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Grizzly bear insulin control mechanism could aid diabetes treatment

Written by Lauren Robertson, Science Writer.

Proteomics and transcriptomics analysis has uncovered the genetic key to the brown bear’s ability to control insulin. Researchers hope this could aid the future development of treatments for human diabetes.

Why don’t bears get diabetes?

A good question. Ever year, a bear will gain an enormous amount of weight and subsequently sleep for months on end. For humans, this is a sure-fire way to develop diabetes. But for bears? It’s part of their yearly cycle thanks to their ability to turn insulin resistance on and off like a switch.

Brown bears (AKA grizzly bears) undergo these seasonal shifts in insulin sensitivity during hibernation. The shifts are the result of metabolic reprogramming – a process that contributes to a variety of metabolic disorders, such as diabetes. During hibernation, the bear’s adipose tissues and muscles no longer store or incorporate glucose from the blood. In spring, their sensitivity to insulin is restored.

In a bid to uncover the mechanism behind this incredible insulin control – and hopefully aid the future development of diabetes treatments in humans – Joanna Kelley and her team at Washington State University observed changes in gene expression during brown bear hibernation.

But first, honey!

During their research for another study, the team fed captive brown bears honey water for a 10-day period during hibernation and collected pre-adipocytes and serum before and after the feeding. They then also studied serum from brown bears during active season and hibernation for comparison.

“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,” said Joanna Kelley, a WSU evolutionary geneticist and corresponding author of the study.

They found more than 6,000 differentially expressed genes throughout the sample, including genes linked to 17 pathways involved in regulation of the cytoskeleton, chromatin, and cell cycle. Cells taken during hibernation seemed to experience more dramatic shifts in gene expression, and these shifts were dependent on circulating serum factors and intrinsic cell characteristics.

Proteomics analysis of serum suggested that despite widespread changes in adipocyte gene expression, there are ultimately eight proteins responsible for seasonal shifts in insulin sensitivity in brown bears. These include a few that have not been previously linked to glucose homeostasis, and three of the eight proteins are linked to immune responses.

“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,” said Kelley. “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.”

Translating to humans

As the authors note, this is just a starting point. The eight identified proteins need to be studied further to elucidate the mechanisms responsible for insulin regulation in brown bears. They also suggest that there may be other unidentified serum factors at play here that have not yet been identified, and that further research should focus on cellular senescence in bears – this information could aid translation into other metabolic disorders in humans.

As for the team’s next steps, their plan is to investigate how the eight proteins work to reverse insulin resistance and translate this to humans. “This [study] 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,” said Blair Perry, the study’s co-first author and a WSU post-doctoral researcher.

“There’s inherent value to studying the diversity of life around us and all these unique and strange adaptations that have arisen. 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.”