Sleep Deprivation Elderly Blood Sugar
December 12, 2013

Aging Worsens Effects Of Sleep Deprivation On Blood Sugar Levels

redOrbit Staff & Wire Reports - Your Universe Online

Normal aging may exacerbate the negative effect of sleep deprivation on pancreatic cells that maintain normal blood sugar levels, according to a study published this month in the journal Aging Cell.

Sleep, or the lack of it, seems to affect nearly every aspect of human physiology, although the molecular pathways through which sleep deprivation wreaks havoc on the body remain poorly understood. Numerous studies have looked at the consequences of sleep deprivation on the brain, but few have directly tested its effects on peripheral organs.

During sleep deprivation, cells upregulate the unfolded protein response (UPR), a process where misfolded proteins get refolded or degraded.

Five years ago, researchers at the University of Pennsylvania showed that the UPR is an adaptive response to stress induced by sleep deprivation, and is impaired in the brains of old mice. Those findings suggested that inadequate sleep in the elderly, who typically experience sleep disturbances, could exacerbate an already-impaired protective response to protein misfolding that happens in aging cells.

Such protein misfolding and clumping is associated with many diseases such as Alzheimer's and Parkinson's, said research associate professor Nirinjini Naidoo, one of the leaders of that study.

In the current study, Naidoo has shown for the first time the effect of sleep deprivation on the UPR in peripheral tissue – in this case, the pancreas. The study revealed that stress in pancreatic cells due to sleep deprivation may contribute to the loss or dysfunction of these cells important to maintaining proper blood sugar levels, and that these functions may be exacerbated by normal aging.

"The combined effect of aging and sleep deprivation resulted in a loss of control of blood sugar reminiscent of pre-diabetes in mice," Naidoo said. "We hypothesize that older humans might be especially susceptible to the effects of sleep deprivation on the disruption of glucose homeostasis via cell stress."

Naidoo and Penn State colleague Joseph Baur, assistant professor of physiology, collaborated to examine the relationship of sleep deprivation, the UPR, and metabolic response with age.

Other researchers have suggested that the death of beta cells associated with type-2 diabetes might be due to stress in a cell compartment called the endoplasmic reticulum (ER). The UPR is one part of the quality control system in the ER, where some proteins are made.

Given this, Naidoo and Baur wondered whether sleep deprivation (SD) might cause ER stress in the pancreas through an increase in protein misfolding and, in turn, how this relates to aging.

The team examined tissues in mice for cellular stress following acute SD, and also looked for cellular stress in aging mice. Their results showed that both age and SD combine to induce cellular stress in the pancreas, with older mice faring markedly worse when subjected to sleep deprivation.

Pancreas tissue from older mice or from young animals subjected to sleep deprivation exhibited signs of protein misfolding, yet both were able to maintain insulin secretion and control blood sugar levels. However, pancreatic tissue from acutely sleep-deprived aged animals exhibited a noticeable increase in CHOP, a protein associated with cell death, suggesting a maladaptive response to cellular stress with age that was amplified by sleep deprivation.

Acute sleep deprivation caused increased plasma glucose levels in both young and old animals, although this change was not overtly related to stress in beta cells, since plasma insulin levels were not lower following acute lack of sleep. Accordingly, young animals subjected to acute sleep deprivation remained tolerant to a glucose challenge.

In a chronic sleep deprivation experiment, young mice were sensitized to insulin and had improved control of their blood sugar, whereas aged animals became hyperglycemic and failed to maintain appropriate plasma insulin concentrations.

While changes in insulin secretion are unlikely to play a major role in the acute effects of SD, cellular stress in pancreatic tissue suggests that chronic SD may contribute to the loss or dysfunction of endocrine cells, and that these effects may be exacerbated by normal aging, the researchers concluded.