Insulin signaling in skeletal muscle during inflammation and/or immobilisation
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-03-01
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| Series: | Intensive Care Medicine Experimental |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40635-023-00503-9 |
| _version_ | 1797854064805937152 |
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| author | Julius J. Grunow Thomas Gan Heidrun Lewald J. A. Jeevendra Martyn Manfred Blobner Stefan J. Schaller |
| author_facet | Julius J. Grunow Thomas Gan Heidrun Lewald J. A. Jeevendra Martyn Manfred Blobner Stefan J. Schaller |
| author_sort | Julius J. Grunow |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T20:01:01Z |
| format | Article |
| id | doaj.art-9015186afeb64b9e88b21454a2d6ce89 |
| institution | Directory Open Access Journal |
| issn | 2197-425X |
| language | English |
| last_indexed | 2024-04-09T20:01:01Z |
| publishDate | 2023-03-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Intensive Care Medicine Experimental |
| spelling | doaj.art-9015186afeb64b9e88b21454a2d6ce892023-04-03T05:13:41ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2023-03-0111111310.1186/s40635-023-00503-9Insulin signaling in skeletal muscle during inflammation and/or immobilisationJulius J. Grunow0Thomas Gan1Heidrun Lewald2J. A. Jeevendra Martyn3Manfred Blobner4Stefan J. Schaller5Charité - Universitätsmedizin Berlin, corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CVK, CCM)Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Anesthesiology and Intensive CareTechnical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Anesthesiology and Intensive CareDepartment of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children®-Boston, and Harvard Medical SchoolTechnical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Anesthesiology and Intensive CareCharité - Universitätsmedizin Berlin, corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CVK, CCM)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.https://doi.org/10.1186/s40635-023-00503-9Intensive care unit acquired weaknessImmobilisationInflammationMuscle atrophyInsulin signaling |
| spellingShingle | Julius J. Grunow Thomas Gan Heidrun Lewald J. A. Jeevendra Martyn Manfred Blobner Stefan J. Schaller Insulin signaling in skeletal muscle during inflammation and/or immobilisation Intensive Care Medicine Experimental Intensive care unit acquired weakness Immobilisation Inflammation Muscle atrophy Insulin signaling |
| title | Insulin signaling in skeletal muscle during inflammation and/or immobilisation |
| title_full | Insulin signaling in skeletal muscle during inflammation and/or immobilisation |
| title_fullStr | Insulin signaling in skeletal muscle during inflammation and/or immobilisation |
| title_full_unstemmed | Insulin signaling in skeletal muscle during inflammation and/or immobilisation |
| title_short | Insulin signaling in skeletal muscle during inflammation and/or immobilisation |
| title_sort | insulin signaling in skeletal muscle during inflammation and or immobilisation |
| topic | Intensive care unit acquired weakness Immobilisation Inflammation Muscle atrophy Insulin signaling |
| url | https://doi.org/10.1186/s40635-023-00503-9 |
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