Enzyme linked to birth anomalies
Research has shown that, even when women with diabetes work vigilantly to control their blood sugar levels around the time of conception, there is still a two-fold increased risk of defects.
The centre had previously shown maternal hyperglycaemia causes oxidative stress in the embryo, and inhibits expression of the Pax3 gene, which is essential to the formation of the neural tube.
But until now, it was not known how cells that express Pax3 sense the oxidative stress.The enzyme AMP kinase (AMPK) appears to be the key. Researchers used mice and cell lines to test whether AMPK was stimulated in the embryo, and if that stimulation was responsible for blocking Pax3 expression.
In their experiments, both high glucose and oxidative stress stimulated the enzyme, which signalled to the cell nucleus to block expression of Pax3.
Diabetologia, online first,13 October 2011