Interrelationships of glucose and insulin uptake by muscle of normal and diabetic man. Evidence of a difference in metabolism of endogenous and exogenous insulin.

A forearm perfusion technique was used to study glucose and insulin uptake by muscle. In normal subjects at glycaemic levels above 130 mg/100 ml, glucose uptake was independent of glucose concentration;it was directly related in insulin concentration but not to insulin uptake. In non-obese maturity-onset diabetic subjects, glucose uptake was dependent on glucose concentration and insulin uptake, but not on insulin concentration. In both groups there was a strong correlation between insulin concentration and insulin uptake; diabetics had a normal insulin uptake in relation to concentration. For a given change in insulin concentration the increase in glucose uptake was as great in diabetics as in controls, but the effect of insulin was mediated through a mechanism involving its uptake. Thus in the non-obese maturity-onset diabetic, forearm muscle is not insulin resistant. The apparent uptake of insulin measured by a radioimmunoassay in relation to its arterial concentration was lower and more variable for heterologous than for endogenous insulin. With a receptor assay the venous insulin concentrations were lower than with the immunoassay and differences in uptake between endogenous and exogenous insulin disappeared. It is concluded that in muscle exogenous insulin was less severely degraded than endogenous insulin.