Insulin, folate metabolism influence circadian rhythms, according to Penn study
While scientists have known for several years that our body's internal clock helps regulate many biological processes, researchers have found that the reverse is also true: Many common biological processes - including insulin metabolism - regulate the clock, according to a new study by investigators at the University of Pennsylvania School of Medicine, the Genomics Institute of the Novartis Research Foundation, and the University of California at San Diego.
The new data, published online in Cell this week, suggest that someday physicians may be able to use small molecules that inhibit or stimulate these biological processes in order to influence a person's clock when it gets out of sync due to jetlag or shift work, and to devise new ways to treat metabolic disorders that are intimately tied to the body's daily cycles.
Using a genome-wide screen, the investigators found that reducing expression of any one of hundreds of genes could substantially alter the length of the circadian cycle, which controls the 24-hour sleep/wake cycle. The clock-influencing genes are involved in a large number of biological processes, but the researchers found that components of insulin metabolism, folate metabolism, and the cell cycle were overrepresented in the gene screen, suggesting that these pathways are closely linked to the clock.
"Clock biologists all appreciated that the communication went one direction - from the clock to biological processes - but I don't think anyone anticipated that there would be this level of integration with cell metabolism and the cell cycle, or all these other pathways impinging on clock function," says John Hogenesch, PhD, Associate Professor of Pharmacology in the Institute for Translational Medicine and Therapeutics at Penn. Hogenesch is a co-senior author on the paper with Steve Kay, Dean of the Division of Biological Sciences at UCSD. "There were some hints this might occur for some genes, but not to this extent."