The circadian clock system allows organisms to anticipate and adapt to periodic changes in geophysical time. Almost all cells contain a molecular clock that regulates and synchronizes metabolic functions with a 24-hour day/night cycle..

Today, a growing body of evidence shows that disruptions in the internal clock caused by frequent jet lag, irregular work schedules, and aging have a significant impact on the development of metabolic diseases in humans, including type 2 diabetes..

Such disturbances seem to interfere with normal cell function.. in the pancreatic islet, which secretes insulin and glucagon, hormones that regulate blood sugar levels. By comparing pancreatic cells from people with type 2 diabetes with donors from healthy people, researchers from the University of Geneva (UNIGE) and University Hospitals of Geneva (HUG), Switzerland, were able to demonstrate for the first time that pancreatic islet cells obtained from people with type 2 diabetes carry.

The destruction of the circadian clock was accompanied by a violation of the secretion of hormones. Moreover, using a clock modulator molecule, called Nobiletin, extracted from the peel of a lemon, the researchers were able to “repair” the disturbed cell clock and partially restore the function of islet cells.. These results, published in the Proceedings of the National Academy of Sciences, provide the first insight into an innovative approach to diabetes management..

Two years ago, a team led by Charna Diebner, Principal Investigator at UNIGE Faculty of Medicine, had already shown that in rodents, disruption of the pancreatic cell clock leads to disruption of insulin and glucagon secretion, which contributes to diabetes.. But what is the situation with people?

Vladimir Petrenko, a researcher in Dr. Dibner's lab and the first author of these publications, says: “We also previously observed that if the human pancreatic cell clock was artificially disrupted in cell culture, the secretion of key islet hormones insulin and glucagon was compromised.. Therefore, our next step, which we report here, was to find out if the circadian rhythms in human pancreatic islets in type 2 diabetes were disrupted and, if so, how this disruption would affect islet function.”.

Using combined bioluminescent fluorescence time-lapse microscopy, a technology that can very accurately track the activity of the molecular clock in living cells over time, the scientists compared the behavior of pancreatic cells in patients with type 2 diabetes and those in healthy people during the day.. “The verdict is undeniable,” says Charna Dibner. “The biological rhythms of islet cells in type 2 diabetes exhibit both reduced amplitudes of circadian oscillations and poor synchronizing ability.. As a result, hormone secretion is no longer coordinated. Moreover, the defects in timing of insulin and glucagon secretion observed in patients with type 2 diabetes were comparable to those measured in healthy islet cells with an artificially disturbed circadian clock.”.

Step two in their study: Geneva scientists used Nobiletin, a small molecule clock modulator and a natural ingredient in lemon peel, to resynchronize clocks. “Acting on one of the components of the core clock frequency, it effectively resets the amplitude of oscillations in human islets,” says Vladimir Petrenko. “And once we synchronized the clocks, we also saw an improvement in insulin secretion.”.

" “We will continue to study this recovery mechanism, first in animal models.. Our society is experiencing an epidemic increase in metabolic diseases, accompanied by a change in work and eating patterns, as well as a lack of sleep.. By resynchronizing perturbed molecular clocks, we hope that either through personalized meal and exercise schedules or clock modulators, we may eventually find an innovative solution to the epidemic metabolic problem affecting an ever-increasing proportion of the world's population."

medical-heal. en.