High glucose levels are unhealthy for adults but dangerous for foetuses as well. Babies born to women with high glucose in their blood during pregnancy are two to five times more likely to develop congenital heart disorders than other babies. The severity of such disorders varies from from a slightly weakened heart muscle and no symptoms to severe heart deformations that require surgery.
Researchers at the University of California, Los Angeles have now used human embryonic stem cells to grow heart muscle cells in in varying glucose environments in the lab to find how exactly the heart muscle cells are affected. Cells that were exposed to small amounts of glucose matured normally but the cells that had been mixed with high levels of glucose matured late or failed to mature altogether. Instead, they generated more immature cells. The researchers found that the cells exposed to too much glucose over-activated a cellular pathway, called the the pentose phosphate pathway, that generates nucleotides, which are the building blocks of DNA. So, these cells have nucleotides than usual and this keeps the cells from maturing.
The authors pointed out that although more nutrition is generally considered to be better for growth, in this case it worked the opposite way. The team also observed the same effect in pregnant diabetic mice – heart cells of mice foetuses divided quickly but matured slowly. By depleting glucose at the right point in development, the cells stop proliferating and start maturing instead to make the heart muscle stronger.
The researchers say that the findings, published in the journal eLife, may lead to better methods of making heart muscle cells from stem cells.