Fine-Tuning Liver Glucose Metabolism

Researchers have traced the biochemical mechanism responsible for modulating the uptake, release, and synthesis of glucose by the liver.

Previous findings had shown that hormonal and nutrient regulation of glucose synthesis in the liver was controlled by modulation of the transcriptional coactivator protein PGC-1-alpha. In the current study, investigators at Johns Hopkins University (Baltimore, MD, USA) learned that PGC-1-alpha resides in a multi-protein complex containing the acetyltransferase GCN5. Fine-tuning of glucose metabolism depends on inactivation of PGC-1-alpha by this enzyme and its subsequent sequestering away from the genes it was normally meant to activate.

This mechanism was demonstrated experimentally by using an adenovirus vector to implant the gene for GCN5 into the livers of a group of starved mice. Normally such animals are actively releasing glucose into the blood, but results published in the June 2006 issue of Cell Metabolism showed that glucose release in these genetically engineered animals was significantly reduced.

"These results show that changing GCN5 is sufficient to control the sugar balance in mice,” explained senior author Dr. Pere Puigserver, assistant professor of cell biology at Johns Hopkins University. "Therefore, GCN5 has the potential to be a target for therapeutic drug design in the future. Understanding the ways that energy production and use are controlled is crucial to developing new drugs and therapies.”



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