Dual pathways for the intracellular processing of insulin. Relationship between retroendocytosis of intact hormone and the recycling of insulin receptors

Journal Article · Tue Nov 05 04:00:00 EST 1985 · J. Biol. Chem.; (United States)

OSTI ID:6182115

Marshall, S

Adipocytes process insulin through either of two pathways: a retroendocytotic pathway that culminates in the release of intact insulin, and a degradative pathway that terminates in the intracellular catabolism and release of degraded ligand. Mechanistically, these pathways were found to differ in several ways. First, temporal differences were found in the rate at which intact and degraded products were extruded. After SVI-insulin was preloaded into the cell interior, intact ligand was completely released during the first 10 min (t 1/2 = 2 min), whereas degraded insulin was released at a much slower rate over 1 h (t 1/2 greater than 8 min). Secondly, it was found that chloroquine profoundly inhibited the insulin degradative pathway, resulting in the intracellular accumulation of intact ligand and a reduction in the release of degraded products. In contrast, however, chloroquine was without effect on the retroendocytotic processing of insulin. Based on the known actions of chloroquine, it appears that retroendocytosis of insulin does not involve vesicular acidification or dissociation of the insulin-receptor complex and that insulin is most likely carried to the cell exterior in the same vesicles (either receptor-bound or free) as those mediating recycling receptors. Interestingly, accumulation of undergraded insulin within chloroquine-treated cells did not result in the release of additional intact ligand, suggesting that once insulin enters the degradative compartment it is committed to catabolism and cannot exit the cell through the retroendocytotic pathway. A third difference was revealed by the finding that extracellular unlabeled insulin (100 ng/ml) markedly accelerated the rate at which preloaded SVI-insulin was released from adipocytes (t 1/2 of 3 min versus 7 min in controls cells).

• Research Organization: Univ. of California, San Diego
• OSTI ID: 6182115
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 25; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADIPOSE TISSUE
ALCOHOLS
ANIMAL TISSUES
ANIMALS
AROMATICS
AZAARENES
AZINES
BIOLOGICAL PATHWAYS
BODY
CARBOXYLIC ACIDS
CATABOLISM
CHELATING AGENTS
CONNECTIVE TISSUE
DOSE-RESPONSE RELATIONSHIPS
EGTA
GLYCOLS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROXY COMPOUNDS
IN VITRO
INSULIN
LIGANDS
MAMMALS
METABOLISM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HORMONES
PYRIDINES
QUINOLINES
RATS
RECEPTORS
RODENTS
TISSUES
VERTEBRATES