The disruption of our internal clocks seems to play a significant role in the explosion of metabolic diseases observed in recent decades, and particularly of diabetes. Researchers at the University of Geneva (UNIGE) are deciphering how insulin sensitivity fluctuates according to circadian cycles.

Shift workers and people who have inconsistent sleep patterns are at most risk.

Body Balance

The balance between the secretion and action of hormones is essential for the body to function properly. Secretion of several hormones, including insulin, varies over a 24-hour period and any change in this rhythm seems to predispose people to metabolic diseases.

To synchronize itself, the body takes into account two essential elements: the alternation of light and darkness as well as that of feeding and fasting. The light perceived by retinal neurons is transmitted to the brain, which in turn regulates the peripheral clocks located in the different parts of the body.

“Our hypothesis was that insulin sensitivity varied according to the daily 24-hour cycle but also according to type of tissue.” explains Roberto Coppari, Professor at the Diabetes Centre of UNIGE Faculty of Medicine, who led this work.

The scientists evaluated insulin action in different tissues in mice kept in a cycle of 12 hours of light and 12 hours of darkness and observed significant variation in all tissues involved.

They then repeated the same measurements on animals in which the gene linked to the regulation of core molecular clock components was deleted.

Modulating Light Changes IR for some Tissues

By modulating the time of exposure to light, the researchers demonstrated that the neurons regulating the core molecular clock plays a key role in the action of insulin in the gastrocnemius muscle but not in other tissues.

“This teaches us two things: Different neurons have the task of conveying light/darkness cycle inputs to diverse organs and the disruption of only one of these regulatory pathways is enough to increase the individual’s risk of developing diabetes,” said  Roberto Coppari.

Effect of Light on Insulin Sensitivity

Researchers measured insulin-induced glucose absorption.

Small disturbance in photic inputs (e.g. an hour of light exposure in the middle of the dark cycle, or light removal for 2 days) is enough to cause a negative effect. Increased or decreased light exposure can profoundly influence the sensitivity of tissues to insulin and the alteration, however minimal, of this mechanism, is sufficient to significantly disrupt metabolic equilibrium.

This would explain why people exposed to light at the wrong time — workers in shift patterns, for example — are more likely to develop metabolic diseases (e.g. diabetes).

Implications

“The amount of insulin administered to patients is calculated on the basis of carbohydrate intake,” says Roberto Coppari. “Our results indicate that insulin sensitivity varies with time of day and individuals’ circadian rhythm. This parameter should be taken into account for patients to better manage their treatment and limit its risks.”

Sources

Materials provided by Université de Genève. Note: Content may be edited for style and length.

Light Entrains Diurnal Changes in Insulin Sensitivity of Skeletal Muscle via Ventromedial Hypothalamic Neurons — Cell Reports