Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation

Cell Metab. 2014 Aug 5;20(2):376-82. doi: 10.1016/j.cmet.2014.07.008.


The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Retracted Publication

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Blood Glucose / analysis
  • Body Weight
  • Female
  • Haploinsufficiency
  • Hibernation
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Resistance*
  • Male
  • Obesity / metabolism
  • Obesity / pathology
  • PTEN Phosphohydrolase / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Seasons
  • Signal Transduction
  • Ursidae


  • Blood Glucose
  • Insulin
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase