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Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization
Shur, Natalie F. Simpson, Elizabeth J. Crossland, Hannah Constantin, Despina Lobo, Dileep N. Szewczyk, Nate Macdonald, Ian A. Greenhaff, Paul L.
Shur, Natalie F.
Simpson, Elizabeth J.
Crossland, Hannah
Constantin, Despina
Lobo, Dileep N.
Szewczyk, Nate
Macdonald, Ian A.
Greenhaff, Paul L.
Abstract
Background: Bed rest (BR) reduces whole-body insulin-stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers are maintained in energy balance. Method(s): Healthy males (n = 10, 24.0 +/- 1.3 years), maintained in energy balance, underwent 3-day BR (acute BR). A second cohort matched for sex and body mass index (n = 20, 34.2 +/- 1.8 years) underwent 56-day BR (chronic BR). A hyperinsulinaemic euglycaemic clamp (60 mU/m2/min) was performed to determine rates of whole-body insulin-stimulated GD before and after BR (normalized to lean body mass). Indirect calorimetry was performed before and during steady state of each clamp to calculate rates of whole-body fuel oxidation. Muscle biopsies were taken to determine muscle glycogen, metabolite and intramyocellular lipid (IMCL) contents, and the expression of 191 mRNA targets before and after BR. Two-way repeated measures analysis of variance was used to detect differences in endpoint measures. Result(s): Acute BR reduced insulin-mediated GD (Pre 11.5 +/- 0.7 vs. Post 9.3 +/- 0.6 mg/kg/min, P Result(s): Acute BR reduced insulin-mediated GD (Pre 11.5 +/- 0.7 vs. Post 9.3 +/- 0.6 mg/kg/min, P Result(s): Acute BR reduced insulin-mediated GD (Pre 11.5 +/- 0.7 vs. Post 9.3 +/- 0.6 mg/kg/min, P Result(s): Acute BR reduced insulin-mediated GD (Pre 11.5 +/- 0.7 vs. Post 9.3 +/- 0.6 mg/kg/min, P Result(s): Acute BR reduced insulin-mediated GD (Pre 11.5 +/- 0.7 vs. Post 9.3 +/- 0.6 mg/kg/min, P Conclusion(s): Acute BR suppressed insulin-stimulated GD and storage, but the extent of this suppression increased no further in chronic BR. However, insulin-mediated inhibition of fat oxidation after chronic BR was less than acute BR and was accompanied by blunted CHO oxidation. The juxtaposition of these responses shows that the regulation of GD and storage can be dissociated from substrate oxidation. Additionally, the shift in substrate oxidation after chronic BR was not explained by IMCL accumulation but reflected by muscle mRNA and pyruvate dehydrogenase kinase 4 protein abundance changes, pointing to lack of muscle contraction per se as the primary signal for muscle adaptation.Copyright © 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.
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Date
2022
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Shur, N.F., Simpson, E.J., Crossland, H., Chivaka, P.K., Constantin, D., Cordon, S.M., ConstantinTeodosiu, D., Stephens, F.B., Lobo, D.N., Szewczyk, N., Narici, M., Prats, C., Macdonald, I.A. and Greenhaff, P.L. (2022) 'Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization', Journal of Cachexia, Sarcopenia and Muscle, 13(6), pp. 2999-3013. doi: 10.1002/jcsm.13075 https://doi.org/10.1002/jcsm.13075.