An investigation into skeletal muscle insulin signalling and systemic inflammation as potential mechanisms responsible for the impairment in glucose regulation following acute sleep restriction in healthy males

Abstract

Sleep restriction is associated with impaired glucose regulation, which is a risk factor for developing type 2 diabetes. However, the underlying mechanisms leading to this impairment are unknown. This thesis aims to examine the effects of partial sleep restriction on whole body metabolism, and investigate whether the impairment in insulin sensitivity observed after sleep restriction is coupled with changes in systemic inflammation and skeletal muscle insulin signalling. A pilot study was carried out to assess whether or not two nights of partial sleep restriction would alter glucose regulation and substrate utilisation. 10 healthy males then participated in a separate randomised crossover study involving two nights of habitual sleep (control) and two nights of 50% of habitual sleep (sleep restriction). An oral glucose tolerance test was carried out after the second night of each condition to assess whole body glucose tolerance, insulin sensitivity and inflammation, and to examine skeletal muscle insulin signalling. The pilot study findings confirmed that two nights of partial sleep restriction impaired glucose tolerance. Findings from the main study revealed no effect of trial on glucose tolerance (P = .222). Insulin sensitivity estimated by the Matsuda Index was 18.6% lower in the sleep restriction condition (P = .010). CRP and TNFα were similar between trials (P > 0.05). Fold change in PKB activity from baseline tended to be lower following sleep restriction at 30 min (P = .098) and 120 min (P = .087). AUC for insulin to PKB index was significantly higher in the sleep restriction condition (P = .012). Phosphorylated to total PKB was similar between conditions (P = .217). Two nights of sleep restriction decreased insulin sensitivity in healthy males. This impairment was not coupled by increased systemic inflammation. Skeletal muscle insulin signalling showed conflicting findings, suggesting a possible disruption of skeletal muscle insulin signalling.