Like the sun, insulin levels rise and fall in a daily rhythm. Disrupting that cycle may contribute to obesity and diabetes, a new study suggests.
Many body systems follow a daily clock known as a circadian rhythm. Body temperature, blood pressure and the release of many hormones are on circadian timers. But until now, no one had shown that insulin — a hormone that helps control how the body uses sugars for energy — also has a daily cycle. Working with mice, researchers at Vanderbilt University in Nashville have found that rodents are more sensitive to insulin’s effects at certain times of day. Disrupting the animals’ circadian timers interferes with the hormone’s daily rise and fall and makes mice prone to obesity.
If the findings hold up in humans, they could help explain why people who work night shifts tend to be overweight and suffer health problems. The discovery may also tie the obesity epidemic in part to staying up late and eating at the wrong time.
Many people had thought that it was best for the body to maintain insulin at a relatively constant level, says Carl Johnson, a circadian biologist who led the new study. “But that’s not how organisms have adapted,” he says. Since the environment cycles through light and dark, body processes often coordinate with that rhythm.
To uncover insulin’s natural rhythm, Johnson and his colleagues performed an “insulin clamp” procedure on mice. The clamp infuses glucose or insulin around the clock into mice that are moving freely in their cages. Measuring how much insulin or glucose the mice need to maintain constant blood sugar levels tells the researchers how responsive the animals are to the hormone at any given time of day.
Mice are naturally less sensitive to insulin during the day, when the nocturnal animals normally sleep, the team found.
Mice with a genetic flaw that breaks their circadian clock don’t follow the regular insulin cycle. Neither do mice whose circadian clocks have been disrupted by living in constant light. Both groups of animals are more resistant to insulin than normal mice are, the researchers discovered. Insulin resistance is one hallmark of diabetes.
Mice with broken clocks also became obese despite eating the same amount as other mice. The team then found that feeding normal mice a high-fat diet could throw off their circadian rhythms.
The findings suggest that timing meals to coincide with insulin sensitivity could help protect against diabetes, says Satchidananda Panda, a geneticist and biologist at the Salk Institute for Biological Studies in La Jolla, Calif. Chronically mistimed clocks could contribute to insulin resistance and eventually lead to diabetes, he says.
People who hope to bend their biological clocks to fit modern lifestyles are probably out of luck, says neuroscientist Randy Nelson of the Ohio State University Wexner Medical Center. After billions of years of adapting to the world’s natural rhythms, he says, “We’re stuck with these clock genes and these metabolic processes. Electric lights, that’s what’s strange.” Besides avoiding after-dinner snacks, people might protect their body clocks by using dim red lights at night. Red light doesn’t confuse the circadian clock the way bright white or blue lights do.
But Johnson warns that it is early to apply his findings directly to humans. He says eating the main meal at lunch time and not eating overnight are probably healthful practices, but people shouldn’t expect to lose a lot of weight by just shifting when they eat. Poor diet and lack of physical activity are the main drivers of obesity, he says.
S.-q. Shi et al. Circadian disruption leads to insulin resistance and obesity. Current Biology Published online February 21, 2013. [Go to]
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