The ability of hibernating bears to regulate insulin has shrunk to eight proteins – WSU Insider

COACH, Wash. – Giving honey to hibernating bears helped Washington State University researchers find potential genetic keys to bear insulin control, a breakthrough that could eventually lead to a treatment for human diabetes.

Each year, bears gain an enormous amount of weight, 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 as much. a switch. In search of the secret of the bears, WSU scientists have observed thousands of changes in gene expression during hibernation, but now a research team has narrowed the number to eight proteins.

“There appear to be eight proteins that are working independently or together to modulate the insulin sensitivity and resistance seen in hibernating bears,” said Joanna Kelley, evolutionary geneticist at WSU and corresponding author of the study. iScience. β€œAll of these eight proteins have human homologues. They are not exclusive to bears. The same genes are found in humans, so this means that perhaps there is a direct opportunity for translation. “

The research team analyzed changes in bear cell cultures that were exposed to blood serum taken from grizzly bears hosted at the WSU Bear Center. Both cells and blood serum were taken from the bears during active and hibernating seasons, as well as during an interrupted hibernation period when researchers fed honey water to the bears.

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.

Across all combinations, it was the whey from the mid-hibernation feeding period that helped most to identify key proteins.

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

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

Photo by WSU Photo Shoot

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

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

“This is a progress towards a better understanding of what is happening 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-graduate researcher. WSU doctorate.

The tools for understanding genetics are becoming more sophisticated, and recently Kelley, Perry and their colleagues published an updated genome assembly for brown bears, of which grizzly bears are a subspecies. This more complete and contiguous genome can help provide even better information on bear genetics, including how they handle hibernation.

“There is intrinsic value in studying the diversity of life around us and all 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 in this study include co-first author Michael Saxton along with co-authors Brandon Evans Hutzenbiler, Shawn Trojahn, Alexia Gee, Anthony Brown, Omar Cornejo, Charles Robbins, and Heiko Jansen, all of the WSU, as well as Michael MacCoss, Gennifer Merrihew. and Jay Park of the University of Washington.

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