Hepatic processing of insulin
- 1 May 1989
- journal article
- Published by Wiley in JBIC Journal of Biological Inorganic Chemistry
- Vol. 181 (2), 287-294
- https://doi.org/10.1111/j.1432-1033.1989.tb14723.x
Abstract
The effect of selected weak bases on the subcellular distribution and processing of internalized insulin by the liver has been studied. The effect of these bases on both the degradation products formed and on the kinetics of degradation have also been studied. 1. Methylamine, ammonium chloride and dansyl cadaverine but not chloroquine reduce the total amount of insulin endocytosed. 2. Ammonium chloride, dansyl cadaverine and chloroquine but not methylamine inhibit subsequent degradation and/or translocation of degradation products. 3. None of the weak bases changed the species of the degradation products found within the endocytic vesicles. 4. Kinetic analysis of intravesicular degradation indicates that dissociation from the receptor is the rate-limiting process in degradation. 5. Chloroquine and dansyl cadaverine but not methylamine or ammonium chloride showed specific inhibition of insulin degradation in isolated endocytic vesicles. 6. The effect of chloroquine and dansyl cadaverine on the kinetics of degradation suggest that they are acting by switching the receptor into a tight-binding conformation thereby slowing dissociation.Keywords
This publication has 37 references indexed in Scilit:
- Reversal of insulin-induced negative cooperativity by monoclonal antibodies that stabilize the slowly dissociating (“Ksuper”) state of the insulin receptorBiochemical and Biophysical Research Communications, 1988
- Identification of A chain cleavage sites in intact insulin produced by insulin protease and isolated hepatocytesBiochemical and Biophysical Research Communications, 1987
- The insulin-receptor interaction: Is the kinetic approach for inferring negative-cooperative site-site interactions valid?Biochemical and Biophysical Research Communications, 1987
- Insulin and insulin receptor uptake into rat liver. Chloroquine action on receptor recyclingDiabetes, 1985
- Characterization of insulin uptake into subcellular fractions of perfused rat liver using two different iodinated tracersCell Biochemistry and Function, 1985
- A Possible Role for Insulin-Receptor Subunit in Degrading Receptor-Bound InsulinHormone and Metabolic Research, 1984
- Lysosomal and Non-Lysosomal Pathways of Intracellular Insulin Degradation in Isolated Rat HepatocytesHormone Research, 1981
- Chloroquine and ammonium ion inhibit receptor-mediated endocytosis of mannose-glycoconjugates by macrophages: Apparent inhibition of receptor recyclingBiochemical and Biophysical Research Communications, 1980
- Transglutaminase is essential in receptor-mediated endocytosis of α2-macroglobulin and polypeptide hormonesNature, 1980
- Lysosomal association of internalized 125I-insulin in isolated rat hepatocytes. Direct demonstration by quantitative electron microscopic autoradiography.JCI Insight, 1979