Almost all cells have a circadian rhythm, which regulates their biological functions over a 24-hour period. Cells accomplish this by employing a biological clock that cycles several genes on and off during the day and night.
Scientists already know that when our biological clock malfunctions, such as due to shift work or sleep difficulties, our metabolic health suffers. However, it’s unclear how type 2 diabetes patients’ biological clocks differ from healthy persons.
A group of international experts has now discovered that persons with type 2 diabetes have a distinct circadian rhythm in their skeletal muscles. They believe this is due to a failure in communication between a cell’s timekeeping components and mitochondria, which provide chemical energy for cells.
“The promise of this research is that it may help us to fine-tune the timing of interventions and other medications to treat type 2 diabetes, in order to optimize their effectiveness,” says Professor Juleen R. Zierath from Karolinska Institutet and the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.
A different pattern of daily gene expression
The researchers examined which genes displayed cycle behavior over two days in skeletal muscle cells from people with type 2 diabetes and compared them to cells from similar healthy persons in the study, which was published in Science Advances.
They revealed that cells from persons with type 2 diabetes contained fewer cycling genes, as well as ones that were altered. They used data from clinical studies in humans with type 2 diabetes and mice, as well as cell-based investigations, to conduct additional research.
Exercise and diet are regularly used treatment interventions for people with type 2 diabetes, and both of these treatments can affect the time-keeping molecules and mitochondria.
Dr. Brendan Gabriel
These investigations showed that mitochondria communicate with the molecules in our cells that keep time and that this connection is impaired in type 2 diabetes patients.
Diabetes treatments may be more effective if timed to the body clock
Some of the most commonly prescribed pharmacological treatments for type 2 diabetes impact mitochondria, which means they may work differently depending on the time of day.
As a result, our findings emphasize the need of taking cellular cycles into account when prescribing diabetic therapies.
“Exercise and diet are regularly used treatment interventions for people with type 2 diabetes, and both of these treatments can affect the time-keeping molecules and mitochondria,” says Dr. Brendan Gabriel from the Department of Physiology and Pharmacology at Karolinska Institutet.
Brendan Gabriel is the paper’s first author, along with CBMR Assistant Professor Ali Altintas.
“Given that disrupted sleeping patterns are known to be associated with an increased risk of developing type 2 diabetes, our findings provide evidence of how these disruptions may link to the molecular biology within cells,” says Ali Altintas.
