RECEPTOR‐MEDIATED 125I‐LABELLED INSULIN DEGRADATION IN THE RAT HEPATOCYTE. STUDIES USING CHLOROQUINE

Abstract
Degradation of insulin during incubation with target cells occurs via receptor-mediated processes. In this study, receptor-mediated degradation of 125I-labelled insulin was investigated in rat hepatocytes, using the agent chloroquine. Chloroquine increased specific cell-associated 125I-labelled insulin at 37°. The increased radioactivity with chloroquine was intracellular (53.3 1.2% of initially bound label was displaced by excess cold insulin; in control cells 67.02.1 % was displaced. P3 or 1 g/1 bacitracin, which indicated a post-internalization site of action. Chloroquine had no effect on degradation of 125I-labelled insulin in buffer alone or in buffer previously incubated with cells. Specific studies of receptor-mediated degradation at 37° showed that more 125I-labelled insulin remained associated with hepatocytes when chloroquine was present (P125I-labelled insulin released during processing of surface-bound label at 37° showed that chloroquine-sensitive mechanisms accounted for at least 50% of receptor-mediated insulin degradation in rat hepatocytes.

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