Insulin serves as a master switch to finely regulate circulating glucose levels despite regular intervals of fasting and eating, by manipulating signaling pathways. Glucose homeostasis requires the generation and maintenance of glycogen and lipid stores that are utilized in times of fasting or starvation.
Low levels of circulating glucose in Drosophila and mammals causes the evolutionarily conserved signaling protein, cAMP response element-binding protein (CREB), to stimulate the production of glucose from noncarbohydrate sources, such as fat or amino acids. Collaborative work between researchers at UCSD, Novartis and the Salk Institute have identified a CREB coactivator in Drosophila, TORC, which stimulates CREB activation in the brain during starvation. Their recent report illustrates that TORC mutant flies are more sensitive to oxidative stress and starvation and exhibited reduced stores of carbohydrates and fat. Thus, TORC is necessary to maintain normal energy balance in flies.
TORC genes (target of rapamycin (TOR) complexes) are highly conserved and orthologs exist in organisms ranging from algae to humans and recent studies show an important role for TOR kinases in metabolism and aging in yeast. Thus, related kinases may prove important in human glucose metabolism and oxidative stress response.
