Genes controlling insulin ‘alter’ body clock

Washington, Sept 18 (ANI): Scientists at University of California, San Diego have identified certain insulin-regulating genes that can also alter the timing of the body clock.

They said that the findings can lead to 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.

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. They found that hundreds altered the timing.

“We just suddenly discovered 350 new genes that affect the clock that weren’t known before,” Kay said.

However, subsequent screening to confirm the genes’ effect on a second clock gene narrowed the list to 200.

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 signalling. There’s a reciprocal relationship between circadian dysfunction and metabolic dysfunction,” said Kay.

The researchers suggest that genetically altered mice with malfunctioning clocks become obese and develop diet-induced diabetes.Understanding this close relationship between circadian regulation and metabolic homeostasis should provide novel ways of identifying new therapies for metabolic disease,” Kay added.

The study appears in journal Cell. (ANI)

The biological basis for the 8-hour work-shift

Washington, April 24 (ANI): Your usual nine to five office shift has a biological reason behind it, and now scientists have found that some genes in the body are switched on once every 12 or 8 hours, which in turn keeps us actively involved in the work, according to a new study.

The findings by researchers at the University of Pennsylvania School of Medicine and the Salk Institute for Biological Studies indicated that shorter cycles of the circadian rhythm are also biologically encoded.

Already, scientists know that some genes are controlled by the clock and are turned on only one time during each 24-hour cycle.

In the new study, researchers looked at gene activity in the mouse liver every hour for 48 hours using a novel time-sampling approach.

They also found 10-fold more genes controlled by the 24-hour clock than previously reported.

This the first report where researchers have found other periodicities than the 24-hour cycle functioning in a live animal.

According to researchers, these findings have implications for better understanding disruptions to normal circadian rhythms that contribute to a host of pathologies such as cardiovascular and metabolic disease, cancer, and aging-related disorders.

“The principal frequency, which is not a surprise, is the 24-hour cycle, and it is the most prevalent. What was a surprise to us – although we set up the experiment to see exactly this – are the 12-hour and the 8-hour cycles,” said senior author John Hogenesch, PhD, Associate Professor of Pharmacology in the Institute for Translational Medicine and Therapeutics at Penn.

To uncover these shorter oscillations, researchers isolated RNA from the livers of mice every hour for 48 hours.

Microarray analysis showed that more than 3,000 genes were expressed on a circadian rhythm – which account for approximately 4 percent of all of the genes expressed in the liver.

In addition, 260 genes were expressed on a 12-hour cycle and 63 genes were expressed on an 8-hour cycle.

The researchers saw similar 12-hour gene expression patterns in five other tissues.

“There is an obvious biological basis to a 12-hour rhythm. The 12-hour genes predicted dusk and dawn. These are two really, really stressful transitions that your body goes through and your mind goes through. Anybody who has young children realizes that they are more likely to cry around those times – and you’re more likely to cry with them,” said Hogenesch.

The shift in gene expression controlled by these harmonics can help an animal prepare for the behavioural and physiological changes that accompany the shift from light to dark and back.

“We have less of a handle on the 8-hour rhythms, but the fact that we can see them reliably means to me there is the possibility that there could be a biological basis to an 8-hour cycle,” he said.

The study appears in the April issue of PLoS Genetics (ANI)