Researchers at the Salk Institute for Biological Studies have discovered a missing link between the body’s biological clock and sugar metabolism system, a finding that may help avoid the serious side effects of drugs used for treating asthma, as well as allergies and arthritis. The researchers report in the journal Nature that cryptochromes, proteins that control the body’s biological rhythms, also interact with metabolic switches that are targeted by certain anti-inflammatory drugs.
The findings suggest that side effects of current drugs might be avoided by considering patients’ biological rhythms when administering drugs, or by developing new drugs that target cryptochromes.
Glucocorticoids are steroid hormones that occur naturally in the body and help control the amount of sugar in a person’s blood, so that nutrient levels rise in the morning to fuel daily activities and fall again at night. They function in cells by interacting with glucocorticoid receptors, molecular switches on the outside of the nucleus.
Glucocorticoids also play a role in regulating inflammation and are used as anti-inflammatory drugs for diseases caused by an overactive immune system, such as asthma, allergies, and rheumatoid arthritis. They are also used to treat inflammation in cancer patients.
However, because of their role in sugar metabolism, the steroids can disrupt a person’s normal metabolism, resulting in dangerous side effects, including excessively high blood sugar levels, insulin resistance, and diabetic complications.
The researchers may have found a way around these side effects by discovering a new function for cryptochromes 1 and 2, proteins that were previously known for their function in the biological clock.
The cryptochromes serve as breaks to slow the clock’s activity, signaling our biological systems to wind down each evening. In the morning, they stop inhibiting the clock’s activity, helping our physiology ramp up for the coming day.
In their new study on mouse cells, the researchers made the discovery that cryptochromes also interact with glucocorticoid receptors, helping to regulate how the body stores and uses sugar. Mouse cells function much like human cells, so the findings could have important implications for treatment of autoimmune diseases and cancer. By taking into account the daily rise and fall of cryptochrome levels, the researcgers say, doctors might be able to better time administration of glucocorticoid drugs to avoid certain side effects related to sugar metabolism.
The discovery also raises the possibility of developing new anti-inflammatory drugs that avoid some side effects by targeting cryptochromes instead of directly targeting the glucocorticoid switches.
More broadly, according to the researchers, the study may help explain the connection between sleep and nutrient metabolism in our bodies, including why people with jobs that require night work or erratic hours are at higher risk for obesity and diabetes.
Source: Salk Institute of Biological Studies
