During fasting, mammals maintain glucose homeostasis by stimulating glucose production from the liver. Elevations in circulating glucagon trigger expression of the gluconeogenic program in part through induction of the cAMP responsive factor CREB. The effects of CREB on the gluconeogenic program are mediated by the cAMP responsive coactivator TORC2, which potentiates CREB activity in liver specifically under fasting but not feeding conditions. Sequestered in the cytoplasm under ad libitum feeding conditions, TORC2 is de-phosphorylated translocated to the nucleus in response to fasting where it stimulates gene expression through a direct interaction with CREB. To monitor the effects of nutrient and energy sensing pathways on TORC2 activity in real time, we developed an in vivo hepatic imaging approach. We found that pancreatic and adipose-derived signals modulate glucose output through acute and long-term effects on TORC2 activity. The results illustrate a distinct mechanism through which nutrient and hormonal cues regulate the gluconeogenic program.