Tuned insulin signals may keep animals free of diabetes
Grizzly bears have figured out how to be fat and fit.
Though the animals beef up before hibernating, they may avoid diabetes by tweaking signals in fat cells, researchers report in the Aug. 5 Cell Metabolism.
Whether scientists will be able to use the signals to develop drugs for humans is uncertain, says molecular biologist Sandy Martin of the University of Colorado Denver. “But it’s certainly worth pursuing,” she says. “There’s a huge amount we can learn from bears. They actually manage obesity and use it to their advantage.”
Grizzlies layer on fat every fall and slim down every spring, but scientists don’t quite understand how the bears deal with the yo-yo dieting. After months of gorging on salmon in Alaska or berries in Yellowstone, grizzly bears can double their body fat. If humans did that, says study coauthor Heiko Jansen, they’d start showing signs of type 2 diabetes, such as high blood sugar and insulin resistance.
Grizzlies don’t seem to suffer the same consequences. But no one had directly measured insulin sensitivity in the animals before, says Jansen, a neuroendocrinologist at Washington State University in Pullman.
His team studied 10 captive bears, four of which had been raised by humans since infancy. These hand-raised grizzlies are “trained pretty much like dogs,” Jansen says. For a honey reward, “they sit down, they lie down, they stick their foot out and let us take a blood sample.”
By injecting insulin into the bears, the researchers found that the animals’ response to the hormone varied depending on the season. Normally, insulin tells cells to remove sugar from the blood and start storing fat.
Even at their fattest in the fall, the animals managed to stay sensitive to insulin’s call — a feat uncommon in obese humans with diabetes. But during hibernation, grizzlies ignored the message and became insulin resistant, a hallmark of the metabolic disease. In the spring, the bears’ bodies bounced back and responded to insulin again.
The researchers wondered how the bears’ bodies orchestrate this back-and-forth switch. So Heiko and colleagues looked at an assortment of molecules that direct insulin’s message to cells. In fat cells, one protein stood out: Bears shut it down in the fall and the spring but not when hibernating in the winter. The protein acts as a kind of roadblock, stopping insulin’s message from getting to cells. By toggling the protein on and off, bears might be able to control when insulin delivers its message, and when cells store and burn fat.
Still, the idea of “healthy obesity” might be best left to the bears, says Maren Laughlin, a program director at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md. “The thing to remember is these bears don’t stay obese for very long.”
Bears’ metabolic adaptations to a cycle of feasting and fasting might be what keep the grizzlies healthy.
Editor's Note: This article was updated August 15, 2014, to correct the name of the National Institute of Diabetes and Digestive and Kidney Diseases.
O.L. Nelson et al. Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation. Cell Metabolism. Vol. 20, August 5, 2014, p. 376. doi: 10.1016/j.cmet.2014.07.008.