Clock genes regulate blood sugar.

Numerous studies have shown that what we eat is vital to our health. New research suggests that when we eat may be just as important.

In mice, as in people, blood sugar concentration rises to a peak once a day. Mealtimes strongly influence this daily oscillation in blood sugar, or glucose, concentrations.

Previous studies have shown that when researchers damage an area of a mouse's brain known to regulate circadian rhythm, the body's 24-hour time clock, the rodents stop regulating blood sugar concentrations. To determine whether circadian-clock genes play a direct role in controlling blood sugar, Garret FitzGerald of the University of Pennsylvania in Philadelphia and his colleagues examined mutant mice in which either of two such genes, known as Bmal1 and Clock, was impaired.

Unlike normal mice, the mutants had no daily spike in blood sugar concentrations. When the researchers injected the mutant mice with insulin, which normally knocks down blood sugar concentrations, they found that the mutants failed to bring their blood sugar back to normal. The cells of mutant mice also made less glucose from raw molecular materials than did those of normal mice.

The effects of mutating the circadian-clock genes weren't all negative, however. When the mutants were fed a high-fat diet, they didn't develop diabetes, a consequence that normal mice and people typically experience.

FitzGerald's team published its findings in the Nov. 2 PLOS Biology.

Although the researchers don't fully understand how circadian-clock genes control blood sugar, they note that these findings could provide clues to the causes of diabetes and cardiovascular disease in people.--C.B.