Receptor-mediated endocytosis of [125I]insulin into pancreatic acinar cells in vivo.

One of the highest concentrations of insulin receptors is found in the cell membrane of the pancreatic acinar cell. A radioautographic study has been carried out to monitor the fate of in vivo injected 125I-labeled insulin after binding to the acinar cell membrane. [125I]Insulin remained for long periods of time (greater than 45 min) within the exocrine cell. Quantitative radioautography at the electron microscopic level revealed endocytosis of hormone and localization to zymogen granules and, to a lesser extent, multivesicular bodies, lysosomes, structures that were receptosome like, and small undefined structures of about 50-100 nm in diameter found dispersed among endoplasmic reticulum saccules. Treatment with the lysosomotropic agent chloroquine produced large secondary lysosomes which were seldom labeled. Rather, there was an increase in the proportion of label over zymogen granules and receptosome-like structures without increased retention of label by acinar cells. Thus, in pancreatic exocrine cells, nonlysosomal structures are of major quantitative importance in insulin internalization. The high concentration of grains about the bounding membrane of zymogen granules points to a merging of the endocytic and exocytic pathways in pancreatic acinar cells.