Our metabolic health can suffer when our biological clock breaks down. However, it is not fully understood how the biological clock of people with type 2 diabetes (T2D) differs from healthy people. Now, a team of international scientists has shown that the skeletal muscle in people with T2D has a different circadian rhythm. They suggest that this might arise because of a communication breakdown between a cell’s time-keeping molecules and mitochondria.
Their findings are published in the journal Science Advances in a paper titled, “Disrupted circadian oscillations in type 2 diabetes are linked to altered rhythmic mitochondrial metabolism in skeletal muscle.”
“Circadian rhythms are generated by an autoregulatory feedback loop of transcriptional activators and repressors,” the researchers wrote. “Circadian rhythm disruption contributes to T2D pathogenesis. We elucidated whether altered circadian rhythmicity of clock genes is associated with metabolic dysfunction in T2D.”
“The promise of this research is that it may help us to fine-tune the timing of interventions and other medications to treat T2D, in order to optimize their effectiveness,” explained Juleen R. Zierath, PhD, professor, Karolinska Institutet and the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.
The scientists obtained skeletal muscle cells from people with T2D and measured which genes showed cycling behavior over two days and compared them with cells from similar healthy people. They carried out further experiments using data generated from clinical tests in people with T2D and mice, as well as cell-based experiments.
Their findings demonstrated that mitochondria communicate with the molecules that keep time in our cells, and that this communication is disrupted in people with T2D.
“Exercise and diet are regularly used treatment interventions for people with T2D, and both of these treatments can affect the time-keeping molecules and mitochondria,” said Brendan Gabriel, PhD, research fellow in the department of physiology and pharmacology at Karolinska Institutet.
“Given that disrupted sleeping patterns are known to be associated with an increased risk of developing T2D, our findings provide evidence of how these disruptions may link to the molecular biology within cells,” said Ali Altintas, assistant professor, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.