Hibernating bears could hold a clue to treating diabetes

If a human were to eat tens of thousands of calories a day, get bloated, and then barely move for months, the health outcomes would be catastrophic. Scientists have long puzzled why this same behavior does not lead to diabetes in grizzly bears, until now.

By feeding hibernating bears water with honey, Washington State University researchers have uncovered genetic clues to how these bears can control their insulin. Its results, published in iScience—may lead to better diabetes treatments for people.

Insulin is a hormone found in most mammals that regulates the body’s blood sugar levels, for example by telling the liver, muscle and fat cells to take up blood sugar, a source of energy But if too much blood sugar enters the bloodstream, over time the cells stop responding and become resistant to insulin. This is one of the main causes of type 2 diabetes, a disease that can lead to heart attacks, strokes and blindness. About 1 in 10 Americans, or about 37 million people, have type 2 diabetes. Unlike humans, however, bears can mysteriously control their insulin resistance, turning it on and off like a switch .

To find out how, researchers took blood serum from six grizzly bears in captivity, ages five to 13, at the WSU Bear Center, a research facility in Pullman, Washington. They also collected bear fat tissue that they used to grow cell cultures in the lab. “It gives us a way to test things that we couldn’t do in a full-grown bear,” says study co-author Blair Perry, a postdoctoral researcher at the university. (Read how bottlenose dolphins can turn diabetes on and off.)

This experiment helped the team narrow down the bears’ secret to controlling their insulin: eight key proteins that appear to play unique roles in bear biology, working independently or in concert to regulate insulin during hibernation.

Because humans share most of our genes with bears, understanding the role of these eight proteins could teach scientists more about human insulin resistance, Perry says.

Seasons of bears

Grizzly bears, found in parts of the western US, Canada and Alaska, experience three stages in a year: active, hyperphagia and hibernation. In the spring and summer, the massive mammals spend their time foraging, mating and caring for their young. Then, in the fall, the animals go into hyperphagia, when “virtually all their energy goes into eating as much as possible,” Perry says. (Read about the fascinating ways animals prepare for fall.)

During this time, bears consume up to 20,000 calories a day and gain up to eight pounds each day to prepare for the coming winter.

When bears begin hibernating in early winter, they rely on their fat stores to sustain them through the cold months. Hibernation is “more than deep sleep,” says Perry. “Many physiological changes allow bears to survive these long winters without food.” Their metabolic rate, heart rate and body temperature decrease and they become insulin resistant.

Hibernating bears experience periods of wakefulness, during which they move but do not eat. When the bears in the study woke up, the team fed them honey water, a favorite treat, for two weeks, then collected their blood. The team already took blood samples from the same bears during the spring and summer.

Next, in the laboratory, the researchers combined various blood sera with cell cultures of various types; for example, they mixed a cell culture of adipose tissue taken from hibernating bears with blood serum taken from active bears. This allowed the team to see what genetic changes would occur in the cells.

Of all the combinations studied, serum from wintering bears fed honey did the most to reduce eight key proteins involved in regulating insulin sensitivity and resistance. (Learn more about how bears’ bodies change during hibernation.)

For Mike Sawaya, a bear biologist at Sinopah Wildlife Research Associates who was not involved in the study, the big takeaway from this “fascinating study” is how many implications bear hibernation can have for human health.

“Identifying these eight proteins is an important step,” he says, as well as identifying “exactly what turns on and off” when bears change their insulin resistance, he says.

One step closer to preventing diabetes?

Although insulin resistance and its consequences are well understood, there is much to learn about its genetics. Studying how a bear goes in and out of insulin resistance each year gives scientists a “unique opportunity” to better understand it, Perry adds. (Learn about a link between COVID-19 and the development of diabetes.)

For example, figuring out how to manipulate these eight proteins in people could “reverse insulin resistance in a human being,” Perry says. Such drugs or interventions are a long way off, “but we’re getting closer,” he says.

Sawaya agrees that this is “definitely another piece of the puzzle” and hopes that unraveling the mysteries of bear physiology could lead to diabetes prevention.

In future studies, the team hopes to investigate exactly how these specific proteins turn off insulin resistance in bears.

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