Impaired Insulin Signaling in Human Adipocytes After Experimental Sleep Restriction A Randomized, Crossover Study

Broussard JL, Ehrmann DA, Van Cauter E, et al. — Tue, 16 Oct 2012 00:00:00 GMT

Chinese translation

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.

A New Challenge to Widely Held Views on the Role of Sleep

Cappuccio FP, Miller MA. — Tue, 16 Oct 2012 00:00:00 GMT

In this issue, Broussard and colleagues show that cellular insulin sensitivity was reduced in adipocytes from subcutaneous fat samples collected after 4 nights of sleep restriction compared with 4 nights of normal sleep. This editorial discusses how the study's findings challenge traditional views that the purpose of sleep is confined to its restorative effects on the central nervous system.

Annals of Internal Medicine: Sleep Disorders Topic Collection

Impaired Insulin Signaling in Human Adipocytes After Experimental Sleep Restriction A Randomized, Crossover Study

A New Challenge to Widely Held Views on the Role of Sleep