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Aging mice who are deprived of sleep displayed cellular stress in the pancreas. Researchers from the University of Pennsylvania claim that this disrupts glucose homeostasis and is associated with type 2 diabetes.
Lack of sleep has long been associated with adverse effects on human physiology. Previous studies have linked insomnia with a higher risk of death, increased risk of Alzheimer's disease and other chronic illnesses.
But while numerous studies have focused on the consequences of sleep deprivation on the brain, relatively few have looked at the effects it has on the peripheral organs.
So, the team from the University's Perlman School of Medicine set out to explore this and look at the molecular pathways through which lack of sleep wreaks havoc on the body.
Publishing the results in Aging Cell, the authors explain that sleep deprivation makes cells increase their response to a molecular stimulus - in this case, the unfolded protein response (UPR).
This is a process whereby misfolded proteins are either refolded or degraded. Protein misfolding and clumping is linked with many diseases, including Alzheimer's disease and Parkinson's.
In a previous study, Nirinjini Naidoo, lead author and research associate professor in the Division of Sleep Medicine, showed that the stress induced by sleep deprivation causes the "upregulating" of UPR and particularly affects older mice.
Aging cells often have impaired protective responses, she explains, adding that inadequate or disturbed sleep in elderly people may exacerbate the protein misfolding.
Prof. Naidoo bulit on the results of that study to explore the effect of sleep deprivation on the UPR in the pancreas. Pancreatic cells are essential to maintaining blood sugar levels, and the stress caused by lack of sleep may contribute to the dysfunction of these cells.
"The combined effect of aging and sleep deprivation resulted in a loss of control of blood sugar reminiscent of pre-diabetes in mice. We hypothesize that older humans might be especially susceptible to the effects of sleep deprivation on the disruption of glucose homeostasis via cell stress."
She also drew on previous research that suggested the death of beta cells associated with type 2 diabetes may be due to stress in the endoplasmic reticulum (ER) - a compartment in the cell where some proteins are made. UPR is part of the "quality control system" regulating the ER.
The team examined tissues for cellular stress in mice that had been acutely sleep deprived. They found that older mice fared worse than their younger counterparts, indicating that both age and lack of sleep contribute to cellular stress in the pancreas.
The older animals also exhibited increased levels of CHOP, a protein associated with cell death.
All the mice had increased plasma glucose levels, but the younger animals demonstrated improved control of their blood sugar levels, whereas the aged mice became hyperglycemic and were unable to maintain plasma insulin concentrations.
The researchers claim that the stress in the pancreatic cells caused by sleep deprivation may contribute to the dysfunction of endocrine cells and that the effects of this may be more severe with age.
The importance of sleep is well established. Medical News Today has reported studies that claim it "detoxes" the brain, and others that link regular sleep patterns to a healthy weight in both children and adults.
Written by Belinda Weber
Copyright: Medical News Today
Not to be reproduced without the permission of Medical News Today.
Aging and sleep deprivation induce the unfolded protein response in the pancreas: implications for metabolism, Nirinjini Naidoo, James G. Davis, Jingxu Zhu, Maya Yabumoto, Kristan Singletary, Marishka Brown, Raymond Galante, Beamon Agarwal, Joseph A. Baur, Aging Cell, 12 November 2013. DOI: 10.1111/acel.12158.
Additional source: Penn Medicine news release.
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Weber, Belinda. "Sleep deprivation and increasing age linked to diabetes." Medical News Today. MediLexicon, Intl., 16 Dec. 2013. Web.
24 Apr. 2014. <http://www.medicalnewstoday.com/articles/270120>
Weber, B. (2013, December 16). "Sleep deprivation and increasing age linked to diabetes." Medical News Today. Retrieved from
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