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Clinical Science (2008) Immediate Publication, doi:10.1042/CS20080087
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Ischemia and insulin, but not ischemia and contraction, act synergistic in stimulating muscle glucose uptake in vivo in humans
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Marlies Bosselaar, Paul Smits and Cees J Tack
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General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, The Netherlands. m.bosselaar@aig.umcn.nl
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Ischemia, 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 likely mediated by activation of AMPK. We hypothesized that in vivo in humans, ischemia- and insulin-induced glucose uptake are additive, and that the combined impact of ischemia and contraction on glucose uptake is of a similar magnitude when each is applied separately. We assessed the effects of ischemia with and without euglycemic hyperinsulinemia (clamp, protocol 1) and with and without muscle contraction (protocol 2) on muscle forearm glucose uptake (FGU) in healthy subjects. Furthermore, we assessed the impact of ischemia on forearm blood flow (FBF, plethysmography).
In protocol 1, ischemia increased FGU from 0.6±0.1 to 5.5±1.9, while insulin increased FGU to 1.6±0.3 μmol/min/dl (P<0.05 for both). The combination of ischemia and insulin increased FGU to 15.5±2.2 μmol/min/dl (P<0.05 versus each stimulus only). Maximal FBF obtained after ischemia was similar with and without hyperinsulinemia. In protocol 2, isometric contraction increased FGU from 0.3±0.1 to 2.7±0.8 μmol/min/dl (P<0.05), but FGU was not significantly different from ischemia compared with ischemia and contraction. However, combined contraction and ischemia resulted in a larger increase in FBF.
In summary, ischemia and insulin independently stimulate skeletal muscle glucose uptake in vivo in humans, while ischemia and contraction do not. The observed differential effects of these stimuli on glucose uptake seem to be unrelated to changes in muscle blood flow.
doi:10.1042/CS20080087
Received 13 March 2008/29 May 2008; Accepted 20 June 2008
Published as Immediate Publication 20 June 2008
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