The effect of phenformin on insulin-stimulated isoaminobutyric acid (AIB) transport by isolated hepatocytes

Hepatocytes isolated from adult rat livers by collagenase perfusion were used to investigate the effect of phenformin on amino acid transport by measuring the uptake of aminoisobutyric acid (AIB). At concentrations between 0.01 and 100 μg/ml, phenformin hydrochloride did not affect AIB uptake, but concentrations of 500 and 1000 μg/ml were inhibitory. Incubating hepatocytes with insulin increased their accumulation of AIB. Inclusion of up to 100 μg/ml, phenformin hydrochloride during maximal and submaximal stimulation by insulin did not affect AIB uptake, but inhibition occurred with 500 and 1000 μg/ml. The continued presence of phenformin after addition of AIB was not required in order to produce inhibition. Furthermore, increasing the duration of exposure of hepatocytes to phenformin increased the degree of inhibition, suggesting that it is a non-competitive inhibitor. We conclude that phenformin does not enhance the sensitivity of hepatocytes to insulin and that at higher concentrations it may exert an inhibitory effect on basal and insulin stimulated aminoacid transport.