Joseph T. Bass, MD, PhD
Researcher, Northwestern University
|ADA Research Funding|
Basic Science Award
It’s important to get a good night’s rest, of course. But did you know that the amount of sleep you need—and the fact that your body prefers to get it after the sun goes down—is hardwired into the building blocks of your being?
Over the past two decades, scientists have established that the so-called body clock, a built-in time regulator, is part of our genetic code. The clock keeps us tied to the same circadian rhythm that once governed the days of our distant ancestors, explaining why some of the most basic processes of life, like the urges to sleep and eat, follow predictable patterns throughout the day.
The first experiments that suggested sleeping cycles were beyond our control took place at the California Institute of Technology in the 1960s and ’70s. Using short-lived, fast-reproducing fruit flies to quickly isolate certain genetic traits, biologist Seymour Benzer discovered that certain mutations made the insects sleep and wake up at random intervals, indicating that the circadian rhythm was found in the genes.
Since then, biologists have pursued the links between genes and body clocks. “Over the past 15 years, astounding genetic experiments have uncovered the rhythms of all life on the planet, and strongly implied the existence of [them] in humans,” says Joe Bass, an endocrinology researcher at Northwestern University. (The implication has to be enough: Humans, for ethical reasons, are tough to conduct dramatic genetic experiments on.)
These experiments have helped scientists identify, isolate, and tweak a central gene that controls the circadian rhythms in humans and mice. With the help of a grant from the American Diabetes Association, Bass and colleague Shin Imai, a biologist at Washington University in St. Louis, are trying to further unravel the links between the body clock and diabetes—and, it is hoped, use the knowledge to come up with better treatments.
Bass is using genetically altered mice to understand how a body-clock gene affects the pancreas. “If you alter the gene’s function, it alters the 24-hour behavior of the mouse,” Bass explains. While a normal mouse sleeps and wakes according to a regular pattern, mice with the altered gene “eventually lose the capability to tell time altogether.”
Though the mice don’t have to show up at the office or pick their baby mice up at school, it turns out the genes that help the body stick to a schedule affect the entire body, not just the brain. The idea is to keep things coordinated: A mouse’s pancreas, for example, ramps up its insulin production when the animal is likely to be awake and slows down when it’s time to sleep.
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That means that disruptions in the body clock can have dramatic consequences. Mutant mice genetically altered to have no functioning body clock “eat more, and eat more at the wrong times of the light-dark cycle. Rather than eating individual meals, they’re eating a lot at night,” Bass says.
The experiments also showed that mice eating at the wrong time of day gained more weight, even when fed the same number of calories as normal mice. Says Bass: “The actual timing of feeding is critical, both with respect to [the absorption of glucose after a meal] and weight gain.”
Though most of the experiments in this area have been conducted using mice, the basic findings are supported by observations of human patients. “If you deliver identical calories in a meal at different times of the day, it gives rise to different rates of glucose absorption,” says Bass. And the body’s response to ingesting glucose, one measure doctors use to monitor diabetes in patients, “changes significantly at different times of the day.”
These discoveries are important for people with diabetes because the body clock controls many of the same systems that are central to the disease. “It’s been known that many aspects of diabetes care and glucose management are strongly rhythmic,” Bass says. “If you eat at one time of day, your insulin response may be different from another time of day.”
If scientists can understand how the clocks in the cells of the pancreas control the body’s insulin production, they might be able to tap into this powerful system to come up with better treatments.