Study shows direct link between circadian clock in pancreas and diabetes.

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The pancreas has its own molecular clock. Now, for the first time, a Northwestern University study has shown this ancient circadian clock regulates the production of insulin. If the clock is faulty, the result is diabetes.

The researchers show that insulin-secreting islet cells in the pancreas, called beta-cells, have their own dedicated clock. The clock governs the rhythmic behavior of proteins and genes involved in insulin secretion, with oscillations over a 24-hour cycle.

The findings, which will be published June 18 by the journal Nature, shine a light on a system that hasn't been recognized as having a strong effect on the process of glucose homeostasis.

"This is the first evidence of how the circadian clock may affect the development of diabetes," said Joe Bass, M.D., associate professor of medicine at the Feinberg School of Medicine and of neurobiology and physiology at the Weinberg College of Arts and Sciences. "The biological programs in animals for harvesting energy -- much like the photosynthesis of plants -- are under control of the clock. Our findings will help us figure out the causes of glucose abnormalities, but we still have a lot to learn."

The research, led by Bass and Biliana Marcheva, a doctoral candidate in Bass' lab and first author of the paper, represents many years of work and involved key collaborators Louis H. Philipson of the University of Chicago, Joseph S. Takahashi of the University of Texas Southwestern Medical Center and Seth D. Crosby of the Washington University School of Medicine.

In their study, the researchers knocked out the clock genes in islet beta-cells in mice and found the animals developed impaired glucose tolerance and abnormally low levels of insulin and went on to develop diabetes. The clock of the beta-cell coordinates glucose management, and the loss of the clock inhibited the cells from secreting insulin.