Use of glucose uptake and glucose clearance for the evaluation of insulin action in vivo

Glucose uptake displays saturation kinetics both in vitro and in vivo. Accordingly, as glucose concentrations increase, glucose uptake will increase less and less until a maximum rate of glucose uptake is reached. Since glucose clearance is calculated by dividing glucose uptake by the prevailing glucose concentration, it must of necessity decrease as glucose concentrations increase and thus cannot be independent of glucose concentration. Because the use of glucose clearance to standardize glucose uptake measurements obtained at different glucose concentrations presumes that glucose clearance is independent of glucose concentration, this use of glucose clearance is not valid. It is important to distinguish between glucose uptake simply due to the mass action effects of glucose from that due to insulin when evaluating insulin action since the relative influences of plasma glucose and plasma insulin concentrations on glucose uptake can vary considerably under different experimental and clinical conditions. Finally, kinetic analysis of both non-insulin-mediated and insulin-mediated glucose uptake may prove useful in characterizing the pathologic mechanisms involved in conditions associated with insulin resistance.