Researchers 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. The study was published 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," senior author 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.
Researchers 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," senior author 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."
The group observed the same thing at work in pregnant mice with diabetes: The heart cells of fetuses divided quickly but matured slowly.
The senior author 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.
https://stemcell.ucla.edu/news/research-reveals-how-diabetes-pregnancy-affects-baby%E2%80%99s-heart
https://elifesciences.org/articles/29330
Latest News
Tumor infiltration of immun…
By newseditor
Posted 28 May
New light-controlled 'off s…
By newseditor
Posted 28 May
Gene function during embryo…
By newseditor
Posted 28 May
Formation of 3D blood vesse…
By newseditor
Posted 27 May
Liver regeneration during c…
By newseditor
Posted 27 May
Other Top Stories
3D mapping of extracellular pH of single living cells
Read more
Transporting large drug molecules into cells via nanoparticles
Read more
Why doesn't deep-brain stimulation work for everyone?
Read more
A method to watch neurons compute
Read more
Developing universal protein translocation system using bacterial t…
Read more
Protocols
SEMORE: SEgmentation and MO…
By newseditor
Posted 26 May
Spatially resolved lipidomi…
By newseditor
Posted 24 May
Efficient expansion and CRI…
By newseditor
Posted 21 May
Massively parallel in vivo…
By newseditor
Posted 20 May
Breast cancer-on-chip for p…
By newseditor
Posted 16 May
Publications
Circadian tumor infiltratio…
By newseditor
Posted 28 May
Kalium channelrhodopsins ef…
By newseditor
Posted 28 May
Double-duty isomerases: a c…
By newseditor
Posted 28 May
Signal switching may enhanc…
By newseditor
Posted 28 May
Emerging paradigms and rece…
By newseditor
Posted 28 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar