Membrane transport in relation to net uptake of glucose in the perfused rat hindlimb. Stimulatory effect of insulin, hypoxia and contractile activity

Abstract

The paired-tracer dilution method applied to the perfused rat hindlimb model was used to study glucose transport in relation to net glucose uptake in skeletal muscle tissue. 2-deoxyglucose was used as an analogue for glucose, since this eliminates the problem with release of labelled metabolites. The affinity of 2-deoxyglucose for the glucose carrier was shown to be indistinguishable from that of glucose. An insulin dose-response study showed maximal stimulation of glucose uptake and transport at 0.1 unit/l, and 75% of maximal stimulation at 0.01 unit of insulin/l. Hypoxia and contractile activity stimulated the 2-deoxyglucose transport rate similarly, and the stimuli were not additive, suggesting a common mechanism. The presence of insulin did not increase the effect of hypoxia or contractile activity, indicating no permissive effect of insulin. The 2-deoxyglucose transport rate was closely correlated with and always higher than that of glucose uptake, demonstrating that the transport is never rate-limiting for the net glucose uptake and that both processes are regulated together. Significant correlations between the 2-deoxyglucose transport rate and the intramuscular concentration of phosphocreatine suggest regulation of the glucose utilization by the energy state of the skeletal muscle tissue.