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12 Sep 2014

A Bear of a Revelation: What Diabetic Grizzlies Can Tell Us About Human Obesity

Written by  Wyatt Orme

Most researchers studying grizzly bears are from the U.S. Fish and Wildlife Service or university ecology departments, not biotechnology companies.

Still, Kevin Corbit, a senior scientist at the Southern California-based biotech firm Amgen, spends his days in a lab in Pullman, Wash., analyzing bear blood. He leaves the actual touching of the 700-pound predator to the capable handlers and their trusty anesthesia. Corbit chuckles as he reflects on his work: “I guess it’s not logical to study bears with a biotech job.”

Maybe it is logical, though, judging from a study he recently published, in collaboration with Washington State University’s Bear Center. With the goal of developing a better long-term treatment for human obesity, Corbit strayed from the status quo of testing mice and rats, which aren’t great predictors of human response. Instead of trying medications on rodents, he decided to examine the genetics of grizzlies and their metabolism. The bears were the perfect fit: Before hibernating each year, they become extraordinarily obese.

In the new study, Corbit and his colleagues discovered a natural state of diabetes in bears that not only serves a real biological purpose, but also is reversible. The bears’ bodies effectively turn up or down their responsiveness to the hormone insulin—much, Corbit says, “like a dimmer switch.” The bears are at their fattest in the late summer, sometimes consuming more than 50,000 calories and gaining up to 16 pounds in a day. But despite the weight gain, they’re at their least diabetic. Their insulin dial is turned up, which helps them store fat for seven months of hibernation.

When the bear hibernates and needs to live off its fat stores, it turns its insulin responsiveness way down. The animal becomes, in human terms, like a Type 2 diabetic, and insulin-resistant. Yet the bear is actually losing, rather than gaining, weight. Year in, year out, despite the extremes of fall gorging, then foodlessness for the entire winter, the bear’s blood sugar remains consistent. It stays healthy thanks to PTEN, a unique genetic mutation (that appears in only some humans) that allows for the insulin dimmer switch.

In addition to pointing out that diabetes is a natural and temporary condition for grizzlies, the research shows that the dominant theory that human obesity and diabetes go hand-in-hand may need rethinking.

Corbit is already thinking about what this could mean for how people are currently treated for the condition. “I worry that giving people insulin over the long-term may end up hurting them,” he says. While injecting insulin in the bloodstream can bring down high blood sugar, it also prevents the breakdown of fat, which leads to cardiovascular problems and other serious medical issues. An alternative treatment for obesity, Corbit thinks, could lie in discovering how exactly grizzlies use the PTEN gene to control their insulin levels.

Ultimately, Corbit wrote in a New York Times op-ed last winter, drug development could take a hint from “millions of years of evolutionary experimentation.” Through unique genetic mutations, animals have evolved in ways to overcome conditions that continue to afflict humans. The new grizzlies research is just one example of how we can learn from them.

“Nature has figured it out,” he says.

Now he just needs to find a way to translate thousands of years of evolution into a treatment for obesity. Slumbering grizzlies may have brought Corbit closer than ever.

This article originally appeared in High Country News.

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