The human body has many biological clocks at work whose functioning is coordinated by a master clock in the brain. These clocks trigger hormones that make us sleepy, keep us awake or signal hunger according to circadian rhythms – naturally occurring 24-hour cycles. Scientists have now discovered that muscles have such circadian clocks, the disruption of which can lead to the development of diabetes.
Researchers from the University of Geneva, Switzerland, together with colleagues from the University of Bath, the Université Claude Bernard in Lyon, the University of Surrey, and the Nestlé Institute of Health Sciences, discovered that levels of different types of fats called lipids in muscle cells varied at different times of the day. The team conducted an experiment to test whether muscle circadian clocks regulate these lipid levels.
They asked volunteers to adhere to a daily eating and sleeping routine one week before the experiment, thus synchronising their circadian rhythms. Every four hours, researchers extracted very small samples of thigh muscle tissue and analyse its lipid composition. They found a clear correlation between muscle cells’ lipid composition and the time of day.
However, since combinations of lipids varied substantially from one individual to another, they corroborated the findings with an in-vitro experiment. The team cultivated human muscle cells and artificially synchronised them by using a signal molecule that is normally secreted in the body. They researchers observed a periodic variation in the cells’ lipid composition, similar to what they noticed in human subjects.
When they disrupted the clock by inhibiting the genes responsible for the circadian mechanism, there were very few variations in the lipid levels, which the researchers say, shows the influence of circadian rhythms on lipid production.
The researchers think that the mechanism could help in regulating muscle cells’ sensitivity to insulin. Lipids make up a large part of cell membranes and influence the ability of molecules like insulin to travel into and out of muscle cells. Changes in a cell’s lipid composition could change the muscle’s sensitivity to insulin and its ability to take in blood sugar.
Low sensitivity of muscle to insulin leads to insulin resistance, which causes type 2 diabetes. The researchers will now have to conduct experiments to see if there is indeed this link between circadian mechanisms and type 2 diabetes via lipid metabolism. If such a link is established it could also lead to new therapies for diabetes. The study was published in the journal Proceedings of the National Academy of Sciences.