The enhanced ability of liver to extract glucogenic precursors from plasma in insulinopenic diabetes was investigated at the cellular level by measuring amino acid transport in isolated hepatocytes from streptozotocin-diabetic rats. The concentrative Na+-dependent uptake of α-amino[1-14C]isobutyric acid (AIB), a nonmetabolizable analog of alanine, was increased in hepatocytes from diabetic rats compared with controls. This increase was observed both at a low (0.1 mM) and high (30 mM) extracellular concentration of the amino acid. Analysis of the relationship between AIB influx and AIB concentration revealed that the increased uptake in diabetic rat hepatocytes was due to an enhanced capacity (i.e., a twofold increase in the Vmax) of the transport system whereas the apparent affinity (Km) for AIB was unaltered.
The increased amino acid transport activity in diabetic rat hepatocytes was due mainly to an increased transport through system A (alanine-preferring) and, to a much lesser extent, through system ASC (alanine, serine, cysteine). System L (leucine-preferring) and AIB entry through simple diffusion were not affected in diabetic rat hepatocytes compared with controls. Increased AIB transport of diabetic rat hepatocytes was returned to normal by insulin treatment.