If a human ate tens of thousands of calories a day, ballooned in size, then barely moved for months, the health outcomes would be catastrophic. Scientists have long been puzzled why this same behavior doesn’t lead to diabetes in grizzly bears—until now.
By feeding honey water to hibernating bears, researchers at Washington State University have discovered genetic clues to how these bruins can control their insulin. Their results—published in iScience—might lead to better diabetes treatments for people.
Insulin is a hormone found in most mammals that regulates the body’s blood sugar levels, for instance by telling the liver, muscle, and fat cells to absorb blood sugar, a source of energy. But if a lot of blood sugar enters the bloodstream, over time the cells stop responding, and become resistant to insulin. This is a leading cause 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. However, unlike humans, bears can mysteriously control their insulin resistance—turning it on and off like a switch.
To find out how, researchers drew blood serum from six captive grizzly bears—aged between five and 13 years—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 fully 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 seem to have a unique role in bear biology, working either independently or together 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.
Grizzly bears—found in parts of the western U.S., 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 young. Then in the fall, the animals transition into hyperphagia, when “pretty much all their energy is devoted to 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 daily calories and gain up to eight pounds each day to prepare for the upcoming winter.
When the bears begin hibernating in early winter, they rely on their fat deposits to sustain them through the cold months. Hibernation is “more than just a deep sleep,” Perry says. “Lots of 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 around but don’t eat. When the study bears awoke, the team fed them honey water—a favorite treat—for two weeks, then collected their blood. The team already had blood samples taken from the same bears during the spring and summer.
Next, in the lab, the researchers combined various blood serums with cell cultures of various types—for instance, they mixed a cell culture from fat tissue taken from hibernating bears with blood serum taken from active bears. This allowed the team to see what genetic changes would occur within the cells.
Of all the combinations studied, the serum taken from the honey-fed hibernating bears helped the most in narrowing down those eight key proteins involved in regulating insulin sensitivity and resistance. (Learn more 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 take home of this “fascinating study” is how many implications bear hibernation can have for human health.
“Identifying those eight proteins is an important step,” he says, as is identifying “exactly what is being turned on and off” when bears change their insulin resistance, he says.
One step closer to diabetes prevention?
While 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 this, adds Perry. (Learn about a link between COVID-19 and developing diabetes.)
For instance, figuring out how to manipulate those eight proteins in people could potentially “reverse a human out of insulin resistance,” Perry says. Such medications or interventions are very far off, "but we're getting closer,” he says.
Sawaya agrees that this is “definitely one more piece of the puzzle” and hopes that unravelling 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.