Hibernating bears’ ability to regulate insulin is reduced to eight proteins

Feeding hibernating bears honey has helped Washington State University researchers find potential genetic keys to bears’ insulin control, a breakthrough that could eventually lead to a cure for human diabetes.

Each year, bears gain tremendous weight and then barely move for months, a behavior that would mean diabetes in humans, but not for bears whose bodies can turn insulin resistance on and off almost like a switch. . In the bear hunt, WSU scientists observed thousands of changes in gene expression during hibernation, but now a research team has narrowed that number down to eight proteins.

“There appear to be eight proteins that work independently or together to modulate the insulin sensitivity and resistance observed in hibernating bears,” said Joanna Kelley, evolutionary geneticist at WSU and corresponding author of the study published in iScience. “These eight proteins all have human counterparts. They are not unique to bears. The same genes are in humans, which means maybe there is a direct opportunity for translation. »

The research team analyzed changes in bear cell cultures exposed to blood serum collected from grizzly bears housed at the WSU Bear Center. Cells and blood serum were collected from the bears during active and hibernation seasons as well as during a period of interrupted hibernation when the researchers fed the bears honey water.

In the lab, the researchers combined different cell cultures and sera, such as a cell culture from a hibernation season with serum from the active season, to analyze the genetic changes that occurred.

In all combinations, serum from the mid-hibernation feeding period was most helpful in identifying key proteins.

“By feeding the bears for only two weeks during hibernation, it allowed us to control other things like day length and temperature as well as food availability,” Kelley said.

Bears usually get up and move around a bit during hibernation, but they usually don’t eat, urinate, or defecate. Researchers used these waking moments to offer bears honey water, one of their favorite treats, in another study, which found that the extra sugar disrupted their eating behavior. hibernation. Kelley and his colleagues then used the samples from this study period to perform their genetic analysis.

When the researchers placed the serum from the interrupted hibernation on a cell culture taken from regularly hibernating bears, they found that these cells began to show changes in gene activity similar to active-season cells.

Next, the team plans to study how these proteins work specifically to reverse insulin resistance, research that could ultimately lead to the development of ways to prevent or treat human diabetes.

“This is progress towards a better understanding of what’s going on at the genetic level and the identification of specific molecules that control insulin resistance in bears,” said Blair Perry, co-first author of the study and post-doctoral researcher at WSU.

Tools for understanding genetics are increasingly sophisticated, and recently Kelley, Perry and their colleagues published an updated genome construct for brown bears, of which grizzly bears are a subspecies. This more complete and contiguous genome may help provide even better insights into bear genetics, including how they manage hibernation.

“There’s an inherent value in studying the diversity of life around us and all of these unique and strange adaptations that have arisen,” said Perry, who has also studied the genetic makeup of snake venom. “By understanding the genomic basis of these adaptations, we gain a better understanding of what we share with other species and what makes us unique as humans. »

Other researchers on this study include co-first author Michael Saxton with co-authors Brandon Evans Hutzenbiler, Shawn Trojahn, Alexia Gee, Anthony Brown, Omar Cornejo, Charles Robbins and Heiko Jansen all of WSU as well as Michael MacCoss, Gennifer Merrihew and Jea Park of the University of Washington.

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