The relationship between insulin binding, insulin activation of insulin-receptor tyrosine kinase, and insulin stimulation of glucose uptake in isolated rat adipocytes

We have studied the relationship between insulin activation of
insulin-receptor kinase and insulin stimulation of glucose uptake
in isolated rat adipocytes. Glucose uptake was half-maximally or
maximally stimulated, respectively, when only 4% or 14% of the
maximal kinase activity had been reached. To investigate this
relationship also under conditions where the insulin effect on
activation of receptor kinase was decreased, the adipocytes were
exposed to 10 microM-isoprenaline alone or with 5 micrograms of
adenosine deaminase/ml. An approx. 30% (isoprenaline) or approx.
50% (isoprenaline + adenosine deaminase) decrease in the insulin
effect on receptor kinase activity was found at insulin
concentrations between 0.4 and 20 ng/ml, and this could not be
explained by decreased insulin binding. The decreased
insulin-effect on kinase activity was closely correlated with a
loss of insulin-sensitivity of glucose uptake. Moreover, our data
indicate that the relation between receptor kinase activity and
glucose uptake (expressed as percentage of maximal uptake) remained
unchanged. The following conclusions were drawn. (1) If activation
of receptor kinase stimulates glucose uptake, only 14% of the
maximal kinase activity is sufficient for maximal stimulation. (2)
Isoprenaline decreases the coupling efficiency between insulin
binding and receptor-kinase activation, this being accompanied by a
corresponding decrease in sensitivity of glucose uptake. (3) Our
data indicate that the signalling for glucose uptake is closely
related to receptor-kinase activity, even when the coupling
efficiency between insulin binding and kinase activation is
altered. They thus support the hypothesis that receptor-kinase
activity reflects the signal which originates from the receptor and
which is transduced to the glucose-transport system.