Degradation of endocytosed insulin in rat liver is mediated by low-density vesicles

Uptake of 125I-insulin by the liver of intact rats is followed by rapid translocation of label to low-density vesicles. Subcellular-fractionation studies indicate that, although the 125I associated with these vesicles is predominantly trichloroacetic acid-precipitable, there is an acid-soluble component arising from processing of the hormone in vivo. H.p.l.c. analysis indicates that the acid-precipitable 125I is not intact iodoinsulin, but may correspond to 'clipped insulin'. Isolated low-density vesicles degrade the acid-precipitable iodopeptide intravesicularly when incubated at 37 degrees C in iso-osmotic medium at pH7. The rate constant for intravesicular degradation is consistent with the rate of insulin clearance by the liver in vivo. Pretreatment of the rats with chloroquine resulted in a decrease in proteolysis of the iodopeptide within the isolated vesicles.