Why fat grizzlies don't get diabetes like we do

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Sometimes nature comes up with elegant solutions to difficult problems, like how to gain weight and not get diabetes.

Take, for instance, the grizzly bear. How does this 750-pound mammal survive long, lean winters? Well, it just gets really fat beforehand and then sleeps the hungry season away.

Grizzly bears can easily double their body fat in the months leading up to hibernation. For us humans, this kind of weight gain could result in some pretty serious health consequences — one of the most common being Type 2 diabetes.

But grizzly bears are adept at staying healthy despite their dramatic fluctuations in weight, reports a study published Tuesday in Cell Metabolism.

According to the report, the grizzly's ability to pack on the pounds and then use that energy efficiently during hibernation might have to do with the surprising way that its body responds to the hormone insulin.

"The results were so different from what we see in humans and rodents that we were all very skeptical at first," says Kevin Corbit, a senior scientist at Amgen Inc., a biotechnology firm in Thousand Oaks, Calif., who led the research team. "This was a complete surprise," he says. Amgen is interested in the potential this research has to help treat obesity and diabetes.

Insulin is a hormone produced by the pancreas, and it instructs fat, liver and muscle tissue to suck up blood sugar and convert it into fat. In humans, weight gain is believed to lead to insulin resistance — the pancreas must produce more and more insulin to control blood sugar, until eventually it shuts down, causing Type 2 diabetes.

Corbit and his team wanted to know if packing on the pounds prior to hibernation also made grizzlies more resistant to insulin. So they decided to study six former "nuisance" bears in a rescue facility in Washington. These bears live in conditions that are as close to the wild as possible, so they still gorge out in the summer and hibernate in the winter. But being in captivity made them ultimately easier to wrangle.

Nevertheless, Corbit describes working with the bears as "a highly orchestrated ballet."

Assuming that, like humans, bears became less sensitive to insulin when they gained weight, the researchers waited until the bears were at their fattest — right before hibernation — and injected them with what they thought was a tiny dose of insulin, about the same amount you would give to a human.

The bears almost died of insulin overdose.

"That's when we knew something surprising was happening in the bears," says Corbit.

It turns out that despite all their excess poundage, the bears were very sensitive to insulin — a sign of great health.

Corbit and his team then looked at how the bears responded to insulin at other points during the year — before hibernation, during hibernation and after hibernation. They found that the bears were actually most sensitive to insulin just before hibernation, when they were at their largest. During hibernation, they became extremely resistant to insulin. Then after hibernation, they became sensitive to insulin again.

Based on the results, Corbit hypothesized that the bear's fat cells can actually change how they respond to insulin throughout the year.

"I look at it as a dimmer switch within the tissue," says Corbit, referring to how the cells turn their sensitivity to insulin up and down.

Evolutionarily, this insulin "dimmer switch" is actually very helpful to the bear. Before hibernation, when they are busy chowing down on berries and salmon, their high sensitivity to insulin helps them convert all that excess sugar in their bloodstream into fat. And during hibernation, their low sensitivity to insulin helps them maintain enough sugar in their bloodstream to survive.

And Corbit says that if scientists can pinpoint the mechanism underlying the insulin dimmer switch, it might help in treating people who are showing early signs of diabetes.

"I think giving insulin is making people much sicker," he says. "I'm hoping that whatever we find is going to ramp up the insulin sensitivity enough that we don't have to supplement with insulin at all."

Maren Laughlin, a program director at the National Institute of Diabetes and Digestive and Kidney Disorders who was not affiliated with the study, agrees that it would be beneficial to be able to treat people with smaller doses of insulin.

And Corbit's hypothesis that cells can flip their insulin sensitivity on and off is an intriguing one, she says, but the researchers would need to look at the bear's sensitivity to insulin at more points during the year to verify that.

This paper joins another, released in May, showing that specific genes in polar bears have evolved to let them eat as much fat as they please without succumbing to heart disease.

It seems that bears are just really good at being fat.

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