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cells turn on genes to make more glucose to fuel the body.

The research team found that GCN5 chemically alters another protein called PGC-1alpha that normally turns on a set of genes to manufacture enzymes required for glucose release. When GCN5 is fully functional in liver cells, this cascade is turned off and glucose is not released from those cells. Removal of functional GCN5 from liver cells restores the cells' ability to release glucose.

The researchers showed that GCN5 alters its target, sabotaging it by adding a chemical tag called an acetyl group. By using molecules that glow fluorescently, the researchers saw under high-power microscopes that GCN5 carries its tagged target to a different location in the cell's nucleus – sequestering it away from the genes it's normally meant to turn on.

‘GCN5 has been generally shown to turn on genes. No one knew that GCN5 could be used to turn off pathways’ says Lerin. ‘It was a bit of a surprise.’

When the researchers put GCN5 into live mice, they found that it can in fact decrease blood glucose levels. Liver cells in mice that were given no food for 16 hours actively release glucose into the bloodstream. Introducing GCN5 into their livers, however, causes blood glucose levels in these mice to be reduced.

‘These results show that changing GCN5 is sufficient to control the sugar balance in mice,’ says Puigserver. ‘Therefore, GCN5 has the potential to be a target for therapeutic drug design in the future.’

Souce: Eurekalert
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