personalisierung, Registrierung und ... der Produktion und Implementierung von Identitätsmanagementlösungen. Zahlreiche ... im Januar teilgenommen, aber Decatur wurde als ...
(Date:6/2/2016)... LONDON , June 2, 2016 ... Systems, Manned Platforms, Unmanned Systems, Physical Infrastructure, Support & ... intelligence provider visiongain offers comprehensive analysis of ... that this market will generate revenues of $17.98 billion ... Systems acquired DVTEL Inc, a leader in software and ...
(Date:5/20/2016)...  VoiceIt is excited to announce its new ... By working together, VoiceIt and VoicePass will offer ... take slightly different approaches to voice biometrics, collaboration ... usability. Both ... "This marketing and technology partnership allows ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... Mass. , June 23, 2016   ... development of novel compounds designed to target cancer ... napabucasin, has been granted Orphan Drug Designation from ... the treatment of gastric cancer, including gastroesophageal junction ... stemness inhibitor designed to inhibit cancer stemness pathways ...
(Date:6/23/2016)... Houston Methodist Willowbrook Hospital has signed ... to serve as their official health care provider. ... will provide sponsorship support, athletic training services, and ... volunteers, athletes and families. "We are ... and to bring Houston Methodist quality services and ...
(Date:6/23/2016)... June, 23, 2016  The Biodesign Challenge (BDC), a ... ways to harness living systems and biotechnology, announced its ... in New York City . ... students, showcased projects at MoMA,s Celeste Bartos Theater during ... , MoMA,s senior curator of architecture and design, and ...
(Date:6/23/2016)... ... 2016 , ... STACS DNA Inc., the sample tracking software company, today announced ... has joined STACS DNA as a Field Application Specialist. , “I am thrilled ... COO of STACS DNA. “In further expanding our capacity as a scientific integrator, Hays ...
Breaking Biology Technology: