Feeding hibernating bears with honey helped researchers at Washington State University find potential genetic keys to insulin control in bears, an advance that may eventually lead to a cure for human diabetes.
Each year, bears gain an enormous amount of weight and then barely move for months, a behavior that would lead to diabetes in humans, but not to bears whose bodies can turn insulin resistance on and off almost like a switch. In the search for the bears’ secret, scientists at Washington State University have observed thousands of changes in gene expression during hibernation, but now a research team has narrowed that down to eight proteins.
“It appears that there are eight proteins that work either independently or together to modulate insulin sensitivity and resistance seen in hibernating bears,” said Joanna Kelly, an evolutionary geneticist at WSU and corresponding author of the study published in iScience. “All of these eight proteins have human homologs. They are not unique to bears. The same genes are found in humans, meaning there may be a direct opportunity for translation.”
The research team analyzed changes in bear cell cultures that were exposed to serum taken from grizzly bears housed at the WSU Bear Center. Both cells and blood serum were taken from the bears during active and hibernating seasons as well as from intermittent hibernation when the researchers fed the bears honey water.
In the lab, the researchers combined different cell cultures and sera, such as a culture of cells from the hibernation season with serum from the active season, to analyze the genetic changes that occurred.
By all combinations, it was serum from the mid-hibernation feeding period that most helped identify key proteins.
“By feeding the bears only for two weeks while they hibernate, it allowed us to control other things like day length and temperature as well as food availability,” Kelly said.
Bears usually get up and move around a little while hibernating, but they usually don’t eat, urinate, or defecate. Researchers used these waking moments to offer bears honey water, one of their favorite foods, as part of another study, which found that extra sugar disrupted their hibernation behavior. Kelly and her colleagues then used samples from that study period to perform their genetic analysis.
When the researchers put serum from inactivated hibernation into a cell culture taken from regularly hibernating bears, they found that those cells began to show changes in gene activity similar to those in active season cells.
Next, the team plans to investigate how these proteins specifically work to reverse insulin resistance, research that could eventually lead to the development of ways to prevent or treat diabetes.
“This is a progression toward getting a better understanding of what’s going on at the genetic level and identifying the specific molecules that control insulin resistance in bears,” said Blair Berry, co-first author of the study and a postdoctoral researcher at WSU.
Tools for understanding genetics are becoming more complex, and Kelly, Berry and their colleagues recently published an updated genome set of brown bears, of which grizzly bears are a subspecies. This more complete and contiguous genome may help provide better insights into bear genetics including how to manage hibernation.
“There is an inherent value in studying the diversity of life around us and all these unique and strange adaptations that have arisen,” said Berry, 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 special as humans.”
Other researchers in this study include co-first author Michael Saxton along with co-authors Brandon Evans Hotzenbiller, Sean Trojan, Alexia J, Anthony Brown, Omar Cornejo, Charles Robbins, and Heiko Jansen, all from WSU as well as Michael Makos and Jennifer Mireio Jia Park from the University of Washington.