Insulin signaling in skeletal muscle during inflammation and/or immobilisation

Julius J Grunow; Thomas Gan; Heidrun Lewald; J A Jeevendra Martyn; Manfred Blobner; Stefan J Schaller

doi:10.1186/s40635-023-00503-9

Insulin signaling in skeletal muscle during inflammation and/or immobilisation

Intensive Care Med Exp. 2023 Mar 27;11(1):16. doi: 10.1186/s40635-023-00503-9.

Authors

Julius J Grunow¹, Thomas Gan², Heidrun Lewald², J A Jeevendra Martyn³, Manfred Blobner², Stefan J Schaller^{4

5}

Affiliations

¹ Charité - Universitätsmedizin Berlin, corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CVK, CCM), Charitéplatz 1, 10117, Berlin, Germany.
² Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Anesthesiology and Intensive Care, Ismaninger Straße 22, 81675, Munich, Bavaria, Germany.
³ Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children®-Boston, and Harvard Medical School, 51 Blossom Street, Room 206, Boston, 02114, MA, USA.
⁴ Charité - Universitätsmedizin Berlin, corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CVK, CCM), Charitéplatz 1, 10117, Berlin, Germany. s.schaller@tum.de.
⁵ Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Anesthesiology and Intensive Care, Ismaninger Straße 22, 81675, Munich, Bavaria, Germany. s.schaller@tum.de.

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.

Keywords: Immobilisation; Inflammation; Insulin signaling; Intensive care unit acquired weakness; Muscle atrophy.

Grants and funding

Junior Clinician Scientist/Berlin Institute of Health