Disturbance of the “internal body clock” that regulates the 24-hour cycle of biological processes can have health drawbacks. Disruption of two genes that control circadian rhythm can lead to diabetes, according to recent research at UT Southwestern Medical Center.
Mice with defective copies of the genes known as CLOCK and BMAL1 develop abnormalities in pancreatic cells that, over time, render the cells useless at releasing sufficient insulin quantities, according to the study, which appeared in the journal Nature.
The mice were genetically engineered to have defective CLOCK genes and some were engineered to lack the BMAL1 gene also. The fluctuating glow of engineered bioluminescent molecules allowed researchers to study the circadian clock (the “internal body clock” that regulates the (approximately) 24-hour cycle of biological processes in humans and other life-forms) in the mice’s pancreatic cells. Cells with defective CLOCK genes produced nearly flat rhythms, while normal islet cells glowed in a 24-hour pattern.
Dr. Joseph Takahashi, an investigator with the Howard Hughes Medical Institute at UT Southwestern and co-senior author of the study, said the results “indicate that disruption of the daily clock may contribute to diabetes by impairing the pancreas' ability to deliver insulin.”
Circadian rhythms include biological activities such as sleeping, eating, body temperature and hormone production. Imbalance in the rhythm caused by shift work, pregnancy, medication, routine changes and time-zone changes, among other factors, has been linked to: cancer; depression; sleep disturbances; gastrointestinal, metabolic and cardiovascular disorders; decreased immune responses and mortality.
According to the UT Southwestern study, mice with defective CLOCK genes were prone to obesity, other signs of metabolic syndrome and liver dysfunction, Mice who lacked the BMAL1 gene only in the pancreas followed normal circadian routines but displayed abnormally high blood-sugar levels.
"This finding indicates that disruption of clock genes only in the pancreas, and not the rest of the body clock, can produce early signs of diabetes," Takahashi said.
Takahashi suggested a direct link between the clock in pancreatic beta-cells and glucose regulation.
“This should aid our understanding of the causes of glucose abnormalities,” he said.
