Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research reveals how diabetes in pregnancy affects baby's heart

13.12.2017

UCLA scientists show that high levels of glucose keep heart cells from maturing normally

Researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have discovered how high glucose levels -- whether caused by diabetes or other factors -- keep heart cells from maturing normally. Their findings help explain why babies born to women with diabetes are more likely to develop congenital heart disease.


Human heart cells grown from stem cells show less robust muscle fibers (green) in high glucose conditions (left) compared to reduced glucose conditions (right).

Credit: UCLA Broad Stem Cell Research Center/eLife

The study, which was led by Atsushi "Austin" Nakano, a UCLA associate professor of molecular, cell, and developmental biology and member of the Broad Stem Cell Research Center, was published today in the journal eLife.

When developing heart cells are exposed to high levels of glucose, the researchers found, the cells generate more building blocks of DNA than usual, which leads the cells to continue reproducing rather than mature.

"High blood sugar levels are not only unhealthy for adults; they're unhealthy for developing fetuses," Nakano said. "Understanding the mechanism by which high blood sugar levels cause disease in the fetus may eventually lead to new therapies."

Although genetics plays a large role in the development of congenital heart disease, the leading non-genetic risk factor for the disease is a mother having diabetes during pregnancy. Babies born to women with high levels of glucose in their blood during pregnancy are two to five times more likely to develop the disorder than other babies. However, researchers have never been able to define the precise effect of glucose on the developing fetus.

Nakano and his colleagues used human embryonic stem cells to grow heart muscle cells, or cardiomyocytes, in the lab and then exposed them to varying levels of glucose. Cells that were exposed to small amounts of glucose matured normally. But cardiomyocytes that had been mixed with high levels of glucose matured late or failed to mature altogether, and instead generated more immature cells.

The researchers discovered that, when exposed to extra glucose, the cardiomyocytes over-activated the pentose phosphate pathway -- a cellular process that, among other things, generates nucleotides, the building blocks of DNA. In cells with high glucose levels, the pentose phosphate pathway made more nucleotides than usual. The scientists showed that the excess of building blocks kept the cells from maturing.

"More nutrition is generally thought to be better for cells, but here we see the exact opposite," Nakano said. "By depleting glucose at the right point in development, we can limit the proliferation of the cells, which coaxes them to mature and makes the heart muscle stronger."

Nakano's group observed the same thing at work in pregnant mice with diabetes: The heart cells of fetuses divided quickly but matured slowly.

Nakano said the finding could lead to better methods of making cardiomyocytes from stem cells. Today, most protocols for generating cardiomyocytes in the lab lead to immature cells, but targeting the pentose phosphate pathway could help generate more mature cells for regenerating heart cells or for research purposes.

Congenital heart disease affects nearly 1 in 100 children born in the U.S., making it the most common birth defect. The severity of the symptoms it causes varies, ranging from a slightly weakened heart muscle and no symptoms to severe heart deformations that require surgery.

The pentose phosphate pathway as a target for cardiac maturation is covered by a provisional patent application filed by the UCLA Technology Development Group on behalf of the University of California Regents, with Austin Nakano and Haruko Nakano, a UCLA assistant researcher, as inventors.

###

The research was supported by grants from the Oppenheimer Foundation, the National Institutes of Health, the National Center for Research Resources and the Chinese Scholarship Council of Chemistry and Chemical Engineering, as well as funding from the Center for Duchenne Muscular Dystrophy at UCLA and the Broad Stem Cell Research Center.

Media Contact

Mirabai Vogt-James
mvogt@mednet.ucla.edu
310-983-1163

 @uclahealth

http://www.uclahealth.org/ 

Mirabai Vogt-James | EurekAlert!

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

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>