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
To further evaluate the role of the lysosomal system in insulin degradation, the authors have compared the effects of inhibitors of lysosomal function on the degradation of /sup 125/I-insulin with /sup 125/I-asialofetuin, a lysosomally targeted molecule, by the intact, perfused rat liver and the isolated rat hepatocyte. The inhibitors employed were chloroquine (/sup 125/ microM), NH/sub 4/Cl (10 mM), and leupeptin (50 micrograms/ml). In the intact, perfused liver the observed inhibition of /sup 125/I-asialofetuin degradation at 30 min was as follows: chloroquine, 38%; NH/sub 4/Cl, 32%; and leupeptin, 86%. Chloroquine also inhibited /sup 125/I-insulin degradation in the intact, perfused liver (29%), but NH/sub 4/Cl and leupeptin had no effect. Using the isolated hepatocyte, the observed values for inhibition of 125I-asialofetuin at 60 min were: chloroquine, 85%; NH/sub 4/Cl, 76%; and leupeptin, 81%. Chloroquine produced a 28% inhibition of 125I-insulin degradation, while NH/sub 4/Cl and leupeptin had no effect. Chloroquine and NH/sub 4/Cl decreased cell-associated radioactivity when isolated hepatocytes were incubated with 125I-asialofetuin (leupeptin had no effect), whereas chloroquine caused a 107% increase in cell-associated radioactivity when 125I-insulin was added to the incubation media (NH/sub 4/Cl and leupeptin had no effect). These results indicate that the effects of chloroquine on insulin degradation are an extralysosomal action and that lysosomes appear not to be involved in the physiologic degradation of the insulin molecule.
- Research Organization:
- Univ. of Texas Health Science Center, San Antonio
- OSTI ID:
- 5264652
- Journal Information:
- Diabetes; (United States), Journal Name: Diabetes; (United States) Vol. 5; ISSN DIAEA
- Country of Publication:
- United States
- Language:
- English
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560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMMONIUM CHLORIDES
AMMONIUM COMPOUNDS
AMMONIUM HALIDES
ANIMALS
AROMATICS
AZAARENES
AZINES
BETA DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CELL CONSTITUENTS
CHEMICAL REACTIONS
CHLORIDES
CHLORINE COMPOUNDS
COMPARATIVE EVALUATIONS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HALIDES
HALOGEN COMPOUNDS
HETEROCYCLIC COMPOUNDS
HORMONES
IN VITRO
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIVER
LYSOSOMES
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PEPTIDE HORMONES
PERFUSED ORGANS
PROTEINS
PYRIDINES
QUINOLINES
RADIOISOTOPES
RATS
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