The researchers discovered cryptochrome's role in gluconeogenesis while studying how a signaling molecule known as cyclic AMP interacted with the biological clock.
"It had been known for some time now that there was a connection between cyclic AMP signaling and circadian rhythm regulation and that's where we started," said Kay, "by asking the question: How are those two connected?"
Zhang and his UCSD colleagues conducted a series of experiments that found that the production of the next step after cyclic AMP, a protein called Creb, ebbed and flowed rhythmically in the livers of mice. That led the scientists to their initial discovery that cryptochrome was regulating the production of Creb in the liver.
In their studies with fasting and insulin-resistant mice at the Salk Institute, the scientists found that cryptochrome was regulating how the hormone glucagon, which controls gluconeogenesis, works in a very specific way. By controlling the production of cyclic AMP, crytochrome regulates the activity of Creb in the liver. In this way, the production of glucose in the liver is tied through our daily eating, sleeping and fasting activities through the biological clock.
The scientists say their discovery may open up a whole new area of research into how cryptochrome may be regulating other cell functions outside the nucleus.
"There's a wide role that the biological clock may be playing in influencing other hormones, not just glucagon, that are important for metabolism," said Kay.
In addition, studies on human populations have found links between disturbances in the biological clock, such as shift work and chronic jet lag, and the propensity to develop certain kinds of cancers as well as diabetes. Because of this, the scientists p
|Contact: Kim McDonald|
University of California -- San Diego