Researchers have discovered how high glucose levels-whether caused by diabetes or other factors keep heart cells from maturing normally, this shows the reason why babies born to women with diabetes are more likely to develop congenital heart disease. 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. the leading non-genetic risk factor for congenital heart 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 cardiomyocin 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. 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 same thing occurred in pregnant mice with diabetes-the heart cells of fetuses divided quickly but matured slowly.
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