Impaired Insulin Signaling in Human Adipocytes After Experimental Sleep Restriction: A Randomized, Crossover Study
Publication: Annals of Internal Medicine
Volume 157, Number 8
Abstract
Background:
Insufficient sleep increases the risk for insulin resistance, type 2 diabetes, and obesity, suggesting that sleep restriction may impair peripheral metabolic pathways. Yet, a direct link between sleep restriction and alterations in molecular metabolic pathways in any peripheral human tissue has not been shown.
Objective:
To determine whether sleep restriction results in reduced insulin sensitivity in subcutaneous fat, a peripheral tissue that plays a pivotal role in energy metabolism and balance.
Design:
Randomized, 2-period, 2-condition, crossover clinical study.
Setting:
University of Chicago Clinical Resource Center.
Participants:
Seven healthy adults (1 woman, 6 men) with a mean age of 23.7 years (SD, 3.8) and mean body mass index of 22.8 kg/m2 (SD, 1.6).
Intervention:
Four days of 4.5 hours in bed or 8.5 hours in bed under controlled conditions of caloric intake and physical activity.
Measurements:
Adipocytes collected from subcutaneous fat biopsy samples after normal and restricted sleep conditions were exposed to incremental insulin concentrations. The ability of insulin to increase levels of phosphorylated Akt (pAkt), a crucial step in the insulin-signaling pathway, was assessed. Total Akt (tAkt) served as a loading control. The insulin concentration for the half-maximal stimulation of the pAkt–tAkt ratio was used as a measure of cellular insulin sensitivity. Total body insulin sensitivity was assessed using a frequently sampled intravenous glucose tolerance test.
Results:
The insulin concentration for the half-maximal pAkt–tAkt response was nearly 3-fold higher (mean, 0.71 nM [SD, 0.27] vs. 0.24 nM [SD, 0.24]; P = 0.01; mean difference, 0.47 nM [SD, 0.33]; P = 0.01), and the total area under the receiver-operating characteristic curve of the pAkt–tAkt response was 30% lower (P = 0.01) during sleep restriction than during normal sleep. A reduction in total body insulin sensitivity (P = 0.02) paralleled this impaired cellular insulin sensitivity.
Limitation:
This was a single-center study with a small sample size.
Conclusion:
Sleep restriction results in an insulin-resistant state in human adipocytes. Sleep may be an important regulator of energy metabolism in peripheral tissues.
Primary Funding Source:
National Institutes of Health.
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Information & Authors
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Published In
Annals of Internal Medicine
Volume 157 • Number 8 • 16 October 2012
Pages: 549 - 557
History
Published online: 16 October 2012
Published in issue: 16 October 2012
Keywords
Copyright
© 2012 American College of Physicians.
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Impaired Insulin Signaling in Human Adipocytes After Experimental Sleep Restriction: A Randomized, Crossover Study. Ann Intern Med.2012;157:549-557. [Epub 16 October 2012]. doi:10.7326/0003-4819-157-8-201210160-00005
Impaired Insulin Signaling in Human Adipocytes After Experimental Sleep Restriction: A Randomized, Crossover Study. Ann Intern Med.2012;157:549-557. [Epub 16 October 2012]. doi:10.7326/0003-4819-157-8-201210160-00005
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