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
- Country of Publication:
- United States
- Language:
- English
Similar Records
Insulin-induced surface redistribution regulates internalization of the insulin receptor and requires its autophosphorylation
Effects of lysosomal inhibitors on /sup 125/I-insulin and /sup 125/I-asialofetuin degradation by the isolated, perfused rat liver and isolated rat hepatocytes
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ANOXIA
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
GROWTH FACTORS
HORMONES
INHIBITION
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGANDS
LIVER CELLS
MAMMALS
MEMBRANE PROTEINS
METABOLISM
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
VERTEBRATES