Bear Hibernation Study Could Inform Diabetes Treatment

Every year, bears gain an enormous amount of weight, then barely move for months. Such behavior would result in diabetes in humans, but bears’ bodies can turn insulin resistance on and off, almost like a switch. In the hunt for the bears’ secret, scientists at Washington State University (WSU) observed thousands of changes in gene expression during hibernation and narrowed this ability to regulate insulin to just a handful of proteins.

“There seem to be eight proteins that are working either independently or together to modulate the insulin sensitivity and resistance that's seen in hibernating bears,” says Joanna Kelley, a WSU evolutionary geneticist and corresponding author of the study. “All of these eight proteins have human homologues. They’re not unique to bears. The same genes are in humans, so that means maybe there’s a direct opportunity for translation.”

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

In the lab, the researchers combined different cell cultures and serums, such as a cell culture from a hibernation season with serum from the active season, to analyze the genetic changes that occurred. Through all the combinations, it was the serum from the mid-hibernation feeding period that helped the most in identifying the key proteins.

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

Bears do typically get up and move a little during hibernation, but they usually do not 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 the extra sugar did disrupt their hibernation behavior. Kelley and her colleagues then used the samples from that study period to do their genetic analysis.

When the researchers put the serum from the disrupted hibernation onto a cell culture taken from regularly hibernating bears, they found that those cells started to exhibit changes in gene activity similar to that of active season cells.

The team next plans to investigate how those proteins specifically work to reverse insulin resistance, research which could ultimately lead to the development of ways to prevent or treat human diabetes. “This is progress toward getting a better understanding of what’s happening at the genetic level and identifying specific molecules that are controlling insulin resistance in bears,” says Blair Perry, the study’s co-first author and a WSU post-doctoral researcher.

Perry says that there’s inherent value to studying diversity and its “unique and strange adaptations… 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.”

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, contiguous genome may help provide even better insights into bear genetics including how they manage hibernation.

The findings were published recently in iScience.