Atypical Exposure To Light & Darkness Disrupts Skeletal Muscle’s Sensitivity to Insulin Via Neurons

Research out of the University of Genevas has pinpointed how disruption of the circadian clock by light exposure affects insulin production.

In the human body, insulin production — as well as other hormone production — varies over a 24-hour period. The most important influencers for insulin production are the yin and yang of feeding and fasting as well as exposure to light and darkness.

Over the past several decades, scientists have found that exposure to light and darkness at atypical times can disrupt our internal clocks. This, in turn, has an effect on metabolic disease, such as diabetes.

But how? While our understanding of this disruption and its effects has improved, scientists still didn’t know exactly what organs were most affected by these day-night disruptions, and what triggered them.

So researchers at the University of Geneva (UNIGE) began to track how insulin production changes during circadian cycles and how different organs and tissues in the body are affected by these changes.

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They found that SF1 neurons are responsible for governing how skeletal muscle responds to insulin on a daily basis. The loss (or gain) of function due to light exposure can cause insulin resistance.

The research was published in the journal Cell Reports and led by Roberto Coppari, a professor at the Diabetes Centre of UNIGE Faculty of Medicine.

“Our hypothesis was that insulin sensitivity varies according to the daily 24-hour cycle, but also according to the tissues,” Coppari said. “Since we already knew that some neurons in the ventromedial hypothalamic nucleus (VMH)—a region of the hypothalamus—controls the sympathetic nervous system output to skeletal muscle in mice, we looked at these neurons—called VMH SF1 neurons—in regulating insulin action in this tissue.”

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When looking at the SF1 neurons in mice, they found significant variation in all tissues involved. This was affected by the presence or absence of the SIRT1 gene, which is a gene that helps regulate the body’s circadian clock.

Scientists measured the insulin variation in mice that had SF1 neurons without the SIRT1 gene. They found that the SIRT1 gene in those neurons plays a pivotal role in insulin involvement in the gastrocnemius muscle, but not in other tissues.

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

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Even small alterations in light and darkness at atypical times (such as an hour of light exposure during a dark cycle), can have a negative impact. Light exposure can have a profound impact on metabolic homeostasis.

This could explain why people who are exposed to light at atypical times — like shift workers — are more likely to develop metabolic diseases like diabetes.

For diabetics, the amount of insulin they need to administer to themselves is currently based on carbohydrate intake. However, this study shows that we need to keep other influences in mind, as well.

“Beyond insulin, the influence of time of day on the effectiveness of drug treatments should be studied much more broadly,” said Coppari.

Researchers hope that the study’s results will encourage a conversation between doctors and patients about the best time of day to administer insulin to control its effects as well as reduce the risk of hypoglycemia.

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