Abstract
BACKGROUND: The decline in the downstream signal transduction pathway of anabolic hormone, insulin, could play a key role in the muscle atrophy and insulin resistance observed in patients with intensive care unit acquired weakness (ICUAW). This study investigated the impact of immobilisation via surgical knee and ankle fixation and inflammation via Corynebacterium parvum injection, alone and in combination, as risk factors for altering insulin transduction and, therefore, their role in ICUAW. RESULTS: Muscle weight was significantly decreased due to immobilisation [estimated effect size (95% CI) - 0.10 g (- 0.12 to - 0.08); p < 0.001] or inflammation [estimated effect size (95% CI) - 0.11 g (- 0.13 to - 0.09); p < 0.001] with an additive effect of both combined (p = 0.024). pAkt was only detectable after insulin stimulation [estimated effect size (95% CI) 85.1-fold (76.2 to 94.0); p < 0.001] irrespective of the group and phosphorylation was not impaired by the different perturbations. Nevertheless, the phosphorylation of GSK3 observed in the control group after insulin stimulation was decreased in the immobilisation [estimated effect size (95% CI) - 40.2 (- 45.6 to - 34.8)] and inflammation [estimated effect size (95% CI) - 55.0 (- 60.4 to - 49.5)] groups. The expression of phosphorylated GS (pGS) was decreased after insulin stimulation in the control group and significantly increased in the immobilisation [estimated effect size (95% CI) 70.6-fold (58.8 to 82.4)] and inflammation [estimated effect size (95% CI) 96.7 (85.0 to 108.5)] groups. CONCLUSIONS: Both immobilisation and inflammation significantly induce insulin resistance, i.e., impair the insulin signaling pathway downstream of Akt causing insufficient GSK phosphorylation and, therefore, its activation which caused increased glycogen synthase phosphorylation, which could contribute to muscle atrophy of immobilisation and inflammation.