A compartmental model to quantitate in vivo glucose transport in the human forearm

Glucose transport is a critical step in the control of glucose disposal that, until presently, has not been quantitated in vivo in humans. We have employed the perfused forearm and euglycemic insulin-clamp techniques in combination with a dual-tracer injection to measure basal and insulin-mediated glucose transport in six normal subjects. L-[3H]glucose, which is not transported, was used to trace extracellular glucose kinetics; 3-O-[14C]-methyl-D-glucose, transportable but not metabolizable, was used to monitor glucose movement across the cell membrane. After bolus intra-arterial injection of the two tracers, plasma samples were obtained every 15-30 s for 10 min from a deep forearm vein to determine the washout curves. A linear compartmental model was developed that accounts for blood flow heterogeneity. It consists of three parallel, two-compartment chains merging into the sampling compartment to which cellular compartments are appended. A priori identifiability analysis was performed. The uniquely identifiable parameterization includes the transport rate constants of glucose into and out of the cell. The model was identified using nonlinear least-squares parameter estimation. Transport parameters are estimated with very good precision, and their reproducibility is satisfactory. The model also allows the estimation of the mean arteriovenous transit times of both the extracellular and the transported tracer. The compartmental model provides a novel approach to investigate glucose transport in vivo in humans.