Apolipoprotein B (apo B) secretion is reduced by insulin in rat hepatocytes. To evaluate possible mechanisms by which insulin action leads to inhibition of apo B secretion, we evaluated the effect of suppression of the protein-tyrosine phosphatase LAR on apo B secretion by McA-RH7777 (McA) rat hepatoma cells. A reduction in cellular LAR levels was accomplished by stable transfection of McA cells with LAR antisense cDNA. Previous studies indicate that LAR-antisense transfectants demonstrate increased insulin receptor signaling. In current studies, reduced LAR expression results in a 60% to 70% reduction in apo B secretion compared with null vector control. The reduction in apo B secretion correlated with a significant decrease in cellular apo B mRNA levels. Results suggests there is a relationship of protein tyrosine phosphorylation with regulation of apo B mRNA abundance in McA cells.