Can Exercise Prevent Diabetes Complications on a Cellular Level?
Jacob Haus, PhD
Kinesiologist, University of Illinois
American Diabetes Association Research Funding
Junior Faculty Award
Exercise is one of the most commonly prescribed and effective ways to prevent or treat type 2 diabetes. Researchers have shown that working out regularly can be more effective at controlling blood glucose than drugs like metformin. Tight blood glucose control, in turn, helps to keep complications—such as eye disease, nerve damage, and kidney disease—at bay.
What’s not entirely clear is why exercise works so well. There’s emerging evidence that exercise does more than just burn off glucose. At the cellular level, workouts may help the body reshape the way its cells work, making cells more resilient.
That remodeling may also help reduce inflammation, which is thought to be a culprit in many diabetes-related illnesses. “When you become obese, there’s a chronic level of inflammation that leads to more complications,” says Jacob Haus, PhD, a professor of kinesiology and nutrition at the University of Illinois in Chicago.
Inflammation, Haus explains, is the equivalent of a constant low-grade infection: The body’s immune cells are active when they shouldn’t be, and over time that takes a toll. The biology is complex, but at its most basic, one source of inflammation associated with obesity and type 2 diabetes is the result of a lack of physical activity or structured exercise. “When you take in more calories than you expend, you store the extra energy as fat. The body needs somewhere for the excess calories to go,” Haus says. “It starts to push fat into fat cells, and the fat cell isn’t able to adapt. As a result, the fat cells become angry.”
This pressure on the fat cell resembles what might happen to the body when coming under attack by a virus. “It starts to get angry and calls in for immune cells,” Haus says. The immune cells, rather than acting as the body’s defenders, instead chew up the irritated fat cell and spit it into the blood. Researchers now think that this constant destructive churn contributes to type 2 diabetes and many of its complications, such as nerve and kidney damage, eye problems, and heart disease.
Appropriately enough, one of the signature byproducts of these angry fat cells and inflammation is something called a receptor for advanced glycation end products—RAGE, for short. Advanced glycation end products (AGEs) are harmful substances created when sugars combine with fat or protein in the body—a recipe that’s highly prevalent in poorly managed diabetes. Researchers think they may play a big role in diabetes. RAGEs, in turn, increase the likelihood that AGEs will be absorbed into the cells. Too many RAGEs result in a higher risk of type 2 diabetes and its complications.
Haus thinks exercise might be a good way to reduce RAGEs. To learn more, Haus is working to measure the effects of intense exercise on the chemistry of muscle cells. His experiment, which is funded by the American Diabetes Association, explores whether regular workouts can remodel the cells of overweight and obese older adults with type 2 diabetes to resemble those of lean, healthy people in their 20s.
In a lab full of exercise equipment, Haus pushes participants close to their limits. By the end of the experiment, he hopes to have brought 40 people with diabetes into the lab to exercise on a treadmill at 75 percent of what they can do for about an hour, five days a week. Another group of 40 people with type 2 diabetes will get diet and exercise counseling but no intense workouts. Finally, Haus is having a smaller group of lean, healthy participants work out to see if their bodies respond in the same way to exercise.
After the workouts, Haus and his team take muscle tissue samples, comparing the people with diabetes and the healthy participants. The goal is to see if people with diabetes can use exercise as a tool to improve the way their cells respond to inflammation, producing proteins that reduce it rather than ramp it up. “We’re trying to understand how exercise remodels the body,” Haus explains. “Just like muscles become stronger and more adapted with exercise, exercise is important to remodeling the cell walls and decreasing low-grade inflammation that leads to complications.”
Early results suggest exercise is enough to make the cells of people with diabetes resemble those of people without, but only sometimes. More research is needed to figure out why some people respond better than others. If the mechanisms can be identified, there might be a way to develop treatments to recreate the beneficial cellular effects of workouts. “If we can identify proteins and how they work in the cell, they can be targeted for drugs in the future,” Haus says.
In the meantime, Haus, a rugby referee in his spare time who has had type 1 diabetes for over 20 years, recommends simply spending more time working out. “Exercise is a beautiful tool to stress the body [in a good way],” he says.
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