Effect of age on glucose utilization and responsiveness to insulin in forearm muscle.

To determine the effect of age on responsiveness to insulin, 35 healthy subjects (age range, 22--73 years) were studied. A glucose-clamp technique was used to obtain a range of values for steady-state arterial glucose and arterial insulin concentrations; total body glucose utilization was estimated from the rate of glucose infusion needed to maintain the steady state; and the uptake of glucose and insulin by forearm muscle was determined by a forearm perfusion procedure. The results were examined by multiple regression analyses. The rate of glucose utilization by the whole body as well as by forearm muscle was dependent upon the insulin concentration. Age had no apparent effect on body glucose utilization, the uptake of glucose or insulin by muscle, or the steady-state insulin concentration in response to hyperglycemia. It is concluded that the abnormal glucose tolerance commonly associated with increased age is not due to a decrease in either insulin secretion or insulin stimulation of glucose uptake.

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.

Effect of exercise on glucose and insulin utilization in the forearm.

Glucose and insulin utilization by forearm muscle was examined at rest and during exercise. Care was taken to have a steady state with regard to arterial plasma concentrations for 1 hr prior to as well as during the measurements. At rest, insulin uptake was linearly related to arterial insulin concentration. During exercise with no change in arterial plasma concentration of either glucose or insulin, there was an increase in uptake of both substances, and the relation of insulin uptake to concentration became exponential. It is hypothesizes that the latter phenomenon is due to an increase in cellular uptake of insulin by a mechanism independent of membrane receptors.