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Know the West

What diabetic grizzlies can tell us about human obesity


Sept. 2, 2015 update: It has been announced that one of the authors of this study manipulated data, and the study has now been retracted. Here is the retraction note:

This article has been retracted at the request of the authors. Amgen requested the retraction as an outcome of an internal review where it was determined that one of the Amgen authors had manipulated specific experimental data presented in Figures 1 and 3. Because of data manipulation, this author is no longer employed by Amgen. The authors at Washington State University and University of Idaho are confident that the physiological data generated for this manuscript are accurate and representative of the true metabolic responses of these grizzly bears and are currently repeating the mechanistic portions of the study. Amgen deeply regrets this circumstance and extends their sincere apologies to the scientific community.

Most researchers studying grizzly bears are from U.S. Fish and Wildlife or university ecology departments, not biotechnology companies. Still, Kevin Corbit, a senior scientist at the Southern California biotech firm Amgen, spends his days in a lab in Pullman, Washington, 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.

A grizzly roams in Yellowstone National Park. Photo by Flickr user, Shane Lin.

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. And 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.

Wyatt Orme is an editorial intern at High Country News. He tweets @wyatt_orme.