Evidence for multiple pathways of sup 125 I-insulin internalization in isolated rat hepatocytes
Insulin internalization has been characterized frequently as occurring by the coated pit pathway of receptor-mediated endocytosis. The present study in rat hepatocytes demonstrates that insulin internalization is, in part, receptor-mediated, but also occurs by nonreceptor-mediated or fluid-phase endocytosis. Endocytosis was probed with four perturbations: depletion of metabolic energy with anoxia, inhibition of endocytosis with phenylarsine oxide, disruption of coated pits with hyperosmolar sucrose, and inhibition of receptor recycling or ligand-receptor dissociation with monensin. Internalization of {sup 125}I-epidermal growth factor and {sup 125}I-asialofetuin was compared to {sup 125}I-insulin internalization. Pretreatment of cells with anoxia or hyperosmolarity inhibited {sup 125}I-insulin internalization by 40%; pretreatment with phenylarsine oxide resulted in inhibition by 54%. Monensin has no effect on uptake or degradation of a high insulin concentration, but inhibited degradation of a low insulin concentration resulting in intracellular accumulation of insulin. In contract, all four perturbations inhibited {sup 125}I-asialofetuin internalization by greater than 90%. Phenylarsine oxide almost completely abolished {sup 125}I-epidermal growth factor uptake; the other perturbations caused partial inhibition. Competition studies demonstrated that insulin internalization was receptor-mediated over a wide concentration range.
- Research Organization:
- Texas Univ., San Antonio, TX (USA). Health Science Center
- OSTI ID:
- 7147008
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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550501* - Metabolism- Tracer Techniques