Researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research UCLA have discovered that high glucose levels prevent heart cells from normal maturing, and this explains why babies born to women with diabetes are more likely to develop congenital heart disease.

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

Atsushi Nakano, UCLA, Associate Professor and the study author says that "High blood sugar levels are not only unhealthy for adults; they're unhealthy for developing fetuses". "Understanding the mechanism by which high blood sugar levels cause disease in the fetus may eventually lead to new therapies."

The leading non-genetic risk factor for the disease is a mother having diabetes during pregnancy. Babies born to women with high blood glucose levels 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 had their pentose phosphate pathway over-activated thus generating more nucleotides than usual. This excess of building blocks kept the cells from maturing. Nakano's group observed the same thing in pregnant mice with diabetes: the heart cells of fetuses divided quickly but matured slowly.

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