Ischaemia, like muscle contraction, has been reported to induce skeletal muscle glucose uptake in in vitro models. This stimulating effect appears independent of insulin and is probably mediated by activation of AMPK (AMP-activated protein kinase). In the present study, we hypothesized that in vivo in humans ischaemia- and insulin-induced glucose uptake are additive, and that the combined impact of ischaemia and contraction on glucose uptake is of a similar magnitude when each is applied separately. We assessed the effects of ischaemia with and without euglycaemic–hyperinsulinaemia (clamp; protocol 1) and with and without muscle contraction (protocol 2) on muscle FGU (forearm glucose uptake) in healthy subjects. Furthermore, we assessed the impact of ischaemia on FBF (forearm blood flow; plethysmography). In protocol 1, ischaemia increased FGU from 0.6±0.1 at baseline to 5.5±1.9 μmol·min−1·dl−1, and insulin increased FGU to 1.6±0.3 μmol·min−1·dl−1 (P<0.05 for both). The combination of ischaemia+insulin increased FGU to 15.5±2.2 μmol·min−1·dl−1 (P<0.05 compared with each stimulus alone). Maximal FBF obtained after ischaemia was similar with and without hyperinsulinaemia. In protocol 2, isometric contraction increased FGU from 0.3±0.1 to 2.7±0.8 μmol·min−1·dl−1 (P<0.05), but FGU was not significantly different from ischaemia compared with ischaemia+contraction. However, combined ischaemia+contraction resulted in a greater increase in FBF. In summary, ischaemia and insulin independently stimulate skeletal muscle glucose uptake in vivo in humans, whereas ischaemia and contraction do not. The observed differential effects of these stimuli on glucose uptake appear to be unrelated to changes in muscle blood flow.
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January 2009
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Research Article|
December 15 2008
Ischaemia and insulin, but not ischaemia and contraction, act synergistically in stimulating muscle glucose uptake in vivo in humans
Marlies Bosselaar;
*Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Correspondence: Dr Marlies Bosselaar (email m.bosselaar@aig.umcn.nl).
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Paul Smits;
Paul Smits
*Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
†Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
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Cees J. Tack
Cees J. Tack
*Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
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Publisher: Portland Press Ltd
Received:
March 13 2008
Revision Received:
May 29 2008
Accepted:
June 20 2008
Accepted Manuscript online:
June 20 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2009 Biochemical Society
2009
Clin Sci (Lond) (2009) 116 (2): 157–164.
Article history
Received:
March 13 2008
Revision Received:
May 29 2008
Accepted:
June 20 2008
Accepted Manuscript online:
June 20 2008
Citation
Marlies Bosselaar, Paul Smits, Cees J. Tack; Ischaemia and insulin, but not ischaemia and contraction, act synergistically in stimulating muscle glucose uptake in vivo in humans. Clin Sci (Lond) 1 January 2009; 116 (2): 157–164. doi: https://doi.org/10.1042/CS20080087
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