Diabetes: resetting the internal clock as a new therapeutic approach

Relationship between circadian rhythm and diabetes

The number of diabetes diseases has increased significantly in recent years and many people still rely on lifelong therapy. In a recent study, researchers from the Université de Genève (UNIGE) and the Hôpitaux universitaires de Genève (HUG) found a connection between the disease and disorders of the internal clock and then corrected these disorders. A promising new approach to curing the disease.

In the new study, the research team from UNIGE and HUG were able to clearly demonstrate the connection between circadian rhythm disorders in the cells of the pancreas and type 2 diabetes and successfully correct these disorders. The study results were published in the journal "Proceedings of the National Academy of Sciences" (PNAS).

Circadian rhythm affects almost all cells

The circadian rhythm allows organisms to anticipate periodic changes in geophysical time and to adapt to these changes. Almost all of the cells in our body have internal clocks that regulate and synchronize the metabolic functions in a 24-hour cycle of day-night changes, the researchers explain.

Connection with metabolic diseases

In the meantime, there is increasing evidence that disturbances in our internal clocks (e.g. due to frequent time zone changes or irregular working hours) have a significant impact on the development of metabolic diseases in humans, including type 2 diabetes. "Such disorders appear to prevent the proper functioning of the cells in the pancreatic islets that secrete insulin and glucagon, the hormones that regulate blood sugar levels," reports the research team.

Impaired rhythm of the pancreatic cells

In their investigations, the Geneva researchers were able to “for the first time demonstrate, by comparing the pancreatic cells of type 2 diabetes human donors with those of healthy people (…), that the pancreatic islet cells originating from the type 2 diabetes human donors , wear compromised circadian oscillators, ”said UNIGE.

Hormone secretion is no longer properly coordinated

Using the combined bioluminescence-fluorescence time-lapse microscopy, a technology that allows the molecular activity in living cells to be monitored very precisely over time, the researchers compared the pancreatic cells of the participants. They found that the biological rhythms of the islet cells in type 2 diabetes showed reduced amplitudes of the circadian vibrations and also poor ability to synchronize. The result of this is that hormone secretion is no longer properly coordinated.

Possible cause of diabetes

"In addition, the defects in the timing of insulin and glucagon secretion observed in patients with type 2 diabetes were comparable to those observed in healthy islet cells with artificially disturbed circadian clocks," the research team continued. The disturbance of the internal clocks in the pancreatic cells was clearly accompanied by a disturbance in hormone secretion, which, according to the researchers, can be the cause of the diabetes disease.

Two years ago, the research team led by Charna Dibner from the Diabetes Center at the medical faculty of the UNIGE and at the HUG had already shown that in rodents, the disturbance of the pancreas's internal clock leads to a disturbance in insulin and glucagon secretion and thus promotes the outbreak of diabetes . A corresponding connection was therefore also assumed for humans.

Natural active ingredient can "repair" the internal clock

This connection now seems to be confirmed and the researchers have also succeeded in “repairing” the disturbed cell clocks with the help of the molecule nobiletin extracted from the lemon peel and partially restoring the function of the islet cells, reports UNIGE. Nobiletin formed a small “clock modulator molecule”, the influence of which on the circadian rhythms was only recently discovered. The researchers explain that its effect effectively resets the internal clock.

Circadian rhythm primarily dependent on light

The circadian rhythm represents the daily cycles that go through the various cell functions and is mainly influenced by light. Starting from the central clock in the cerebral hypothalamus, the peripheral internal clocks of the organs and cells are conducted like an orchestra, the researchers explain. The latter are therefore partially controlled centrally, but function differently in each organ and even in each cell depending on their function.

Impairment of metabolic functions

"The cells of the pancreas are also subject to the rhythm of fasting and eating, as well as strict hormonal regulation," explains study leader Charna Dibner. It is only through the coordination of all regulatory levels that the optimization of the metabolic functions becomes possible and the disruption of the internal clocks of the pancreatic cells leads to an impairment of the metabolic functions - with far-reaching consequences.

Can new treatment approaches be derived?

"If you eat the same food at night and not during the day, you can gain much more quickly because of a suboptimal reaction in your metabolism," the study leader explains a possible effect. Apparently, the disturbance of the internal clock can be remedied in a targeted manner so that negative effects can be avoided. A corresponding intervention based on the natural active ingredient nobiletin also appears to open up new treatment approaches for diabetes, which now have to be examined in further studies. (fp)

Author and source information

This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.

Dipl. Geogr. Fabian Peters


  • Volodymyr Petrenko, Nikhil R. Gandasi, Daniel Sage, Anders Tengholm, Sebastian Barg, and Charna Dibner: In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis; in: PNAS (published January 21, 2020),
  • Université de Genève (UNIGE): Could resetting our internal clocks help control diabetes? (published January 31, 2020),

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