Many of the genes that regulate insulin also alter the timing of the circadian clock, a new study has found.
Although insulin responses were known to follow daily rhythms, the finding that components of the insulin-control system can reset the body's clock surprised the study's authors and suggests new approaches to treating disorders such as metabolic syndrome that can result, at least in part, from chronic disruption of the sleep-wake cycle.
"People knew that the clock regulates many different processes, but what they didn't realize what that when you tweak those processes, it feeds back and alters the clock," said Steve Kay, Dean of the Division of Biological Sciences at the University of California, San Diego, who led the study along with John Hogenesch of the University of Pennsylvania.
Several other important physiological control systems shift the clock as well, they report online this week in the journal Cell.
A molecular clock controls daily physiological rhythms in many types of cells, even cells grown in culture. By engineering cultured cells to glow yellow when a particular clock gene switched on, the team made the cycle visible. They then interfered with every human gene to see which would shift the clock. Hundreds altered the timing.
"We just suddenly discovered 350 new genes that affect the clock that weren't known before," Kay said. Subsequent screening to confirm the genes' effect on a second clock gene narrowed the list to 200.
Genes belonging to four systems appeared on the "hit" list more often than chance would predict: insulin and folate metabolism, and two systems that govern the life cycle and fate of cells. Seven genes involved in insulin control also influenced the rhythms of the clock.
"What came out very strongly was this close relationship between circadian regulation and insulin signaling," Kay said. "There's a reciprocal relationship between circadian dysfunction and metabolic dysfunction."