An important
disease among
human metabolic disorders is
type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high
blood glucose content and eventually
lead to the onset of
insulin resistance. The combination of
insulin resistance, increased
glucose production, and decreased
insulin secretion creates a diabetic metabolic
environment that leads to a lifetime of management. Appropriate models are critical for the success of
research. As such, a unique model providing insight into the mechanisms of reversible
insulin resistance is mammalian
hibernation. Hibernators, such as ground
squirrels and
bats, are excellent examples of
animals exhibiting reversible
insulin resistance, for which a rapid increase in
body weight is required prior to entry into dormancy. Hibernator studies have shown differential
regulation of specific molecular pathways involved in reversible resistance to
insulin. The present
review focuses on this growing area of
research and the molecular mechanisms that regulate
glucose homeostasis, and explores the
roles of the Akt signaling pathway during
hibernation. Here, we propose a link between
hibernation, a well-documented response to periods of environmental stress, and reversible
insulin resistance, potentially facilitated by key alterations in the Akt signaling network,
PPAR-γ/PGC-1α
regulation, and
non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during
insulin resistance in
human type 2 diabetes. Hence, the molecular networks that may regulate reversible
insulin resistance in hibernating
mammals represent a novel approach by providing insight into medical
treatment of
insulin resistance in
humans.