Proteins that are expressed at different levels during hibernation, the active season. Disturbances in the natural rhythm can lead to metabolic diseases
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Joanna Kelley collected blood serum samples from active and hibernating bears at the WSU Bear Center to measure protein expression.
WSU researchers are investigating eight proteins that could be natural indicators of insulin resistance in bears, which could provide new insights into human diabetes.
Bears are sensitive to insulin during their active cycle and naturally enter an insulin resistant state during hibernation, said Joanna Kelley, associate professor at the WSU School of Biological Sciences.
Insulin resistance in humans has been linked to type 2 diabetes, she said.
“That’s part of [bears’] natural annual cycle, “said Kelley,” while this is not natural in humans, it is a disease condition. “
Insulin is a protein that regulates the uptake of glucose by cells. When an organism is insulin resistant, glucose builds up in the blood, which leads to high blood sugar.
Kelley compared blood serum samples from active bears and hibernating bears and found eight key proteins that were expressed in different concentrations. Applying blood serum from an active bear to cells of a hibernating bear triggered physiological changes in the cells associated with insulin sensitivity, she said.
All eight proteins have a homologue in humans, which means they don’t have the same protein sequence but are otherwise similar, she said.
One protein or any combination of the eight could be responsible for insulin resistance, Kelley said. The next step is to test individual proteins and various combinations to see which are associated with changing metabolic states.
Bears have both circadian and circan rhythms – daily and annual internal clocks – that control their metabolic state. People have circadian rhythms, but there isn’t enough evidence that they have circan rhythms, said Heiko Jansen, professor of integrative physiology and neuroscience at WSU.
“It is the cellular clocks, we call them,” said Jansen, “that make these rhythms appear in our physiology and behavior.”
Organisms become more prone to metabolic diseases like diabetes and obesity when their circadian rhythms are disrupted, he said.
Maintaining a consistent sleeping and eating cycle could protect organisms from some diseases, he said.
Bears maintain a normal sleep / wake cycle during hibernation, although it’s not as obvious as it is during the active season, Jansen said. Researchers are trying to find out if this will protect bears from diabetes.
“Having a working circadian clock,” he said, “even while hibernating may have been a way to protect yourself from the negative effects of insulin resistance.”
There are many ways a bear’s physiology can change during hibernation as different body systems are affected, Jansen said. These changes are likely caused by multiple genes.
Kelley hopes this research will eventually lead to a therapeutic treatment in humans that induces cells to increase production of the key protein or proteins, thereby curing diabetes.
Kelley’s research was supported by a $ 40,000 grant from WSU’s Cougar Cage competition. She will submit a paper for publication in the next few weeks.
