Could resetting our internal clocks help control diabetes?

The circadian clock system allows the organisms to anticipate periodical changes of geophysical time, and to adjust to these changes. Nearly all the cells in our body comprise molecular clocks that regulate and synchronize metabolic functions to a 24-hour cycle of day-night changes. Today, increasing evidence shows that disturbances in our internal clocks stemming from frequent time zone changes, irregular working schedules or ageing, have a significant impact on the development of metabolic diseases in human beings, including type-2 diabetes. Such disturbances seem to prevent the proper functioning of the cells in the pancreatic islet that secrete insulin and glucagon, the hormones that regulate blood sugar levels. By comparing the pancreatic cells of type 2 diabetic human donors with those of healthy people, researchers were able to demonstrate, for the first time, that the pancreatic islet cells derived from the Type 2 Diabetic human donors bear compromised circadian oscillators.

Setting the right time again

Step two of their research: the Geneva scientists used Nobiletin, a small clock modulator molecule – a natural ingredient of lemon peel whose impact on circadian clocks has been recently discovered – in order to resynchronize the clocks. “By acting on one of the core clock components, it resets efficiently the amplitude of the oscillations in the human islets,” says Volodymyr Petrenko. “And as soon as we got the clocks back in sync, we also observed an improvement in insulin secretion.”

The disruption of the circadian clocks was concomitant with the perturbation of hormone secretion. Moreover, using a clock modulator molecule dubbed Nobiletin, extracted from lemon peel, the researchers succeeded in "repairing" the disrupted cellular clocks and in partial restoring of the islet cell function. These results, published in the Proceedings of the National Academy of Sciences of the United States, provide the first insight into the innovative approach for diabetes care.

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