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Critical illness myopathy and GLUT4 - significance of insulin and muscle contraction

Official URL:https://doi.org/10.1164/rccm.201209-1649OC
PubMed:View item in PubMed
Creators Name:Weber-Carstens, S. and Schneider, J. and Wollersheim, T. and Assmann, A. and Bierbrauer, J. and Marg, A. and Al Hasani, H. and Chadt, A. and Wenzel, K. and Koch, S. and Fielitz, J. and Kleber, C. and Faust, K. and Mai, K. and Spies, C.D. and Luft, F.C. and Boschmann, M. and Spranger, J. and Spuler, S.
Journal Title:American Journal of Respiratory and Critical Care Medicine
Journal Abbreviation:Am J Respir Crit Care Med
Volume:187
Number:4
Page Range:387-396
Date:15 February 2013
Keywords:Analysis of Variance, Artificial Respiration, Biopsy, Critical Illness, Electric Stimulation, Glucose Clamp Technique, Glucose Transporter Type 4, Hypoglycemic Agents, Insulin, Microdialysis, Muscle Contraction, Muscular Diseases, Organ Dysfunction Scores, Pilot Projects, Prospective Studies, Sepsis, Signal Transduction
Abstract:Rationale: Critical illness myopathy (CIM) has no known cause and no treatment. Immobilization and impaired glucose metabolism are implicated. Objectives: We assessed signal transduction in skeletal muscle of patients at risk for CIM. We also investigated the effects of evoked muscle contraction (ISRCTN77569430). Methods: Prospective observational and interventional pilot study. We screened 874 mechanically ventilated patients with sepsis-related organ-failure assessment score >= 8 for three consecutive days in the first five days of ICU. 30 patients at risk for CIM underwent euglycemic-hyperinsulinemic clamp, muscle microdialysis studies, and muscle biopsies. Controls were healthy. In five additional patients at risk for CIM, we performed corresponding analyses after 12-day, daily, unilateral electrical muscle stimulation (EMS) with the contralateral leg as control. Measurements: We performed successive muscle biopsies, assessed systemic insulin sensitivity and signal transduction pathways of glucose utilization at mRNA and protein level and glucose transporter-4 (GLUT4) localization in skeletal muscle tissue. Main results: Skeletal muscle GLUT4 was trapped at perinuclear spaces, most pronounced in CIM patients, but resided at the sarcolemma in controls. Glucose metabolism was not stimulated during euglycemic-hyperinsulinergic clamp. Insulin signal transduction was competent up to p-Akt activation; however, p-AMPK was not detectable in CIM muscle. EMS increased p-AMPK, repositioned GLUT4, locally improved glucose metabolism, and prevented type-2 fiber atrophy. Conclusions: Insufficient GLUT4 translocation results in decreased glucose supply in CIM patients. Failed AMPK activation is involved. Evoked muscle contraction may prevent muscle-specific AMPK failure, restore GLUT4 disposition, and diminish protein breakdown.
ISSN:1073-449X
Publisher:American Thoracic Society (U.S.A.)
Item Type:Article

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