Sleep Disruption and Glucose Tolerance

Sleep disturbances, including sleep fragmentation, are known to occur more frequently in individuals with type 2 diabetes than in the general population.   Poor sleep has been shown to negatively impact glycemic control and may exacerbate negative metabolic outcomes when combined with other risk factors. Chronic systemic inflammation with well-established links to diabetes and obesity and many of the inflammatory pathways activated by metabolic stress are also stimulated by lack of sleep.  A recent paper by Ho et al. further examined the effects of sleep fragmentation on the metabolic regions of the brain to determine whether or not a direct connection exists between sleep loss, diet and glucose regulation.

To establish sleep fragmentation, mice were housed individually in novel sleep disruption devices with floors that rotate for 8 out of every 30 seconds.   Both direction of rotation, and placement of the rotation within the 30 second interval were varied to prevent habituation.   Sleep fragmentation as implemented for 18 hours per day with rotations halted for 6 hours a day at the beginning of the light cycle to allow mice to behave freely including sleep uninterrupted if they chose.  Mice were subjected to sleep fragmentation for zero, three or nine days and were fed either standard or high fat chow (both fed ad libitum).

Glucose tolerance was determined after either 3 or 9 days of sleep disruption.  Mice were also sacrificed and plasma corticosterone levels were also measured (Arbor Assays Corticosterone EIA Kit, K014-H) at both 3 days and 9 days. After 3 days, corticosterone levels were significantly elevated in the sleep fragmented mice regardless of diet.  After 9 days of sleep fragmentation, the control and sleep fragmented mice eating standard chow had higher corticosterone levels than their counterparts eating the high fat diet.  Iba1 levels in the brain were elevated both by sleep fragmentation and by the high fat diet. Elevated Iba1 is a marker for microglial activation and inflammation indicating that inflammatory effects were observed in response to the testing conditions.  To further investigate inflammatory response levels of the cytokines IL-1β, IL6 and TNF-α were determined in samples from the brain stem, hypothalamus, liver and adipose tissues.  The largest cytokine response was observed in the liver, with increased IL-1β concentrations after three days and increases in both IL-1β and IL-6 after 9 days.  In the hypothalamus IL-1β levels were unchanged after 3 days, but at nine days increased IL-1β levels were observed in mice fed the high fat diet, while decreased levels of IL-β were observed in mice subjected to sleep fragmentation.

Both sleep disruption and inflammation have demonstrated links to glucose tolerance, possibly with an inflammatory component, while high fat diet is separately known to cause inflammatory response.  The authors of this paper were specifically interested in whether those inflammatory effects might be additive, and whether or not they could be mapped to parts of the brain responsible for energy regulation and metabolism.  Their data shows that sleep disruption induced a rapid increase in microglial activation within the brain that was even more potent than that induced by high fat diet.  Suggesting that inflammation does indeed have a significant role in the physical effects of disturbed sleep.   Evidence to specifically tie that neuroinflammatory response to glucose tolerance was not as substantial.   In this experiment, peripheral inflammatory response in the liver correlated better to glucose tolerance results than the neuroinflammation.   However, these results may have been limited by the fairly short duration of this particular experiment, and further work will be needed to fully understand how sleep and diet interact to affect metabolism.

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