0071 ROLE OF SLEEP RESTRICTION IN ADIPOCYTE INSULIN SENSITIVITY DURING AN INTRAVENOUS GLUCOSE TOLERANCE TEST IN HEALTHY ADULT MEN

Abstract

Sleep restriction, or chronic partial sleep loss, increases obesity and diabetes risk by disrupting glucose metabolism and reducing whole-body insulin sensitivity without a compensatory increase in insulin secretion. Healthy adipocytes suppress hormone sensitive lipase (HSL) activity in response to insulin, which severely limits non-esterified fatty acid (NEFA) release. Elevated overnight NEFA levels are correlated with the reduction in insulin sensitivity that occurs in sleep restriction. Additionally, subcutaneous adipose biopsies from sleep-restricted subjects have reduced pAKT, evidence that sleep restriction decreases insulin sensitivity in adipocytes. The objective of this pilot study was to extend previous findings of the effects of sleep restriction on plasma glucose to mechanistic shifts within adipocyte metabolism. Subjects (20–35 y/o) were enrolled in an 11-day in-lab protocol; light exposure, activity, temperature, and diet were carefully controlled. An intravenous glucose tolerance test (IVGTT) was performed at three time points: after three nights of baseline sleep (10 hrs/night), after five nights of sleep restriction (5 hrs/night), and after two nights of recovery sleep (10 hrs/night). NEFA were quantified (Wako Diagnostics) and parameters describing NEFA kinetics (i.e. rate of NEFA production, utilization, suppression threshold) in the Boston and Moate minimal model were calculated using WinSAAM Compartmental Modeling software. Five subjects completed the sleep restriction protocol; one did not complete IVGTT procedures for safety reasons. Preliminary results from four subjects show the fractional rate of NEFA utilization was increased by 0.024 [0.009, 0.039] min-1 in the restricted condition (p=0.008). Restriction also increased the modifier of the inhibitory effect of remote glucose on NEFA production by 4.3 fold [1.2, 15.9] from baseline (p=0.04). Sleep restriction induces symmetrical changes in both glucose and lipid markers of insulin sensitivity in vivo. Preliminary evidence indicates that NEFA rate of utilization is increased in response to sleep restriction. In the context of whole-body metabolism, this indicates a shift in Randle cycle fuel selection by metabolic tissues. Additionally, a greater concentration of glucose was required to initiate NEFA suppression, evidence that sleep restriction functionally impairs HSL activity. UL1TR000127 (Chang PI) T32GM108563 (to KMN; Korzick PI).